Fucoxanthin Enhances Cisplatin-Induced Cytotoxicity via NFκB-Mediated Pathway and Downregulates DNA Repair Gene Expression in Human Hepatoma HepG2 Cells

Cisplain, a platinum-containing anticancer drug, has been shown to enhance DNA repair and to inhibit cell apoptosis, leading to drug resistance. Thus, the combination of anticancer drugs with nutritional factors is a potential strategy for improving the efficacy of cisplatin chemotherapy. In this study, we investigated the anti-proliferative effects of a combination of fucoxanthin, the major non-provitamin A carotenoid found in Undaria Pinnatifida, and cisplatin in human hepatoma HepG2 cells. We found that fucoxanthin (1–10 μΜ) pretreatment for 24 h followed by cisplatin (10 μΜ) for 24 h significantly decreased cell proliferation, as compared with cisplatin treatment alone. Mechanistically, we showed that fucoxanthin attenuated cisplatin-induced NFκB expression and enhanced the NFκB-regulated Bax/Bcl-2 mRNA ratio. Cisplatin alone induced mRNA expression of excision repair cross complementation 1 (ERCC1) and thymidine phosphorylase (TP) through phosphorylation of ERK, p38 and PI3K/AKT pathways. However, fucoxanthin pretreatment significantly attenuated cisplatin-induced ERCC1 and TP mRNA expression, leading to improvement of chemotherapeutic efficacy of cisplatin. The results suggest that a combined treatment with fucoxanthin and cisplatin could lead to a potentially important new therapeutic strategy against human hepatoma cells

Wildfire: distributed, Grid-enabled workflow construction and execution

BACKGROUND: We observe two trends in bioinformatics: (i) analyses are increasing in complexity, often requiring several applications to be run as a workflow; and (ii) multiple CPU clusters and Grids are available to more scientists. The traditional solution to the problem of running workflows across multiple CPUs required programming, often in a scripting language such as perl. Programming places such solutions beyond the reach of many bioinformatics consumers. RESULTS: We present Wildfire, a graphical user interface for constructing and running workflows. Wildfire borrows user interface features from Jemboss and adds a drag-and-drop interface allowing the user to compose EMBOSS (and other) programs into workflows. For execution, Wildfire uses GEL, the underlying workflow execution engine, which can exploit available parallelism on multiple CPU machines including Beowulf-class clusters and Grids. CONCLUSION: Wildfire simplifies the tasks of constructing and executing bioinformatics workflows

iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

BACKGROUND: The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. RESULTS: To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. CONCLUSION: The iHAP resource, available at , provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies

A five-year experience in endoscopic endonasal excision of juvenile nasopharyngeal angiofibroma

Introduction: Juvenile nasopharyngeal angiofibroma (JNA) is a histological benign but locally aggressive vascular tumour which can invade the base of skull. Aim: This is a retrospective study with the aim to examine the outcome of patients with JNA and endoscopic endonasal excision of tumour at a tertiary center in Malaysia. Material and methods: 9 patients were identified from the medical record office from 2015 to 2019. We review the data on patient demographics, clinical presentations, laboratory investigations, intraoperative blood loss and duration of hospital stay. Results and discussion: 8 patients were male, 1 was female. The average age of diagnosis was 15 (range 11 to 29) years. The commonest chief complaint was recurrent epistaxis, followed by nasal obstruction and nasal discharge. Three patients were at stage I, 4 patients at stage II, 1 patient at stage III and 1 patient at stage IV based on Fisch classification. All patients underwent primary endoscopic endonasal excision of tumour with no vascular, ophthalmological or neurological complication. Seven patients had preoperative embolization done. Average operation time was 137 minutes (range 60–360 minutes). Intraoperative blood lost varied from 500 mL to 1300 mL (mean 777.7 mL). All patients were discharged well with no recurrence. Conclusions: The management of JNA can be challenging. The current shift in management favouring endoscopic endonasal excision of JNA reduces postoperative morbidity. It is possible to be applied on all stages of tumour with good success rate

A five-year experience in endoscopic endonasal excision of juvenile nasopharyngeal angiofibroma

Introduction: Juvenile nasopharyngeal angiofibroma (JNA) is a histological benign but locally aggressive vascular tumour which can invade the base of skull. Aim: This is a retrospective study with the aim to examine the outcome of patients with JNA and endoscopic endonasal excision of tumour at a tertiary center in Malaysia. Material and methods: 9 patients were identified from the medical record office from 2015 to 2019. We review the data on patient demographics, clinical presentations, laboratory investigations, intraoperative blood loss and duration of hospital stay. Results and discussion: 8 patients were male, 1 was female. The average age of diagnosis was 15 (range 11 to 29) years. The commonest chief complaint was recurrent epistaxis, followed by nasal obstruction and nasal discharge. Three patients were at stage I, 4 patients at stage II, 1 patient at stage III and 1 patient at stage IV based on Fisch classification. All patients underwent primary endoscopic endonasal excision of tumour with no vascular, ophthalmological or neurological complication. Seven patients had preoperative embolization done. Average operation time was 137 minutes (range 60–360 minutes). Intraoperative blood lost varied from 500 mL to 1300 mL (mean 777.7 mL). All patients were discharged well with no recurrence. Conclusions: The management of JNA can be challenging. The current shift in management favouring endoscopic endonasal excision of JNA reduces postoperative morbidity. It is possible to be applied on all stages of tumour with good success rate

Tonsillar tuberculosis with coexisting lymphoma: A case report

The co-existence of tuberculosis (TB) and lymphoma share similar presentations and both may masquerade each other leading to diagnostic dilemmas. Herein, we would like to report a case of an elderly man with existing TB in whom failing to respond to treatment led to investigations that unveiled the coexistence of a non-Hodgkin lymphoma. A 71-year-old man presented to our department with a one-month history of odynophagia and left submandibular swelling. He was treated with multiple courses of antibiotics but symptoms not resolving. Physical examination showed enlarged tonsils bilaterally with exudates. There was also a left cervical lymph node enlargement. Biopsy taken from both tonsils and histopathological examination (HPE) showed no malignancy. Biopsy was also sent for a Genexpert test for tuberculosis and the result was positive for Mycobacterium tuberculosis. A fine needle aspiration was taken from the neck mass and the result was non-diagnostic. As the result from the Genexpert test was positive, he was started on anti-TB treatment. After three months of treatment, the tonsils were still hypertrophied and the left neck nodes never resolved. Suspicion was raised and a second biopsy was done with an incisional biopsy taken from the left neck nodes. The tonsils biopsy still showed no malignancy but the HPE from the neck nodes showed diffuse large B-cell lymphoma. Patient was counselled for chemotherapy but refused. He succumbed to the disease three months after refusal of chemotherapy. The co-existence of extrapulmonary tuberculosis and lymphoma is rare, which leads to a diagnostic dilemma especially if one was not known to have underlying lymphoma. Tuberculosis will usually be suspected first due to our endemic nature and in this case, further investigations were only done when the symptoms were not resolving with anti-TB treatment. Therefore, suspicion of both conditions occurring concurrently should arise early if treatment was unsuccessful

A five-year experience in endoscopic endonasal excision of juvenile nasopharyngeal angiofibroma

Introduction: Juvenile nasopharyngeal angiofibroma (JNA) is a histological benign but locally aggressive vascular tumour which can invade the base of skull. Aim: This is a retrospective study with the aim to examine the outcome of patients with JNA and endoscopic endonasal excision of tumour at a tertiary center in Malaysia. Material and methods: 9 patients were identified from the medical record office from 2015 to 2019. We review the data on patient demographics, clinical presentations, laboratory investigations, intraoperative blood loss and duration of hospital stay. Results and discussion: 8 patients were male, 1 was female. The average age of diagnosis was 15 (range 11 to 29) years. The commonest chief complaint was recurrent epistaxis, followed by nasal obstruction and nasal discharge. Three patients were at stage I, 4 patients at stage II, 1 patient at stage III and 1 patient at stage IV based on Fisch classification. All patients underwent primary endoscopic endonasal excision of tumour with no vascular, ophthalmological or neurological complication. Seven patients had preoperative embolization done. Average operation time was 137 minutes (range 60–360 minutes). Intraoperative blood lost varied from 500 mL to 1300 mL (mean 777.7 mL). All patients were discharged well with no recurrence. Conclusions: The management of JNA can be challenging. The current shift in management favouring endoscopic endonasal excision of JNA reduces postoperative morbidity. It is possible to be applied on all stages of tumour with good success rate

Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation

Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety

What are the barriers faced by patients using insulin? a qualitative study of Malaysian health care professionals' views

BACKGROUND: Patients with type 2 diabetes often require insulin as the disease progresses. However, health care professionals frequently encounter challenges when managing patients who require insulin therapy. Understanding how health care professionals perceive the barriers faced by patients on insulin will facilitate care and treatment strategies. OBJECTIVE: This study explores the views of Malaysian health care professionals on the barriers faced by patients using insulin. METHODS: Semi-structured qualitative interviews and focus group discussions were conducted with health care professionals involved in diabetes care using insulin. Forty-one health care professionals participated in the study, consisting of primary care doctors (n = 20), family medicine specialists (n = 10), government policymakers (n = 5), diabetes educators (n = 3), endocrinologists (n = 2), and one pharmacist. We used a topic guide to facilitate the interviews, which were audio-recorded, transcribed verbatim, and analyzed using a thematic approach. RESULTS: FIVE THEMES WERE IDENTIFIED AS BARRIERS: side effects, patient education, negative perceptions, blood glucose monitoring, and patient adherence to treatment and follow-up. Patients perceive that insulin therapy causes numerous negative side effects. There is a lack of patient education on proper glucose monitoring and how to optimize insulin therapy. Cost of treatment and patient ignorance are highlighted when discussing patient self-monitoring of blood glucose. Finally, health care professionals identified a lack of a follow-up system, especially for patients who do not keep to regular appointments. CONCLUSION: This study identifies five substantial barriers to optimizing insulin therapy. Health care professionals who successfully identify and address these issues will empower patients to achieve effective self-management. System barriers require government agency in establishing insulin follow-up programs, multidisciplinary diabetes care teams, and subsidies for glucometers and test strips