Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to Cisplatin.

MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.

MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer.

Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions.

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

[The molecular mechanism of interaction of trivalent dimethylarsinous acid (DMA(III)) binding to rat hemoglobin].

In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.

[Randomized controlled study on ear-electroacupuncture treatment of endometriosis-induced dysmenorrhea in patients].

OBJECTIVE: To observe the therapeutic effect of ear-electroacupuncture (Ear-EA) on dysmenorrhea in patients with endometriosis and to explore its underlying mechanism. METHODS: A total of 80 endometriosis patients were randomly and equally divided into ear-EA group and body-EA group. EA (50 Hz, 0.5-0.8 mA) was applied to auricular points (Uterus, Subcortex, Shenmen, Endocrine, etc.) and body acupoints [Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4), Sanyinjiao (SP 6), Diji (SP 8), Uterus (EX-CA 1), etc.] respectively for 30 min, once every other day for 3 months. Dysmenorrhea severity score (DSS) was assessed and plasma prostaglandin (PGE2) and 6-Keto-PGF1alpha levels detected by radioimmunoassay. RESULTS: Compared with pre-treatment, DSS lowered significantly during the 1st and 2nd menstrual cycle in body-EA group, and during the 1st, 2nd and 3rd menstruation in ear-EA group; and the DSS of ear-EA group during the 3rd menstruation was evidently lower than that of body-EA group (P < 0.05). During the 3rd menstrual onset after the treatment, plasma PGE2 contents in both groups decreased obviously (P < 0.01), and plasma 6-Keto-PGF1alpha, levels increased considerably in comparison with pre-treatment (P < 0.01). Comparison between two groups during the 3rd menstruation showed that plasma PGE2 level of ear-EA group was markedly lower than that of body-EA group, and 6-Keto-PGF1alpha, level of ear-EA group was significantly higher than that of body-EA group (P < 0.05). No significant difference was found between two groups in clinical therapeutic effect (P > 0.05). CONCLUSION: Both ear-EA and body-EA can effectively relieve endometriosis-induced dysmenorrhea, and the former is superior to the later in reducing pain severity, which may be closely related to their effects in reducing plasma PGE2 and raising 6-Keto-PGF1alpha level.

[Treatment of hypomenorrhea by acupoint catgut embedding].

OBJECTIVE: To observe therapeutic effect of acupoint catgut embedding on hypomenorrhea. METHODS: The patients were divided into an acupoint catgut embedding group and an electroacupuncture group. They were treated respectively by acupoint catgut embedding and electroacupuncture at Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Ciliao (BL 32) , etc. The effects of the two therapies on the menses amount in different therapeutic periods were compared and their therapeutic effects were analyzed. RESULTS: The total effective rate was 100.0% in the acupoint catgut embedding group and 95.0% in the electroacupuncture group with no significant difference. One month and two months after treatment, the acupoint catgut embedding group in improving degree of the menses amount was better than the electroacupuncture group. CONCLUSION: Both acupoint catgut embedding and electroacupuncture can effectively treat hypomenorrhea, but the former more rapidly produces the effect and has a better short-term therapeutic effect.

Effect of Gengnianchun Recipe on bone mineral density, bone biomechanical parameters and serum lipid level in ovariectomized rats.

OBJECTIVE: To observe the effect of Gengnianchun Recipe (GNC) on bone mineral density (BMD), bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized (OVX) rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia. METHODS: OVX SD rats, 10 - 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0.125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and to compare the effect of the two drugs on the morphology of the uterus. RESULTS: There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae (P < 0.01) and increase of serum TC and LDL-C levels (P < 0.01) in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae (P < 0.05 or P < 0.01), and reduced the serum TC and LDL-C levels (P < 0.01). In the Nilestriol group, the wet weight of uterus got increased obviously (P < 0.01), the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group. CONCLUSION: GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TC and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.

[Emodin sensitizes HeLa cell to arsenic trioxide induced apoptosis via the reactive oxygen species-mediated signaling pathways].

Since reactive oxygen species(ROS) has been known to play an important role in apoptosis induced by arsenic trioxide, we attempt to elevate the cellular ROS level on HeLa cell by an natural anthraquinone-emodin, then to study its effect on apoptotic sensitivity to arsenic, and finally to investigate the mechanisms of the involved signaling pathway. The results showed that emodin 10 micromol/L could enhance arsenic induced apoptosis via generation of ROS, whereas rendered no detectable effect on normal fibroblast. Increased ROS promoted mitochondrial transmembrane potential collapse; inhibited the activation of transcription factors NF-kappa B. The study elucidated that emodin sensitize HeLa cells via generation of ROS which result in enhancement of apoptosis signaling pathway and inhibition of survival signaling pathway.

The Susceptibility of Leukemia Cells to Arsenic Trioxide-induced Apoptosis is Determined by Cellular Reactive Oxygen Species Level.

To explore the relationship between the susceptibility to arsenic trioxide (As(2)O(3))-induced apoptosis of leukemia cells and the level of reactive oxygen species (ROS) of cells, flow cytometry and electron microscopy were applied to identify apoptosis, and dihydrorhodamine123 was used to display the ROS level of cells. As(2)O(3) alone or in combination with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ, 2.5 &mgr;mol/L for NB4 cells, 10 &mgr;mol/L for U937 cells) were used to induce cell apoptosis. The results showed that NB4 cells possessed higher level of ROS than U937 cells. DMNQ raised ROS levels of NB4 and U937 cells, sensitized U937 cells to As(2)O(3)-induced apoptosis, and enhanced the efficacy of As(2)O(3)-induced apoptosis of NB4 cells. Catalase reversed the effect of DMNQ on NB4 and U937 cells. It was concluded that the susceptibility of leukemia cells to arsenic trioxide-induced apoptosis is determined by ROS level in the cells.