IN VITRO ANTI-HEPATOMA EFFECTS OF MONOCYTES AND KUPFFER CELLS ISOLATED FROM HEPATOMA PATIENTS AFTER TREATMENT WITH BIOLOGICAL IMMUNE STIMULANTS

Monocytes (MC), lymphocytes (LC) and Kupffer cells (KC) were isolated respectively from blood and surgical liver samples of patients suffering from he-patocellular carcinoma (HCC). 13 patients were given BCG, mixed bacterium vaccine (MBV) and human white blood cell interferon (IFN), the other 3 patients were not treated with any biological immune stimulants (BIS) and served as controls. The cytosta-tic and cytotoxic effects of MC and KC on human hepatoma SMMC-7721 (TC) were assayed in vitro and the numbers of T total (Tt), T helper (Th) and T suppressor (Ts) cells were counted using CD monoclonal antibody immunofluorescence. The results were as follows: (1) On the 7th day after the first administration of BIS, the cytostatic and cytotoxic effects of MC on TC showed obvious increase over pre-administration. The activity of BIS was 1 ?5 times as high as that in the controls. (2) After 3 administrations, the cytostatic effect of MC on TC increased to the normal level (84%), while the controls remained as before (45%). (3) On the 7th day after first administration, cytostatic and cytotoxic effects of KC on TC were 0.5 and 1 times higher respectively than those of the controls. (4) The numbers of Tt and Th of patients given BIS increased continuously; on the contrary Ts decreased in number. These results indicate that combined use of BCG, MBV and IFN can actively enhance the immune anti-hepatoma function of patients suffering from HCC.

Blood and Histopathological Biomarkers of Immune-related Adverse Effects of Treatment with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors have been a recent major breakthrough in the management of tumors.They have broadened the scope of management in medical oncology,which has been heavily dependent on chemotherapy.Immune checkpoint inhibitors have renewed the hope of many patients for a more effective treatment.However,Immune checkpoint inhibitors are also associated with a variety of adverse effects,most commonly immunerelated adverse events,and these are often different from the known chemotherapy-induced toxicities.Hence,there is a need to identify specific biomarkers which are able to predict or diagnose these immune-related adverse events.

RADIOIMMUNOTOXICOLOGICAL EFFECT OF ENRICHED URANIUM ON CENTRAL AND PERIPHERAL IMMUNE CELLS AND THE PROTECTIVE ACTION OF IL－1 AND IL－2

Accumulation of enriched 235U-UO2F2 in the body had injurious effects on theimmune function of central and peripheral immune cells. After an intravenousinjection of beaU--UO,F,, the spontaneous ’H--TdR incorporation in thymocytes andbone marrow cells decreased, with the thymocytes damaged more markedly. Theproliferation ability of spleen T and B lymphocytes were both inhibited, with Blymphocytes inhibited more severely. In spleen B lymphocytes the IL-- 1 production andIL--2 consumption were diminished. The inhibition of spleen B lymphocyteproliferation by 'U-- UOZFZ was partially restored by adding exogenous IL-- 1 or IL--2to the cultured lymphocytes obtained from 'U injected mice.

Metabolic peculiarity of^（134）Cs and its radioimmunotoxicological effect on central and peripheral immune cells

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Immune response induced by hematoporphyrin derivatives mediated photodynamic therapy:Immunogenic cell death and elevated costimulatory molecules

Photodynamic therapy(PDT)not only destroys tumor cells directly but also induced anti-tumor immune response through damage-associated molecular patterns(DAMPs).It is reported that anti-tumor response was associated with light dose and photosensitizer used in PDT.In this study,4T1 tumor cells were implanted on both the right and left flanks of mice.Only the right tumor was treated by HpD-PDT,while the left tumor was not irradiated.The anti-tumor immune response induced by HpD-PDT was investigated.The expression of DAMPs and costimulatory molecules induced by HpD-PDT were tested by immuno fluorescence and flow cytometry in vivo.Different light doses of PDT were designed to treat 4T1 cells.The killing effect was assessed by CCK-8 kit and apoptosis kit.The expression of DAMPs on 4T1 cells after HpDPDT were evaluated by flow cytometry,western blot and ATP kit.This study showed that CD4^(+)T,CD8^(+)T and the production of IFN-γwere increased significantly on day 10 in righttumor after PDT treatment compared with control group.HpD-PDT enhanced the expression of calreticulin(CRT)on tumor tissue.Importantly,co-stimulatory molecular OX-40 and 4-1BB were elevated on CD8^(+)T cells.In vitro,immunogenic death of 4T1 cells was induced after PDT.Besides,the expression of DAMPs increased with the increasing of energy density.This study indicates that anti-tumor immune effect was induced by HpD-PDT.The knowledge of the involvement of CRT,ATP and co-stimulatory molecules uncovers important mechanistic insight into the anti-tumor immunogenicity.It was the first time that co-stimulatory molecules were investigated and found to elevate after PDT.

Immunological effect of aqueous extract of Vernonia amygdalina and a known immune booster called immunace and their admixtures on HIV/AIDS clients:a comparative study

Objective:To investigate the immunological effect of Vernonia amygdalina(V.amygdalina) leaf extract and immunace on HIV infected patients taking highly active antiretrwiral therapy. Methods:Fresh V.amygdalina leaves were collected within Nsukka area in Enugu State.The leaves were rinsed with distilled water.Two handful of cleaned fresh leaves were soaked in 200 mL water and squeezed gently by hand to a mixture.Clients were divided into four groups and each group was given different combination.They took the medication for four weeks.The immune effect was tested against marketed immune booster in some retroviral clients.Results:The mean absolute CD4 count was increased in the client who took the extract or supplement.And the clients who took both the extract and supplement had a greater increase in the CD4 count.The increased CD4 was significant as compared with the control group(P<0.05).The skin rashes were also improved in the entire groups.Conclusions:It can be concluded that the aqueous extract of V.amygdalina and immunace or both have immunological effect on HIV infected patients. Therefore,we suggest that the V.amygdalina extract or immunace or both could be used as adjuvant in the management of HIV/AIDS clients.

Evaluation of the Immunoregulatory Capacities of Feed Microbial Materials in Porcine Intestinal Immune and Epithelial Cells

The establishment of drug-free feeding systems has been required for secure and healthy livestock production. Although functional feed materials containing microorganisms as alternatives to enhance intestinal immunity are expected to be beneficial for reducing diarrhoea caused by pathogens in weaned piglets, the effects of such materials on porcine intestinal cells have not been investigated in detail. Therefore, this work evaluated the immunoregulatory functions of microbial feed materials in porcine intestinal immune and epithelial cells. Porcine immune cells isolated from Peyer’s patches and mesenteric lymph nodes were stimulated with six different feed materials containing microorganisms, and evaluated for lymphocyte mitogenicity and cytokine inductions. In addition, porcine intestinal epithelial cells were stimulated with the materials before treatment with heat-killed enterotoxigenic Escherichia coli (ETEC), and analyzed for the proinflammatory cytokine expressions. The material containing Bifidobacterium thermophilum significantly augmented lymphocytes’ mitogenicity and also induced a high expression of IL-2, IL-6 and IFN-γ in immune cells, and inhibited ETEC-induced overexpression of IL-6 and IL-8 via regulation of Toll-like receptor signaling. These results suggest that this feed material stimulates intestinal epithelial and immune cells to exert immunoregulation, suggesting that this feed is expected to contribute to promoting the health of piglets without using antimicrobial feed materials.

The immune function injury and its mechanism in drug abuser

Objective To explore the immune function injur y and its mechanism in drug abuser.Methods The immune function changes in50drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells,transformation rate of lymphocytes,IgA,IgM,IgG,IgE,com pliment C 3 ,C 4 ,IL-1,IL-2,IL-6TNF and NO.Result In peripheral blood the percentage o f Th 1 cell,transformation rate of lymphocyte,IgA,IgM,IgG,IgE content,complime nt C4,C4,IL-1,IL-2,IL-6,and TNF le vels were significantly lower than normal (P <0.01).The value of Th 1 /Th 2 was lower than normal as well(P <0.05).NO content was significantly higher than normal (P <0.001).Conclusion The mechanism of immune function inj ury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymu s-hypothalamus-hypophysis-adren al axis.

Sintilimab-induced autoimmune diabetes:A case report and review of the literature

BACKGROUND With the widespread application of immune checkpoint inhibitor(ICI)therapy,the number of immune-related adverse effects(irAEs)has increased over the years.Autoimmune diabetes mellitus(DM)is a rare irAEs of ICIs and can be troublesome and life threatening.CASE SUMMARY We report a 78-year-old woman with no history of diabetes who presented with hyperglycemia up to 23.4 mmol/L(random blood glucose level)after 14 courses of sintilimab.Hemoglobin A1c was 8.2%,fasting insulin was 0.29 mIU/mL,and fasting C-peptide was decreased to a level with negative autoantibodies.Combing her medical history and laboratory examination,she was diagnosed with programmed cell death(PD)-1-inhibitor-induced,new-onset autoimmune DM.After controlling her blood glucose,she was treated with daily insulin by subcutaneous injection.She was allowed to continue anti-PD-1 therapy and she still obtained some therapeutic efficacy.We also reviewed some published cases(n=36)of PD-1/PD-ligand 1(PD-L1)inhibitor-induced DM.We also discuss potential pathogenic mechanisms,clinical features,prognostic markers(βcell antibodies,human leukocyte antigen type,PD-L1 Level)of this rare adverse effect.CONCLUSION It is important for all clinicians to be aware of DM as an irAEs of ICIs.

Synergy in antibacterial activities of Ampicillin trihydrate, stabilized with a synthetic aluminum-magnesium silicate and immune-stimulants, on resistant <i>Escherichia coli</i>infection

To treat resistant Escherichia coli infection in chicks, Ampicillin was stabilized with a synthetic aluminum-magnesium silicate (AMS) to prolong its bioavailability. Its dose was also reduced to minimize adverse side effects. Vitamins A, C, E and Selenium levels in the chicks’ feeds were increased to enhance immune response of the chicks. E. coli coloning forming units, per ml of bile of the chicks, treated with Ampicillin and with Ampicillin in AMS, were: 228800.00 ± 90103.50 and 134500.00 ± 44937.97 at 10 mg/kg, 104400.00 ± 36024.44 and 34800.00 ± 8014.97 at 7.5 mg/kg, 198400.00 ± 129301.80 and 156800.00 ± 109392.70 at 5 mg/kg. Mean bacterial loads of the untreated groups, fed normal feed and those fed the fortified feed were 824400.00 ± 322424.80 and 534800.00 ± 277832.80. At 7.5 mg/kg. Ampicillin in the AMS, effectively (P E. coli infection in chicks, fed immune-stimulants, with the infection rate reduced by 95.8%.

Progress in nanoparticle-based regulation of immune cells

Immune cells are indispensable defenders of the human body,clearing exogenous pathogens and toxicities or endogenous malignant and aging cells.Immune cell dysfunction can cause an inability to recognize,react,and remove these hazards,resulting in cancers,inflammatory diseases,autoimmune diseases,and infections.Immune cells regulation has shown great promise in treating disease,and immune agonists are usually used to treat cancers and infections caused by immune suppression.In contrast,immunosuppressants are used to treat inflammatory and autoimmune diseases.However,the key to maintaining health is to restore balance to the immune system,as excessive activation or inhibition of immune cells is a common complication of immunotherapy.Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors,nucleic acid,and proteins.Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function.In this review,we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

Research Article Ferric iron coordinated cisplatin prodrug reprograms the immunecold tumor microenvironment through tumor hypoxia relief for enhanced cancer photodynamic-immunotherapy

The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade(ICB)therapy in solid tumors.It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors.In this study,the oxygen(O_(2))self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors.The nanoplatform can produce O_(2)by catalyzing hydrogen peroxide(H_(2)O_(2))in tumor site effectively,showing excellent photodynamic therapy(PDT)performance.Meanwhile,it can further trigger immunogenic cell death(ICD),enhance T cell infiltration,reverse immunosuppression,and reprogram the immune-cold tumor microenvironment.In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect.The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

Efficacy of Bee Products(Anzer Honey,Pollen and Propolis)in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells:Cytotoxic,Genotoxic and Biochemical Studies

Background and Objective Although drugs are powerful therapeutic agents,they have a range of side effects.These side effects are sometimes cellular and not clinically noticeable.Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients.In this study,we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells“hTERT-HPNE”,and we aimed to improve these harmful effects by natural products.To benefit from the healing effect,we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.Methods Cytotoxic and genotoxic effects of the drug were investigated by different tests,such as MTT,flow cytometry-apoptosis and comet assays.Anzer honey,pollen and propolis were analyzed by gas chromatography/mass spectrometry(G/C-MS).A total of 19 compounds were detected,constituting 99.9%of the samples.Results The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control(P<0.05).A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey,pollen and propolis in hTERT-HPNE cells(P<0.05).Conclusion This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells.In particular,Anzer honey,pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location(acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli(ST36) acupoint using microneedles containing thymopentin.The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients

Background Immune-related hematocytopenia （IRH） is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage （Me） in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Me in hematopoietic cell injury. Methods ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-y levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase （POX）, nonspecific esterase （NSE）, hemosiderin granules, and HLA-DR activity of Me in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Me membrane Fcyllreceptor （FcyllR）, mannitose receptor （MR）, IFN-y, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity （ADCC） hematopoietic cell islands （HI） in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Me bloodthirsty phenomenon; if necessary, association of Cyclosporine A （CsA） should be used and chalybeate should be supplemented. Results In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-y were increased. After treatment, the cytokine levels gradually became normal. The activated Me in the marrow highly expressed NSE and POX, and Me swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Me expressed HLA-DR, MR, ICAM-1, IFN-y, and IL-12. For patients with humoral immunity activation and bacterial infection, Me weakly expressed IL-17A but highly expressed FcyIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count （WBC） significantly reduced, Me weakly expressed FcyIIR, secretory highly expressed IL-17A, and the phenomena that Me adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Me occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. Conclusions Me is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Me, upregulate the impression of immune molecule and receptors, form ADCC HI. aeGravate hematoBoietic iniurv, and accelerate the destruction on hematoDoietic cell.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma(HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells’ expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancerassociated fibroblasts(CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-tomesenchymal transition(EMT) model and the mechanism of drug resistance, as well as its clinical value.

Combination therapy using low‐dose anlotinib and immune checkpoint inhibitors for extensive‐stage small cell lung cancer

Background:This study evaluated the efficacy and safety of low‐dose anlotinib combined with immune checkpoint inhibitors as second‐line or later treatment for extensive‐stage small cell lung cancer(ES‐SCLC).Methods:The study included 42 patients with ES‐SCLC who were treated with low‐dose anlotinib combined with programmed cell death protein 1/programmed cell death‐ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022.We retrospectively analyzed the efficacy and safety data for these patients.Indicators assessed included progression‐free survival(PFS),overall survival(OS),the overall response rate(ORR),the disease control rate(DCR),and adverse events(AEs).Prognostic factors were identified in univariate and multivariate analyses.Results:Median PFS was 11.0 months(95%CI:7.868–14.132)and median OS was 17.3 months(95%CI:11.517–23.083).The ORR was 28.5%and the DCR was 95.2%.Treatment‐related AEs were noted in 27 patients(64.3%),the most common of which was thyroid dysfunction(26.2%).Grade 3/4 treatmentrelated AEs were observed in two patients(4.8%).Conclusions:A combination of low‐dose anlotinib and immune checkpoint inhibitors as second‐line or later treatment for ES‐SCLC may achieve longer PFS and OS and have manageable AEs.

Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma

INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.