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Background: Proton nuclear magnetic resonance spectroscopy method (1H-NMR) was applied to investigate the urinary patterns of type 2 diabetes mellitus (T2DM) patients to identify possible disturbances that may accompany T2DM. We investigate the potential relationship between diabetic retinopathy (DR), diabetic neuropathy (DN), estimated glomerular filtration rate (eGFR), anthropometric indicators (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to stature ratio (WSR)), duration of T2DM and urinary metabolites in T2DM. Materials and Methods: Serial urine samples of 167 healthy subjects and 185 T2DM patients were investigated by 1H-NMR. The 1H-NMR spectra have been recorded on a Bruker Avance DRX 400 MHz spectrometer. The results are evaluated in mmol/ mol of creatinine. p<0.05 was taken as significant. A significant difference between the urinary excretion of valine, 3-hydroxyisolateric acid, alanine, gamma-aminobuthyrate, betaine, citric acid, trimethylamine- N-oxide and glycine at the healthy individuals and T2DM patients was found. The values for 3-hydroxyisolateric acid and gamma-aminobuthyrate increase in T2DM patients with retinopathy vs. without retinopathy. There was no correlation between DN and urinary metabolite picture in T2DM patients. Results: We found significant correlations between eGFR and dimethylamine (r=0.194, p=0.031), gamma-aminobuthyrate (r=0.239, p=0.049), acetate (r=0.29, p=0.035) and pyruvate (r=0.275, p=0.014) in T2DM patients. Our analysis revealed significant decreased concentrations for citrate, dimethylamine and glycine in T2DM patients with the increase of BMI. WC were positively correlated with gamma-aminobuthyrate (r=0.42, p=0.01) and dimethylamine (r=0.39, p=0.03) and, no correlation were observed between WHR, WSR and urinary metabolites in T2DM patients. There are higher urinary concentrations for alanine, 3-hydroxyisovaleric acid, citrate and dimethylamine in newly diagnosed type 2 DM patients, while the hippurate increased with the increase of duration of type 2 DM. Conclusions: 1H-NMR spectroscopy can be a method to explore urinary metabolite as markers for early detection of associated diseases and complications in diabetes. [ABSTRACT FROM AUTHOR]

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results : The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m 2 vs. 55.8 mL/min/1.73 m 2 , p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found ( F (1,70) = 5.15, p = 0.026), with an R 2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions : some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Gene therapy is one of the most potential therapeutic approaches in direct and specific regulation of biological functions of macrophages at the gene level for efficient cell therapy. However, the delivery of genetic material to macrophages is extremely challenging, because of low stability, specificity and inability of therapeutic genes to efficiently enter the cells. Here, we present a method that uses the hybrid electrospun architectures based on gelatin-alginate decorated with carboxylated graphene oxide (HAG/G) as efficient substrate for loading and in vitro local and controlled delivery of plasmid DNA (pDNA) to macrophages as an alternative to systemic gene delivery carriers. Polyethyleneimine (PEI) is employed to assemble PEI/pDNA nanoparticles (Np) - used as model of carrier. The dispersion of GO-COOH sheets shifts the surface zeta potential of HAG/G to high negative value (SZP = -16.8 ± 2.21 mV) and further increases the encapsulation efficiency of PEI/pDNA Np onto hybrid HAG/G electrospun architectures to ∼ 69 % (HAG/G-Np). The in vitro biological investigations show a good metabolic activity of macrophages seeded onto HAG/G-Np (MTT assay), while gene expression experiments (fluorescent microscopy) show a 30 % increase in transient gene transfection of cells cultured in the presence of HAG/G-Np as compared to those incubated with free PEI/pDNA Np., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)