2-Methoxy-1,4-naphthoquinone (MNQ) regulates cancer key genes of MAPK, PI3K, and NF-κB pathways in Raji cells.

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

The predictive and diagnostic accuracy of vascular endothelial growth factor and pentraxin-3 in severe dengue.

This study aimed to evaluate vascular endothelial growth factor (VEGF) and pentraxin 3 (PTX-3) as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The study was conducted in Ampang Health Clinic, Ampang Hospital and Serdang Hospital. The plasma levels of VEGF and PTX-3 were compared between severe dengue and non-severe dengue by ELISA from the day of presentation until discharged. Multiple logistic regression was used to develop predictive and diagnostic models by incorporating other clinical parameters. The receiver operating characteristics (ROC) analysis was used to assess the accuracy of the biomarkers and the developed models. Eighty-two patients were recruited, 29 with severe dengue and four died. The Area Under the Curve (AUC) was statistically significant in VEGF as diagnostic marker at Day 2 and 3 of illness with sensitivity of 80.00%-100.00% and specificity of 76.47%-80.00%. The predictive model with AUC of 0.84 (p < 0.01) has a sensitivity of 100.00% and specificity of 79.25% for predicting severe dengue. The diagnostic model with AUC of 0.71 (p < 0.01) has a sensitivity of 76.19% and specificity of 73.58% for diagnosing severe dengue. The AUC for PTX-3 was not statistically significant. VEGF may be used in combination with other clinical parameters to predict the severity of the disease. As a single biomarker, it may be used as an adjunct investigation to support the diagnosis of severe dengue. PTX-3 was not able to differentiate severe dengue from non-severe dengue.

Geographical distribution and spatio-temporal patterns of hospitalization due to dengue infection at a leading specialist hospital in Malaysia.

Increasing numbers of dengue infection worldwide have led to a rise in deaths due to complications caused by this disease. We present here a cross-sectional study of dengue patients who attended the Emergency and Trauma Department of Ampang Hospital, one of Malaysia's leading specialist hospitals. The objective was to search for potential clustering of severe dengue, in space and/or time, among the annual admissions with the secondary objective to describe the spatio-temporal pattern of all dengue cases admitted to this hospital. The dengue status of the patients was confirmed serologically with the geographic location of the patients determined by residency, but not more specific than the street level. A total of 1165 dengue patients were included in the analysis using SaTScan software. The mean age of these patients was 27.8 years, with a standard deviation of 14.2 years and an age range from 1 to 77 years, among whom 54 (4.6%) were cases of severe dengue. A cluster of general dengue cases was identified occurring from October to December in the study year of 2015 but the inclusion of severe dengue in that cluster was not statistically significant (P=0.862). The standardized incidence ratio was 1.51. General presence of dengue cases was, however, detected to be concentrated at the end of the year, which should be useful for hospital planning and management if this pattern holds.

Global dengue death before and after the new World Health Organization 2009 case classification: A systematic review and meta-regression analysis.

BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate. METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables. RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant. CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

Induced pluripotent stem cells from human hair follicle keratinocytes as a potential source for in vitro hair follicle cloning.

BACKGROUND: Human hair follicles are important for the renewal of new hairs and their development. The generation of induced pluripotent stem cells (iPSCs) from hair follicles is easy due to its accessibility and availability. The pluripotent cells derived from hair follicles not only have a higher tendency to re-differentiate into hair follicles, but are also more suited for growth in hair scalp tissue microenvironment. METHODS: In this study, human hair follicular keratinocytes were used to generate iPSCs, which were then further differentiated in vitro into keratinocytes. The derived iPSCs were characterised by using immunofluorescence staining, flow cytometry, and reverse-transcription PCR to check for its pluripotency markers expression. RESULTS: The iPSC clones expressed pluripotency markers such as TRA-1-60, TRA-1-81, SSEA4, OCT4, SOX2, NANOG, LEFTY, and GABRB. The well-formed three germ layers were observed during differentiation using iPSCs derived from hair follicles. The successful formation of keratioctyes from iPSCs was confirmed by the expression of cytokeratin 14 marker. DISCUSSION: Hair follicles represent a valuable keratinocytes source for in vitro hair cloning for use in treating hair balding or grafting in burn patients. Our significant findings in this report proved that hair follicles could be used to produce pluripotent stem cells and suggested that the genetic and micro-environmental elements of hair follicles might trigger higher and more efficient hair follicles re-differentiation.