A NETWORK PHARMACOLOGY-BASED TREATMENT ANALYSIS OF LUTEOLIN FOR REGULATING PYROPTOSIS IN ACUTE LUNG INJURY.

ABSTRACT: Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. The relevant targets of luteolin and ALI were first obtained, and the key target genes were analyzed using a protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The targets of luteolin and ALI were then combined to ascertain the relevant pyroptosis targets, followed by Gene Ontology analysis of core genes and molecular docking of key active compounds to the antipyroptosis targets of luteolin in resolving ALI. The expression of the obtained genes was verified using the Gene Expression Omnibus database. In vivo and in vitro experiments were performed to explore the potential therapeutic effects and mechanisms of action of luteolin against ALI. Results: Fifty key genes and 109 luteolin pathways for ALI treatment were identified through network pharmacology. Key target genes of luteolin for treating ALI via pyroptosis were identified. The most significant target genes of luteolin in ALI resolution included AKT1, NOS2, and CTSG. Compared with controls, patients with ALI had lower AKT1 expression and higher CTSG expression. Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.

Cdc25C/cdc2/cyclin B, raf/MEK/ERK and PERK/eIF2α/CHOP pathways are involved in forskolin-induced growth inhibition of MM.1S cells by G2/M arrest and mitochondrion-dependent apoptosis.

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM.

Impact of Buzhong Yiqi Prescription on the Gut Microbiota of Patients with Obesity Manifesting Polycystic Ovarian Syndrome.

Gut microbiota disorders are closely related to polycystic ovarian syndrome (PCOS). Buzhong Yiqi prescription (BZYQ) has a significant clinical effect on the treatment of patients with obesity exhibiting PCOS and phlegm-dampness syndrome caused by spleen deficiency (SPSD). Hence, this study aimed to explore gut microbiota and fecal metabolite alterations in such patients treated with BZYQ. Fifty eligible patients with obesity manifesting PCOS and SPSD participated and agreed to undergo 3 months of BZYQ treatment. Results showed that BZYQ significantly alleviated the serum dehydroepiandrosterone sulfate (p < 0.001) and testosterone levels (p < 0.001) and markedly changed the gut microbiota structure in these patients. Furthermore, 106 differential fecal metabolites and 14 KEGG enrichment pathways were quantified. The phylum Spirochaetae and the genera [Eubacterium]_rectale_group, Escherichia-Shigella, and Fusicatenibacter were significantly more abundant, but Megamonas was significantly less abundant after treatment than before treatment. Disorders in the gut microbiota and fecal metabolites of these patients were closely related to hyperandrogenemia and insulin resistance. In conclusion, BZYQ could ameliorate the serum androgen level and had an impact on the gut microbiota and metabolites in patients with obesity manifesting PCOS and SPSD.

Efficacy of "Pinggan Formula" in Controlling Acute Type B Aortic Dissection Perioperative Blood Pressure: A Randomized Controlled Clinical Trial.

OBJECTIVE: To explore a new treatment that can proceed from the whole, control blood pressure smoothly and coordinate the treatment of multiple factors causing blood pressure fluctuations. METHOD: We conducted a single-center, double-blinded, and randomized controlled clinical trial. 48 patients with acute Type B aortic dissection were randomly assigned into two groups: the experimental group, who received pinggan formula treatment, and the control group, who received placebo treatment. The drug was taken orally after meals three times a day. Only when the patients' blood pressure fluctuated, conventional antihypertensive drugs were given to maintain the blood pressure within the target range and the dosage was recorded to convert the DDD value. Meanwhile, the international standardized score was used to evaluate the defecation, sleep, pain, anxiety, and depression of patients in the two groups during the hospitalization. RESULT: Univariate analysis was conducted on variables that might affect the assessment results, and it was found that grouping factors had a significant impact on the outcome variables, that is, after the intervention, the mean value of DDDs used in the perioperative period in the control group was 2.19 (0.38, 4.00). (P=0.0219), defecation score (2.13 (1.59, 2.67); P < 0.0001), sleep score (0.95 (0.40, 1.50); P=0.0014), pain score (1.77 (0.61, 2.93); P=0.0045), depression score (4.04 (2.95, 5.12); and P < 0.0001) were significantly higher than that of the experimental group, and the difference was statistically significant. CONCLUSION: Pinggan formula has a clear therapeutic regulation effect on the overall hemodynamics of acute Stanford type B aortic dissection during the perioperative period and can be recommended as an auxiliary drug for conventional antihypertensive drugs at the current stage.

Baicalin inhibits recruitment of GATA1 to the HSD3B2 promoter and reverses hyperandrogenism of PCOS.

High androgen levels in patients suffering from polycystic ovary syndrome (PCOS) can be effectively reversed if the herb Scutellaria baicalensis is included in traditional Chinese medicine prescriptions. To characterize the effects of baicalin, extracted from S. baicalensis, on androgen biosynthesis in NCI-H295R cells and on hyperandrogenism in PCOS model rats and to elucidate the underlying mechanisms. The optimum concentration and intervention time for baicalin treatment of NCI-H295R cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and enzyme-linked immunosorbent assays. The functional genes affected by baicalin were studied by gene expression profiling (GEP), and the key genes were identified using a dual luciferase assay, RNA interference technique, and genetic mutations. Besides, hyperandrogenic PCOS model rats were induced and confirmed before and after baicalin intervention. As a result, Baicalin decreased the testosterone concentrations in a dose-and time-dependent manner in NCI-H295R cells. GEP revealed that 3ß-hydroxysteroid dehydrogenase type II (HSD3B2) was the key enzyme of androgen biosynthesis, and baicalin inhibited the expression of HSD3B2 by regulating the binding of transcription factor GATA-binding factor 1 (GATA1) to the HSD3B2 promoter. Hyperandrogenic PCOS model rats treated with baicalin significantly reversed the high androgen levels of serum and the abnormal ovarian status, restored the estrous cyclicity, and decreased the expression of HSD3B2 in ovarian. In summary , our data revealed that GATA1 is an important transcription factor activating the HSD3B2 promoter in steroidogenesis, and baicalin potentially be an effective therapeutic agent for hyperandrogenism in PCOS by inhibiting the recruitment of GATA1 to the HSD3B2 promoter in ovarian tissue.

Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe-/- mice.

BACKGROUND AND AIMS: Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine. METHODS: Apoe-/- mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3-V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated. RESULTS: Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice. CONCLUSIONS: Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis.

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1ß, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

Meta-Analysis of Chinese Traditional Medicine Bushen Huoxue Prescription for Endometriosis Treatment.

OBJECTIVES: To evaluate the efficacy and safety of Bushen Huoxue prescription (BSHXP) for endometriosis. METHODS: A meta-analysis was performed, and studies were searched from the seven databases from the date of database establishment to April 30, 2017. Randomized controlled trials (RCTs) that explored the efficacy and safety of BSHXP for patients with endometriosis were included. Two assessors independently reviewed each trial. The Cochrane Risk of Bias assessment tool was used for quality assessment. RESULTS: In the 13 included studies, the total effectiveness rates of BSHXP were higher than those of Western medicine (RR, 1.55; 95% CI, 1.03-2.32; P = 0.04), but the dysmenorrhea alleviation rates of the two treatments did not significantly differ (RR, 1.28; 95% CI, 0.70-2.34; P = 0.42). The pregnancy rates of BSHXP were also higher than those of hormone therapy (RR, 1.99; 95% CI, 1.17-3.39; P = 0.01). However, whether BSHXP is more effective than Western medicine in diminishing endometriotic cyst remains unknown. CONCLUSIONS: Our study provides evidence that BSHXP is effective and safe for endometriosis, but this evidence is inconclusive because of the low methodological quality of the included RCTs. Our findings suggest that BSHXP is an alternative drug for endometriosis, but it should be further examined in future clinical research.

The effects and possible mechanisms of puerarin to treat endometriosis model rats.

Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17ß-hydroxysteroid-2 (17ß-hsd-2) and downregulating the expression of 17ß-hydroxysteroid-1 (17ß-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERß and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic.

Wrist-ankle acupuncture and ginger moxibustion for preventing gastrointestinal reactions to chemotherapy: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of wrist-ankle acupuncture combined with ginger moxibustion against gastrointestinal tract reactions (nausea, vomiting, and constipation) to chemotherapy in cancer patients. METHODS: A total of 60 patients with gynecological tumors treated by chemotherapy were randomly divided into two groups. The treatment group (30 cases) underwent wrist-ankle acupuncture and ginger moxibustion, whereas tropisetron hydrochloride and dexamethasone were intravenously administered to the control group (30 cases) during chemotherapy. RESULTS: The frequency of nausea in the treatment group was significantly less than that of the control group from the 2nd to the 5th day of chemotherapy (P<0.01). The anti-emetic effect in the treatment group was significantly better than that in the control group on the 3rd day of therapy (P<0.05). The incidence rate of constipation was significantly lower in the treatment group than that in the control group (P<0.01). Furthermore, the cost of therapy for the treatment group was significantly lower than that of the control group (P<0.01). Only 1 patient manifested a post-acupuncture side effect in the form of subcutaneous blood stasis. CONCLUSION: Wrist-ankle acupuncture combined with ginger moxibustion could prevent gastrointestinal tract reactions to chemotherapy in cancer patients. In addition, the proposed method had fewer side effects, lower cost, and less risk.

Role of JNK Activation and Mitochondrial Bax Translocation in Allicin-Induced Apoptosis in Human Ovarian Cancer SKOV3 Cells.

Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3. Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis. Activation of the signaling pathway was screened by human phospho-kinase array analysis, and the activated pathway and its related proteins were further confirmed by western blot analysis. Results. Allicin induced SKOV3 cell apoptosis and JNK phosphorylation in a time- and dose-dependent manner, but these were significantly blocked by SP600125 (an inhibitor of JNK). The findings suggest that JNK phosphorylation is related to the action of allicin on SKOV3 cells. Furthermore, JNK activation induced Bcl-2 family activation, triggered mitochondria-mediated signaling pathways, and led to the translocation of a considerable amount of Bax and cytochrome c release. Conclusions. JNK activation and mitochondrial Bax translocation are involved in allicin-induced apoptosis in SKOV3 cells. Our data input new insights to the literature of allicin-induced apoptosis.

Cryptotanshinone Reverses Reproductive and Metabolic Disturbances in PCOS Model Rats via Regulating the Expression of CYP17 and AR.

Objective. To explore the effect of Cryptotanshinone on reversing the reproductive and metabolic disturbances in polycystic ovary syndrome (PCOS) model rats and the possible regulatory mechanisms. Methods. PCOS model rats were induced by subcutaneous injection of dehydroepiandrosterone (DHEA) and verified by histological screening of vaginal exfoliated cells. After Cryptotanshinone intervention, the rats' body weight and ovary morphological were observed; the serum biochemical assessments were analyzed by radioimmunoassay (RIA) and key genes and proteins related with anabolism of androgen and insulin were detected by Real-Time PCR and Immunohistochemical (IHC). Results. The estrous cyclicity of PCOS model rats was significantly recovered by Cryptotanshinone. The body weight, ovarian coefficient, and ovarian morphology had been improved and the serum biochemical indicators including testosterone (T), androstenedione (A2), luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), sexual binding globulin (SHBG), low density cholesterol (LDL-C), fasting insulin (FINS) were reversed after Cryptotanshinone intervention. Specifically, the levels of Cytochrome P450, 17-a hydroxylase/17,20 lyase (CYP17), and androgen receptor (AR) were downregulated significantly. Conclusions. Our data suggest that Cryptotanshinone could rebalance reproductive and metabolic disturbances in PCOS model rats and could be a potential therapeutic agent for the treatment of PCOS.

Puerarin suppresses proliferation of endometriotic stromal cells in part via differential recruitment of nuclear receptor coregulators to estrogen receptor-α.

BACKGROUND AND OBJECTIVES: Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17ß-estradiol and producing an anti-estrogenic effect. In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. This study was to investigate whether puerarin could suppress the proliferation of endometriotic stromal cells (ESCs) and to further elucidate the potential mechanism. METHODS AND RESULTS: The ESCs were successfully established. The effects of puerarin on the proliferation of ESCs, cell cycle and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry. The mRNA and protein levels of cyclin D1 and cdc25A were detected by real-time PCR and Western blot analysis. Coimmunoprecipitation was applied to examine the recruitment of nuclear receptor coregulators to the estrogen receptor-α. We found that puerarin can suppress estrogen-stimulated proliferation partly through down-regulating the transcription of cyclin D1 and cdc25A by promoting the recruitment of corepressors to estrogen receptor-α as well as limiting that of coactivators in ESCs. CONCLUSIONS: Our data suggest that puerarin could suppress the proliferation of ESCs and could be a potential therapeutic agent for the treatment of endometriosis.

[Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model].

OBJECTIVE: To compare angiopoiesis ability of eutopic and ectopic endometrial tissue isolated from women with endometriosis and endometrium isolated from women without endometriosis (control), and to explore the inhibitory effects of medicated serum of Neiyi Recipe, a compound traditional Chinese herbal medicine. METHODS: Chick chorioallantoic membrane (CAM) model of endometriosis was established by transplanting endometrium onto CAM. The CAMs were then hatched with blank serum or medicated serum of danazol or Neiyi Recipe, which were prepared in rats by orally administering. The sizes of the transplanted tissue and new vessels around the transplanted tissue were measured. Expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method. RESULTS: There was no difference in the sizes of transplanted tissue among CAM models of ectopic and eutopic endometrial tissue isolated from women with endometriosis or control (P>0.05), and more new vessels were found around the ectopic and eutopic endometrial tissue than the endometrial tissue of control (P<0.05). Compared with the controls, the size of the transplanted tissue and positive area of new vessels were significantly inhibited by Neiyi Recipe-medicated serum (P<0.01, P<0.05), and similar changes happened in the danazol groups, except for the size of transplanted tissue from ectopic endometrial tissue (P>0.05). Expression of VEGF was significantly higher in eutopic and ectopic endometrial tissue than in the control (P<0.01); the level of VEGF obviously reduced in the Neiyi Recipe and danazol groups (P<0.01), but no significant difference was detected between them. CONCLUSION: Endometrium from women with endometriosis stimulates the formation of new vessels by increase the expression of VEGF. Neiyi Recipe-medicated serum significantly decreases the expression of VEGF in eutopic and ectopic endometrial tissues and thus restrains the formation of new vessels, reduces the blood supply and inhibits growth of ectopic endometrial tissue, which are similar to danazol, but has greater efficacy in suppressing the expression of VEGF.

[Adhesive and invasive effects and mechanism of neiyi recipe on the endometriosis].

OBJECTIVE: To assess the inhibitory effects of Neiyi Recipe by comparing adhesive and invasive effects of eutopic and ectopic endometrial tissues from endometriosis women and the endometrium from endometriosis-free women. METHODS: The invasive capacity of endometrial stromal cells from endometriosis-free women, eutopic and ectopic endometrial stromal cells from women with endometriosis were compared using Boyden chamber, the chick chorioallantoic membrane (CAM) ectopy transplant, and immunohistochemical EnVision method. The expressions of adhesion and invasion correlated cytokines in the transplanted tissue and effect of Neiyi Recipe on them were observed. RESULTS: The numbers of invasion stromal cells of eutopic and ectopic endometrial tissues were obviously more than those in the endometriosis-free women (P<0.05). After treatment with Neiyi Recipe and danazol respectively, the number of invasion stromal cells was significantly less in the Neiyi Recipe group than in the danazol group (P<0.05). Compared with endometriosis-free women, the expression of ICAM-1 in the ectopic endometrium tissue, and MMP-9 expressions in the eutopic and ectopic endometrium were significantly higher (all P<0.05) and TIMP-1 expressions obviously lower (P<0.01). In the eutopic endometrium, Neiyi Recipe and danazol serum could significantly lower the expression of MMP-9, and up-regulate expressions of TIMP-1 and ICAM-1 (P<0.01). In the ectopic endometrium, Neiyi Recipe could significantly lower the expression of MMP-9 (P<0.01) and ICAM-1 (P<0.05), and danazol serum could lower the expression of ICAM-1 (P<0.05). Compared with danazol, Neiyi Recipe showed more obvious effect in down-regulating MMP-9 (P<0.05). CONCLUSIONS: High expression of MMP-9 and low expression of TIMP-1 existed in eutopic and ectopic endometrial tissues of endometriosis, which could enhance the ectopic invasion and transplant of endometrial cells. Neiyi Recipe could inhibit the invasion of endometrial stromal cells and the expression of MMP-9.

[Effects of Chinese herbal medicine Bushen Shugan Recipe in regulating the hypothalamus-pituitary-ovarian axis in a rat model of stress-induced anorexia].

OBJECTIVE: To investigate the effects of Bushen Shugan Recipe (BSSGR), a compound traditional Chinese herbal medicine, in regulating the hypothalamus-pituitary-ovarian axis (HPOA) in a rat model of stress-induced anorexia. METHODS: Anorexia was induced in rats by the methods of separation, diet restriction and constraint. Rats were divided into 4 groups randomly: control group, untreated group, sham-operated group and BSSGR group. After the experiments, body weights and oestrous cycles of the 4 groups were compared. The levels of serum estradiol (E(2)), hypophysis luteotrophic hormone (LH), hypophysis follicle stimulating hormone (FSH) and hypothalamus ß-endorphin (ß-EP) were detected by radioimmunoassay. The level of serum corticosterone (CORT) was detected by enzyme-linked immunosorbent assay. RESULTS: Body weight of BSSGR group was significantly increased in comparison with sham-operated group(P<0.01); the oestrous cycle disordering rate was higher than those of the untreated group and sham-operated group; hypophysis LH and serum E(2) were obviously increased in comparison with untreated group (P<0.05); hypothalamus ß-EP was obviously decreased in comparison with sham-operated group (P<0.05); serum CORT was obviously decreased in comparison with untreated group (P<0.05), and significantly decreased in comparison with sham-operated group (P<0.01). CONCLUSION: BSSGR increased hypophysis LH and serum E(2), and decreased serum CORT and hypothalamus ß-EP in rats with stress-induced anorexia.

The hepatotoxicity of multi-walled carbon nanotubes in mice.

The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg(-1) by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- alpha, NF-kappaB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

[The change of certain biochemical indexes and apotosis protein (Fas/FasL) expression in rat liver of selenium and iodine deficiency].

OBJECTIVE: To investigate the effect of selenium (Se) and iodine (I) deficiency on certain biochemical indexes and apotosis protein (Fas/FasL) expression. METHOD: Healthy SD rats were divided into 4 groups at random, including control group, Se deficient group, I deficient group and both Se and I deficient group.The rats in each group were given different man-made feeds containing different levels of Se and I to breed. The second generation rats were chosen as research subjects. The GPX-Px activity and MDA and NO contents and expression of apoptosis protein (Fas/FasL) in liver were determined by chromometry and western blot. RESULT: GPX-Px of rat liver in Se deficient group significantly reduced, MDA and NO content s and expression of apoptosis of Fas/FasL increased. There were no apparent change in GPX-Px activities and NO contents of rat liver in I deficient group, while the contents of MDA and Fas/FasL expressions were much higher. The changes of GSH-Px activities and contents of MDA, NO as well as the Fas/FasL expressions in both Se and I deficiency groups are much higher than those of Selenium and Iodine deficiency groups. CONCLUSION: Se deficiency can cause the decrease of GPX-Px activities of rat liver and the increase of contents of MDA and NO. It can also lead to over expression of Fas/FasL. It seems that I deficiency can enhance the effect of selenium deficiency.

[Research of integrated traditional Chinese and Western medicine on regularity of clinical acupuncture].

In the present article, the authors, in the light of their research in recent a decade of years, make an overall summary on the regularities of clinical acupuncture from the stimulated points, the superficial and deep layers, the literature basis and the innovation points. These basic regularities include symmetry or corresponding, segmental innervation, center or central axis, superiority of distal limbs, ending-stimulation accelerating analgesia, periphery-stimulation accelerating easiness and smooth, local feed back, specific feed back, selection of the stimulated points, acupuncture of different layers, etc.. They also discuss the possibility of integration of traditional Chinese and Western medicine from the view-points of neuroanatomy, neurophysiology and rehabilitation medicine. Systematic analysis on the regularities of clinical acupuncture makes the ancient meridian-collateral theory and abundant clinical experience summed up in definite concepts, simplifies the complicated theory system of acupuncture learning, and favors the communication about the terminology of Chinese medicine and Western medicine.