The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell ...growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1
) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1
by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.
•Fatty liver disease (FLD) is a common clinical complication, is associated with high morbidity and mortality.•A machine learning model has been using to predict liver disease that could assist ...physicians in classifying high-risk patients and make a novel diagnosis.•The random forest model shows higher performance than other classification models.
Fatty liver disease (FLD) is a common clinical complication; it is associated with high morbidity and mortality. However, an early prediction of FLD patients provides an opportunity to make an appropriate strategy for prevention, early diagnosis and treatment. We aimed to develop a machine learning model to predict FLD that could assist physicians in classifying high-risk patients and make a novel diagnosis, prevent and manage FLD.
We included all patients who had an initial fatty liver screening at the New Taipei City Hospital between 1st and 31st December 2009. Classification models such as random forest (RF), Naïve Bayes (NB), artificial neural networks (ANN), and logistic regression (LR) were developed to predict FLD. The area under the receiver operating characteristic curve (ROC) was used to evaluate performances among the four models.
A total of 577 patients were included in this study; of those 377 patients had fatty liver. The area under the receiver operating characteristic (AUROC) of RF, NB, ANN, and LR with 10 fold-cross validation was 0.925, 0.888, 0.895, and 0.854 respectively. Additionally, The accuracy of RF, NB, ANN, and LR 87.48, 82.65, 81.85, and 76.96%.
In this study, we developed and compared the four classification models to predict fatty liver disease accurately. However, the random forest model showed higher performance than other classification models. Implementation of a random forest model in the clinical setting could help physicians to stratify fatty liver patients for primary prevention, surveillance, early treatment, and management.
Tumour necrosis family superfamily (TNFSF) member 15 (TNFSF15), encoded by TNFSF15, regulates immune responses and inflammation. However, the roles of TNFSF15 single‐nucleotide variants (SNVs; ...formerly SNPs) in oral cavity squamous cell carcinoma (OCSCC) remain unclear. This case–control study included 2523 participants (1324 patients with OCSCC 52.5% and 1199 healthy controls 47.5%). The effects of TNFSF15 rs3810936, rs6478108 and rs6478109 on cancer development and prognosis were analysed by real‐time PCR genotype assay. The Genotype‐Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to validate our findings. The results demonstrated that the patients with altered TNFSF15 SNVs had poorer histological differentiation than did those with wild‐type alleles. TNFSF15 SNVs were significantly associated with moderate‐to‐poor histological differentiation in univariate logistic regression. In the GTEx database, the expression of altered TNFSF15 SNVs in whole blood was lower than that of wild‐type alleles. However, the expression of altered SNVs in the upper aerodigestive mucosa was higher than that of wild‐type alleles. In the TCGA database, the patients with higher TNFSF15 expression had shorter overall survival than did those with lower TNFSF15 expression, especially for human papillomavirus‐negative and advanced staging groups. In conclusion, although TNFSF15 SNVs did not affect OCSCC development, the patients with altered TNFSF15 SNVs exhibited poorer histological differentiation. The patients with higher TNFSF15 expression had poorer prognosis than did those with lower TNFSF15 expression.
► Bacterial cellulose (BC) was produced in large scale from culture of Acetobacter xylinum. ► The addition of chitosan (Ch) into BC (BC–Ch) increased the antibacterial activities. ► BC and BC–Ch ...membranes helped maintain a moist wound healing environment. ► Wounds treated with BC–Ch epithelialized faster than those treated with Tegaderm.
Bacterial cellulose (BC) and bacterial cellulose–chitosan (BC–Ch) membranes were successfully produced in large scale. BC was synthesized by Acetobacter xylinum. BC–Ch was prepared by immersing BC in chitosan followed by freeze-drying. The surface morphology of BC and BC–Ch membranes were examined by a scanning electron microscope (SEM). SEM images showed that BC–Ch possessed a denser fibril network with smaller pores than BC. Infrared spectroscopy was used to confirm the incorporation of chitosan in BC–Ch. The swelling behavior, water retention capacity, and mechanical properties of BC and BC–Ch were further evaluated. Results indicated that both membranes maintained proper moisture contents for an extensive period without dehydration. The tensile strength and elongation at break for BC–Ch were slightly lower while the Young's modulus was higher. Cell culture studies demonstrated that BC and BC–Ch had no cytotoxicity. In the antibacterial test, the addition of chitosan in BC showed significant growth inhibition against Escherichia coli and Staphylococcus aureus. The effects of BC and BC–Ch on skin wound healing were assessed by rat models. Histological examinations revealed that wounds treated with BC–Ch epithelialized and regenerated faster than those treated with BC or Tegaderm. Therefore, BC–Ch was considered as a potential candidate for wound dressing materials.
Oral squamous cell carcinoma (OSCC) has a high recurrence rate and poor prognosis. Hispolon, a polyphenolic compound with antiviral, antioxidant, and anticancer activities, is a potential ...chemotherapy agent. However, few studies have investigated the anti‐cancer mechanism of hispolon in oral cancer. This present study used the cell viability assay, clonogenic assay, fluorescent nuclear staining, and flow cytometry assay to analyse the apoptosis‐inducing effects of hispolon in OSCC cells. After hispolon treatment, the apoptotic initiators, cleaved caspase‐3, −8, and − 9, were upregulated, whereas the cellular inhibitor of apoptosis protein‐1 (cIAP1) was downregulated. Furthermore, a proteome profile analysis using a human apoptosis array revealed the overexpression of heme oxygenase‐1 (HO‐1) by hispolon, which was determined to be involved in caspase‐dependent apoptosis. Moreover, cotreatment with hispolon and mitogen‐activated protein kinase (MAPK) inhibitors revealed that hispolon induces apoptosis in OSCC cells through activation of the c‐Jun N‐terminal kinase (JNK) pathway and not the extracellular signal‐regulated kinase (ERK) or p38 pathway. These findings indicate that hispolon may exert an anticancer effect on oral cancer cells by upregulating HO‐1 and inducing caspase‐dependent apoptosis by activating the JNK pathway.
The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is ...generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori.
We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes.
In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval CI, 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence.
HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.
Semaphorins (SEMAs) are axon guidance factors that participate in axonal connections and nerve system development. However, the functional roles of SEMAs in tumorigenesis are still largely uncovered. ...By using in silico data analysis, we found that SEMA6C was downregulated in pancreatic cancer, and its reduction was correlated with worse survival rates. RNA sequencing revealed that cell cycle-related genes, especially cyclin D1, were significantly altered after blockage of SEMA6C by neutralizing antibodies or ectopic expressions of SEMA6C. Mechanistic investigation demonstrated that SEMA6C acts as a tumor suppressor in pancreatic cancer by inhibiting the AKT/GSK3 signaling axis, resulting in a decrease in cyclin D1 expression and cellular proliferation. The enhancement of cyclin D1 expression and cyclin-dependent kinase activation in SEMA6C-low cancer created a druggable target of CDK4/6 inhibitors. We also elucidated the mechanism underlying SEMA6C downregulation in pancreatic cancer and demonstrated a novel regulatory role of miR-124-3p in suppressing SEMA6C. This study provides new insights of SEMA6C-mediated anti-cancer action and suggests the treatment of SEMA6C-downregulated cancer by CDK4/6 inhibitors.
Cdk1 (cyclin-dependent kinase 1) is critical regulator of the G2-M checkpoint. Cyclin-dependent kinase pathways are considered possible targets for cancer treatment; however, the prognostic role of ...Cdk1 in colorectal cancer is still controversial. Therefore, we attempted to determine the impact of Cdk1 on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer.
Cdk1 immunoreactivity was analyzed by immunohistochemistry (IHC) in 164 cancer specimens from primary colorectal cancer patients. The medium follow-up time after surgery was 3.7 years (range: 0.01 to 13.10 years). The prognostic value of Cdk1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models.
All samples displayed detectable Cdk1 expression with predominant location in the cytoplasm and nucleus. A high Cdk1 nuclear/cytoplasmic (N/C) expression ratio was correlated with poor overall survival (5-year survival rate: 26.3% vs 46.9%, N/C ratio ≥1.5 vs N/C ratio <1.5, log-rank p = 0.027). Accordingly, a Cdk1 N/C expression ratio ≥1.5 was identified as an independent risk factor by multivariate analysis (hazard ratio = 1.712, P = 0.039).
We suggest that Cdk1 N/C expression ratio determined by IHC staining could be an independent prognostic marker for colorectal cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Frailty in older adults is a common geriatric syndrome that could be prevented; thus, coping strategies for the aging population are essential. Self-management behaviors may ...represent cost-effective strategies to prevent physical frailty in community-dwelling older adults. This study aimed to describe the changes in frailty status among community-dwelling older adults in Taiwan and investigate the association between transitions of self-management behaviors and frailty status over 4 years of follow-up (2007 to 2011).
Methods
Data were retrieved from the Taiwan Longitudinal Study of Aging (TLSA), years 2007 and 2011. In this prospective cohort study, 1283 community-dwelling older adults aged 65 years and older without cognitive impairment were recruited. Frailty was defined based on Fried’s frailty phenotype. Self-management behaviors (maintaining body weight, quitting smoking or no smoking, drinking less or no drinking, exercising, keeping diet control, and maintaining a regular lifestyle) were assessed using a questionnaire. Multinomial logistic regression analyses were used to investigate the associations between changes in self-management behaviors and in frailty status. The age group was further stratified to examine the moderation effect in the relationship between changes in self-management behaviors and in frailty status among older adults.
Results
The prevalence of frailty was 8.7% at baseline and 14.9% after 4 years of follow-up, with 196 (15.3%) deaths. Overall, 514 (40.1%) participants maintained their frailty status, 424 (33.0%) worsened, and only 149 (11.6%) improved. Being aged ≥75 years old, having chronic diseases, and an absence of self-management behaviors were associated with frailty at baseline and after follow-up. Among individuals aged 65–74, compared to those who maintained no self-management behaviors, those who decreased the exercise behaviors (yes-to-no) had a higher risk of worsening (RRR = 2.518), while increasing (no-to-yes) and maintaining (yes-to-yes) frequent physical exercise were associated with a lower risk of worsening (RRR = 0.466 and 0.572, respectively) than stable frailty; those who maintained body weight (yes-to-yes) were associated with a lower risk of worsening (RRR = 0.327) than stable frailty after controlling for individual covariates and chronic diseases. Among individuals over 75 years old, compared to no exerciser, older old who decreased their physical exercise had a higher risk of frailty worsening (RRR = 3.255), and increasing frequent physical exercise (no-to-yes) was associated with an improvement in frailty status (RRR = 3.684). Age was a moderator between the effects of maintaining body weight on frailty worsening. There were no associations between the behavioral transitions of smoking, drinking, diet control, or regular lifestyle on the frailty status changes.
Conclusions
Maintaining body weight and frequent physical exercise increased the ratio of frailty stability among individuals 65–74 years old. Increasing exercise behavior is the only factor to improve their frailty status among older adults aged 75 years and over. Older adults should be encouraged to perform adequate physical exercise and maintain a healthy body weight to maintain the frailty status in younger old aged 65–74 years, and especially perform more frequent exercise to improve frailty status in older old over 75 years.
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