Allulose mitigates chronic enteritis by reducing mitochondria dysfunction via regulating cathepsin B production.

Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10-/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.

Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection.

Persistent infection with the carcinogenic human papillomavirus (HPV) is a prerequisite for the progression of cervical lesions and cancer. A growing body of research has focused on the functional role of the vaginal microbiota in the persistence of HPV infection. Understanding the microbial composition and structure in women with high-risk (hr)-HPV infection may help reveal associations between the vaginal microbiota and HPV infection, and identify potential biomarkers. Our study investigated the vaginal microbial community in women with and without hr-HPV infection, by using 16s rRNA gene sequencing. We found that microbial perturbations occurred in the early phase of hr-HPV infection. Lactobacillus and Sporolactobacillus were decreased, while bacteria related to bacterial vaginosis (BV), such as Gardnerella, Prevotella, Dialister, Slackia, Actinomyces, Porphyromonas, Peptoniphilus, Anaerococcus, Peptostreptococcus, Streptococcus, Ureaplasma, Megasphaera, and Mycoplasma were increased. Our results could offer insights into the correlations between hr-HPV and the vaginal microbiota in the early infection period, and provide indications that the predominance of some BV-associated bacteria during hr-HPV infection may increase the risk for cervical neoplasia.

Chaperone-mediated autophagy regulates apoptosis and the proliferation of colon carcinoma cells.

Chaperone-mediated autophagy (CMA) is one of the three types of autophagy. In recent years, CMA has been shown to be associated with the pathogenesis of several types of cancer. However, whether CMA is involved in the pathogenesis of colorectal cancer (CRC) remains unclear. In this study, we investigated CMA activity in tissue specimens from CRC patients and mouse models of colitis-associated CRC (induced by administration of AOM plus DSS). In addition, we down-regulated CMA in CT26 colon carcinoma cells stably transfected with a vector expressing a siRNA targeting LAMP-2A, the limiting component in the CMA pathway, to explore the role of CMA in these cells. Apoptosis was detected using TUNEL assay, and the apoptosis-related proteins were detected using western blotting. Cell proliferation was assessed using MTT assay, Ki-67 labelling and western blotting for PCNA. We found that LAMP-2A expression was significantly increased in CRC patients and mouse models and varied according to the stage of the disease. Inhibition of CMA in CT26 cells facilitated apoptosis, as evidenced by increased TUNEL immunolabeling, increased expression of Bax and Bnip3, and decreased expression of Bcl-2. Cell proliferation assays showed that inhibition of CMA impeded the proliferation of CT26 cells. These data support the hypothesis that CMA is up-regulated in CRC, and inhibition of CMA may be a new therapeutic strategy for CRC patients.

Gemcitabine Plus Vinorelbine as Second-Line Therapy in Patients With Metastatic Esophageal Cancer Previously Treated With Platinum-Based Chemotherapy.

We evaluated the efficacy and feasibility of the combination of gemcitabine plus vinorelbine in patients with platinum-based chemotherapy-refractory esophageal cancer. We enrolled 35 patients who received gemcitabine plus vinorelbine as second-line treatment after platinum-based chemotherapy failure between May 2009 and April 2012. Dosage: gemcitabine 1,000 mg/m(2) plus vinorelbine 25 mg/m(2); all drugs were administered on days 1 and 8 of a 21-day cycle, and this was continued until failure or unacceptable toxicity. A total of 125 cycles of treatment were administered, and all patients received at least two cycles of treatment (two to five cycles; median number of cycles: three). Thirty-two patients were evaluable for response. The response rate was 31.3%, and the disease control rate (partial response plus stable disease) was 62.5%. The progression-free survival (PFS) was 4.3 ± 0.2 months [95% confidence interval (CI), 4.0-4.6], and the median overall survival (OS) was 7.3 ± 0.3 months (95% CI, 6.7-7.8). In the subgroup analysis, median PFS was 4.0 ± 0.2 months (95% CI, 3.6-4.3) in patients with high expression of miRNA-214, while it was 4.6 ± 0.3 months (95% CI, 4.1-5.1) in patients with low expression of miRNA-214 (log rank = 0.023). Myelosuppression with neutropenia and thrombocytopenia was the most common side effect observed with this combination regimen, and higher than grade 3 neutropenia and thrombocytopenia were observed in 10 (31.3%) and 8 patients (25.0%), respectively. Grade 3 fatigue was the most common nonhematologic toxicity, which was observed in 2 (6.1%) patients. The combination of gemcitabine plus vinorelbine was well tolerated as second-line treatment for platinum-based chemotherapy-refractory esophageal cancer patients and appeared to provide enhanced clinical activity especially in patients with low expression of miRNA-214.

Cervical cancer gene therapy by gene loaded PEG-PLA nanomedicine.

BACKGROUND AND AIMS: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. METHODS: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/ DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. RESULTS: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. CONCLUSIONS: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

Characterization and expression profiles of MaACS and MaACO genes from mulberry (Morus alba L.).

1-Aminocyclopropane-1-carboxylic acid synthase (ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) are encoded by multigene families and are involved in fruit ripening by catalyzing the production of ethylene throughout the development of fruit. However, there are no reports on ACS or ACO genes in mulberry, partly because of the limited molecular research background. In this study, we have obtained five ACS gene sequences and two ACO gene sequences from Morus Genome Database. Sequence alignment and phylogenetic analysis of MaACO1 and MaACO2 showed that their amino acids are conserved compared with ACO proteins from other species. MaACS1 and MaACS2 are type I, MaACS3 and MaACS4 are type II, and MaACS5 is type III, with different C-terminal sequences. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) expression analysis showed that the transcripts of MaACS genes were strongly expressed in fruit, and more weakly in other tissues. The expression of MaACO1 and MaACO2 showed different patterns in various mulberry tissues. MaACS and MaACO genes demonstrated two patterns throughout the development of mulberry fruit, and both of them were strongly up-regulated by abscisic acid (ABA) and ethephon.

MicroRNA-9 expression is a prognostic biomarker in patients with osteosarcoma.

BACKGROUND: The purpose of the present study was to examine the expression levels of microRNA-9 (miR-9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma. METHODS: The expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. RESULTS: Compared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan-Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival. CONCLUSIONS: The findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma.

Overexpressed FOXC2 in ovarian cancer enhances the epithelial-to-mesenchymal transition and invasion of ovarian cancer cells.

Ovarian cancer is a highly invasive and metastatic disease with poor prognosis, particularly if this disease is diagnosed at an advanced stage, which is often the case. Researchers have argued that ovarian cancer cells that have undergone epithelial­to­mesenchymal transition (EMT) acquire aggressive malignant properties; however, the relevant molecular mechanisms in this setting are poorly understood. In cancer cases, the transcription factor forkhead box protein C2 (FOXC2) has been detected, but the function of this factor in ovarian cancer tumorigenesis remains unclear. In the present study, FOXC2 was overexpressed in invasive ovarian cancer cell lines and tissues. The invasive potential of ovarian cancer cells was significantly increased by ectopic FOXC2 expression but it was significantly decreased by RNA interference targeting FOXC2. E­cadherin and vimentin expression levels were modulated by FOXC2. These results indicated that FOXC2 was required for the maintenance of the mesenchymal phenotype after TGF­ß1 induced EMT in human ovarian cancer cells. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies. These therapies can then be performed to treat invasive ovarian tumor.

[Comparative effect of different media in in vitro cultivation of Trichomonas vaginalis].

OBJECTIVE: To investigate the optimal condition for in vitro cultivation of Trichomonas vaginalis for obtaining a better harvest of T. vaginalis. METHODS: An isolate of T. vaginalis from clinical specimens was cultivated in three different media with initial inoculation of 9.0 x 10(4)/ml under pH 5.6. RESULTS: There was distinct difference after 96 h incubation in the cumulative harvest of T. vaginalis. The highest harvest was received in cysteine/liver/peptone/maltose medium, followed by the liver/peptone/maltose medium and soybean/liver/peptone/maltose medium. CONCLUSION: The cysteine/liver/peptone/maltose medium may be a suitable environment for in vitro multiplication of T. vaginalis.