Efficacy and safety of recombinant Bifidobacterium breve carrying HPV16 E7 shRNA and IL-12 gene against mouse cervical cancer xenografts / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评价口服携带HPV16 E7 shRNA和IL-12基因的重组短双歧杆菌在小鼠体内抗宫颈癌移植瘤的效果。方法：将pMG36e-E7 shRNA、pMG36e-mIL-12D质粒分别转化短双歧杆菌，经筛选鉴定并扩增获得携带HPV16 E7 shRNA和IL-12 基因的重组短双歧杆菌。通过小鼠皮下宫颈癌细胞移植建立荷瘤小鼠模型。口服重组短双歧杆菌1、7 d后，检测小鼠主要器官（心、肝、脾、肺、肾）和肿瘤组织匀浆液或血清在PYG培养基中形成的菌落数量，评价短双歧杆菌的肿瘤靶向性，以小鼠体内肿瘤生长曲线评估重组短双歧杆菌的抗肿瘤效果，通过主要器官切片H-E染色和检测荷瘤小鼠血清相关细胞因子水平评价口服重组短双歧杆菌的安全性。结果：成功制备重组短双歧杆菌和宫颈癌TC-1细胞移植瘤小鼠。7 d后，移植瘤组织匀浆液和血清的菌落数量证实短双歧杆菌具有靶向体内瘤组织的定殖能力，口服重组短双歧杆菌明显抑制荷瘤小鼠的肿瘤生长（P<0.05或P<0.01），但联合使用携带HPV16 E7 shRNA和IL-12基因的重组双歧杆菌的肿瘤抑制率与单独使用的并无显著差异，治疗后未见对荷瘤小鼠主要器官的损伤和血清中IL-12及IFN-γ的水平明显变化。结论：短双歧杆菌可用作靶向肿瘤的治疗性基因分子递送载体，其对宫颈癌移植瘤的疗效明显且安全可控。

Levels of IL-8 and IL-12p70 in the aqueous humor of patients with primary acute angle-closure glaucoma and its clinical significance / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To measure the levels of IL-8 and IL-12p70 in the aqueous humor of patients with primary acute angle-closure glaucoma(AACG)and age-related cataract(ARC), and to investigate the clinical significance.<p>METHODS:Totally 29 eyes of 29 AACG patients, and 17 eyes of 17 ARC patients were enrolled in the study from October 2019 to December 2020. The levels of IL-8 and IL-12p70 were measured in the aqueous humor using Cytometric Beads Array. The clinical information was recorded in the same time for the correlation.<p>RESULTS:The level of IL-8 in AACG group was statistically elevated compared with the control group(Z= -5.384, P<0.05). However the IL-12p70 level did not differ in AACG group compared with ARC group(Z= -1.587, P=0.112). The IL-8 level was positively correlated with the duration of acute attack(rs=0.387, P=0.038). The concentrations of IL-8 and IL-12p70 in the filtration surgery group were significantly increased than that of the non-filtration surgery group(P<0.05).<p>CONCLUSION: The level of the inflammatory factor IL-8 in the aqueous humor of patients with AACG was significantly elevated. With the progression of the disease, the concentration of the immune-related factor IL-12p70 increased differentially. Both inflammation and immunity may play an important role in the pathogenesis of AACG.

Immunogenicity to biological drugs in psoriasis and psoriatic arthritis

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.

In Vitro Anti-Inflammatory And Hepatoprotective Activity Of Turmesac®

Objective: In this study, we investigated the hepatoprotective activity of Turmesac® on Human liver cells (HepG2 cell line) and anti-inflammatory effect on Murine macrophages (Raw 264.7 cell line) by flow Cytometry. Methods: Cell viability of HepG2 and Raw 264.7 cells determined by the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay to identify a non-cytotoxic concentration of Turmesac® for the respective cell lines after 24 h exposure period. Further hepatoprotective effect of Turmesac® was performed in H2O2 treated liver cells using H2DCF-DA staining by flow cytometry. The anti-inflammatory potency of Turmesac® was evaluated in Lipopolysaccharide (LPS 2µg/ml) stimulated Murine Raw 264.7 macrophages by measuring the relative fluorescence intensity of 2 cytokines, Interleukin-8(IL-8) and (Interleukin-12) IL-12 by flow cytometric analysis. Results: Turmesac® concentrations of less than 50μg/ml did not show significant cytotoxicity on both HepG2 and Raw 264.7, cell lines following the treatment period of 24 h and selected 50μg/ml as the optimum concentration for hepatoprotective and anti-inflammatory models. The reactive oxygen species (ROS) study revealed that Turmesac® (50μg/ml) effectively suppressed the H2DCF-DA expression in HepG2 cells. Secondly, Turmesac® significantly suppressed the anti-inflammatory cytokine expressions of IL-8 and IL-12 in LPS pre-stimulated cells categorising as a potentially potent anti-inflammatory drug. The mean fluorescence intensity percentage of IL-8 is control 8.86, LPS 50.49, Turmesac® 19.63 and IL12 is control 10.41, LPS 68.94, and Turmesac® 15.79 respectively. Conclusion: This study highlighted that Turmesac® could be considered as a promising hepatoprotective and anti-inflammatory compound and a therapeutic agent in curing liver-related and inflammation-related diseases.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

Regulatory Effect of Modified Erchentang on Levels of Lymphokines Relating to Th1,Th2 and Th9 Cells and Expressions of IL-4R1/IL-13RA1 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.

IL-12 Levels in Pregnancies with Preeclampsia and Periodontitis

Introduction: Periodontal pathology has become amomentous concern of public health due to its increasingprevalence in adults around the globe. Study was aimed tocompare serum IL-12 p-70 levels in preeclampted and nonpreeclamptic women and to observe serum IL-12 p-70 levelsin preeclamptic with and without chronic periodontitis.Material and methods: It was a Longitudinal Cohort Study.The sampled population belonged to Narowal District ofPunjab, Pakistan. Duration of the study was from June 2016to February 2018. All pregnant subjects’ aged in-between18-34 years were participated though convenience samplingand consented. Out of total 73 subjects, 33 were with healthyperiodontium (6 preeclamptic and 27 normotensives) and40 were with chronic periodontitis (6 preeclamptics and 34normotensives). Sampling was performed in two phases; Firstwhen all subjects were in 2nd trimester and second when allwere in postpartum period. Periodontal status was assessed byCPITN (Community Periodontal Index for Treatment Need)probing technique and for preeclampsia, monthly bloodpressure profile of each participant was taken by her doctor.Serum estimation of IL-12 p-70 was confirmed throughsandwich ELIZA technique. Microsoft Excel and Minitabwere used for data analysis.Results: Normotensives with healthy periodontium showed17.4% high serum IL-12 p70 (pg/ml) in antepartum thanpostpartum. Similarly preeclamptics with healthy periodontiumexhibited 13.4% high serum IL-12 p70 in antepartum thanpostpartum. While normotensives with periodontitis displayed10% high serum IL-12 p70 in postpartum than antepartum.Preeclamptics with periodontitis exhibited 17.4% high serumIL-12 p70 in postpartum than antepartum.Conclusion: Preeclampsia and chronic periodontitisboth decrease serum IL-12 p-70 levels in antepartum andpuerperium.

Clinical significance and correlations of IL-10, IL-12 and IFN-γ levels in the patients with chronic hepatitis B virus infection / 中华实验和临床病毒学杂志

Objective@#To determine the changes in peripheral plasma concentrations of interleukin-10 (IL-10), interleukin -12 (IL-12) and interfoeron-γ(IFN-γ) in the patients with chronic hepatitis B virus (HBV) infection and their correlations with HBV infection stage or HBV DNA load of HBV carriers.@*Methods@#Data of 135 patients with chronic HBV infection from March 2016 to March 2017 were collected, the patients included 32 chronic HBV carriers, 61 with chronic hepatitis and 42 with cirrhosis. Forty healthy subjects served as controls. The concentrations of IL-10, IL-12 and IFN-γ were determined using enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed using the Pearson correlation test, which was performed to analyze the correlation between IL-10, IL-12, IFN-γ and HBV infection stage, HBV DNA load of HBV carriers.@*Results@#Compared with those in healthy controls, plasma IL-10 and IL-12 levels in patients with chronic hepatitis and cirrhosis increased significantly (F=22.06, 15.67, P=0.013, 0.021), plasma IL-10 and IL-12 levels in cirrhosis cases were higher than those in chronic hepatitis (all P<0.001), plasma IL-10 and IL-12 levels in chronic hepatitis were higher than those in chronic HBV carriers (all P<0.001). Plasma IFN-γ level in chronic HBV carriers, chronic hepatitis and cirrhosis were significantly higher than those in healthy controls (F=18.36, P=0.017). There were statistically significant differences in IFN-γ levels among the three groups in the chronic HBV carriers, chronic hepatitis and cirrhosis. IL-10, IL-12 and IFN-γ levels of the low, medium and high HBV DNA load groups were statistically significant (all P<0.05). There was no correlation between IL-10 and HBV DNA. IFN-γ, IL-12 and HBV DNA load were negatively correlated. There was no correlation between IL-10 and IFN-γ (r=0.103, P>0.05), IL-12 and IFN-γ were significantly positively correlated (r=0.687, P<0.05).@*Conclusions@#IL-10, IL-12 and IFN-γ may play an important role in the chronic HBV infection.

Effect of IFN-γ and IL-12 expressions on intrauterine transmission in HBsAg-positive parturientsin late pregnancy / 中华流行病学杂志

Objective@#To investigate the influence of IFN-γ and IL-12 levels in prenatal peripheral blood of HBsAg-positive parturients on intrauterine transmission of hepatitis B virus (HBV).@*Methods@#A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B in peripheral blood of parturients. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of cytokines IFN-γ and IL-12 levels were conducted with liquid chip-based flow cytometry method. The serum levels of five serological markers of hepatitis B and HBV DNA in 285 newborns were detected within 24 hours after birth.@*Results@#The incidence of intrauterine dominant infection (DBI), occult infection (OBI) and intrauterine transmission of HBV in HBsAg positive parturients were 7.37% (21/285), 40.70% (116/285) and 48.07% (137/285), respectively. The level of IFN-γ in peripheral blood of HBsAg-negative parturients was significantly lower than those of HBsAg-positive parturients (t=-2.55, P=0.011), NBIT group (t=-2.54, P=0.012) and OBI group (t=-2.33, P=0.021). In HBV DNA load of 103-106 copies/ml group, the levels of IFN-γ in the DBI group were significantly lower than those in OBI group and NBIT group (P<0.01). The level of IFN-γ in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=6.40, P=0.041). In the antiviral treatment group, the level of IL-12 in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=8.90, P=0.012). Multivariate analysis showed that there was a significant linear relationship between maternal IFN-γ level and maternal age, placenta previa and hepatitis B vaccine injection (P<0.05). The linear relationship between the level of maternal IL-12 and the mode of rupture and hepatitis B vaccine injection had statistical significance (P<0.05).@*Conclusions@#HBV can stimulate the expression of IFN-γ and inhibit the secretion of IL-12 in pregnant and lying-in women, but the expression of IFN-γ in HBsAg-positive parturients showed intra-group differentiation, and the maternal level of IFN-γ will decrease in HBeAg-positive and high-HBV DNA loadstatus. Increasing the levels of IFN-γ and IL-12 in HBsAg-positive parturients is beneficial to block intrauterine transmission of HBV, especially DBI.

Establishment of Modified Model of Psoriasis Mice / 中国药房

OBJECTIVE： To establish psoriasis animal model with a longer duration and more typical psoriatic characteristics by modifying psoriasis model induced by imiquimod. METHODS： Mice were randomly divided into normal group （treated with vaseline）， model group [treated with Imiquimod cream 60 mg/（2×3 cm2·d）] and modified group [treated with Imiquimod cream 60 mg/（2×3 cm2·d）+subcutaneous injection of rmIL-12 and LPS once a week]， for consecutive 21 d， with 10 mice in each group. The skin of the model site was observed daily from the first day of modeling. Psoriasis area and severity index （PASI） score was conducted for skin lesions such as erythema， scales and thickening. 21 d after modeling， mice were sacrificed， and histopathological examination of the skin lesions was performed. The spleen index was calculated， and the contents of IL-17A and IL-12 in the skin were detected by ELISA. RESULTS： From the third and second day of medication， erythema， scales and thickening were both observed in model group and modified group respectively. The PASI score reached peak on the 12th day. From the 11th day， erythema， scales and thickening of the modified group were more serious than that in model group. PASI scores of modified group was significantly higher than that of model group for 9 consecutive days （P＜0.05）. Histopathological observation showed that Munro microabscess， acanthosis and dermal inflammatory cell infiltration occurred in both model group and modified group. Compared with model group， spleen indexes of modified group were higher （P＜0.05）. Compared with normal group， the contents of IL-17A and IL-12 in mice skin of model group and modified group were both increased， and there was statistical significance in modified group （P＜0.05）. CONCLUSIONS： The estbalished modified model has the longer duration of typical characteristics of psoriasis.

Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells

Udenafil, which is a PDE5 inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafil-treated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.

Eicosane, pentadecane and palmitic acid: The effects in in vitro wound healing studies

Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-microbial activities of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for realtime mRNA genes expression studies of TNF-α and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast. Results: None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-α and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation. Conclusions: This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.

IL-12 reverses inhibitory effect of cisplatin on immune function of human NK cells and its mechanism / 中国肿瘤生物治疗杂志

@# Objective: To investigate the reverse effect and mechanism of IL-12 on chemotherapeutic medicine suppressing the immune function of NK cells. Methods: Purified NK cells were stimulated with PMAplus Ionomycin in the presence or absent of Cisplatin (DDP) and IL-12. The levels of IFN-γ and TNF-α in culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA); The content of IFN-γ and TNF-α, TRAIL (TNF-related apoptosis inducing ligand) and transcription factors including T-bet and p-STAT-4 in NK cells were analyzed by Flow cytometry. The cytotoxicity of purified NK cells (pretreated with/without chemotherapeutics and IL-12 for 48 h) to Jurkat cells was measured by Flow cytometry. Results: Chemotherapeutics significantly inhibited the production of IFN-γ, TNF-α and the expression of TRAILin NK cells, which were significantly reversed by IL-12 (P<0.05 or P<0.01). Further study revealed that chemotherapeutics down-regulated while IL-12 reversed the expression of p-STAT4 to restore cytokine production. In addition, DDP also inhibited but IL-12 recovered the cytotoxicity of NK cells against tumor cells by inducing the expression of TRAIL (P<0.05 or P<0.01). Conclusion: Chemotherapeutics inhibited the cytotoxicity of NK cells and its secretion of cytokines (IFNγ and TNF-α), which were reversed by IL-12 via up-regulating TRAIL and p-STAT-4; this might provide experimental evidence for the clinical application of IL-12 for rebuild the immune function of tumor patients receiving chemotherapy.

Eicosane, pentadecane and palmitic acid: The effects inin vitro wound healing studies

Objective:To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis.Methods: Anti-microbial activities of Staphylococcus aureus,Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for real-time mRNA genes expression studies of TNF-α and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast.Results:None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-α and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation.Conclusions:This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.

Study on the effect of IL-12 and IL-15 on the proliferation of CIK cells from of peripheral blood and the activity of killing SMMC-7721 hepatoma cell line in vitro / 国际检验医学杂志

Objective To observe the influence of IL-12,IL-15 on CIK cell in the normal culture;to observe the anti-tumor effect in the circumstance of different combination of cytokines,and to provide a new insight for preparing high effective and qualified CIK cell in vitro.Methods The optimal concentrations of IL-2,IL-12 and IL-15 were determined,respectively.After the peripheral blood from healthy blood donors was collected,monocytes were selected and co-cultured with different cytokines into different groups,as group A(IL-2 normal culture group),group B(IL-2 and IL-12 group),group C(IL-2 and IL-15 group),group D(IL-2,IL-12 and IL-15 group),and group E(cytokine control group).The monocytes in different groups were calculated by globulimeter,the activity of cells was detected by Trypan blue staining,positive ratio of CD3,CD8,CD56 on the celluar membrane was detected by flow cytometry,and the anti-tumor effect of CIK to SMMC-7721 was detected by MTSmethod,inthedayof0,5,10,15,20 after the culture.Results Statistical analysis indicated that,the proliferation multiplication of CIK cells was significantly higher in group B,group C and group D after 10,15 and 20 days of culture than those in group A(P＜0.05);and group D had higher proliferation multi-plication than that of group C(P＜0.05).The percentage of CD3 + CD8 +,CD3 + CD56+ in CIK cell membrane in group B,C,D was significantly higher than that in group A after 15 and 20 days of culture (P＜0.05).The percentage of CD3+ CD8+,CD3+ CD56+ in CIK cell membrane in group D was significantly higher than that in group B after 15 and 20 days of culture (P＜0.05).The killing rate of CIK cells for liver cancer in each group at 10,15,20 days of culture was significantly higher than that of group A when the target target ratio was 5 ∶ 1 (P＜0.05).The killing rate of CIK cells for liver cancer in group D,C at 10,15,20 days of culture was significantly higher than that of group B(P＜0.05).Conclusion IL-12and IL-15 could improve the proliferation of CIK cells,and IL-15 also has the effect of enhancing CIK cells the tumor-killing to SMMC-7721 activity.

Chemicals from Cimicifuga dahurica and Their Inhibitory Effects on Pro-inflammatory Cytokine Production by LPS-stimulated Bone Marrow-derived Dendritic Cells

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

Influence of isoniazid on immune function of rat / 药物评价研究

Objective To study the influence of isoniazid on lymphocyte factor expression and macrophage function of rats.Methods Healthy male SD rats were randomly divided into three groups,which was treated for one month,three months and withdrawal for one month after treated for three months,and each group was randomly divided into isoniazid group and control group.The isoniazid groups were ig with isoniazid at dose of 120 mg/kg every other day and control groups were fed on normal saline.At the corresponding time points,the level of interleukin-12 (IL-12) and interferon-γ (IFN-γ) was detected with ELISA method,detected serum lysozyme content by agar plate method,and Comori method was used for the detection of acid phosphatase levels in peritoneal fluid.Results At all the time points,levels of IL-12,IFN-γ and lysozyme in isoniazid group were not significantly different compared with control group.There were statistically significant differences in acid phosphatase between isoniazid group and control group after treated for one month (P ＜ 0.05),but the significant differences disappeared at the next two time points.Conclusion Isoniazid of 120 mg/kg may have no obvious influence on the immune function of rat.We don't detect the immune injury.

Influence of isoniazid on immune function of rat / 药物评价研究

Objective To study the influence of isoniazid on lymphocyte factor expression and macrophage function of rats.Methods Healthy male SD rats were randomly divided into three groups,which was treated for one month,three months and withdrawal for one month after treated for three months,and each group was randomly divided into isoniazid group and control group.The isoniazid groups were ig with isoniazid at dose of 120 mg/kg every other day and control groups were fed on normal saline.At the corresponding time points,the level of interleukin-12 (IL-12) and interferon-γ (IFN-γ) was detected with ELISA method,detected serum lysozyme content by agar plate method,and Comori method was used for the detection of acid phosphatase levels in peritoneal fluid.Results At all the time points,levels of IL-12,IFN-γ and lysozyme in isoniazid group were not significantly different compared with control group.There were statistically significant differences in acid phosphatase between isoniazid group and control group after treated for one month (P ＜ 0.05),but the significant differences disappeared at the next two time points.Conclusion Isoniazid of 120 mg/kg may have no obvious influence on the immune function of rat.We don't detect the immune injury.

Expression and Clinical Significance of Serum Levels of IL-12, IFN-γ,EPO and Ferritin in Patients with Acute Leukemia / 现代生物医学进展

Objective:To study the expressions of serum levels of intedeukin-12 (IL-12),interferon-γ (IFN-γ),erythropoietin (EPO) and ferritin in patients with acute leukemia and its clinical significance.Methods:76 patients with acute leukemia who were treated in our hospital from July 2015 to July 2016 were selected as the observation group,including 31 cases of newly diagnosed group,25 cases of remission group and 20 cases of relapse group.And another 76 cases who had taken the physical examination in our hospital were selected as the control group.Then the levels of serum IL-12,IFN-γ,EPO and ferritin in patients were observed and compared between the two groups.Results:The levels of IL-12 and IFN-γ in the observation group were significantly lower than those of the control group,and the levels of EPO and ferritin were significantly higher than those of the control group (P ＜0.05).The levels of serum IL-12 and IFN-γ in the untreated group and the relapse group were significantly lower than those of the remission group [(84.21± 5.43)pg/mL,(98.7± 7.98)pg/mL VS(112.43± 10.21) pg/mL,(38.54± 3.56)pg/mL,(49.87± 4.02)pg/mL VS(108.32± 8.43)pg/mL](P ＜0.05),and the levels of EPO and ferritin were significantly higher than those of the remission group [(402.32± 42.31) mIU/mL (321.58± 30.21)mIU/mL VS (98.21 ± 9.45) mIU/mLM (653.21 ± 54.24) ng/mLM (512.87 ± 43.45)ng/mL VS (342.15 ± 25.12)ng/mL] (P＜0.05).Conclusion:The serum levels of IL-12 and IFN-γ in patients with acute leukemia were lower,and the expression of EPO and ferritin was higher,and the disease and prognosis could be evaluated by monitoring the changes of these indexes.

Expression and variation of MIP-1β, MIP-2, and IL-12p70 in mouse models with bloodstream infection caused by different bacteria / 中国感染控制杂志

Objective To investigate the expression and variation of MIP 1β,MIP-2,and IL-12p70 in mice with bloodstream infection caused by 4 kinds of bacteria.Methods CD-1 (ICR) mouse models of bloodstream infection with Staphylococcus aureus (S.aureus),Enterococcus f aecalis (E.f aecalis),Escherichia coli (E.coli),and K lebsiella pneumoniae (K.pneumoniae) were established.After mice in each trial group and PBS control group were infected by bacteria for 0.5h,1h,3h,6h,12h,24h,and 48h,concentrations of MIP-1β,MIP-2,and IL-12p70 were detected by Luminex liquid suspension chip system.Results Concentrations of MIP-1β increased significantly 1h after bacteria was in blood,S.aureus,E.faecalis,E.coli,K.pneumoniae,and control groups were (134.5 ± 18.3),(61.5 ± 15.4),(3 354.0 ±809.0),(6 888.4 ± 1 100.2),and (28.9 ± 4.6) pg/mL respectively;the peak values of IL-12p70 were (389.3 ± 118.1),(127.6 ± 10.0),(42.2 ± 3.5),(62.8 ± 8.4),and (4.8 ± 0.3) pg/mL respectively.Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were significantly higher than other trial groups and control group (all P＜0.01),while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than E.coli,K.pneumoniae,and control groups (all P＜0.01).Conclusion Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were both significantly higher than those in S.aureus and E.faecalis groups,while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than those in E.coli and K.pneumoniae groups.The combination detection of multiple cytokines or chemokines are valuable in predicting gram-positive or gram-negative bacterial infection,and can provide basis for treatment of early infection.