Objective To investigate the immunomodulatory effects and the mechanism of interferon (IFN)-γ-pretreated adult autologous adipose tissue-derived mesenchymal stem cells (ADSCs) on peripheral blood lymphocytes. Methods ADSCs were obtained from adult subcutaneous adipose tissues. IFN-γ with and without pretreated ADSCs were used as IFN-γ-pretreated group and IFN-γ-unpretreated group, which were cultured with autologous peripheral blood mononuclear cells (PBMCs) at different concentrations of ADSCs-to-PBMCs ratios in presence of concomitant phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation. After 5 days of culture, the proliferatory inhibitory rate of activated T cells, the percentage of CD4+CD25+ regulatory T cells (Treg), and the expression of indoleamine 2,3-dioxygenase (IDO) mRNA were assessed. Results ADSCs were isolated from autologous adipose tissue, which strongly expressed CD73, CD90, and CD105, as well as displayed adipogenic and osteogenic differentiation. The percentage of CD4+CD25+Treg was significantly higher in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The expression level of IDO mRNA in ADSCs was significantly increased in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The proliferation inhibition of activated T cells was significantly decreased in IDO-blocker group than that of IFN-γ-pretreated group (P < 0.01). Conclusion These results suggest that IFN-γ can promote immunosuppressive effects of ADSCs on activated T cells through increased expression of IDO.

In recent years, with the rapid development of Chinese materia medica (CMM) industry, its clinical applications have become more and more widespread. While, adverse reactions of CMM have also become increasingly prominent. However, for adverse reactions of some CMM, the applications of conventional toxicology studies cannot draw definitive conclusions. These CMM, which were not defined as toxic drugs in traditional Chinese medicine (TCM) theories, have unknown potential toxicities and affect the safety in their clinical use. This paper reviewed recent advances in studies on potential toxicity of non-toxic CMM. It analyzed and summarized potential toxic compounds among them, and introduced application for metabolomics researches on potential toxicities in non-toxic CMM.

Objective To study the potential protective and toxic effects of Acanthopanax senticosus harms(AS)in rats. Methods Twenty male SD rats were divided into the AS-treated and control groups by random number table method. Each group comprised 10 rats. The rats in the AS-treated group were gavage-fed with AS extracts 31. 6 mg/ kg(equivalent to crude drug 0. 386 g/ kg in human)once daily for 20 days and the volume of the drug was 10 ml/ kg. The rats in the control group received an equal volume of saline once daily for 20 days. The urinary samples of 24 h from rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days were collected respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was used to detect the ion intensities of metabolites from urinary samples. The ion intensities of urinary metabolites at different time points in the 2 groups were compared. The ion intensity of each metabolite was normalized with respect to the total ion intensities to generate a data matrix. The data matrix at different time points were processed by partial least-squares-discrimination analysis(PLS-DA)of EZinfo software. Characteristic metabolites were screened according to the PLS-DA score plot. Two sets of data matrix with relatively large distance were further processed by orthogonal partial least-squares-discrimination analysis(OPLS-DA)and the variable importance of project(VIP)scores were calculated. Characteristic metabolites induced by AS intervention were screened from variables with VIP > 1 and P < 0. 05 and their mass-charge ratios were detected and compared to the information in Human Metabolome Database(HMDB),and the corresponding metabolites were identified at last. The potential protective or toxic effects of AS in rats represented by these metabolites were analyzed through literature review. Results PLS-DA score plot showed that the urinary metabolic profiles at different time points in the 2 groups had good similarity within groups or time period and presented clustering phenomenon. The urinary metabolic profiles in rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days partly overlapped. The urinary metabolic profiles in rats in the AS-treated group with 20 days of AS treatment were far from those in the control group. Two sets of data matrix with relatively large displacement were further processed and 6 potential intervention targets of AS with VIP > 1 and P < 0. 05 were screened and identified as 3-methylguanine,3-methylglutarylcarnitine,3-hydroxydodecanedioic acid, tiglylcarnitine, kynurenic acid,and 13-cis-retinoic acid by comparing with the information of HMDB. At the 20 d of AS-treated group, the expression of 3-methylguanine,kynurenic acid,and 3-hydroxydodecanedioic acid were up-regulated and the expression of tiglylcarnitine,3-hydroxydodecanedioic acid,and 13-cis-retinoic acid were down regulated. By reviewing the related literature,kynurenic acid,13-cis-retinoic acid,and 3-methylguanine may have potential protective effects in rats which were treated with AS and the other 3 metabolites may have potential toxicity. Conclusion The potential intervention effects of AS in rats had two sides,which may have protective effects,and may also have toxic effects.

Objective To study the potential protective and toxic effects of Acanthopanax senticosus harms(AS)in rats. Methods Twenty male SD rats were divided into the AS-treated and control groups by random number table method. Each group comprised 10 rats. The rats in the AS-treated group were gavage-fed with AS extracts 31. 6 mg/ kg(equivalent to crude drug 0. 386 g/ kg in human)once daily for 20 days and the volume of the drug was 10 ml/ kg. The rats in the control group received an equal volume of saline once daily for 20 days. The urinary samples of 24 h from rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days were collected respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was used to detect the ion intensities of metabolites from urinary samples. The ion intensities of urinary metabolites at different time points in the 2 groups were compared. The ion intensity of each metabolite was normalized with respect to the total ion intensities to generate a data matrix. The data matrix at different time points were processed by partial least-squares-discrimination analysis(PLS-DA)of EZinfo software. Characteristic metabolites were screened according to the PLS-DA score plot. Two sets of data matrix with relatively large distance were further processed by orthogonal partial least-squares-discrimination analysis(OPLS-DA)and the variable importance of project(VIP)scores were calculated. Characteristic metabolites induced by AS intervention were screened from variables with VIP > 1 and P < 0. 05 and their mass-charge ratios were detected and compared to the information in Human Metabolome Database(HMDB),and the corresponding metabolites were identified at last. The potential protective or toxic effects of AS in rats represented by these metabolites were analyzed through literature review. Results PLS-DA score plot showed that the urinary metabolic profiles at different time points in the 2 groups had good similarity within groups or time period and presented clustering phenomenon. The urinary metabolic profiles in rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days partly overlapped. The urinary metabolic profiles in rats in the AS-treated group with 20 days of AS treatment were far from those in the control group. Two sets of data matrix with relatively large displacement were further processed and 6 potential intervention targets of AS with VIP > 1 and P < 0. 05 were screened and identified as 3-methylguanine,3-methylglutarylcarnitine,3-hydroxydodecanedioic acid, tiglylcarnitine, kynurenic acid,and 13-cis-retinoic acid by comparing with the information of HMDB. At the 20 d of AS-treated group, the expression of 3-methylguanine,kynurenic acid,and 3-hydroxydodecanedioic acid were up-regulated and the expression of tiglylcarnitine,3-hydroxydodecanedioic acid,and 13-cis-retinoic acid were down regulated. By reviewing the related literature,kynurenic acid,13-cis-retinoic acid,and 3-methylguanine may have potential protective effects in rats which were treated with AS and the other 3 metabolites may have potential toxicity. Conclusion The potential intervention effects of AS in rats had two sides,which may have protective effects,and may also have toxic effects.

Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.

The aim of this study is to establish a simple and stable model like poloxamer 407 (P-407)-induced dyslipidemia of golden hamster model, and investigate the mechanism of lipid metabolism disturbance in this model. PPARalpha agonist and HMG-CoA reductase inhibitor were administrated to validate the efficacy on regulating lipid metabolism in the dyslipidemia golden hamster model. Six weeks male golden hamsters were chosen to inject P-407 intraperitoneally at a bolus dose of 300 mg x kg(-1), an intermittent injection at a dose of 200 mg x kg(-1) every 72 hours after the bolus. The results showed that P-407-induced golden hamster model characterized as increased serum triglyceride (TG), total cholesterol (TC), free cholesterol (free-CHO), cholesteryl ester (CE), free fatty acids (FFA) and apoB levels, and the hyperlipidemia state maintained at a stable level persistently. Meanwhile, augmented malondialdehyde (MDA) and nitric oxide (NO) level was observed. LCAT and SR-B I mRNA levels in liver of model group were down-regulated (expression ratio is 0.426; 0.783), while HMG-CoA reductase mRNA level was up-regulated (expression ratio is 1.493) compared with those of the normal group. The serum cholesterol and triglyceride levels were significantly lower in P-407-induced dyslipidemia hamster model after treated with atorvastatin (Ato) at a dose of 50 mg x kg(1) or fenofibrate (Fen) at 100 mg x kg(-1) for two weeks. These findings suggest that serum lipid distribution in dyslipidemia golden hamster is similar to that of human, and which may be relevant to the disturbance of the enzymes expression involved in lipid metabolism in liver. Results obtained from this study support the concept that dyslipidemia golden hamster may be an adequate animal model to evaluate the efficacy of lipid-lowering agents.

Objective To explore the effect of stromal cell-derived factor-1 α (SDF-1 α) on inducing recruitment of bone marrow-derived cells (BMDCs) to wound area. Methods BMDCs were isolated from bone marrow, cultured with routine method and identified by CXCR4 antibody. Cells cultured with CXCR4 antibody (100 ng,/mL) for 6 hours were labeled with CM-DiI and injected into the tail vein of full-thickness incisional wound model (set as anti-CXCR4 group). BMDCs labeled with CM-DiI without antibody treatment were injected to the rats in BMDCs group, and rats were injected with DMEM/F12 serum-free medium in the control group. The quantity of labeled BMDCs at the wound site and the percentage of wound closure were measured. Results (1) All BMDCs expressed CXCR4. (2) The percentages of wound closure at days 7 and 14 in BMDCs group (7 d: 41.3% ±4.6%; 14 d:92.3% ±2. 1%) were significantly higher than those of control group (7 d: 29.3% ±2. 3%; 14 d: 77.3% ±2.5%) and anti-CXCR4 group (7 d: 30.7% ±4.6% ;14 d: 85.7% ±1.5%) (P＜0.05). The percentage of wound closure of anti-CXCR4 group was significantly higher than that of control group at day 14(P ＜ 0.05). (3) The number of CM-DiI labeled BMDCs at wound site at days 7 and 14 in BMDCs group [7 d: (535 ±84) cells/hpf; 14 d: (769 ±124) cells/hpf) were greater than those of anti-CXCR4 group [7 d: (335 ±97) cells/hpf; 14 d: (521 ± 127) cells/hpf] (P＜0.05). Conclusions BMDCs participate in the cutaneous wound healing. SDF-1α plays an important role in recruiting BMDCs to wound area.