Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The ...Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.展开更多
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit ca...Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.展开更多
Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and d...Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.展开更多
AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dua...AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dual-g RNAs) covering the regulatory region of HBV were chosen. The efficiency of each g RNA and 11 dual-g RNAs on the suppression of HBV(genotypes A-D) replication was examined by the measurement of HBV surface antigen(HBs Ag) or e antigen(HBe Ag) in the culture supernatant. The destruction of HBV-expressing vector was examined in Hu H7 cells co-transfected with dual-g RNAs and HBVexpressing vector using polymerase chain reaction(PCR) and sequencing method, and the destruction of ccc DNAwas examined in Hep AD38 cells using KCl precipitation, plasmid-safe ATP-dependent DNase(PSAD) digestion, rolling circle amplification and quantitative PCR combined method. The cytotoxicity of these g RNAs was assessed by a mitochondrial tetrazolium assay.RESULTS: All of g RNAs could significantly reduce HBs Ag or HBe Ag production in the culture supernatant, which was dependent on the region in which g RNA against. All of dual g RNAs could efficiently suppress HBs Ag and/or HBe Ag production for HBV of genotypes A-D, and the efficacy of dual g RNAs in suppressing HBs Ag and/or HBe Ag production was significantly increased when compared to the single g RNA used alone. Furthermore, by PCR direct sequencing we confirmed that these dual g RNAs could specifically destroy HBV expressing template by removing the fragment between the cleavage sites of the two used g RNAs. Most importantly, g RNA-5 and g RNA-12 combination not only could efficiently suppressing HBs Ag and/or HBe Ag production, but also destroy the ccc DNA reservoirs in Hep AD38 cells.CONCLUSION: These results suggested that CRISPR/Cas9 system could efficiently destroy HBV expressing templates(genotypes A-D) without apparent cytotoxicity. It may be a potential approach for eradication of persistent HBV ccc DNA in chronic HBV infection patients.展开更多
Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug carriers.Its usual purpose...Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug carriers.Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility,drug aggregation,low bioavailability,poor biodistribution,lack of selectivity,or to reduce the side effects of therapeutic drugs.During 2015-2018,significant progress in the research on drug delivery systems has been achieved along with advances in related fields,such as pharmaceutical sciences,material sciences and biomedical sciences.This review provides a conciseoverview of current progress in this research area through its focus on the delivery strategies,construction techniques and specific examples.It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.展开更多
OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to ...OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to determine whether GLPP could attenuate RIRI via counteracting the oxidative stress.METHODS Mice subjected to uninephrectomy with the right kidney ischemia for 35 min and reperfusion for 24 hwere used to explore the protective activity of GLPP against RIRI.In GLPP-treated group,100mg·kg-1·d-1 of GLPP were intraperitoneally injected for 7dbefore the procedure.In vitro,NRK-52 Ecells subjected to hypoxia-reoxygenation(H/R)and tunicamycin were used to explore the protective effect of GLPP against oxidative stress.The mechanisms in which GLPP protected kidney from RIRI were studied using a series of physiological and molecular biological methods.RESULTS Kidneys undergone ischemia-reperfusion showed renal dysfunction and characteristic morphological changes including cellular necrosis,brush border loss,cast formation,vacuolization and tubular dilatation while these damages were significantly attenuated by GLPP treatment.The abnormal levels of MPO,MDA and SOD caused by renal ischemia-reperfusion were significantly reversed by GLPP treatment.More apoptotic cells were found in the renal ischemia-reperfusion group than the sham group whereas GLPP reduced apoptotic cells in the ischemia-reperfusion mice by21.75%(P<0.01).The GLPPs(25-1μg·mL)alleviated H/R induced cell viability loss by 20.12%(P<0.01)andΔφm dissipation by 27.3%(P<0.01)in vitro as well and its pretreatment dramatically reduced H/R and tunicamycin induced cell injury.CONCLUSION Our study found that GLPP had a protective effect on RIRI via its anti-oxidative capacity,which suggests that GLPP may be developed as a candidate drug for preventing acute kidney injury.展开更多
Regulated cell death(RCD),also well-known as programmed cell death(PCD),refers to the form of cell death that can be regulated by a variety of biomacromolecules,which is distinctive from accidental cell death(ACD).Acc...Regulated cell death(RCD),also well-known as programmed cell death(PCD),refers to the form of cell death that can be regulated by a variety of biomacromolecules,which is distinctive from accidental cell death(ACD).Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis,which may ultimately lead to the establishment of different potential therapeutic strategies.Hitherto,targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue,which has rapidly progressed in many types of human cancers.Thus,in this review,we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways,but the crucial pathways of other RCD subroutines,including necroptosis,pyroptosis,ferroptosis,parthanatos,entosis,NETosis and lysosomedependent cell death(LCD)in cancer.Moreover,we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment,such as single-target,dual or multiple-target small-molecule compounds,drug combinations,and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.展开更多
This paper presents a review of recent rolling robots including Rollo from Helsinki University of Technology, Spherical Mobile Robot from the Politecnico of Bad, Sphericle from the University of Pisa, Spberobot from M...This paper presents a review of recent rolling robots including Rollo from Helsinki University of Technology, Spherical Mobile Robot from the Politecnico of Bad, Sphericle from the University of Pisa, Spberobot from Michigan State University, August from Azad University of Qazvin and the University of Tehran, Deformable Robot from Ritsumeijan University, Kickbot from the Massachusetts Institute of Technology, Gravitational Wheeled Robot from Kinki University, Gyrover from Carnegie Mellon University, Roball from the Université de Sherbrooke, and Rotundus from the Angstroem Space Technology Center. Seven rolling robot design principles are presented and discussed （Sprung central member, Car driven, Mobile masses, Hemispherical wheels, Gyroscopic stabilisation, Ballast mass - fixed axis, and Ballast mass - moving axis）. Robots based on each of the design principles are shown and the performances of the robots are tabulated. An attempt is made to grade the design principles based on their suitability for movement over an unknown and varied but relatively smooth terrain. The result of this comparison suggests that a rolling robot based on a mobile masses principle would be best suited to this specific application. Some wonderful rolling organisms are introduced and defined as ＂active＂ or ＂passive＂ depending on whether they generate their own rolling motion or external forces cause their rolling.展开更多
The saponin ginsenoside Rk1 is a major compound isolated from ginseng.Ginsenoside Rk1 has been reported to have anti-inflammatory and anti-tumor properties and to be involved in the regulation of metabolism.However,th...The saponin ginsenoside Rk1 is a major compound isolated from ginseng.Ginsenoside Rk1 has been reported to have anti-inflammatory and anti-tumor properties and to be involved in the regulation of metabolism.However,the effect and mechanism of anti-inflammatory action of ginsenoside Rk1 has not been fully clarified.We investigated whether ginsenoside Rk1 could suppress the inflammatory response in lipopolysaccharide-stimulated RAW264.7 macrophages and to explore its mechanism of the action.RAW264.7 cells were treated with LPS(1 μg×mL^(–1))in the absence or the presence of Ginsenoside Rk1(10,20,and 40 μmol×L^(–1)).Then the inflammatory factors were tested with Griess reagents,ELISA,and RT-PCR.The proteins were analyzed by Western blotting.Ginsenoside Rk1 inhibited lipopolysaccharide-induced expression of nitric oxide(NO),interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,and monocyte chemotactic protein(MCP)-1.Ginsenoside Rk1 inhibited the lipopolysaccharide-stimulated phosphorylation of NF-κB and janus kinase(Jak)2 and signal transducer and activator of transcription(Stat)3 at Ser727 and Tyr705.These data suggested that ginsenoside Rk1 could inhibit expression of inflammatory mediators and suppress inflammation further by blocking activation of NF-κB and the Jak2/Stat3 pathway in LPS-stimulated RAW264.7 cells.展开更多
To differentiate traditional Chinese medicines(TCM) derived from congeneric species in TCM compound preparations is usually challenging. The roots of Panax ginseng(PG), Panax quinquefolium(PQ) and Panax notoginseng(PN...To differentiate traditional Chinese medicines(TCM) derived from congeneric species in TCM compound preparations is usually challenging. The roots of Panax ginseng(PG), Panax quinquefolium(PQ) and Panax notoginseng(PN) are used as popular TCM. They contain similar triterpenoid saponins(ginsenosides) as the major bioactive constituents. Thus far, only a few chemical markers have been discovered to differentiate these three species. Herein we present a multiple marker detection approach to effectively differentiate the three Panax species, and to identify them in compound preparations. Firstly, 85 batches of crude drug samples(including 32 PG, 30 PQ, and 23 PN) were analyzed by monitoring 40 major ginsenosides in the extracted ion chromatograms(EICs) using a validated LC–MS fingerprinting method. Secondly, the samples were clustered into different groups by pattern recognition chemometric approaches using PLS-DA and OPLS-DA models, and17 diagnostic chemical markers were discovered. Aside from the previously known Rf and p-F11, ginsenoside Rs1 could be a new marker to differentiate PG from PQ. Finally, the above multiple chemical markers were used to identify the Panax species in 60 batches of TCM compound preparations.展开更多
Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s ame...Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.展开更多
Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis usin...Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators(rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995–2015and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.展开更多
Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an i...Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage.However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering(TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.展开更多
Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific in...Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific ingredients have been found in Ephedra herb, mainly including alkaloids, flavonoids, tannins, polysaccharides, organic acids, volatile oils, and many other active compounds. These components from Ephedra herb account for its use as the accurate treatment of cold, cough, cardiovascular and immune system disease, cancer, microbial infection, and other diseases. Moreover, with the fast development of novel chemistry and medicine technology, new chemical constituents and pharmacological effects of Ephedra herb are increasingly identified, demonstrating their great potential for various diseases treatment. Therefore, further detailed understanding and investigation of this ancient herb will offer new opportunities to develop novel therapeutics. This study systematically reviews its progress of phytochemistry, traditional and modern pharmacology based on research data that have been reported, aiming at providing useful insight for commercial exploitation, further study and precision medication of Ephedra herb in future.展开更多
In the present study,we aimed to investigate the chemical constituents and analgesic activity of Aconitum kusnezoffii Reichb. The isolation and purification of components were achieved by a series of chromatography, i...In the present study,we aimed to investigate the chemical constituents and analgesic activity of Aconitum kusnezoffii Reichb. The isolation and purification of components were achieved by a series of chromatography, including silica gel, Sephadex LH-20 and HPLC. By using spectroscopic analysis, their structures were identified. Using PDE-4A as analgesic target, moleculardocking was conducted between isolated compounds by using Schrodinger software. Neoline is a typical non-ester diterpene alkaloid. It was studied by using the mouse torsion body method and hot plate method. A total of 12 diterpene alkaloids were obtainedand identified as Mesaconitine(1), Bewutine (2), Bewudine (3), Songoramine (4), Songorine (5), Neoline (6), Talasamine (7), isotalatizidine (8), Hokbusine A (9), Mesaconine (10), 8-OEt-14-benzoylmesaconine (11), 8-Methoxy-14-benzoyl-beiwutinine (12).Compounds 9 and 12 were isolated from Aconitum kusnezoffii Reichb. for the first time. Twelve diterpenealkaloids could act on the analgesic target. Neoline is a typical non-ester diterpene alkaloid. It had significant analgesic effect. Diterpene alkaloids were the main components of Aconitum kusnezoffiiReichb., and they had good analgesic activity.展开更多
Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a ther...Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.展开更多
Three new phenanthrenes,along with one known phenanthrene,were isolated from the ethanolic extract of the tubers of Cremastra appendiculata（D.Don） Makino.Their structures were elucidated on the basis of extensive sp...Three new phenanthrenes,along with one known phenanthrene,were isolated from the ethanolic extract of the tubers of Cremastra appendiculata（D.Don） Makino.Their structures were elucidated on the basis of extensive spectroscopic analysis.Compounds 1-4 were tested for in vitro cytotoxic activities against human lung（A549）,colon（HCT-116）,liver（HepG2）,and breast（MCF-7 and MDA-MB-231） cancer cell lines.展开更多
At the time of implanting bone-related implants into human body,a variety of biological responses to the material surface occur with respect to surface chemistry and physical state.The commonly used biomaterials(e.g.t...At the time of implanting bone-related implants into human body,a variety of biological responses to the material surface occur with respect to surface chemistry and physical state.The commonly used biomaterials(e.g.titanium and its alloy,Co–Cr alloy,stainless steel,polyetheretherketone,ultra-high molecular weight polyethylene and various calcium phosphates)have many drawbacks such as lack of biocompatibility and improper mechanical properties.As surface modification is very promising technology to overcome such problems,a variety of surface modification techniques have been being investigated.This review paper covers recent advances in surface modification techniques of bone-related materials including physicochemical coating,radiation grafting,plasma surface engineering,ion beam processing and surface patterning techniques.The contents are organized with different types of techniques to applicable materials,and typical examples are also described.展开更多
The alpha-7 nicotinic acetylcholine receptor(α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca^(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7...The alpha-7 nicotinic acetylcholine receptor(α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca^(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease(AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.展开更多
Objective：To explore the regulative efficacy of Pu＇er tea（普洱茶）extract on metabolic syndrome. Methods：Ninety patients with metabolic syndrome were randomly divided into two groups,the intervention group adminis...Objective：To explore the regulative efficacy of Pu＇er tea（普洱茶）extract on metabolic syndrome. Methods：Ninety patients with metabolic syndrome were randomly divided into two groups,the intervention group administered with Pu＇er tea extract,and the placebo group with placebo capsules.After 3 months＇ treatment, body mass index,waist hip ratio,blood lipids,blood sugar,immune and inflammatory index,and oxidation index of the patients with metabolic syndrome were tested and analyzed.Results：In the intervention group,the body mass index,waist-hip ratio,fasting and 2 h postprandial blood glucose,serum total cholesterol,triglycerides, low density lipoprotein and apolipoprotein B-100 all decreased in the patients with metabolic syndrome,and also the high-density lipoprotein level increased and apolipoprotein A-1 showed the tendency to increase. Serum C-reactive protein,tumor necrosis factor-α,and interleukin-6 were decreased in the intervention group. lnterleukin-10 level was increased,MDA was decreased and superoxide dismutase was increased.Compared with before treatment and the placebo group,there were significant differences（P0.05,P0.01）.Conclusions： Pu＇er tea demonstrated excellent potential in improving central obesity,adjusting blood lipid,lowering blood sugar,regulating immunity and resisting oxidation.It can adjust the metabolic syndrome of different clinical phenotypes to different degrees,and is ideally fit for early prevention of metabolic syndrome.展开更多
基金supported by the National Key Research and Development Program of China(grant No.SQ2018YFC100236)the National Natural Science Foundation of China(grant Nos.91857115,81522007,81470554,31401011,and 81700010)+1 种基金the Fundamental Research Funds for the Central Universities:Clinical Medicine Plus X-Young Scholars Project of Peking University(grant No.PKU2018LCXQ013,China)Beijing Nova Program(grant No.Z161100004916056,China)
文摘Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.
基金supported by National Natural Science Foundation of China(Nos.81673436,21472091,81872877,81673437)Mountain-Climbing Talents Project of Nanjing University,the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University(No.KF-GN-201703,China)+1 种基金Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica(No.JKLPSE201802,China)the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD,China)
文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.
文摘Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.
基金Supported by Natural Science Foundation of China,No.81471938the National S and T Major Project for Infectious Diseases,No.2013ZX10002-002 and No.2012ZX10002-005111 Project,No.B07001
文摘AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dual-g RNAs) covering the regulatory region of HBV were chosen. The efficiency of each g RNA and 11 dual-g RNAs on the suppression of HBV(genotypes A-D) replication was examined by the measurement of HBV surface antigen(HBs Ag) or e antigen(HBe Ag) in the culture supernatant. The destruction of HBV-expressing vector was examined in Hu H7 cells co-transfected with dual-g RNAs and HBVexpressing vector using polymerase chain reaction(PCR) and sequencing method, and the destruction of ccc DNAwas examined in Hep AD38 cells using KCl precipitation, plasmid-safe ATP-dependent DNase(PSAD) digestion, rolling circle amplification and quantitative PCR combined method. The cytotoxicity of these g RNAs was assessed by a mitochondrial tetrazolium assay.RESULTS: All of g RNAs could significantly reduce HBs Ag or HBe Ag production in the culture supernatant, which was dependent on the region in which g RNA against. All of dual g RNAs could efficiently suppress HBs Ag and/or HBe Ag production for HBV of genotypes A-D, and the efficacy of dual g RNAs in suppressing HBs Ag and/or HBe Ag production was significantly increased when compared to the single g RNA used alone. Furthermore, by PCR direct sequencing we confirmed that these dual g RNAs could specifically destroy HBV expressing template by removing the fragment between the cleavage sites of the two used g RNAs. Most importantly, g RNA-5 and g RNA-12 combination not only could efficiently suppressing HBs Ag and/or HBe Ag production, but also destroy the ccc DNA reservoirs in Hep AD38 cells.CONCLUSION: These results suggested that CRISPR/Cas9 system could efficiently destroy HBV expressing templates(genotypes A-D) without apparent cytotoxicity. It may be a potential approach for eradication of persistent HBV ccc DNA in chronic HBV infection patients.
基金supported by the projects of National Natural Science Foundation of China(Grant Nos.81773650,81690264 and 81673376)the Drug Innovation Major Project of China(Grant No.2018ZX09721003-004).
文摘Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug carriers.Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility,drug aggregation,low bioavailability,poor biodistribution,lack of selectivity,or to reduce the side effects of therapeutic drugs.During 2015-2018,significant progress in the research on drug delivery systems has been achieved along with advances in related fields,such as pharmaceutical sciences,material sciences and biomedical sciences.This review provides a conciseoverview of current progress in this research area through its focus on the delivery strategies,construction techniques and specific examples.It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
基金The project supported by National Natural Science Foundation of China(81330074,81261160507,81170632,81370783,41376166)the 111Project,and International Science&Technology Cooperation Program of China 2012DFA11070
文摘OBJECTIVE Ganoderma lucidum polysaccharide peptides(GLPP)have an anti-oxidant activity.The oxidative stress implicates in the pathogenesis of renal ischemia-reperfusion injury(RIRI).The objective of this study was to determine whether GLPP could attenuate RIRI via counteracting the oxidative stress.METHODS Mice subjected to uninephrectomy with the right kidney ischemia for 35 min and reperfusion for 24 hwere used to explore the protective activity of GLPP against RIRI.In GLPP-treated group,100mg·kg-1·d-1 of GLPP were intraperitoneally injected for 7dbefore the procedure.In vitro,NRK-52 Ecells subjected to hypoxia-reoxygenation(H/R)and tunicamycin were used to explore the protective effect of GLPP against oxidative stress.The mechanisms in which GLPP protected kidney from RIRI were studied using a series of physiological and molecular biological methods.RESULTS Kidneys undergone ischemia-reperfusion showed renal dysfunction and characteristic morphological changes including cellular necrosis,brush border loss,cast formation,vacuolization and tubular dilatation while these damages were significantly attenuated by GLPP treatment.The abnormal levels of MPO,MDA and SOD caused by renal ischemia-reperfusion were significantly reversed by GLPP treatment.More apoptotic cells were found in the renal ischemia-reperfusion group than the sham group whereas GLPP reduced apoptotic cells in the ischemia-reperfusion mice by21.75%(P<0.01).The GLPPs(25-1μg·mL)alleviated H/R induced cell viability loss by 20.12%(P<0.01)andΔφm dissipation by 27.3%(P<0.01)in vitro as well and its pretreatment dramatically reduced H/R and tunicamycin induced cell injury.CONCLUSION Our study found that GLPP had a protective effect on RIRI via its anti-oxidative capacity,which suggests that GLPP may be developed as a candidate drug for preventing acute kidney injury.
基金The study was supported by the Fundamental Research Funds for the National Natural Science Foundation of China(82003879,81773889,82073998)Science and Technology Department of Sichuan Province(2022JDRC0045)+2 种基金Central Universities(YJ201880)Youth Talent Promotion Project of China Association for Science and Technology(CACM-2020 QNRC1-01)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21061).Parts of images generated from BioRender.com.
文摘Regulated cell death(RCD),also well-known as programmed cell death(PCD),refers to the form of cell death that can be regulated by a variety of biomacromolecules,which is distinctive from accidental cell death(ACD).Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis,which may ultimately lead to the establishment of different potential therapeutic strategies.Hitherto,targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue,which has rapidly progressed in many types of human cancers.Thus,in this review,we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways,but the crucial pathways of other RCD subroutines,including necroptosis,pyroptosis,ferroptosis,parthanatos,entosis,NETosis and lysosomedependent cell death(LCD)in cancer.Moreover,we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment,such as single-target,dual or multiple-target small-molecule compounds,drug combinations,and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.
文摘This paper presents a review of recent rolling robots including Rollo from Helsinki University of Technology, Spherical Mobile Robot from the Politecnico of Bad, Sphericle from the University of Pisa, Spberobot from Michigan State University, August from Azad University of Qazvin and the University of Tehran, Deformable Robot from Ritsumeijan University, Kickbot from the Massachusetts Institute of Technology, Gravitational Wheeled Robot from Kinki University, Gyrover from Carnegie Mellon University, Roball from the Université de Sherbrooke, and Rotundus from the Angstroem Space Technology Center. Seven rolling robot design principles are presented and discussed （Sprung central member, Car driven, Mobile masses, Hemispherical wheels, Gyroscopic stabilisation, Ballast mass - fixed axis, and Ballast mass - moving axis）. Robots based on each of the design principles are shown and the performances of the robots are tabulated. An attempt is made to grade the design principles based on their suitability for movement over an unknown and varied but relatively smooth terrain. The result of this comparison suggests that a rolling robot based on a mobile masses principle would be best suited to this specific application. Some wonderful rolling organisms are introduced and defined as ＂active＂ or ＂passive＂ depending on whether they generate their own rolling motion or external forces cause their rolling.
基金supported by the National Natural Science Foundation of China(Nos.81173369,81303253,81530097,and 81222051)the National Key Technology R&D Program “New Drug Innovation” of China(Nos.2012ZX09301002-002-002 and 2012ZX09304-005)+1 种基金the Natural Science Foundation of Beijing,China(No.132210)the Doctoral Scientific Fund Project of the Ministry of Education of China(No.20120001110105)
文摘The saponin ginsenoside Rk1 is a major compound isolated from ginseng.Ginsenoside Rk1 has been reported to have anti-inflammatory and anti-tumor properties and to be involved in the regulation of metabolism.However,the effect and mechanism of anti-inflammatory action of ginsenoside Rk1 has not been fully clarified.We investigated whether ginsenoside Rk1 could suppress the inflammatory response in lipopolysaccharide-stimulated RAW264.7 macrophages and to explore its mechanism of the action.RAW264.7 cells were treated with LPS(1 μg×mL^(–1))in the absence or the presence of Ginsenoside Rk1(10,20,and 40 μmol×L^(–1)).Then the inflammatory factors were tested with Griess reagents,ELISA,and RT-PCR.The proteins were analyzed by Western blotting.Ginsenoside Rk1 inhibited lipopolysaccharide-induced expression of nitric oxide(NO),interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,and monocyte chemotactic protein(MCP)-1.Ginsenoside Rk1 inhibited the lipopolysaccharide-stimulated phosphorylation of NF-κB and janus kinase(Jak)2 and signal transducer and activator of transcription(Stat)3 at Ser727 and Tyr705.These data suggested that ginsenoside Rk1 could inhibit expression of inflammatory mediators and suppress inflammation further by blocking activation of NF-κB and the Jak2/Stat3 pathway in LPS-stimulated RAW264.7 cells.
基金supported by National Natural Science Foundation of China(No.81222054)
文摘To differentiate traditional Chinese medicines(TCM) derived from congeneric species in TCM compound preparations is usually challenging. The roots of Panax ginseng(PG), Panax quinquefolium(PQ) and Panax notoginseng(PN) are used as popular TCM. They contain similar triterpenoid saponins(ginsenosides) as the major bioactive constituents. Thus far, only a few chemical markers have been discovered to differentiate these three species. Herein we present a multiple marker detection approach to effectively differentiate the three Panax species, and to identify them in compound preparations. Firstly, 85 batches of crude drug samples(including 32 PG, 30 PQ, and 23 PN) were analyzed by monitoring 40 major ginsenosides in the extracted ion chromatograms(EICs) using a validated LC–MS fingerprinting method. Secondly, the samples were clustered into different groups by pattern recognition chemometric approaches using PLS-DA and OPLS-DA models, and17 diagnostic chemical markers were discovered. Aside from the previously known Rf and p-F11, ginsenoside Rs1 could be a new marker to differentiate PG from PQ. Finally, the above multiple chemical markers were used to identify the Panax species in 60 batches of TCM compound preparations.
基金supported by National Natural Science Foundation of China(No.81470050)Beijing Natural Science Foundation(No.7122097)
文摘Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.
文摘Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators(rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995–2015and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.
基金The authors acknowledge the financial support from the Beijing Municipal Natural Science Foundation No.2184119(D.L.)and No.L182005(Y.L.)the Projects of Beijing Nova Programme No.Z171100001117018(Y.L.)+2 种基金Beijing Nova Programme Interdisciplinary Cooperation Project No.Z181100006218135(Y.L.and D.L.)the National Natural Science Foundations of China No.81571815(Y.L.),No.81871492(Y.L.)and No.51902344(D.L.)the Science Foundation of China University of Petroleum No.2462018BJB002(D.L.).
文摘Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage.However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering(TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.
基金the National Natural Science Foundation of China (Nos.31670328,31270383)。
文摘Ephedra herb is a traditional Chinese medicine with a long history. Conventionally, it was used as a folk phytomedicine in many ancient medical books and traditional prescriptions. Up to date, a variety of specific ingredients have been found in Ephedra herb, mainly including alkaloids, flavonoids, tannins, polysaccharides, organic acids, volatile oils, and many other active compounds. These components from Ephedra herb account for its use as the accurate treatment of cold, cough, cardiovascular and immune system disease, cancer, microbial infection, and other diseases. Moreover, with the fast development of novel chemistry and medicine technology, new chemical constituents and pharmacological effects of Ephedra herb are increasingly identified, demonstrating their great potential for various diseases treatment. Therefore, further detailed understanding and investigation of this ancient herb will offer new opportunities to develop novel therapeutics. This study systematically reviews its progress of phytochemistry, traditional and modern pharmacology based on research data that have been reported, aiming at providing useful insight for commercial exploitation, further study and precision medication of Ephedra herb in future.
基金National Natural Science Foundation of China(Grant No.30973628)the National Science and Technology Major Project of China(Grant No.SQ2018ZX090301)
文摘In the present study,we aimed to investigate the chemical constituents and analgesic activity of Aconitum kusnezoffii Reichb. The isolation and purification of components were achieved by a series of chromatography, including silica gel, Sephadex LH-20 and HPLC. By using spectroscopic analysis, their structures were identified. Using PDE-4A as analgesic target, moleculardocking was conducted between isolated compounds by using Schrodinger software. Neoline is a typical non-ester diterpene alkaloid. It was studied by using the mouse torsion body method and hot plate method. A total of 12 diterpene alkaloids were obtainedand identified as Mesaconitine(1), Bewutine (2), Bewudine (3), Songoramine (4), Songorine (5), Neoline (6), Talasamine (7), isotalatizidine (8), Hokbusine A (9), Mesaconine (10), 8-OEt-14-benzoylmesaconine (11), 8-Methoxy-14-benzoyl-beiwutinine (12).Compounds 9 and 12 were isolated from Aconitum kusnezoffii Reichb. for the first time. Twelve diterpenealkaloids could act on the analgesic target. Neoline is a typical non-ester diterpene alkaloid. It had significant analgesic effect. Diterpene alkaloids were the main components of Aconitum kusnezoffiiReichb., and they had good analgesic activity.
基金National Natural Science Foundation of China(U1903210,31530020,81701598,31570880,81471601,81801617)Beijing SciTech Program(Z171100000417007,Z191100006619114)Macao Science and Technology Fund(0094/2018/A3).
文摘Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.
基金supported by National Key Technology R&D Program "New Drug Innovation" of China(Nos. 2012ZX09301002-002-002 and 2012ZX09304-005)
文摘Three new phenanthrenes,along with one known phenanthrene,were isolated from the ethanolic extract of the tubers of Cremastra appendiculata（D.Don） Makino.Their structures were elucidated on the basis of extensive spectroscopic analysis.Compounds 1-4 were tested for in vitro cytotoxic activities against human lung（A549）,colon（HCT-116）,liver（HepG2）,and breast（MCF-7 and MDA-MB-231） cancer cell lines.
基金This work was partly supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Korea(2012R1A1A2040717)the National Basic Research Program of China funded by the Ministry of Science and Technology(MOST)of China(2011CB606205)+1 种基金the National Science and Technology Supporting Program of China funded by the MOST of China(2012BAI17B02)the National Natural Science Fund funded by the National Natural Science Foundation of China(21371106).
文摘At the time of implanting bone-related implants into human body,a variety of biological responses to the material surface occur with respect to surface chemistry and physical state.The commonly used biomaterials(e.g.titanium and its alloy,Co–Cr alloy,stainless steel,polyetheretherketone,ultra-high molecular weight polyethylene and various calcium phosphates)have many drawbacks such as lack of biocompatibility and improper mechanical properties.As surface modification is very promising technology to overcome such problems,a variety of surface modification techniques have been being investigated.This review paper covers recent advances in surface modification techniques of bone-related materials including physicochemical coating,radiation grafting,plasma surface engineering,ion beam processing and surface patterning techniques.The contents are organized with different types of techniques to applicable materials,and typical examples are also described.
文摘The alpha-7 nicotinic acetylcholine receptor(α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca^(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease(AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.
基金Supported by the Major Project of Development of Biotic Resources in Yunnan Province(No.2007YNCXB-01-01)
文摘Objective：To explore the regulative efficacy of Pu＇er tea（普洱茶）extract on metabolic syndrome. Methods：Ninety patients with metabolic syndrome were randomly divided into two groups,the intervention group administered with Pu＇er tea extract,and the placebo group with placebo capsules.After 3 months＇ treatment, body mass index,waist hip ratio,blood lipids,blood sugar,immune and inflammatory index,and oxidation index of the patients with metabolic syndrome were tested and analyzed.Results：In the intervention group,the body mass index,waist-hip ratio,fasting and 2 h postprandial blood glucose,serum total cholesterol,triglycerides, low density lipoprotein and apolipoprotein B-100 all decreased in the patients with metabolic syndrome,and also the high-density lipoprotein level increased and apolipoprotein A-1 showed the tendency to increase. Serum C-reactive protein,tumor necrosis factor-α,and interleukin-6 were decreased in the intervention group. lnterleukin-10 level was increased,MDA was decreased and superoxide dismutase was increased.Compared with before treatment and the placebo group,there were significant differences（P0.05,P0.01）.Conclusions： Pu＇er tea demonstrated excellent potential in improving central obesity,adjusting blood lipid,lowering blood sugar,regulating immunity and resisting oxidation.It can adjust the metabolic syndrome of different clinical phenotypes to different degrees,and is ideally fit for early prevention of metabolic syndrome.
