YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability.

Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was detected by RT-qPCR and Western blot analysis. An interaction of YY1, GAS5, and p53 protein stability was predicted and confirmed by bioinformatics, ChIP, Co-IP, RIP, and FISH assays. Following loss- and gain-function assays, LSCC cell proliferation, colony formation, cell cycle, telomere length and telomerase activity were evaluated by CCK-8 assay, colony formation assay, flow cytometry, and PCR-ELISA, respectively. Nude mice were xenografted with the tumor in vivo. LSCC cell lines presented with upregulated expression of YY1, downregulated GAS5 expression, and decreased p53 stability. YY1 inhibited the expression of GAS5, which in turn recruited p300 and bound to p53, thus stabilizing it. Moreover, YY1 could directly interact with p300 and suppressp53 stability, leading to enhancement of cell proliferation, telomere length and telomerase activity in vitro along with tumor growth in vivo. Collectively, YY1 can stimulate proliferation and telomerase activity of LSCC cells through suppression of GAS5-dependent p53 stabilization or by decreasing p53 stability via a direct interaction with p300, suggesting that YY1 presents a therapeutic target as a potential oncogene in LSCC development and progression.

Effect of vitamin D supplementation on benign paroxysmal positional vertigo recurrence: A meta-analysis.

Benign paroxysmal positional vertigo is characterized by recurrence, which exposes patients to repeated vertigo attacks. Vitamin D deficiency has been found to be a risk factor in benign paroxysmal positional vertigo, although effect of its elimination on recurrence reduction remains unknown. To determine the effect of vitamin D supplementation in preventing recurrence of benign paroxysmal positional vertigo patients with vitamin D deficiency using a meta-analysis study. We searched and retrieved relevant articles from several databases, then used the Cochrane evaluation system or Methodological Index for Non-Randomized Studies (MINORS) to assess the quality of studies. We adopted risk-ratio (RR) with corresponding 95% confidence interval (CI) to determine effect sizes, and further performed statistical analyses under a randomized- or fixed-effects model. Seven studies, comprising 602 and 731 participants in the case and control group respectively, met our inclusion criteria, and were therefore included in the meta-analysis. Assessment based on Cochrane evaluation system or MINORS revealed that most of the studies had high quality. Moreover, the randomized- model revealed that the vitamin D supplementation group had a lower recurrence rate than the control group which did not accepted vitamin D supplementation (RR = 0.41, 95% CI = 0.26-0.65, p < 0.01). Overall, these findings indicate that vitamin D supplementation can significantly lower recurrence in benign paroxysmal positional vertigo and vitamin D deficiency.

Efficacy and Safety of Danshen Compound Tablets in Preventing Thalidomide-Associated Thromboembolism in Patients with Multiple Myeloma: A Multicenter Retrospective Study.

BACKGROUND Currently available antithrombotic prophylaxis is not perfectly reliable in elderly patients. The aim of this retrospective study was to evaluate the efficacy and safety of Compound Danshen Tablet (CDT) in preventing thromboembolism in multiple myeloma (MM) patients treated with thalidomide-based regimens. MATERIAL AND METHODS MM patients treated with thalidomide-based regimens were retrospectively reviewed between January 2008 and March 2015. Patients were categorized into 3 cohorts based on thromboembolic prophylaxis used: CDT, Warfarin Tablet, and no prophylaxis. Venous thromboembolism (VTE), other adverse effects (AEs), and the changes of D-dimer and fibrinogen levels were monitored. RESULTS Seven out of 313 MM patients (2.24%) developed venous thrombosis events (VTE) in this retrospective study, all clustering in the no prophylaxis cohort. Three patients of the Warfarin cohort (3.19%) experienced hemorrhage. Neither VTE events nor serious AEs were observed in the CDT cohort. Following Compound Danshen or Warfarin treatment for 3 months, the D-dimer and fibrinogen levels (in particular the D-dimer level) (all P<0.05), were obviously decreased relative to their respective baselines and the no prophylaxis cohort. In contrast, the 2 blotting parameters were significantly increased in the no prophylaxis cohort relative to the baseline level (All P<0.05), and were even higher in the patients experiencing VTE compared to the no VTE patients (P<0.0001 and P=0.016, respectively). CONCLUSIONS Our findings indicate CDT is an effective therapy for preventing VTE in MM patients treated with thalidomide-based regimens, and is well tolerated in long-term use.

3,4,5-Trimethoxycinnamic acid, one of the constituents of Polygalae Radix exerts anti-seizure effects by modulating GABAAergic systems in mice.

Polygalae Radix is an important medicinal plant that is widely used in most of Africa. 3,4,5-Trimethoxycinnamic acid (TMCA) is one of the constituents of Polygalae Radix. Until now, the mechanisms involved in the anti-seizure property of TMCA are still unclear. We examined the anti-seizure effect of TMCA. TMCA administered at doses of 5, 10 and 20 mg/kg and evaluated anti-seizure effects by maximal electroshock (MES) and pentylenetetrazol (PTZ) models in mice. TMCA administered at doses of 10 and 20 mg/kg significantly reduced the incidence of MES-induced tonic hindlimb extension (THE). TMCA significantly delayed the onset of myoclonic jerks (MJ), and decreased the seizure severity and mortality compared with the vehicle-treated animals in PTZ seizure model. TMCA 10 and 20 mg/kg treated groups also did not determined generalized clonic seizures (GCS). Pretreatment with a GABAA/benzodiazepine (BZ) receptor antagonist flumazenil blocked the anti-seizure effects of TMCA. These data support the further investigation of TMCA as a GABAA/BZ receptor agonist for anti-seizure therapy.

[Hyperthermia increases the sensitivity of RPMI 8226 cells to adriamycin].

This study was purposed to explore the effect of hyperthermia on sensitivity of multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The working concentration of ADM against RPMI 8226 cells was defined by MTT assay. RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42°C) group, chemotherapy (ADM) group and combination group (42°C + ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI 8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate of cells, intracellular ADM concentration and P-gp expression level were measured by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration in the experiment. The results indicated that the hyperthermia promoted the entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the expression of P-gp protein on cells in hyperthermia and combination groups was down-regulated, the intracellular ADM concentration in combination group obviously increased. It is concluded that the hyperthermia combined with ADM obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through down-regulating the expression of P-gp protein on cells and increasing the intracellular ADM concentration.

[Effects of Chinese medicine compound FFJZ on proliferation and apoptosis of leukemia cell line K562].

This study was purposed to explore the biological effects suppressing growth and inducing apoptosis of Chinese medicine compound FFJZ on leukemia cell line K562 and its possible mechanisms of FFJZ. The growth status of K562 cells cultured in vitro was determined by trypan blue exclusion test; the suppressive effect of FFJZ on K562 cells was assayed by MTT method; the inducing apoptosis of FFJZ on K562 cells was detected by flow cytometry. The results showed that after K562 cells were treated with FFJZ in certain concentration range, the inhibited rate of FFJZ on K562 cell growth was remarkably increased along with enhancement of FFJZ, the IC(50) value of FFJZ on K562 cells was 5.6 mg/ml after treatment for 48 hours. At 4 mg/ml of FFJZ the early apoptosis predominated in K562 cells, at 8 mg/ml of FFJZ the late apoptosis ratio significantly increased. As compared with control group without FFJZ, there was significant difference (p < 0.01). It is concluded that the FFJZ in range of certain concentration can suppress growth and proliferation of K562 cells and induce their apoptosis in concentration-dependent manner, the mechanism of which may be associated to inducing apoptosis of K562 cells.

Novel and efficient chiral bisphosphorus ligands for rhodium-catalyzed asymmetric hydrogenation.

A series of structurally novel, operationally convenient, and efficient chiral 2-phosphino-2,3-dihydrobenzo[d][1,3]oxaphosphole ligands was developed. Applications of ligands 3a and 3b in rhodium-catalyzed asymmetric hydrogenation of alpha-(acylamino)acrylates and beta-(acylamino)acrylates provided excellent enantioselectivities (up to >99% ee) and reactivities (up to 10,000 TON).

[Synergistic reversal effect of Chinese medicine compound FFJZ combined with cyclosporine A on multidrug resistance of leukemia K562/VCR cell line].

The study was purposed to investigate the synergistic reversal effect of Chinese medicine compound FFJZ in combination with cyclosporine A (CsA) on the multidrug resistance (MDR) of human leukemia K562/VCR cell line, as to search effective combination of MDR modulators. MTT (methyl-thazol-tetrazolinum) assay were used to determine the cytotoic and reversal effects on K562/VCR cell line, FCM (flow cytometry) was used to assess the intracellular adriamycin (ADM) concentration and the expression of P-gp in cells. The results showed that the FFJZ in combination with CsA could reverse the drug-resistance of K562/VCR cells and increase the sensitivity K562/VCR cells to adriamycin. They had not the toxic effect on the K562/VCR cells in effective dose and no significant influence on P-gp positive rate of the K562/VCR cells. It is concluded that the FFJZ in combination with CsA may become a safe and effective multidrug resistance-reversing agent with low toxicity in leukemia chemotherapy.