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IgA monoclonal gammopathies are accompanied by higher total TGF-β1 levels than IgG or IgM monoclonal gammopathies
No full textThe progression of monoclonal gammopathies is affected by a range of factors, including the microenvironment surrounding plasma cells. It is recognized that TGF-β1 plays a distinct role in stimulating IgA production. Hence, this study aims to investigate whether individuals with serum IgA monoclonal immunoglobulins (paraproteins) exhibit elevated total TGF-β1 levels compared to those with IgG or IgM paraproteins. To achieve this goal, individuals with a positive laboratory finding of monoclonal gammopathy were segregated according to the paraprotein class as well as according to the type of the light chain. Total TGF-β1 levels were assessed in blood serum samples containing IgG (n = 50), IgA (n = 46), and IgM (n = 31) paraproteins. Elevated level of TGF-β1 was confirmed in sera with IgA paraproteins (median 25.8 ng/mL; interquartile range IQR: 19.0–33.7) compared to those having IgG (median: 18.2 ng/mL; IQR: 14.3–22.1; p < 0.001) or IgM paraproteins (21.5 ng/mL; IQR: 15.0–27.4; p = 0.043). Also, a higher TGF-β1 level was detected in sera with IgMλ than those with IgMκ paraproteins (p = 0.043). This research affirms the role of TGF-β1 in the pathophysiology of IgA monoclonal gammopathies and the potential switch towards the IgA isotype, known for a less favourable prognosis
Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications
Get PDFA novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu2+ and F− ions. By examining the natural bond orbital (NBO) analysis and the potential energy curve (PES) of the ground state for the function of the C–H bond, it has been determined from the theoretical study at hand that the deprotonation was taken from the ‘CH’ proton of the pyrazole ring. For F− and Cu2+, the HCPyTSC detection limits were 4.62 nM and 15.36 nM, respectively. Similarly, the binding constants (Kb) for F− and Cu2+ ions in acetonitrile medium were found to be 2.06 × 105 M−1 and 1.88 × 105 M−1. Chemosensor HCPyTSC with and without F− and Cu2+ ions have an emission and absorption response that can imitate a variety of logic gates, including the AND, XOR, and OR gates. Additionally, a paper-based sensor strip with the HCPyTSC was created for use in practical, flexible F− sensing applications. The paper-based sensor was more effective in detecting F− than other anions. The effectiveness of HCPyTSC for the selective detection of F− in living cells as well as its cell permeability were examined using live-cell imaging in T24 cells
The expression of terminal monosaccharides on immune complexes IgG glycans in rheumatoid arthritis
No full textRheumatoid arthritis (RA) is characterised by the presence of rheumatoid factors (RFs;
autoantibodies against Fc region of IgG molecules) and autoantibodies against citrullinated peptides
(ACPAs), mostly of IgG isotype. Both RFs and ACPAs form immune complexes (IC). IgG glycans
are important for IgG proinflammatory effects and in this study, we analysed expression of terminal
monosaccharides of circulating immune complexes (CIC) IgG glycans in RA. IgG from polyethylene
glycol (PEG) precipitable CICs of healthy individuals and RA patients, were isolated by Protein G
chromatography. The expression of IgG heavy and light chains’ terminal galactose (Gal), sialic
acid, N-acetyl galactosamine (GalNAc), fucose (Fuc), and bisecting GalNAc were performed with
reducing SDS-PAGE followed by blotting with RCA I, SNA, GS II, UEA and succ. WGA lectins.
We detected a decreased expression of Gal (39%) and increased expression of sialic acid (31%) on
CIC IgG heavy chains. Due to difference in IgG light chains glycans expression, in both control and
RA, two light chain bands (L1 and L2), slightly different in molecular weight were detected. CIC
IgG L1 (higher molecular weight) expressed increased level of Gal (35%) and decreased level of
GalNAc expression (21%) on RA, comparing to control. On the IgG L2 light chains, an increased
Fuc expression was detected (24%). The difference between RA and control in the expression of
other CIC IgG heavy and light chains’ monosaccharides was not observed. The precise location
(variable vs. constant domains) and glycan monosaccharide composition on IgG light and heavy
chains in RA need further investigation using additional enzymatic and high-performance methods
(HPLC/MS)
FADS1 and FADS2 as biomarkers of Zn status – a systematic review and meta-analysis
Get PDFDespite enormous research efforts, a sufficiently sensitive and reliable biomarker for the assessment of zinc (Zn) status has not been identified to date. Zn affects fatty acid metabolism and alters the activity of certain desaturases; thus, desaturase activity has been proposed as a potential new biomarker of Zn status. This systematic review complied and assessed studies that examined changes in fatty acid desaturase 1 (FADS1) and fatty acid desaturase 2 (FADS2) activities in relation to modifications in dietary Zn intake. A systematic search was performed in PubMed, Web of Science, Scopus, Web of Knowledge, and Central with strictly defined search, inclusion, and exclusion criteria. Twenty-one studies were included, 8 animal and 13 human trials (5 randomized controlled trials, two non-randomized controlled trials, and 6 cross-sectional studies). This systematic review was performed using PRISMA guidelines and where feasible a random-effects meta-analysis was conducted. No significant correlation was seen between the delta 6 desaturase and Zn status (-0.0958, 95% CIs (-0.2912; 0.1074), p = 0.2928). Delta 6 desaturase seems to respond in a greater magnitude than Zn status to Zn-containing interventions (the standardized mean difference for delta 6 desaturase was −0.6052, 95% CIs (-2.7162; 1.5058), p = 0.4289, while for plasma/serum Zn it was 0.0319, 95% CIs (-0.9133; 0.9770), p = 0.9213). Finally, two separate meta-analyses on same studies that assessed the correlations between LA:DGLA and Zn intake and Zn status and Zn intake revealed that the magnitude of correlations was only slightly different (the pooled correlation coefficient between the LA:DGLA ratio and Zn intake had a value of −0.1050, 95% CIs (-0.5356; 0.3690), p = 0.454, while between plasma Zn and Zn intake had a value of −0.0647, 95% CIs (-0.4224; 0.3106), p = 0.5453). According to the descriptive analysis, the magnitude of variation in desaturase activities in response to Zn intake was not consistent among studies, FADS1 and FADS2 activity corresponded to dietary Zn manipulations, both in animals and humans. A plausible explanation for this observation might be the difference between the studies in study populations, types of dietary interventions, study durations, etc. In addition, several potential confounders and covariates are identified from the qualitative synthesis, such as gender, age, the type of fat provided within the dietary intervention, the size of Zn particles, among others. Further high-quality studies are needed to additionally clarify the suggested associations and applicability of utilizing fatty acid desaturase activities as Zn status biomarkers
The Venom of Vipera ammodytes ammodytes: Proteomics, Neurotoxic Effect and Neutralization by Antivenom
No full textDeep proteomic analyses identified, in total, 159 master proteins (with 1% FDR and 2 unique peptides) from 26 protein families in the venom of Vipera ammodytes ammodytes (Vaa). Data are available via ProteomeXchange with the identifier PXD056495. The relative abundance of PLA2s is 11.60% of the crude venom, of which 4.35% are neurotoxic Ammodytoxins (Atxs). The neurotoxicity of the venom of Vaa and the neutralizing effect of the antivenom were tested on the neuromuscular preparation of the diaphragm (NPD) of rats. The activity of PLA2 in the venom of Vaa and its neutralization by the antivenom were determined under in vitro conditions. The Vaa venom leads to a progressive decrease in NPD contractions. We administered pre-incubated venom/antivenom mixtures at various ratios of 1:2, 1:10 and 1:20 (w/w) and observed the effects of these mixtures on NPD contractions. The results show that the mean effective time (ET50) for NPD contractions with the 1:20 mixture is highly significantly different (p < 0.001) from the ET50 for the venom and the ET50 for the 1:2 and 1:10 mixture ratios. We also found a highly significant (p < 0.001) reduction in Na+/K+-ATPase activity in the NPD under the influence of the venom. The reduction in the activity of this enzyme was reversible by the antivenom. Under in vitro conditions, we have achieved the complete neutralization of PLA2 by the antivenom. In conclusion, the antivenom abolished the venom-induced progressive decrease in NPD contractions in a concentration-dependent manner. Antivenom with approximately the same mass proportion almost completely restores Na+/K+-ATPase activity in the NPD and completely neutralizes the PLA2 activity of the venom in vitro
Urtica dioica L. Leaf Extract Dose-Dependently Modulates Oxidative Stress in the Kidney and Exerts Anti-Fibrotic and Anti-Inflammatory Properties by the Molecular Mechanisms Independent of NRF-2 Signalization Mirroring the Effects of Losartan in SHR
No full textPreviously, we confirmed systemic antihypertensive and antioxidant properties of Urtica dioica L. leaf extract (UE) in spontaneously hypertensive rats (SHR). Here, we aimed to evaluate whether UE can alter the NO and Nrf-2 signaling to prevent local oxidative stress and kidney damage in the model of essential hypertension. SHR were divided into five groups: SHRC-control, received 0.5 mL/day of water, SHR+L received 10 mg/kg/day of losartan, SHR+UE10, SHR+UE50, and SHR+UE200 received 10, 50, and 200 mg/kg/day during next 4 weeks. At the end of the experiment, urine samples were collected for albuminuria and nitrate/nitrite assessment. Mean arterial pressure (MAP) was measured, and blood samples were collected for plasma creatinine evaluation. Kidneys were analyzed for nitrate/nitrite, oxidative stress, and target molecules by biochemical, Western blot, and immunofluorescent techniques. Losartan and UE50 significantly reduced MAP, albuminuria, oxidative stress, fibroinflammatory markers, and NRF-2/CAT/SOD signaling, with a significant increase in 6-nitrotryptophan and eNOS expressions compared to control. The effects of UE showed dose dependence. Beneficial effects of UE and losartan were independent of NRF-2 signalization in SHR. Interestingly, all treatments induced the increase in 6-nitrotryptophan expression, thus further studies are needed to elucidate the mechanisms of such nitrated tryptophan
Metabolic Reprogramming of Phospholipid Fatty Acids as a Signature of Lung Cancer Type
No full textBackground: Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues. Methods: Our study included patients with newly diagnosed, histologically confirmed SCLC (n = 27) and NSCLC (n = 37). Samples were collected from both malignant and healthy tissues from each patient, providing they were within subject design. Results: In both NSCLC and SCLC tumor tissues, FA contents were shifted toward pro-inflammatory profiles, with increased levels of some individual n-6 polyunsaturated FA (PUFA), particularly arachidonic acid, and elevated activity of Δ6 desaturase. Compared to healthy counterparts, lower levels of alpha-linolenic acid (18:3n-3) and total saturated FA (SFA) were found in NSCLC, while decreased levels of linoleic acid (18:2n-6) and all individual n-3 FA were found in SCLC tissue in comparison to the healthy tissue control. When mutually compared, SCLC tissue had higher levels of total SFA, especially stearic acid, while higher levels of linoleic acid, total PUFA, and n-3 and n-6 PUFA were detected in NSCLC. Estimated activities of Δ6 desaturase and elongase were higher in SCLC than in NSCLC. Conclusions: Our findings indicate a notable impairment of lipid metabolism in two types of lung cancer tissues. These type-specific alterations may be associated with differences in their progression and also point out different therapeutic targets
The effect of changes in environmental conditions on the growth and yield of bell pepper
No full textPepper (Capsicum annuum L.) is an economically important vegetable species in the Balkan
region. Production of pepper, in recent years, has become very challenging, where abiotic
stresses (extreme temperatures, drought) can reduce crop yield by more than 50%. In our
region, bell pepper is one of the most popular types of pepper on the market. This experiment
was conducted on 14 genotypes of bell peppers (different geographical origin) during two
vegetative seasons (2020, 2021) in an open field and in the greenhouse (semi-controlled
conditions) in Smederevska Palanka. Nine characteristics related to plant development and
yield were observed. The aim of this study was to estimate the impact of abiotic stress
conditions on pepper plant development, fruit quality and yield. The maximum recorded
temperature during the observed growing seasons was 40.7 (flowering and fruiting period).
The total amount of precipitation was below the optimum in both observed years: 540.7 mm
(2020) and 380.1 mm (2021). The average yield recorded in greenhouse trials was higher by
56% (2020) and 78% (2021) in comparison to the trials in the open field. The results from the
open field trial showed that genotype CA11 (USA origin) had the highest yield (2020 and
2021). A lower amount of precipitation in the open field had a negative effect on all observed
traits (plant height, flowering time, fruit setting time, fruit size). Obtained results are essential
in overcoming the problems caused by environmental changes and for improving the response
of pepper plant resistance to abiotic stress
Editorial: Nutrition and urological disorders: the crossroads of contemporary research and clinical perspective
No full textImpact of Vitamin D Status and Nutrition on the Occurrence of Long Bone Fractures Due to Falls in Elderly Subjects in the Vojvodina Region of Serbia
No full textBone fractures are a significant public health issue among elderly subjects. This study examines the impact of diet and vitamin D status on the risk of long bone fractures due to falls in elderly subjects in Vojvodina, Serbia. Conducted at the University Clinical Center of Vojvodina in autumn/winter 2022–2023, the study included 210 subjects >65 years: 105 (F: 80/M: 15) with long bone fractures due to falls and 105 (F: 80/M: 15) controls. Groups were similar regarding age and BMI. Dietary intakes (by two 24-h recalls) and serum vitamin D levels were analyzed. The fracture group had a significantly lower median daily vitamin D intake (1.4 μg/day vs. 5.8 μg/day), intake of calcium, energy, proteins, fats, fibers, dairy products, eggs, fish, edible fats/oils, and a higher intake of sweets (p 50.5 nmol/L decreased fracture risk. Nutritional improvements (increased intake of vitamin D and protein sources such as fish, eggs, and dairy), increased sun exposure, and routine vitamin D supplementation during winter are advised