Effect of GSH and niacin combination on protein oxidation, ER stress, glycation and aggregation in HLE cells under high glucose condition

AIM: To evaluate the effects of reduced glutathione (GSH) and niacin combination on protein oxidative stress, endoplasmic reticulum (ER) stress, glycation, and aggregation of the αβ crystalline in human lens epithelial (HLE) cells treated with high glucose levels. METHODS: HLE cells were cultured and exposed to 25 mmol/L glucose to promote high glucose conditions. Groups of cells were co-treated with three different combinations of dosages: 10 μmol/L GSH+25 μmol/L niacin (P1), 30 μmol/L GSH+25 μmol/L niacin (P2), and 100 μmol/L GSH+25 μmol/L niacin (P3). After 72h incubation, protein carbonyl content (PCC) and glucose reactive protein (GRP78) content were assessed using ELISA examinations. After two-week incubation, advanced glycation end products (AGEs) were also assessed and the expression of αβ crystalline was measured using Western blot examination. RESULTS: PCC and GRP78 levels in the co-treated groups were not significantly reduced compared to control (P>0.05). In contrast, there was a significant decrease of the AGEs levels in all groups co-treated with GSH and niacin when compared with the control group (P<0.05). In addition, the αβ crystalline expression increased after high dose glucose administration, but decreased in all groups co-treated with GSH and combinations of GSH and niacin. CONCLUSION: Combinations of GSH and niacin inhibit the aggregation of proteins and prevent glycation in hyperglycemic HLE cells. This study shows that this combination may play an active role in preventing diabetic cataract mainly from the AGEs pathway.     

A new highly selective “off–on” typical chemosensor of Al3+, 1-((Z)-((E)-(3,5-dichloro-2-hydroxybenzylidene)hydrazono)methyl) naphthalene-2-ol,an experimental and in silico study

A new promising fluorescent chemosensor based on a 2-hydroxynaphthaldehyde skeleton was successfully synthesized through double imine formation as a yellow solid with an overall chemical yield of 63%. The compound showed UV/Visible maxima of at 394 nm in DMSO. Based on spectroscopic data of FTIR, ToF-HRMS, ¹H-NMR, and ¹³C-NMR, the product was characterized as 1-((Z)-((E)-(3,5-dichloro-2-hydroxybenzilydine)hydrazono)methyl)naphthalene-2-ol. Upon experimental study, the compound was confirmed as a highly selective and reversible off–on typical chemosensor against Al³⁺ with an emission quantum yield of 0.203 ± 0.009. The Job''s plot analysis revealed that a highly stable 1:1 complex was formed with an association constant of 8.73 × 10⁵ M⁻¹. A pH-dependent study showed that the sensor was potentially applicable at physiological conditions (pH 7–8) in a mixture of DMSO : H₂O (99 : 1, v/v). The LoD and LoQ of the chemosensor towards Al³⁺ in DMSO were found to be 0.04 and 0.14 μM respectively. Based on DFT and TD-DFT calculation (B3LYP hybrid method/basis set of 6-311+G(d,p)), the sensing mechanism of the chemosensor to the ion was discovered as inhibition of excited-state intramolecular proton transfer (ESIPT).

A new promising fluorescent chemosensor of Al³⁺ based on a 2-hydroxynaphthaldehyde skeleton was successfully synthesized through double imine formation and demonstrated excellent sensing properties through the ESIPT inhibition mechanism.     

Artoindonesianin C, a new xanthone derivative from Artocarpus teysmanii

A new xanthone derivative, artoindonesianin C (1), was isolated from Artocarpus teysmanii, together with two known prenylated flavonoids, cycloartobiloxanthone and artonin J. The structure of artoindonesianin C (1) was determined on the basis of MS and NMR evidence and by comparison with known related compounds.     

Variations in long- and middle-wavelength-sensitive opsin gene loci in crab-eating monkeys.

We analyzed variations in long (L)- and middle (M)-wavelength-sensitive opsin gene loci in crab-eating monkeys. Unlike humans, most monkeys have a single L and a single M gene. Two variant genotypes, one with only one opsin gene (dichromatic) and one with tandemly arrayed multiple genes, were also found in the monkeys. However, the frequency of the former was 0.47%, and that of the latter was 5% in the monkeys, while 2% and 66%, respectively, in Caucasian males. The two variants were found only in Java Island, Indonesia, and South Thailand, respectively. The data suggest that the frequency of each genotype is different among Old World primates.     

C-27 and C-3 Glucosylation of Diosgenin by Cell Suspension Cultures of Costus Speciosus

Abstract

3-O-[β-D-glucopyranosyl-(1″ → 2′)-β-D-glucopyranosyl], 27-O-β-D-glucopyranosyl-(25R)-spirost-5-ene-3β,27-diol was isolated from cell suspension cultures of Costus speciosus, following incubation with diosgenin, and its structure was elucidated using a combination of one- and two-dimensional ¹H and ¹³C NMR spectral data, and positive and negative ion ESMS spectral data.     

The diagnostic performance of <Superscript>18</Superscript>F-FAMT PET and <Superscript>18</Superscript>F-FDG PET for malignancy detection: a meta-analysis

Background

This meta-analysis aims to compare the diagnostic performance of l-3-¹⁸F-α-methyl tyrosine (¹⁸F-FAMT) positron emission tomography (PET) and 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) PET for malignancy detection.

Methods

The workflow of this study follows Cochrane Collaboration Guidelines of a systematic review of diagnostic test accuracy studies. An electronic search was performed for clinical diagnostic studies directly comparing ¹⁸F-FAMT and ¹⁸F-FDG PET for malignant tumors. Study quality, the risks of bias and sources of variation among studies were assessed using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) assessment tool. A separate meta-analysis was performed for diagnostic performance based on visual assessment and diagnostic cut-off values. Whenever possible, a bivariate random-effect model was used for analysis and pooling of diagnostic measures across studies.

Results

Electronic search revealed 56 peer-reviewed basic science investigations and clinical studies. Six eligible studies (272 patients) of various type of cancer were meta-analyzed. The ¹⁸F-FAMT diagnostic accuracy for malignancy was higher than ¹⁸F-FDG based on both visual assessment (diagnostic odd ratio (DOR): 8.90, 95% confidence interval (CI) [2.4, 32.5]) vs 4.63, 95% CI [1.8, 12.2], area under curve (AUC): 77.4% vs 72.8%) and diagnostic cut-off (DOR: 13.83, 95% CI [6.3, 30.6] vs 7.85, 95% CI [3.7, 16.8], AUC: 85.6% vs 80.2%), respectively. While the average sensitivity and specificity of ¹⁸F-FAMT and ¹⁸F-FDG based on visual assessment were similar, ¹⁸F-FAMT was significantly more specific than ¹⁸F-FDG (p?<?0.05) based on diagnostic cut-off values.

Conclusions

¹⁸F-FAMT is more specific for malignancy than ¹⁸F-FDG, while their sensitivity is comparable. ¹⁸F-FAMT PET is equal to ¹⁸F-FDG PET in diagnostic performance for malignancy detection in several cancer types.

     

The expression and down stream effect of lectin like-oxidized low density lipoprotein 1 (LOX-1) in hyperglycemic state

The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses. Low density lipoprotein (LDL), which may be modified by oxidation, glycation, aggregation, association with proteoglycans, or incorporation into immune complexes, is a major cause of injury to the endothelium and vascular smooth muscle cells (VSMC).The major major cell types involved in atherogenesis, macrophages and VSMC, are activated by pro-inflammatory stimuli including modified LDL. Modified LDL induces inflammatory responses in macrophages, migration and proliferation of SMC, and triggers foam cell formation. Scavenger receptors, including LOX-1, play a key role in foam cell formation by mediating the uptake of modified LDL. LOX-1 expression is detected in endothelial cells of early atherosclerosis lesions of human carotid arteries. Advanced lesions showed LOX-1 expression not only in endothelial cells but also in macrophages and more frequently in VSMC, and may be involved in foam cell transformation in macrophages and VSMC. The metabolic abnormalities that characterize diabetes, particularly hyperglycemia, free fatty acids, and insulin resistance, provoke molecular mechanisms that alter the function and structure of blood vessels. These include increased oxidative stress, intracellular signal transduction disturbances, and activation of the receptor for advanced glycation end products (R-AGE). Data showed that LOX-1 expression is enhanced by proatherogenic factors relevant to human diabetes, including high glucose, oxLDL, advance glycation end products, and C-reactive protein. LOX-1 expression increased also through oxygen species (ROS), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha), shear stress, activation of protein kinase-C (PKC), angiotensin-II (ANG-II), and through inflammatory pathways.     

Hypertension: diagnostic problem, challenge and dilemmas

An elevated arterial pressure is probably the most important public health problem. The prevalence of hypertension depends on both the racial composition of the population studied and the criteria used to define the condition. Patients with hypertension die prematurely, the most common cause of death is heart disease, stroke, and renal failure. The JNC-7 report has introduced a new classification that includes term "pre-hypertension". The new classification may make a new dilemma in the management since the main treatment of pre-hypertension is the lifestyle changes. What do we recommend to lean patients with pre-hypertension who are already following a prudent lifestyle? The ultimate public health goal of antihypertensive therapy is the reduction of cardiovascular and renal morbidity and mortality. The question is, what should the blood pressure goal be? For patients without any compiling condition, it was assumed that 140/90 mmHg was desired treatment target level. For diabetic patient, it is reasonable to target a blood pressure well within the normal range, at most 130/80 mmHg. Some newer studies suggest that the target of treatment may force the recommended goal even lower, even for the patient without any compiling condition. For elderly individuals, a goal of 140/90 mmHg is appropriate. Hypertension during pregnancy is one of important aspects, since blood pressure during pregnancy may change related to the gestational age. This is always subject of discussion because there is no evidence that pharmacologic treatment results in improved neonatal outcomes, lower blood pressure may, in fact uteroplacental perfusion and thereby jeopardize fetal development. It means that more attention is needed for hypertensive patients not only for treatment regimens choice but also the blood pressure target. The accurate measurement of blood pressure is the sine qua non for successful management of hypertension. The operator should be trained and regularly retrained in the standardized technique, to avoid the chance of mismanagement.