Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration.

Retraction of: 'Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration', by Tong Xu, Lunhua Huang, Zhiqiang Liu, Dongwen Ma, Guowei Zhang, Xiaofei Ning, Xinyang Lu, Hongsheng Liu, Biao Jiang JBUON 2019;24(2):686-692; PMID:31128024. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

The N-terminal domain of the non-receptor tyrosine kinase ABL confers protein instability and suppresses tumorigenesis.

Chromosome translocation can lead to chimeric proteins that may become oncogenic drivers. A classic example is the fusion of the BCR activator of RhoGEF and GTPase and the ABL proto-oncogene nonreceptor tyrosine kinase, a result of a chromosome abnormality (Philadelphia chromosome) that causes leukemia. To unravel the mechanism underlying BCR-ABL-mediated tumorigenesis, here we compared the stability of ABL and the BCR-ABL fusion. Using protein degradation, cell proliferation, 5-ethynyl-2-deoxyuridine, and apoptosis assays, along with xenograft tumor analysis, we found that the N-terminal segment of ABL, which is lost in the BCR-ABL fusion, confers degradation capacity that is promoted by SMAD-specific E3 ubiquitin protein ligase 1. We further demonstrate that the N-terminal deletion renders ABL more stable and stimulates cell growth and tumorigenesis. The findings of our study suggest that altered protein stability may contribute to chromosome translocation-induced cancer development.

Effects of ivabradine hydrochloride combined with trimetazidine on myocardial fibrosis in rats with chronic heart failure.

Effects of ivabradine hydrochloride (Iva) and trimetazidine on myocardial fibrosis (MF) in rats with chronic heart failure (CHF) werφe explored. Fifty Wistar rats were randomly divided into sham operation, model, Iva, trimetazidine and combined drug group with 10 rats each. All rats except those in sham operation group were subjected to establish CHF model by constricting the abdominal aorta. After successful modeling, rats in the sham operation and model group received normal saline (10 mg/kg) gavage daily, the Iva group received Iva (10 mg/kg) gavage, the trimetazidine group received trimetazidine (10 mg/kg) gavage, and the combined drug group were given Iva (10 mg/kg) and trimetazidine (10 mg/kg) gavage for 12 weeks. The changes of hemodynamic indexes and heart rate, connective tissue growth factor (CTGF) and superoxide dismutase (SOD) levels as well as transforming growth factor ß1 (TGF-ß1) and collagen I (COL-I) expression levels in myocardial tissue of each group were detected. Compared with sham operation group, the left ventricular end-diastolic pressure (LVEDP) level, CTGF expression, TGF-ß1 mRNA and COL-I mRNA expression levels in model group increased significantly, but the ± dp/dtmax and SOD content in myocardial tissue decreased significantly. Compared with model group, the LVEDP level, CTGF expression, TGF-ß1 mRNA and COL-I mRNA expression levels in Iva group, trimetazidine group and combined drugs decreased significantly, but the ± dp/dtmax and the SOD content in myocardial tissue increased significantly (P<0.05). Changes in the combined drug group were the most notable (P<0.05). Iva combined with trimetazidine reduces LVEDP in rat with CHF, increases SOD content, and inhibits CTGF expression and TGF-ß1 and COL-I expression levels in myocardial tissues, thus achieving the inhibitory effect on MF.

Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration.

PURPOSE: Totarol is a plant-derived natural product and has been reported to exhibit important pharmacological activities. However, the anticancer activity of totarol has not been evaluated yet. Therefore, the present research work was designed to evaluate the antitumor effects of totarol in SGC-7901 human gastric cancer cells and human gastric epithelial mucosa cell line GES-1 (used as normal cell line model) together with examining its effects on induction of apoptosis, cell cycle phase distribution and cell migration. METHODS: The effect of totarol on cell cytotoxicity was evaluated by MTT cell viability assay. Inverted phase contrast microscopy was used to identify the effects on cell morphology, while transmission electron microscopy indicated the apoptosis-driven morphological changes in cancer cells. The effects on cell apoptosis were also evaluated by annexin V/PI staining, while cell cycle analysis was done by flow cytometry. In vitro wound healing assay estimated the effects of totarol on cell migration. RESULTS: The results indicated that totarol induced selective cytotoxic effects in SGC-7901 human gastric cancer cells concentration-dependently and exhibited lower toxicity in GES-1 normal cells. The totarol-treated cells showed significant alterations in cell morphology including rounding and cellular shrinkage. Untreated SGC-7901 cells exhibited normal cellular morphology with undamaged plasma membrane. However, treating cells with totarol led to damaged plasma membrane along with appearance of rounded protrusions (apoptotic bodies) containing damaged and broken chromatin material. Treatment with different doses of totarol led to profound suppression of wound healing. Totarol treatment also led to G2/M phase cell cycle arrest in these cells in a concentration-dependent manner. CONCLUSIONS: The present study indicated that totarol diterpene has the tendency to show selective anticancer effects in SGC-7901 human gastric cancer cells along with inducing apoptosis, cell cycle arrest and inhibition of cell migration.

Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis.

Bacterial vaginosis (BV), caused by the vaginal dysbacteriosis as well as the excessive growth of pathogenic bacteria, is a pathological condition of the vagina; its treatment using the antibiotics metronidazole or clindamycin often causes high recurrence rates. Considering the similar physiological environments of the intestinal tract and vaginal tract, as well as the pathological mechanism of intestinal infection and vaginal infection, we first propose the conception of vaginal microbiota transplantation (VMT) and discuss its potential use in BV. This review focuses on the pathology of BV and the side effects caused by its standardised treatment. The extremely dynamic and diverse gut microbiota forms the most intensive microbial system and also plays a significant role in human body, and Lactobacilli dominate in the vaginal tract of women, keeping them healthy. Accordingly, we also propose the concept of VMT based on the effects of faecal microbiota transplantation (FMT) in treating intestinal infections, and list the potential hurdles for the implementation of VMT.

αvß3 integrin receptor specific peptide modified, salvianolic acid B and panax notoginsenoside loaded nanomedicine for the combination therapy of acute myocardial ischemia.

PURPOSE: To achieve the combination therapy of acute myocardial ischemia, arginyl-glycyl-aspartic acid (RGD) conjugated lipid was synthesized and RGD modified, salvianolic acid B (Sal B) and panax notoginsenoside (PNS) co-loaded lipid-polymer hybrid nanoparticles (RGD-S/P-LPNs) was fabricated an evaluated. METHODS: RGD was conjugated to distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG-NH2) through amide linkage. Lipid-polymer hybrid nanoparticles (LPNs) were fabricated by nanoprecipitation method. RGD-S/P-LPNs was characterized in terms of morphology, size, charge, drug loading, entrapment, stability, drug release and cytotoxicity in vitro. Cardiac distribution, pharmacokinetics study and infarct therapy effect were evaluated in vivo. RESULTS: The LPNs are generally spherical in shape with uniform size distribution, have sizes of 100-200nm and zeta potentials range from -30.7∼ -39.8. In vitro release behaviors of drugs loaded LPNs are in a sustained release manner, which does not exhibit obviously cytotoxicity against H9c2 cardiomyocytes. RGD-S/P-LPNs group shows the most significant cardiac distribution and infarct therapy effect in vivo. CONCLUSION: The results illustrated that RGD modified dual drugs co-loaded LPNs are stable, sustained release carriers. Cardiac distribution, pharmacokinetics, and infarct therapy effect results suggested that the RGD-S/P-LPNs could improve the in vivo therapeutic efficacy of the double drugs.

Reclamation of Herb Residues Using Probiotics and Their Therapeutic Effect on Diarrhea.

Residues from herbal medicine processing in pharmaceutical plants create a large amount of waste (herb residues), which consists mainly of environmental pollution and medicinal waste. In order to resolve this problem, probiotics of Bacillus (B.) subtilis, Aspergillus (A.) oryzae, and Lactobacillus (L.) plantarum M3 are selected to reuse herb residue of Jianweixiaoshi tablets (JT), and an antibiotic-associated diarrhea (AAD) mouse model was established to evaluate the therapeutic effects of the herb residue fermentation supernatant. Our results indicated that the fermentation supernatant had scavenged 77.8% of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 78% of O2•-, 36.7% of •OH, 39% of Fe2+ chelation, and 716 mg/L reducing power. The inhibition zones for Salmonella (S.) typhimurium, S. enteritidis, Shigella (Sh.) flexneri, Escherichia (E.) coli, Listeria (L.) monocytogenes, Sh. dysenteriae 301, and Staphylococcus (S.) aureus were 17, 14, 19, 18, 20, 19, and 20 mm, respectively. The in vivo results indicated that the fermentation supernatant resulted in a high diarrhea inhibition rate (56%, p < 0.05), greatly enhanced the disruption of bacterial diversity caused by antibiotics, and restored the dominant position of L. johnsonii in the treatment and recovery stages. Therefore, the combination of the herb residue and probiotics suggests a potential to explore conversion of these materials for the possible development of therapies for AAD.

Analysis of plasma miR-208a and miR-370 expression levels for early diagnosis of coronary artery disease.

Coronary artery disease (CAD) requires more accurate diagnostic methods, for which circulating microRNAs (miRNAs) are promising non-invasive biomarkers. miR-208a and miR-370 are two key molecules in cardiac hemostasis and lipid metabolism, respectively. The aim of the present study was to evaluate their potency as diagnostic biomarkers for CAD. Plasma miR-208a and miR-370 were quantitated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using a TaqMan® MicroRNA Reverse Transcription and PCR kit in 95 CAD patients and 50 non-CAD control subjects. The association between the miRNA levels and CAD was analyzed statistically. The plasma levels of miR-208a (P=0.006) and miR-370 (P=0.003) were significantly higher in the CAD group than in the control group. Using receiver operating characteristic analysis it was shown that the area under the curve (AUC) of miR-208a and miR-370 was 0.819 and 0.745, respectively. The combination of miR-208a and miR-370 exhibited the largest AUC of 0.856. Thus, miR-208a and miR-370 are promising diagnostic biomarkers for discriminating CAD and may facilitate the management of patient care. The combination of the two miRNAs may be more efficacious than either miRNA alone for the diagnosis of CAD.