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.

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.

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.

[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.

[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.