A molybdenum-based coordination polymer {Mo(PDA)(NO)(μ-O)MoO
3
·1.42H
2
O·0.58C
2
H
5
OH}
n
(
1
) (PDA is 1,10-phenanthroline-2,9-dicarboxylate) was synthesized using solvothermal reaction conditions ...and characterized using a suite of analytical techniques. Single-crystal X-ray diffraction studies reveal a 1D chain structure, with close contacts expanding the structure into 3D including π-interactions and hydrogen bonding. The utility of
1
as a sorbent for dispersive micro solid-phase extraction (D-μSPE) of basic organic compounds such as antidepressants is supported by the presence of many functional groups on the surface of
1
(such as pendant carboxylates, Mo=O, Mo–NO, and CH groups) as well as extensive electrostatic interactions. Therefore,
1
can be a suitable choice as sorbent in the D-μSPE of antidepressant drugs from human plasma samples via appreciable adsorbate-adsorbent interactions. Determination of the extracted antidepressant drugs was conducted using high-performance liquid chromatography-ultraviolet (HPLC-UV), with calibration plots being linear in the concentration range 0.1–500 ng mL
−1
for amitriptyline and nortriptyline, 0.2–500 ng mL
−1
for imipramine, and 0.5–300 ng mL
−1
for sertraline. The relative standard deviation (RSD) values were calculated for both intra-day and inter-day precision, and the RSD% values were in the range 3.9 to 5.2% and 4.6–5.4%, respectively. The limits of detection (LODs) was determined as 0.03–0.2 ng mL
−1
. Due to the good stability and reusability of the sorbent, the adsorption capacity had no obvious decrease after being used 20 times. Finally, the D-μSPE-HPLC-UV method was applied for the determination of antidepressant drugs in human plasma samples with recoveries of the analytes in the range 94.9 to 102%.
Graphical abstract
The article describes the synthesis of a robust molybdenum-based coordination polymer, and its application as sorbent for dispersive micro solid-phase extraction of antidepressant drugs from human plasma samples.
Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid β‐oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by ...analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l‐carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography–mass spectrometry was employed for the analysis of esterified fatty acids, while high‐resolution C18‐liquid chromatography‐mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non‐decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in‐depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long‐term impacts.
Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients ...have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc-modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease.
A simple and sensitive high performance thin-layer chromatographic method (HPTLC) was developed and validated for the analysis of two binary mixtures of antiepileptic drugs. The first mixture ...consists of eslicarbazepine acetate (ESL) and oxcarbazepine (OXC). The second one consists of carbamazepine (CBZ) and OXC. These drugs have intercalated metabolic pathways, which was the prime reason for the development of the proposed analytical methodology for their determination. The two mixtures were separated on pre-coated silica gel HPTLC plates G60 F254 utilizing a mixture of n-hexane: methylene chloride: ethanol: glacial acetic acid in the ratio (50:40:10:0.1 v/v/v/v) as a mobile phase. The first mixture was detected at 217 nm, while the second one was detected at 265 nm. The achieved sensitivity is very high as reflected by the limit of detection values ranging from 5.03 to 12.60 ng/spot for the studied drugs. The developed method is the first HPTLC method for separation of these drugs in their dosage forms and in human plasma. Good recovery results were obtained from pharmaceutical tablets in the range from 97.75 to 100.40% without any interference from co-formulated excipients. In addition, high recovery results from plasma samples after utilizing salting out assisted liquid-liquid extraction technique (SALLE) were obtained, which ranges from 88.17 to 101.95%, ensuring the efficiency of the proposed approach. Furthermore, the developed method was successfully applied to detect CBZ clearly in real patients' plasma without any interference from matrix components.
•HPTLC method was developed for estimation of oxcarbazepine in two binary mixtures with metabolically related drugs.•The developed method was optimized and validated according to ICH and US-FDA guidelines.•SALLE was applied successfully as an innovative and efficient technique for extraction of the studied drugs from human plasma.•Method was applied successfully for detection of carbamazepine in real plasma of epileptic patients.
Abstract Combining membrane electrophoresis with silver nanoparticle-based surface-enhanced Raman spectroscopy (SERS), we have developed a novel method for blood plasma analysis for cancer detection ...applications. In this method, total serum proteins are isolated from blood plasma by membrane electrophoresis and mixed with silver nanoparticles to perform SERS spectral analysis. The obtained SERS spectra present information-rich, fingerprint-type signatures of the biochemical constituents of whole proteins. We evaluated the utility of this method by analyzing blood plasma samples from patients with gastric cancer ( n = 31) and healthy volunteers ( n = 33). Principal components analysis of the spectra revealed that the data points for the two groups form distinct, completely separated clusters with no overlap. The gastric cancer group can be unambiguously distinguished from the normal group in this initial test—that is, with both diagnostic sensitivity and specificity of 100%. These results are very promising for developing a label-free, noninvasive clinical tool for cancer detection and screening. From the Clinical Editor In this paper by Lin et al, a novel nanotechnology-based blood plasma test is presented for sensitive detection of malignant cells. The method utilizes membrane electrophoresis followed by silver-nanoparticle based surface-enhanced Raman spectroscopy to analyze the purified proteins for spectral changes to determine if cancer is present.
Retinol-binding protein 4 (RBP4) is a retinol transporter in the blood plasma. Many diseases alter the plasma or serum levels of RBP4. Since serum RBP4 concentrations have been reported to decrease ...in hyperthyroidism, this study investigated whether serum RBP4 concentrations increased or remained constant in hypothyroidism. In sera from patients with hypothyroidism (n=71), hyperthyroidism (n=30), and healthy subjects (n=20), serum concentrations of RBP4 (sum of holo- and apo-RBP4), retinol, albumin, creatinine, and related constituents were measured, and RBP4/retinol molar ratio (as an index of apo-RBP4) and estimated glomerular filtration rate (eGFR) were calculated. The results showed that serum RBP4 concentrations tended to increase with decreasing free thyroxine concentrations, but there were no significant differences among patients with hypothyroidism, hyperthyroidism, and healthy subjects. When patients with hypothyroidism were subdivided by serum RBP4 level using 2.1 μmol/L cut-off value, patients with >2.1 μmol/L were revealed to be patients with older age having lower tri-iodothyronine, higher holo-RBP4, higher apo-RBP4, higher retinol, higher RBP4/retinol molar ratio, and lower eGFR than those in patients with <2.1 μmol/L. Multiple regression analysis showed significant associations between serum RBP4 levels and explanatory variables (retinol and eGFR). Although serum levels of RBP4 prior to the onset of renal dysfunction may affect the present concentrations, we conclude that the increase of serum RBP4 (both holo- and apo-RBP4) in patients with hypothyroidism was attributed to the decline in eGFR. In contrast, serum RBP4 concentration remained constant without renal dysfunction.
The aim of this study was to examine the association of circulating retinol-binding protein 4 (RBP4) levels with β-cell function across the spectrum of glucose tolerance from normal to overt type 2 ...diabetes.
A total of 291 subjects aged 35-60 years with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT), or type 2 diabetes were screened by a standard 2-h oral glucose tolerance test (OGTT) with the use of traditional measures to evaluate β-cell function. From these participants, 74 subjects were recruited for an oral minimal model test, and β-cell function was assessed with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit.
Circulating RBP4 levels were significantly and inversely correlated with β-cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indices, but not with HOMA of β-cell function, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β-cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion.
Circulating RBP4 levels are inversely and independently correlated with β-cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.
Systemic retinol (vitamin A) homeostasis is controlled by the liver, involving close collaboration between hepatocytes and hepatic stellate cells (HSCs). Genetic variants in retinol metabolism ...(PNPLA3 and HSD17B13) are associated with non-alcoholic fatty liver disease (NAFLD) and disease progression. Still, little mechanistic details are known about hepatic vitamin A metabolism in NAFLD, which may affect carbohydrate and lipid metabolism, inflammation, oxidative stress and the development of fibrosis and cancer, e.g. all risk factors of NAFLD.
Here, we analyzed vitamin A metabolism in 2 mouse models of NAFLD; mice fed a high-fat, high-cholesterol (HFC) diet and Leptinob mutant (ob/ob) mice.
Hepatic retinol and retinol binding protein 4 (RBP4) levels were significantly reduced in both mouse models of NAFLD. In contrast, hepatic retinyl palmitate levels (the vitamin A storage form) were significantly elevated in these mice. Transcriptome analysis revealed a hyperdynamic state of hepatic vitamin A metabolism, with enhanced retinol storage and metabolism (upregulated Lrat, Dgat1, Pnpla3, Raldh’s and RAR/RXR-target genes) in fatty livers, in conjunction with induced hepatic inflammation (upregulated Cd68, Tnfα, Nos2, Il1β, Il-6) and fibrosis (upregulated Col1a1, Acta2, Tgfβ, Timp1). Autofluorescence analyses revealed prominent vitamin A accumulation in hepatocytes rather than HSC in HFC-fed mice. Palmitic acid exposure increased Lrat mRNA levels in primary rat hepatocytes and promoted retinyl palmitate accumulation when co-treated with retinol, which was not detected for similarly-treated primary rat HSCs.
NAFLD leads to cell type-specific rearrangements in retinol metabolism leading to vitamin A accumulation in hepatocytes. This may promote disease progression and/or affect therapeutic approaches targeting nuclear receptors.
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Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding ...protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.
We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.
Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 95% confidence interval (CI), 0.71-0.80 and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test.
Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.
Most iron oxide nanoparticles applications, and in special biomedical applications, require the accurate determination of iron content as the determination of particle properties from measurements in ...dispersions is strongly dependent on it. Inductively coupled plasma (ICP) and spectrophotometry are two typical worldwide used analytical methods for iron concentration determination. In both techniques, precise determination of iron is not straightforward and nanoparticle digestion and dilution procedures are needed prior to analysis. The sample preparation protocol has been shown to be as important as the analytical method when accuracy is aimed as many puzzling reported results in magnetic, colloidal, and structural properties are simply attributable to inadequate dissolution procedures. Therefore, a standard sample preparation protocol is needed to ensure the adequate and complete iron oxide nanoparticle dissolution and to harmonize this procedure. In this work, an interlaboratory evaluation of an optimized iron oxide nanoparticle digestion/dilution protocol was carried out. The presented protocol is simple, inexpensive, and does not involve any special device (as microwave, ultrasound, or other high-priced digestion devices). Then, iron concentration was measured by ICP-OES (performed in ICMM/CSIC-Spain) and spectrophotometry (NanoPET-Germany) and the obtained concentration values were analyzed to determine the most probable error causes. Uncertainty values as low as 1.5% were achieved after the optimized method was applied. Moreover, this article provides a list of recommendations to significantly reduce uncertainty in both sample preparation and analysis procedures.
Graphical abstract
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