Quantitative structure-retention relationship(QSRR) method was used to model reversed-phase high-performance liquid chromatography (RP-HPLC) separation of 18 selected amino acids. Retention data for phenylthiocarbamyl (PTC) amino acids derivatives were obtained using gradient elution on ODS column with mobile phase of varying acetonitrile, acetate buffer and containing 0.5 ml/l of triethylamine (TEA). Molecular structure of each amino acid was encoded with 36 calculated molecular descriptors. The correlation between the molecular descriptors and the retention time of the compounds in the calibration set was established using the genetic neural network method. A genetic algorithm (GA) was used to select important molecular descriptors and supervised artificial neural network (ANN) was used to correlate mobile phase composition and selected descriptors with the experimentally derived retention times. Retention time values were used as the network's output and calculated molecular descriptors and mobile phase composition as the inputs. The best model with five input descriptors was chosen, and the significance of the selected descriptors for amino acid separation was examined. Results confirmed the dominant role of the organic modifier in such chromatographic systems in addition to lipophilicity (log P) and molecular size and shape (topological indices) of investigated solutes.
A confirmatory and quantitative HPLC-tandem mass spectrometry (MS-MS) method for human chorionic gonadotropin hormone (hCG) at concentrations as low as 5 IU/l following immunoaffinity extraction of the glycoprotein from urine was developed. The extraction method involved retention of urinary hCG in the immunoaffinity column via specific antigen-antibody interaction. A variety of eluents were then used to quantitatively elute hCG from the immunoaffinity column. Qualitative and quantitative analysis of hCG were undertaken using MS-MS by identifying the amino acid sequence of the marker peptide betaT5 obtained from hCG by tryptic digestion and the peak areas of three product ions b(6)(+), b(9)(+) and y(11)(+), respectively.
Premature neonates of very low birth weight (VLBW) whose treatment required the use of naso-gastric tube feeding were investigated. 10 infants suspected of having GERD (gastroesophageal reflux) received oral lansoprazole therapy by tube administration. 9 other infants formed a control group. In the treated group a fasting pH was determined before treatment and again after 7 days treatment. The control group was similarly assessed at an interval of 7 days. Despite acid reduction, the post-treatment pH mean of 1.31 would continue to pose a threat to the esophageal mucosa. The physiology of neonatal acid secretion is discussed to explain these findings.
Fishbones are of particular interest to otolaryngologists. Most fishbones can be removed transorally or via endoscopic guidance. Transcervical neck exploration is occasionally necessary, especially in cases of an embedded foreign body. Computed tomography is the most sensitive and specific imaging modality for identifying embedded fishbones. To our knowledge, this is the first reported case of a laryngeal foreign body embedded in the paraglottic space that was removed using an open approach via a lateral thyroid cartilage window.
Graphene-based materials have gained remarkable attention in numerous disciplines owing to their unique electrochemical properties. Out of various hybridized nanocomposites, graphene-zirconia nanocomposite (GZ) was distinctive due to its biocompatibility. Zirconia nanoparticles serve as spacers that reduce the stacking of graphene and improve the electrochemical performance of the material. Considering that lungs and skin suffer the greatest exposure to nanoparticles, this study aimed to evaluate the cytotoxicity of the as-synthesized GZ nanocomposites on MRC5 (lung cells) and HaCaT (skin cells) via morphological observation and cell viability assay using 3-(4,5 dimethylthiazol-2-yl)-(2,5-diphenyltetrazolium bromide) tetrazolium (MTT). GZ-treated cells showed a comparable proliferation rate and morphology with untreated cells under microscopic evaluation. Based on MTT results, the IC50 values of GZ were > 500 µg/ml for MRC5 and HaCaT cells. The excellent biocompatibility was the supremacy of GZ over other nanocomposites applied as electrode materials in biosensors. GZ was functionalized with biolinker for the detection of carcinoembryonic antigen (CEA). The proposed immunosensor exhibited good responses towards CEA detection, with a 4.25 pg/ml LOD and correlation coefficient of R2 = 0.99 within a linear working range from 0.01 to 10 ng/ml. The performance of the immunosensor to detect CEA present in human serum was also evaluated. Good recovery of CEA was found, suggesting that the proposed immunosensor possess a high affinity to CEA even in a complex biological matrix, rendering it a promising sensing platform for real sample analysis and open a new way for the detection of cancer-associated proteins.
Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
AIM OF THE STUDY: Orthosiphon stamineus (Labiatae) is a traditional folk medicine widely used in Southeast Asia for the treatment of several kidney disorders, gout and as a diuretic. This study was conducted to examine the diuretic and hypouricemic effects of Orthosiphon stamineus leaf extracts.
MATERIALS AND METHODS: The diuretic effect of different methanol extracts was examined by treating different groups of Sprague-Dawley rats with single (2g/kg) oral doses of methanol and methanol:water (1:1) extracts. Hydrochlorothiazide (10mg/kg) was used as positive control in acute study. Methanol and methanol water (1:1) extracts at 0.5 g/kg were administered for a period of 7 consecutive days. Cumulative urine volume and electrolytes (Na+ and K+) concentrations at different time intervals were measured. On the other hand, hypouricemic activity of methanol:water extract (1:1) was experimented using different oral single doses (0.25, 0.5, 1 and 2g/kg). Allopurinol was used as positive control. Uric acid concentration in serum was analyzed by using RP-HPLC at 280 nm.
RESULTS: Sodium and potassium excretion increased significantly (p<0.05 and <0.01) in the first 8h of treatment with a single dose (2g/kg) of the extracts in a pattern comparable to that of the known diuretic hydrochlorothiazide. Meanwhile, repeated administration of 0.5 g/kg methanol:water (1:1) extract showed a significant increase in urine volume (from day 3 to day 7) (p<0.01) and electrolytes excretion (Na+ and K+) from day 2 to day 7 (p<0.05 and <0.01). On the other hand, 0.5, 1 and 2g/kg of methanol:water (1:1) extract and the standard allopurinol reduced the serum urate level in hyperuricemic rats at hour 6.
CONCLUSION: These results provided an evidence of the high tendency of methanol:water (1:1) extract of Orthosiphon stamineus towards diuretic and hypouricemic effects in rats.
The Community Integration Questionnaire-Revised (CIQ-R) is a self-report standardized instrument designed to assess an individual's degree of community integration. The aim of this study was to translate, validate and conduct a reliability test of the CIQ-R Malay version. The development involved the three phases of translation, content validation and cognitive interviewing, test-retest reliability and internal consistency of the CIQ-R Malay version. The Content Validity Index (CVI) showed perfect agreement between the panel experts. The Intra-class Correlation Coefficient (ICC) demonstrated a moderate to excellent level of test-retest agreement (ICC 0.72 to 0.93). The Total CIQ-R Malay version and Home Integration subscale showed good internal consistency, with values of Cronbach's alpha ranging from 0.81 to 0.90. The findings from the present study provided preliminary support for the psychometric properties of the CIQ-R Malay version as a valid and reliable instrument to be used in Malaysia.
Highly sensitive and selective immunosensors that can detect disease biomarkers at ultra-low levels in early stages are urgently needed to reduce mortality risks. A facile and efficient approach using sonochemical-assisted solvent graphene exfoliation and a hydrothermal synthesis method has been used to prepare graphene/titanium dioxide (G/TiO2) nanocomposites. Nanocomposites containing different ratios of graphene and TiO2 precursors were prepared to determine the optimum composition of G/TiO2 that has the highest conductivity and electrocatalytic properties. Characterisation methods such as X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and high resolution TEM (HRTEM) were used to study the crystallinity, surface characteristics, elemental composition, and morphology of the synthesised nanocomposites. The synthesised materials were also confirmed via Raman spectroscopy. Using ferricyanide as the redox active probe, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analyses indicated that 1 : 8 ratio of G/TiO2 exhibited the best current response and the lowest charge transfer resistance (Rct) of 1525 Ω. The potential of G/TiO2 for electrochemical sensing application was investigated using hydrogen peroxide (H2O2), a by-product of most enzymatic processes, as the analyte of interest. The sensitivity of the sensor towards H2O2 was 0.557 μA mM-1, with a limit of detection (LOD) at 56.89 μM. An in vitro cell proliferation assay was carried out to investigate the biocompatibility of the nanocomposites. The half-maximal inhibitory concentration (IC50) values obtained were >500 μg ml-1 for human lung fibroblasts (MRC5) and 5-25 μg ml-1 for human skin cells (HaCat).
Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.