Advances of SHP2 modulators in the cancer immunotherapy / 药学学报

Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

Effects of subchronic fluoride exposure through drinking water on renal toxicity and the expressions of STIM1 and ORAI1 in renal tissues in mice / 环境与职业医学

Background It has been found that fluoride may cause cell damage by inducing intracellular calcium overload. Store-operated calcium entry (SOCE) plays an important role in maintaining intracellular calcium homeostasis, but the effect of fluoride on renal SOCE is unknown. Objective To explore the renal toxicity and the expression levels of the key proteins of SOCE, stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (ORAI1) in the kidney tissues of mice exposed to fluoride subchronically. Methods Twenty male ICR mice were randomly divided into four groups with five mice in each group, including 0 (control group), 0.3, 3, and 30 mg·L−1 fluoride groups. The mice were given drinking water containing designed fluoride for 12 weeks. Body weight and liver and kidney organ coefficients of the mice were measured after the exposure; histopathological changes of the mouse kidney were observed; 24 h urine was collected at the end of 12 weeks of exposure to determine the levels of urine creatinine (UCr), urine calcium (UCa), albumin (ALB), and β2-microglobulin (β2-MG); the protein expression levels of STIM1 and ORAI1 in the kidney were detected by Western blotting; the fluorescence co-localization of STIM1 and ORAI1 was used to further verify the expression levels of STIM1 and ORAI1. Results After the exposure, there were no differences in body weight as well as liver and kidney organ coefficients among the groups (P > 0.05). Under optical microscope, the renal tubular cell showed degeneration, apical protrusion, shedding, and dilation in the 3 and 30 mg·L−1 fluoride groups. There was no statistical difference in UCr among the mice in each group (P > 0.05). Compared with the control group, the levels of UCa adjusted by UCr in the 3 and 30 mg·L−1 fluoride groups were (0.075±0.014) and (0.081±0.012) mol·mol−1 (represent by UCr per mol), which had a rising trend but showed no statistical difference. No difference was identified in the level of ALB among the groups (P > 0.05). The levels of β2-MG showed difference in different exposure groups, and the level of urine β2-MG in the 30 mg·L−1 fluoride group was (0.077±0.014) g·mol−1, higher than that in the control group (P<0.05). Based on the results of Western blotting, the protein expression levels of STIM1 and ORAI1 showed significant differences among the groups (F=18.411, 6.853; P=0.001, 0.013); compared with the control group, the expression levels of STIM1 protein increased in the 3 and 30 mg·L−1 fluoride groups (P < 0.05), and the protein expression level of ORAI1 in the 30 mg·L−1 fluoride group was increased (P < 0.05). The fluorescence co-localization results of STIM1 and ORAI1 showed that the expressions of STIM1 and ORAI1 were up-regulated in the 3 and 30 mg·L−1 fluoride groups. Conclusion Subchronic exposure to fluoride through drinking water can up-regulate the expression levels of STIM1 and ORAI1 in renal tissues and induce renal injury.

Research progress of cystic fibrosis and its therapies / 药学学报

Cystic fibrosis (CF) is a common and life-threatening autosomal recessive disorder in Caucasians populations. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The absence of mature CFTR at the correct cellular location or dysfunction of CFTR proteins has been observed in CF patients. CF is frequently accompanied by a variety of complex complications, such as impairments in pulmonary functions, which may lead to successive infections and respiratory failure. Recently, with the understanding of the pathogenesis of CF, a wide array of therapeutic strategies for the treatment of CF has been designed. This review summarizes pathogenic mechanisms of CF, mechanisms of action of drugs, routes of administration, and new drug development as well as provides insights into the advanced treatment strategies for CF.

Advances of using antibody against B cell activating factor for treatment of autoimmune diseases / 生物工程学报

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.

Updated research progress of selective PPARγ modulators / 药学学报

Thiazolidinediones (TZDs) are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes. Although their advantages are recognized, the profiles of numerous adverse effects hinder the continued use of these drugs. Peroxisome proliferator-activated receptor γ (PPARγ) is known as a receptor for TZDs, and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored. To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects, the concept of "selective PPARγ modulators (SPPARMs)" has been proposed and developed, guiding the development of new drugs. In this review, we summarize the recent research progress in the definition of SPPARMs, the candidate classification and the molecular underpinnings, as well as present the discovery of the YR series compounds as an example, and discuss the potential application prospects of SPPARMs.

Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.

The study of hemodynamic mechanism of a novel endovascular stent on complicated abdominal aortic aneurysms / 中华胸心血管外科杂志

Objective@#To detect the hemodynamic mechanism of the novel endovascular stent on complicated abdominal aortic aneurysms by Computational Fluid Dynamics(CFD) firstly, and then compare the effect of the novel endovascular stent and the streamliner multilayer flow modulator(SMFM) stent.@*Methods@#All medical images were obtained by computed tomography. A semiautomatic segmentation protocol within Mimics(v17.0; Materialise, Leuven, Belgium) was used to extract the threedimensional aortic aneurysms. The stents was generated numerically and fitted along the aortic aneurysms. The lumen volume represented the fluid domain that was discretised in smaller volumes, which defined a mesh within the ICEM software(Ansys ICEM CFD v15.0). Hemodynamic analysis was performed with software Fluent 16.0.@*Results@#Both kinds of stents can change the pattern of flow distribution. Compared with SMFM, the novel endovascular stent can significantly reduce the flow velocity in aneurysms, the shear force and the pressure on the aneurysms wall.What’s more, the flow velocity of the branch artery was accelerated by the novel endovascular stent.@*Conclusion@#The novel endovascular stent can significantly reduce the flow velocity in aneurysms, the shear force and the pressure on the aneurysms wall, and acceleratethe the flow velocity of the branch artery.

Effect of sublingual immunotherapy on functions of effector T cells and regulatory T cells / 上海交通大学学报（医学版）

Objective • To investigate the effect of sublingual immunotherapy (SLIT) on the functions of effector T cells (Teff) and regulatory T cells (Treg) under allergic rhinitis (AR) condition. Methods • Peripheral blood mononuclear cells (PBMC) were obtained from 20 AR patients who were recruited from Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital North of Fudan University before and after the 24-and 30-month treatments of SLIT. The percentages of Teff and Treg in CD4+ T cells in PBMC were examined and the contents of calcium release-activated calcium channel modulator 1(ORAI1) protein and Ca2+ mean fluorescence intensity (MFI) in PBMC were measured. Then, Teff and Treg after the 30-month treatment were cultured in vitro, and were evaluated for the expression of ORAI1 protein and concentrations of interleukin-4(IL-4) and IL-10 in the cultures. Lentivirus vector (lenti) that encoded short hairpin RNA against ORAI1(lenti-ORAI1) was prepared and transfected into Teff and Treg, and then Ca2+ MFI in Teff and Treg and concentrations of IL-4 and IL-10 in the cultures were assessed again. Results • The percentage of Teff in CD4+ T cells in PBMC reduced gradually after the 24-and 30-month treatments (P=0.000, P=0.027); however, the percentage of Treg was increased (P=0.000, P=0.008). The expression of ORAI1 protein (P=0.000, P=0.003) and Ca2+ MFI (P=0.000, P=0.000) in Teff were also decreased gradually after the 24-and 30-month treatments; however, the expression of ORAI1 protein (P=0.000, P=0.007) and Ca2+ MFI in Treg were enhanced (P=0.000, P=0.000). ORAI1 protein was expressed in these two types of cells cultured in vitro. Furthermore, Ca2+ MFI in them (P=0.004, P=0.000) and IL-4(P=0.009) and IL-10(P=0.000) in the cultures were all decreased after the transfection of lenti-ORAI1. Conclusion • SLIT can control functions of Teff and Treg through regulating the expression of ORAI1 protein.

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system / 药物分析学报

Nitric oxide (NO) is a second messenger playing crucial roles in the signaling of a variety of cellular functions. Due to its pathophysiological significance, various NO modulators have been developed to explore NO pathways and some have been used as therapies. These modulators are often used directly to observe pharmacological effects in cell lines, but their actual effect on intracellular NO level is seldom analyzed. Herein, facilitated by a selective and sensitive fluorescence probe, we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase (eNOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) failing to decrease intra-cellular free NO level in EA. hy926 cells while NO donor diethylamine-NONOate (DEA?NONOate) and eNOS activator calcimycin (A23187) failing to increase free NO level in human umbilical vein endothelial cell line (HUV-EC-C), although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells (primary HUVECs) and RAW 264.7 macrophage cells. Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase (NOS) level and the endogenous glutathione (GSH) level. Genetically manipulating eNOS level in both cells restores the expected response, while decreasing GSH level restores the ability of DEA?NONOate to increase NO level in HUV-EC-C. These results reveal that the cellular microenvironment has a profound impact on pharmacological effect. Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironment-dependent pharmacological effects.

Effects of transient receptor potential vanillic acid subtype 1 receptor and its modulators on neuropathic pain: research advances / 国际药学研究杂志

Neuropathic pain(NPP)has always been a problem that puzzles the medical community because of its unclear pathogenesis and poor drug treatment. With the development of molecular biology and electrophysiological techniques, studies have shown that the complex pathological mechanism of NPP may be related to the activation of transient receptor potential vanillic acid sub-type 1(TRPV1). TRPV1 receptors are mainly expressed in peripheral sensory neurons, which can detect harmful stimuli in the external and internal environment and transmit information to the central nervous system, thereby playing an important role in peripheral neuropathic pain. TRPV1 modulators exert analgesic effects by blocking the pain transmission function of TRPV1 and have become a potential therapeutic agent in the treatment of NPP. This article reviews TRPV1 receptor-mediated NPP models and the role of TRPV1 modulators in NPP treatment.

Effect of Jiawei-Naotai formula on ATF4/CHOP/Puma pathway of ovariectomized rats with cerebral ischemia / 中国病理生理杂志

AIM:To investigate the effects of Jiawei-Naotai formula (JWNTF) on ATF4/CHOP/Puma pathway in hippocampal neurons of ovariectomized female rats with cerebral ischemia.METHODS:The female rats were randomly divided into sham group, model group, JWNTF group and positive control group.The rats, expect in the sham group, were ovariectomized.The rats in each group were intragastric administration 11 days after ovariectomy.The rats in sham group and model group were given a gavage of 0.9％Na Cl, while the rats in other groups were administrated by corresponding therapy intragastrically for 3 d.The regional cerebral ischemia model was established by middle cerebral artery occlusion (MCAO) suture method 14 days after ovariectomy.The behaviors of the rats were evaluated 24 h after cerebral ischemia.The mRNA levels of Bax, Bcl-2 and caspase-3 were detected by RT-qPCR, and the protein expression of Bax, Bcl-2, caspase-3, ATF4, CHOP and Puma was determined by Western blot.RESULTS:Compared with sham group, the neurobehavioral scores significantly increased in other groups (P<0.05).Compared with model group, the neurobehavioral scores were significantly decreased in positive control group and JWNTF group (P<0.05).The protein expression of Bax, caspase-3, ATF4, CHOP and Puma, and the mRNA expression of Bax and caspase-3 in the hippocampus were much higher, and Bcl-2 was lower in model group than those in sham group (P<0.05).JWNTF significantly reduced the protein expression of Bax, caspase-3, ATF4 and CHOP, and the mRNA expression of Puma, Bax and caspase-3, and markedly increased the expression of Bcl-2 at mRNA and protein levels compared with model group.CONCLUSION:The JWNTF protects against brain damage induced by cerebral ischemia, which may be related to inhibitiing the expression of ATF4/CHOP/Puma pathway-related molecules at mRNA and protein levels.

Mechanism and impact of a novel allosteric AMPA receptor modulator on protection against respiratory depression / 中国药理学与毒理学杂志

OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hyp-notics.To explore the mechanism of LCX001 on protection against respiratory depression,a novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration. METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid(fentanyl and TH-030418),propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation. The function of AMPA receptors were determined by location of receptors in the membrane and state of channel opening, and both processes were impressed by AMPA receptor regulatory proteins. Ac-cording to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by west-ern blotting. The variation of receptor surface location was observed by live cell imaging. The regula-tion on neuronal Ca2+and cell function was investigated intensively by Ca2+imaging to clarify mecha-nism of LCX001. RESULTS LCX001 effectively rescued and prevented opioid (fentanyl and TH-030418), propofol, and pentobarbital-induced respiratory depression by strengthening respiratory fre-quency and minute ventilation in rats. The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001,in contrast to some ampakines that did not affect analgesia. Fur-thermore,LCX001 potentiated[3H]AMPA and L-glutamate binding affinity to AMPA receptors,and facili-tated glutamate-evoked inward currents in HEK293 cells stably expressing GluA2(R).Importantly,appli-cation of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioid-induced abnormal intracellular Ca2+load,which might par-ticipate in breathing modulation. CONCLUSION The novel pharmacological effect and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respi-ratory depression.

Uterine fibroid shrinkage after short-term use of selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

OBJECTIVE: The aim of this study was to evaluate the effect of short-term use of selective progesterone receptor modulator (SPRM) or gonadotropin-releasing hormone (GnRH) agonist on uterine fibroid shrinkage among Korean women. METHODS: This retrospective study involved 101 women with symptomatic uterine fibroids who received ulipristal acetate (SPRM, n=51) and leuprolide acetate (GnRH agonist, n=50) for 3 months between November 2013 and February 2015. The fibroid volume was measured both before and after treatment using ultrasonography, computed tomography, and magnetic resonance imaging. The outcomes were compared between the SPRM and GnRH agonist groups. RESULTS: The median rate of fibroid volume reduction after SPRM treatment was 12.4% (IQR −14.5% to 40.5%) which was significantly lower than the reduction rate observed after GnRH agonist treatment (median 34.9%, IQR 14.7% to 48.6%, P=0.004). 19 of 51 (37.3%) patients with SPRM treatment did not show any response of volume shrinkage, while 7 of 50 (14.0%) women with GnRH agonist showed no response (P=0.007). CONCLUSION: Short-term SPRM treatment yields lower volume reduction than GnRH agonist treatment in Korean women with symptomatic fibroids. Further large-scale randomized trials are needed to confirm our findings.

Natural modulators of transient receptor potential channels / 药学学报

Transient receptor potential (TRP) channels are non-selective and cation-permeable channels in the cell membrane, widely distributed in tissues and organs of human body. As biosensors, TRP channels can regulate the functions of vision, hearing, taste, pain, and touch, etc. So far, more than 100 different kinds of natural modulators targeting TRP channels have been identified from 70 species of plants or animals. In this review article, we attempt to summarize the effect of known natural active compounds on TRP channels with focuses on their sources, structures, action features and mechanisms. Hopefully this review can provide some useful information that can facilitate discovery of more specific natural modulators, and development of innovative therapeutic drugs targeting TRP channels.

Recent research progress on anti-microtubule agents targeting multi-drug resistant cancers / 药学实践杂志

In 2015, more than 8 million people died from various kinds of cancers all over the world.Although traditional chemotherapeutic drugs are widely used in clinic, more than 50％ of cancers are significantly resistant to traditional chemotherapeutic drugs.Tubulin targeting agents have been confirmed to be effective anti-cancer drugs in clinic.However, some anti-microtubule agents developed resistance after long-term use, such as paclitaxel and vinblastine.In recent years, it is reported that tubulin modulators targeting on the colchicine-binding site are extremely effective against multi-drug resistant cancer cells.In this article, different anti-microtubule agents targeting multi-drug resistant cancers are reviewed.

Pharmacokinetics of H002, a novel S1PRmodulator, and its metabolites in rat blood using liquid chromatography-tandem mass spectrometry

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2-100 ng/mL for H002 and H002-M, while 0.5-100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from -9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.

Effectiveness of Osteoporosis Drug in Postmenopausal Women with Spinal Compression Fracture: Combined Consecutive Therapy of Teriparatide and Raloxifene versus Bisphosphonate Single / 대한신경손상학회지

OBJECTIVE: Bisphosphonate, a typical bone resorption inhibitor, is an important first-line drug for treating osteoporosis. Recent studies show a novel paradigm in stimulating bone formation. Teriparatide, which is composed of recombinant human parathyroid hormone, stimulates osteoblasts and induces bone regeneration. Bone mineral density (BMD) that was used before and after the treatment with anti-osteoporosis drug was compared for the effectiveness in therapy between a combination of teriparatide and selective estrogen receptor modulator (SERM), and bisphosphonate. METHODS: We retrospectively reviewed the outcomes of 85 postmenopausal women who were concurrently diagnosed with osteoporosis and spinal compression fracture between November 2008 and January 2015. The targeted group were treated with teriparatide and SERM (TS group, n=26) and bisphosphonate (B group, n=59). RESULTS: In both groups, BMD of femur neck was not improved after the medication. In the TS group, on the other hand the BMD and T-score of lumbar spine has significantly improved. BMD ratio of lumbar spine was prominently higher than those of TS group. CONCLUSION: The combination therapy of teriparatide and SERM was very effective in treating the lumbar spine, compared to that of bisphosphonate. Although the period of teriparatide treatment has been relatively short, the preventive effects of compression fracture were considerable. Thus, combination therapy of teriparatide and SERM is highly recommended for patients who are concerned with spinal compression fracture from osteoporosis.

Advances in medical prevention of breast cancer / 中国肿瘤临床

The development of optimal strategies for breast cancer prevention is necessary given the high incidence in China. Several prospective randomized clinical trials have investigated the effects of various pharmacologic agents on the incidence of invasive and noninvasive breast cancer. This review aimed to summarize the different approaches to reduce the incidence of breast cancer.

Investigation of centrally and peripherally acting analgesic and anti-infl ammatory activity of biological immune response modulator (an Amazonian plant extract) in animal models of pain and infl ammation.

Background: Biological immune response modulator (BIRM) - An aqueous extract of dried roots of the species dulcamara (family Solanaceae) grown in Ecuador, considered as a natural remedy for various disease is promoted as a natural herbal medicine. Our aim of the study was to assess the central and peripheral analgesic and anti-infl ammatory property of BIRM and to study its mechanism of action. Methods: Peripheral analgesic and anti-infl ammatory activity was evaluated using acetic acid induced writhing test and carrageenan paw edema test in male Swiss Albino mice (n=8 per group). Formalin test was taken up to evaluate BIRM’s centrally, as well as peripheral antinociceptive action. Results: We observed through our studies that BIRM when administered repeatedly for 7 days (4 ml/kg, p.o.) was able to exert its anti-nociceptive and anti-infl ammatory activity through central and peripheral mechanism. BIRM was able to signifi cantly inhibit both acetic acid induced writhes and carrageenan-induced paw edema indicating it’s possible peripheral analgesic and anti-infl ammatory action. BIRM was also able to inhibit both neurogenic and infl ammatory pain in the formalin test indicating its action through central and peripheral nervous system. Conclusion: Our study results show that BIRM has the potential anti-infl ammatory property and is able to exert its anti-nociceptive effect through both central and peripheral mechanisms.

Advances in Study on Intestinal Microbiota in Intestinal Homeostasis and Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),is characterized by chronic non-specific inflammation of intestinal tract,which is incurable and easily relapsing. Recently,the role of gut microbiota in IBD has become a hot spot of study. This article reviewed the advances in study on intestinal microbiota in intestinal homeostasis and IBD.