The paradox of Picroside II: As a natural antioxidant, but may instead futher aggravate liver injury by exacerbating mitochondrial oxidative stress.

Background: Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl4), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury. Methods: Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl4-treated rat models. Results: In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl4-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl4-induced chronic hepatic injury. Conclusions: Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.

5-Azacytidine promotes HCC cell metastasis by up-regulating RDH16 expression.

The level of DNA methylation could affect the expression of tumor promoting and tumor suppressor genes. DNA methyltransferase inhibitors could reduce high methylation levels in cancer and inhibit the progression of a variety of cancers, including HCC. However, the pro-metastatic effect of DNA methyltransferase inhibitors in some cancers suggest the potential risk of their use. Whether DNA methyltransferase inhibitors also promote metastasis in HCC remains unclear. Our study will explore the effect of DNA methyltransferase inhibitor 5-Azacytidine on HCC metastasis. Our study found that 5-Azacytidine inhibited the proliferation of HCC cells while promoting in vitro and in vivo metastasis of HCC. Mechanistically, our study showed that 5-Azacytidine increased the expression of RDH16 by decreasing the methylation of RDH16 gene promoter. RDH16 is a highly methylated gene and its expression is very low in hepatocellular carcinoma. 5-Azacytidine promoted the migration of hepatocellular carcinoma cells by increasing the expression of RDH16. Our results suggest that 5-Azacytidine up-regulates the expression of RDH16 by decreasing the methylation level of RDH16, and then promoting HCC metastasis. These findings suggest that 5-Azacytidine and even other DNA methyltransferase inhibitors may have the risk of promoting metastasis in HCC treatment. RDH16 could be used as a pro-metastasis biomarker in the treatment of HCC with DNA methyltransferase inhibitors.

Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles / 药物分析学报

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circu-lating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based micro-fluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Effect and safety of Liqing granules in assisting to reduce serum uric acid in rats / 上海预防医学

ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.

Total glucosides of Rhizoma Smilacis Glabrae: a therapeutic approach for psoriasis by regulating Th17/Treg balance / 中国天然药物

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.

Study on the Effect and Mechanism of Hederagenin on Dextran Sodium Sulfate-Induced Ulcerative Colitis in mice / 中药新药与临床药理

Objective To study the effect and its mechanism of hederagenin(hed)on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice.Methods(1)In vitro experiments:after treating RAW264.7 cells with different concentrations(0,2.5,5,10,20,40 μmol·L-1)of hed for 24 hours,the cell survival rate was detected by MTT assay.RAW264.7 cells were divided into:blank group,lipopolysaccharide(LPS)group(1 μg·L-1),LPS+2.5 μmol·L-1 hed group,LPS+5 μmol·L-1 hed group and LPS+10 μmol·L-1 hed group;an in vitro cellular inflammation model was established using LPS intervention for 24 hours and co-incubated with hed for 24 hours.The levels of interleukin 1β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)in the cell supernatant were determined by ELISA;the expression levels of TLR4/NF-κB pathway-related proteins in the cells were detected by Western Blot.(2)In vivo experiments:C57BL/6 mice were randomly divided into a blank group,a model group,a Salazosulfapyridine group(200 mg·kg-1),and an hed low-,medium-,and high-dosage groups(12.5,25,and 50 mg·kg-1),with 5 mice in each group.Mice were induced to establish UC model by drinking 3%DSS solution freely for 7 days.The UC model was then established by gavage once a day for 7 days.At the end of the administration,the Disease Activity Index(DAI)was evaluated;pathological changes in the colonic tissues of mice were observed by HE staining;the levels of IL-1β,IL-6,and TNF-α in the colonic tissue were measured by ELISA;and the expression levels of proteins related to the TLR4/NF-κB pathway in the colonic tissue were detected by Western Blot.Results(1)In vitro experiments:compared with the blank group(0 μ mol·L-1 group),there was no significant change in the cell survival rate in the 2.5-10 μmol·L-1 hed group(P＞0.05),and there was no significant toxicity effect on RAW264.7 cells.Compared with the blank group,the expression levels of IL-1β,IL-6,and TNF-α in RAW264.7 cells in the LPS group were significantly increased(P＜0.01);and the protein expression levels of TLR4 and p-NF-κ B/NF-κ B were significantly increased(P＜0.01).Compared with the LPS group,the expression levels of IL-1β and TNF-α in RAW264.7 cells in the hed 2.5,5,and 10 μmol·L-1 concentration groups were significantly decreased(P＜0.05,P＜0.01),and the protein expression levels of TLR4,p-NF-κB/NF-κB were significantly decreased(P＜0.05,P＜0.01);the IL-6 expression level of RAW264.7 cells in the hed 5 and 10 μmol·L-1 concentration groups was significantly reduced(P＜0.05,P＜0.01).(2)In vivo experiments:compared with the blank group,the body mass of mice in the model group was consistently reduced(P＜0.01),the DAI score was significantly elevated(P＜0.01),and the length of the colon was significantly shortened(P＜0.01);the colonic tissue showed obvious epithelial cell damage,and the histopathological scores were significantly elevated(P＜0.01);and the expression levels of the pro-inflammatory cytokines IL-1β,IL-6 and TNF-α were significantly increased(P＜0.01);protein expression levels of TLR4 and p-NF-κB/NF-κB were significantly increased(P＜0.01)in colon tissue.Compared with the model group,the body mass of mice in the low-,medium-and high-dose groups of hed were significantly increased(P＜0.05,P＜0.01),the DAI score was significantly decreased(P＜0.05,P＜0.01),the pathological damage of colon tissue improved to different degrees,and the protein expression levels of TLR4,p-NF-κB/NF-κB in the colonic tissue were significantly decreased(P＜0.05,P＜0.01);the colon length of mice in the medium-and high-dose groups of hed were significantly increased(P＜0.05,P＜0.01),and the expression levels and histopathological scores of IL-1β,IL-6,and TNF-α in colon tissue were significantly reduced(P＜0.05,P＜0.01).Conclusion Hed were able to effectively ameliorate colonic histopathological injury and reduce the levels of inflammatory factors in DSS-induced UC mice,and their mechanism of action may be related to the inhibition of the TLR4/NF-κB pathway.

Quantification of Uric Acid of Rat Serum by Liquid Chromatography-ultraviolet Detection and Its Comparison Study / 实验动物与比较医学

ObjectiveTo establish a more accurate and sensitive liquid chromatography-ultraviolet (LC-UV) method for the determination of uric acid in rat serum, and compare the results with those of commercial kits, providing a new method for the accurate determination of uric acid in the rat hyperuricemia model induced by potassium oxonate.Methods A hyperuricemia model was established by intraperitoneal injection of potassium oxonate (300 mg/kg) into SPF-grade male SD rats, and the control group was administered an equal amount of 0.5% sodium carboxymethylcellulose solution. Blood samples were collected from the posterior orbital venous plexus and centrifuged to obtain serum samples. After precipitation with 0.1% trifluoroacetic acid-acetonitrile (containing the internal standard 3,4-dihydroxybenzylamine hydrobromide), the supernatant was injected for analysis. Uric acid was separated on a Waters XBridge HILIC column (150 mm×4.6 mm, 3.5 μm) using acetonitrile (containing 0.5% formic acid and 2 mmol/mL ammonium formate) as the organic phase and methanol solution (methanol∶water=1∶1, containing 0.5% formic acid with 2 mmol/L ammonium formate) as the aqueous phase for isocratic elution and detection at 290 nm. Serum samples treated with activated carbon were used as substitute matrices for the methodological verification. Serum uric acid levels in rats with potassium oxonate-induced hyperuricemia were measured using the established LC-UV method and commercially available kits (uricase and phosphotungstic acid methods), and the accuracies of the three methods were compared.Results Serum uric acid showed a good linear relationship (R>0.999) at mass concentration of 10–200 μg/mL in rats, the lower limit of quantification was 10 μg/mL, the accuracy ranged from -2.17% to 2.21%, the intra-batch precision ranged from 0.52% to 1.95%, the inter-batch precision ranged from 3.04% to 4.90%, and the extraction recovery ranged from 83.12% to 89.91%. In the rat model, the results obtained using the commercially available phosphotungstic acid method kit were significantly higher than those of the LC-UV method, and those obtained using the commercially available uricase method kit were significantly lower than those of the LC-UV method, but the LC-UV method showed the best recovery of the spiked sample (95.90%–99.96%).ConclusionThe LC-UV method developed in this study can determine the concentration of uric acid in rat serum with higher accuracy than commercially available kits and is recommended for the determination of serum uric acid in the rat model of hyperuricemia induced by potassium oxonate.

Regulatory mechanism of LDLR and research progress of its related diseases and drugs / 中国临床药理学与治疗学

Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects.

Ameliorative effect of psoralen on acute liver injury induced by carbon tetrachloride in mice / 中国药科大学学报

@#To investigate the ameliorative effect of psoralen (PSO) on carbon tetrachloride (CCl4)-induced acute liver injury in mice and its potential mechanism, female C57BL/6J mice aged 6-8 weeks were continuously administrated with psoralen or positive control drug diallyl sulfide (DAS) intragastrically for 4 days.On day 4, except that the control group were treated with vehicle control, other groups were all given carbon tetrachloride intraperitoneally to establish a carbon tetrachloride acute liver injury model.Serum biochemical indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected; liver pathological changes were observed by HE staining; cytochrome P450 2E1 (CYP2E1) protein levels were detected by Western blot; the protein level of CYP2E1 were detected by immunohistochemistry (IHC) staining; and the gene levels of CYP2E1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR.Compared with the model group, psoralen could improve the inflammatory cell infiltration and hepatocyte necrosis caused by carbon tetrachloride, significantly reducing the serum ALT and AST levels, down-regulating the inflammatory factors TNF-α and IL-6 levels, and inhibiting CYP2E1 protein expression.The results show that psoralen can ameliorate the acute liver injury induced by carbon tetrachloride in mice, with the possible mechanism inhibiting the protein expression of CYP2E1.

A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (

A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

Tight junctions-associated proteins:a novel therapeutic target for cholestatic liver injury / 中国药科大学学报

@#The occurrence of cholestatic liver injury is accompanied by the alterations of hepatocyte polarization and bile acid homeostasis. Located in epithelial cells, tight junctions(TJs)are a special barrier structure which are important in maintaining permeability and bile acid homeostasis. Based on the fully analysis and discussion of TJs, the latest therapeutic drugs for cholestasis were summaried, which may provide new perspectives and potential therapeutic agents for the treatment of cholestatic liver injury.

Verification and application of the rat skin transcutaneous electrical resistance test ( TER) as an alternative method to replace the animal skin corrosion test / 中国实验动物学报

Objective In order to verify an alternative method for the skin corrosion test by using transcutaneous electrical resistance ( TER) test, and to optimize the implementation criteria in OECD TG 430 procedure. Methods According to the OECD TG 430 procedure, Wistar rat skin was used to test the TER values of 16 reference chemicals, and selected the most optimal standard via different implementation criteria. The program B was chosen to make inter-laboratory comparison between 5 laboratories by testing 11 chemicals, which were identified as the optimal standard. Results After the TER test, the result of corrosion test of 16 chemicals were accordant with the reference data ( Kappa value＝0. 64). The program B was the most optimal implementation criteria, and the specificity was 66. 7% and sensitivity was 100%. There were no significant differences between the corrosion estimations of 5 laboratories, and the concordance rate of the 5 laboratories was 72. 7%. Conclusions Transcutaneous electrical resistance (TER) test is an feasible and efficient tool for skin corrosion testing, and may become a good interim test to replace the in vivo test with this ex vivo test in cosmetics chemical safety assessment, thus, to reduce the animal usage in our country.

Improvement of emodin on acute fatty liver in mice / 中国药科大学学报

To observe the effects of emodin ( Emo) on acute fatty liver in mice induced by DL-ethionine ( DL-Eth) or tetracyclin ( Tetra) and its potential mechanism, ICR mice of acute fatty liver model induced by DL-Eth were orally administered with Emo or positive control, ursodeoxycholic acid ( UDCA) for 7 days. On day 7, except that the control and Emo groups were treated with vehicle control, animals were orally administered with DL-Eth to induce acute fatty liver model. ICR mice of acute fatty liver model induced by Tetra were orally administered with Emo or positive control, Dong Bao Gan Tai ( DB) or total flavonoid C-glycosides from Abrus mollis extract ( AME) for 7 days. From day 4, except that the control group was treated with vehicle control, animals were injec-ted with Tetra intraperitoneally for 4 days to induce acute fatty liver model. Liver histopathological analyses were determined by HE staining. Serum aspartate transaminase ( AST) , alanine transaminase ( ALT) , serum triglyceride ( TG) , hepatic TG and hepatic total cholesteol ( TC) were detected. The expression of phosphorylated AMP-activa-ted kinase ( p-AMPK) , phosphorylated acetyl-CoA carboxylase ( p-ACC) , SREBP1 and fatty acid synthase ( FAS) were determined by Western blot. The expression of fatty acid translocase ( CD36 ) , peroxisome proliferator activa-ted receptor alpha ( PPARα) and microsomal triglyceride transfer protein ( MTTP ) in liver were determined by RT-PCR. Compared with model groups, Emo could improve hepatocyte swelling and hepatic steatosis induced by DL-Eth or Tetra. Serum AST, ALT, serum TG, hepatic TG and hepatic TC were decreased by Emo significantly. DL-Eth-induced increase of fatty acid synthetase-associated protein was down-regulated by Emo. Fatty acid uptake was down-regulated by Emo; fatty acid oxidation and secretion were increased by Emo. Emo might be effective in preventing acute fatty liver in mice induced by DL-Eth or Tetra.

Sphingosine 1-phosphate signaling pathway:a novel target for regulation of epithelial and endothelial barrier function / 中国药科大学学报

@#Sphingosine 1-phosphate(S1P)is a pleiotropic sphingolipid metabolite that has been shown to regulate important physiological function by activation of its G-protein-coupled receptors S1PRs. S1P has been identified as an important signaling molecule in maintaining epithelial and endothelial barrier function. S1P signaling pathway is involved in epithelial and endothelial barrier function by regulation of adherens junction and tight junction assembly, cytoskeletal reorganization, and focal adhesion formation. Thus, S1P signaling pathway may become a novel therapeutic target for cell barrier dysfunction during some illnesses such as acute lung injury, inflammatory bowel disease and sepsis. In this review, the research progress of S1P signaling pathway in regulating epithelial and endothelial barrier function and the application of S1P in barrier dysfunction-related diseases were summarized, so as to provide references for future research.

Hepatotoxicity mechanisms of isoniazid: A mini-review.

Isoniazid (INH) is an antituberculosis drug associated with idiosyncratic liver injury in susceptible patients. INH-induced hepatotoxicity remains a significant clinical problem, but the underlying mechanisms are still unclear, despite the growing evidence that INH and/or its major metabolite, hydrazine, play an important role in hepatotoxicity.

Autophagic Cell Death in Glioma Cell Induced by Ceramide through JNK/c-Jun Pathway / 中国康复理论与实践

@#Objective To observe the autophagy of 87-MG and U251 glioma cells induced by ceramide and explore the possible mechanism. Methods The viability and apoptosis of 87-MG and U251 cells were detected by MTT assay and flow cytometry, respectively. Autophagic- related protein expressions of LC3B /LC3A and Beclin-1 were determined by Western blotting. The activation of JNK/c-Jun signaling pathway induced by ceramide with or without the treatment of JNK specific inhibitor SP600125 was also measured. Results 24 hours after treatment of ceramide, the growth of 87-MG and U251 cells was significantly inhibited time-dependently (P<0.05); and the number of autophagic cells increased dose-dependently (P<0.05). The levels of LC3B/LC3A and Beclin-1 significantly increased after ceramide treatment (P<0.05). JNK signaling pathway was activated in the 87-MG and U251 cells and the phosphorylation of c-Jun also increased after ceramide treatment. This activation of autophagy could be reversed by the pre-treatment of SP600125. Conclusion Ceramide may induce autophagy in 87-MG and U251 glioma cells and the mechanism may be related to the activation of JNK/c-Jun signaling pathway.

Advances in the role of steroids in rheumatoid arthritis / 中国药科大学学报

@#Steroids have been used to treat rheumatoid arthritis(RA), especially glucocorticoids and sex hormones, exhibit powerful and rapid therapeutic effects. The relationship between the steroids and inflammatory cytokine, immune response, nuclear receptors, as well as the safety and efficacy of RA treatment, were introduced in this review. Meanwhile, the possible mechanism of glucocorticoids and sex hormones therapy were discussed. The potential relevance of steroids to RA was also discussed to better use steroids in the treatment of RA and to provide references for future research.

The comparative study of two strains on results of Local lymph node assays / 中国比较医学杂志

Objective To analyze and compare results of local lymph node assays (LLNA) between BALB/c and CBA mice.Methods 4 chemicals (2,4-dinitrochlorobenzene, eugenol, hexyl cinnamic aldehyde and isopropanol) and 3 cosmetics were applied to the dorsum of both ears of Balb/c and CBA mice for three consecutive days.BrdU solution was injected inter-peritoneally on day 5.On day 6, the bilateral draining auricular lymph nodes were excised and made into single cell suspension, the lymph cell proliferation was measured by BrdU ELISA kit.Results 2,4-dinitrochlorobenzene, eugenol, hexyl cinnamic aldehyde and NO.3 perm agent pretended positive for both strains, EC1.6 values of three chemicals were found to be 0.08% (very strong), 4.02% (moderate), 6.68% (moderate) and 0.07% (very strong), 6.08% ( moderate), 8.89% ( moderate) for BALB/c and CBA mice respectively.Isopropanol, NO.1 and NO.2 cosmetics pretended to be non-sensitizers with SI <1.6 for both strains.Conclusion This study showed that BALB/c mouse was essentially equal to CBA for LLNA: BrdU-ELISA, which suggested that BALB/c mouse was a good alternative for CBA used in chemicals and cosmetics allergenic evaluation.

Autophagic Cell Death in Glioma Cell Induced by Ceramide through JNK/c-Jun Pathway / 中国康复理论与实践

Objective To observe the autophagy of 87-MG and U251 glioma cells induced by ceramide and explore the possible mecha-nism. Methods The viability and apoptosis of 87-MG and U251 cells were detected by MTT assay and flow cytometry, respectively. Autoph-agic-related protein expressions of LC3B/LC3A and Beclin-1 were determined by Western blotting. The activation of JNK/c-Jun signaling pathway induced by ceramide with or without the treatment of JNK specific inhibitor SP600125 was also measured. Results 24 hours after treatment of ceramide, the growth of 87-MG and U251 cells was significantly inhibited time-dependently (P<0.05);and the number of au-tophagic cells increased dose-dependently (P<0.05). The levels of LC3B/LC3A and Beclin-1 significantly increased after ceramide treat-ment (P<0.05). JNK signaling pathway was activated in the 87-MG and U251 cells and the phosphorylation of c-Jun also increased after ce-ramide treatment. This activation of autophagy could be reversed by the pre-treatment of SP600125. Conclusion Ceramide may induce au-tophagy in 87-MG and U251 glioma cells and the mechanism may be related to the activation of JNK/c-Jun signaling pathway.