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Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Directed evolution experiments usually rely on high-throughput screening of very large libraries of mutants, but most of the mutants do not even yield stable, functional proteins. The concept of neutral drift can be used to generate small but highly polymorphic and stable mutant libraries as a starting point for further evolution. Small libraries for directed evolution can be obtained by neutral drifts that maintain the protein's original function, yielding highly polymorphic, stable and evolvable variants. We describe methods for preparing such libraries, using serum paraoxonase (PON1). An optimized GFP variant fused to PON1 reported levels of soluble, functional enzyme, enabling selection by flow cytometry and identification of enzyme variants exhibiting improved specific and total activities toward several substrates, including toxic organophosphates.

Objective:High-density lipoprotein (HDL) antiatherogenic functions seem to be diminished during inflammatory conditions such as rheumatoid arthritis (RA). The aim of this study was to investigate the effects of tumour necrosis factor (TNF) inhibition on the antioxidative capacity of HDL in RA.Methods:Plasma lipids and paraoxonase (PON-1) activity were investigated in 45 RA patients, before and during 6 months of anti-TNF therapy. In addition, HDL was isolated and tested for its ability to inhibit copper-induced oxidation of low-density lipoprotein in vitro.Results:Plasma HDL concentrations did not change considerably after 6 months of therapy. However, stable increases of PON-1 activities were observed throughout the same period (p<0.03). The increases were more obvious when related to HDL or apolipoprotein AI concentrations. HDL total antioxidative capacity significantly improved 6 months after the initiation of anti-TNF therapy (p = 0.015). The initial improvement of PON-1 activity paralleled a decrease in the inflammatory status, whereas specific TNF blockade was likely to be responsible for the long-term effects.Conclusions:Anti-TNF therapy with infliximab has beneficial effects on lipids through changes in HDL antioxidative capacity, which might be clinically relevant and contribute to the reported protective effect of anti-TNF on cardiovascular morbidity in RA. This emphasises the importance of HDL antiatherogenic capacity for cardiovascular risk in chronic inflammatory conditions.

Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β2-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM.

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and its prevalence increases with age and obesity, and after menopause. Among the ways to treat it, we can mention regular sports exercises and the use of natural supplements. Therefore, the aim of this research is to investigate and compare the effects of aerobic-resistance training with royal jelly supplementation on changes in paraoxonase 1, oxidized LDL, liver function, and lipid profile in postmenopausal women with Dysfunction-Associated Steatotic Liver Disease. Materials and Methods: This semi-experimental study involved 23 women with Dysfunction-Associated Steatotic Liver Disease with an average weight (71.34 ± 11.63 kg), age (48.54 ± 3.88 years), and body mass index (27.63 ± 4.20 kg/m2). They were randomly divided into two groups: exercise + supplement (n = 12) and exercise + placebo (n = 11). Both groups performed eight-station resistance exercises (8–12 repetitions in 2–4 sets) for 8 weeks, with three sessions per week (for 35–40 min, from 10-15 RPE), and then, for 10–15 min of active rest, they performed aerobic exercises with an intensity of 40–85% of the target heart rate, in two-minute intervals with 45 s of active rest. Royal jelly supplement (500 mg on training days, before each training session) was consumed. Blood sampling was done before and 48 h after the last training session. Statistical analysis was performed using a variance test with repeated measures (two groups × two stages of pre-test-post-test) in SPSS software (Version 26) with a significance level of p < 0.05. Results: The results of the statistical analysis show that the effects of eight weeks of exercise + supplement and exercise + placebo on PON1, oxLDL, lipid profiles (HDL, LDL, TC, and TG), and liver enzymes (ALT, AST) in women with non-alcoholic fatty liver showed a significant difference (p < 0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. But significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015) and AST (p = 0.009) were observed in the exercise + supplement group compared to the exercise + placebo group (<0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. However, significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015), and AST (p = 0.009) was observed in the exercise + supplement group compared to the exercise + placebo group. Conclusions: Based on the results, it can be concluded that aerobic-resistance exercises with the addition of royal jelly can probably be an efficient and recommended strategy to minimize the harmful effects of Dysfunction-Associated Steatotic Liver Disease by affecting the activity of liver enzymes, paraoxonase 1, LDL oxidation, and lipid profile. Although exercise alone also yielded favorable results, according to the findings of this research, it can be said that exercise, combined with the use of royal jelly supplements, may have more positive effects on reducing liver complications and improving body function. However, in order to obtain more accurate scientific evidence, it is necessary to investigate more doses and timing of royal jelly in future studies.

Breast milk is a well-balanced ideal nutritional source with high bioavailability for infants. As being a fresh, biological and dynamic product, changes in the breast milk during these storage periods have been the subject of ongoing research. This study aims to evaluate total antioxidant capacity (TAC), total oxidant status (TOS), and paraoxonase-1 (PON-1) levels of fresh and freezestored breast milk. Ten cc of breast milk was obtained from the mothers as the days between 10 and 15 in the morning within a 1-hour period. TAC, TOS, and PON-1 levels were evaluated in the fresh breast milk. Collected breast milk samples were divided into two groups for storage at -20°C or -80°C. Stored samples were tested for TAC, TOS, and PON-1 levels after 72 hours. The highest TAC level was detected in fresh breast milk (p < 0.05). The TOS levels of fresh breast milk showed a statistically significant reduction in rate after storage. The TOS levels at -20°C and -80°C were significantly lower at -80°C (p < 0.05). Our study results show that oxidant and antioxidant activities are at the maximum level in the fresh breast milk. In terms of antioxidant status the effect of freezing temperatures hasn`t been determined. We conclude that it is more convenient to store the breast milk at -80°C than to store at -20°C in terms of preserving the storage TOS level.

Purpose Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients. Methods This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p -nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis. Results There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1 ± 31.6 vs. 164.3 ± 61.5 U/l, p  = 0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2 ± 1.7 vs. 3.9 ± 1.1 mm, p  = 0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT ( r  = −0.484, p  = 0.0001) and a significant positive correlation between PON-1 activity and HDL-C ( r  = 0.417, p  = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT. Conclusion Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.

Background: Paraoxonase (PON1) associated with HDL can be regarded as a cardio- and vasoprotective enzyme. However, because HDL is not a homogeneous fraction, it is important to investigate in which subgroups of HDL active PON1 is located. It would also be useful to determine density profiles of the HDL apolipoproteins (Apo) E and J. Methods: We investigated the density range of HDL (ρ = 1.063–1.256 kg/L) in healthy individuals, using the ultracentrifugation reference method and a newly introduced automated fractionation method. Profiles of PON1 activity and ApoA-I, ApoA-II, ApoE, ApoJ, and cholesterol concentrations were obtained by use of various density gradients. Results: PON1 activity was highest in the more dense HDL3 and VHDL fractions where PON1 was not dissociated from the particles during centrifugation. The fraction in density range 1.175–1.185 kg/L showed not only the highest PON1 activity, but also the highest specific activity (activity per HDL particle). This fraction was the least-dense fraction containing both ApoE and ApoJ. Only the Q192R polymorphism had an effect on the distribution profile of PON1 activity. In contrast, L55M and the T(−107)C polymorphisms (determined by a novel nonradioactive method) were without effect on the density distribution of PON1 activity. Conclusion: The HDL3 fraction, which is important in reverse cholesterol transport, also carries the highest PON1 activity.

Paraoxonase 1 (PON1) is an esterase, exclusively synthesized by liver. The present study has two objectives: to determine the PON1 activity status in various disorders associated with hepatocellular damage and to correlate the changes of PON1 activity with the standard liver function and fasting lipid profile tests in these disorders. The study groups consisted of 95 patients with liver diseases including acute viral hepatitis (14), cirrhosis with portal hypertension (33), leptospirosis (14), sepsis and multi organ failure (15), left ventricular failure (9), and falciparum malaria (10); and 53 healthy controls. Serum PON1 activity was measured manually using spectrophotometer. Liver function test parameters and fasting lipid profile were performed in clinical chemistry auto analyzer (Hitachi 912). The serum PON1 activity in patients with acute viral hepatitis and sepsis decreased significantly ( P < 0.001) and moderately in falciparum malaria ( P < 0.05). However, in patients with cirrhosis, leptospirosis and left ventricular patients, its activity did not change significantly. On applying Pearson correlation, serum PON1 activity correlated positively with high-density lipoprotein-cholesterol (HDL-C) in patients with sepsis (r=0.633, P < 0.05), left ventricular failure patients (r=0.814, P < 0.05) and negatively with acute viral hepatitis patients (r=-0.528, P <0.05). PON1 activity has decreased significantly in acute viral hepatitis, sepsis with multi organ failure and falciparum malaria patients. Determination of PON1 activity may serve as a useful additional test in assessing these conditions.