Targeted therapy uses multiple ways of ensuring that the drug will be delivered to the desired site. One of these ways is an encapsulation of the drug and functionalization of the surface. Among the ...many molecules that can perform such a task, the present work focused on the antibodies of single-chain variable fragments (scFvs format). We studied scFv, which specifically recognizes the dopamine D2 and serotonin 5-HT1A receptor heteromers. The scFvD2–5-HT1A protein was analyzed biochemically and biologically, and the obtained results indicated that the antibody is properly folded and non-toxic and can be described as low-immunogenic. It is not only able to bind to the D2–5-HT1A receptor heteromer, but it also influences the cAMP signaling pathway and—when surfaced on nanogold particles—it can cross the blood–brain barrier in in vitro models. When administered to mice, it decreased locomotor activity, matching the effect induced by clozapine. Thus, we are strongly convinced that scFvD2–5-HT1A, which was a subject of the present investigation, is a promising targeting ligand with the potential for the functionalization of nanocarriers targeting selected areas of the brain.
Idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis share commonalities in pathogenesis shifting haemostasis balance towards the procoagulant and antifibrinolytic activity. ...Several studies have suggested an increased risk of venous thromboembolism in IPF. The association between venous thromboembolism and chronic hypersensitivity pneumonitis has not been studied yet.
A retrospective cohort study of IPF and chronic hypersensitivity pneumonitis patients diagnosed in single tertiary referral center between 2005 and 2018 was conducted. The incidence of symptomatic venous thromboembolism was evaluated. Risk factors for venous thromboembolism and survival among those with and without venous thromboembolism were assessed.
A total of 411 (259 IPF and 152 chronic hypersensitivity) patients were included (mean age 66.7 ± 8.4 vs 51.0 ± 13.3 years, respectively). There were 12 (4.6%) incident cases of venous thromboembolism in IPF and 5 (3.3%) in chronic hypersensitivity pneumonitis cohort. The relative risk (RR) of venous thromboembolism in chronic hypersensitivity pneumonitis was not significantly different to that found in patients with IPF (7.1 vs 11.8/1000 person-years, RR 1.661 95% CI 0.545-6.019, respectively). The treatment with systemic steroids (OR 5.38; 95% CI 1.65-18.8, p = 0.006) and GAP stage 3 (OR 7.85; 95% CI 1.49-34.9; p = 0.037) were significant risk factors for venous thromboembolism in IPF. Arterial hypertension and pulmonary hypertension significantly increased risk of venous thromboembolism in chronic hypersensitivity pneumonitis. There were no significant differences in survival between patients with and without venous thromboembolism.
The patients with chronic hypersensitivity pneumonitis have a marked increase in the risk of venous thromboembolism, similar to the patients with IPF. Venous thromboembolism does not affect the survival of patients with IPF and chronic hypersensitivity pneumonitis.
Background We have previously reported, increased plasma IL‐6 concentration in chronic urticaria. In addition, it has been suggested that IL‐6 and C‐reactive protein (CRP) may be useful markers of ...the disease activity.
Aim The aim of this study was to evaluate whether a systemic inflammation is present in delayed pressure urticaria (DPU).
Methods Plasma IL‐6 and serum CRP concentrations, biomarkers of acute phase response, were measured in DPU, and the healthy subjects matched by age, gender, and BMI using ELISA method.
Results DPU patients showed significantly higher plasma IL‐6 and serum CRP concentrations than the healthy subjects.
Conclusions Similarly to the known locally increased IL‐6 activity in DPU lesions, the elevated circulating levels of IL‐6 and CRP have been currently found in DPU. This indicates that the disease induces a systemic inflammatory process, termed the acute phase response.
This study presents a comprehensive analysis of the potential utilization of sewage sludge in agriculture, focusing on the assessment of heavy metal contaminants and their mobility in sewage ...sludge-soil mixtures. The innovative approach of investigating heavy metal fractions in these mixtures sheds light on their environmental implications. In this study, sludge and soil samples from three different soil categories were collected, and the mobility of heavy metals was investigated using sequential BCR analysis. A thorough assessment of the risk of environmental contamination associated with the agricultural use of sludge was also carried out. This study included the calculation of various risk indicators, such as the Geoaccumulation Index of heavy metals in soil (Igeo), the risk assessment code (RAC), and the author’s element mobility ratio (EMR), which included a comparison of the overall metal concentrations in sludge, soil, and mixtures. This study demonstrates that the key to using sludge is to know the form of mobility of the metals present in the sludge and how they behave once they are introduced into the soil.
The production of hot water for bathing in Poland accounts for around 15% of the total energy consumption of a typical household. According to EU data, final energy consumption for lighting and ...appliances is similar to final energy consumption for hot water preparation. This makes it a significant contributor to housing and utility costs, exceeded only by heating expenses. Research has indicated that only about 10% of the water utilized during a shower is necessary for hygiene purposes. Consequently, around 90% of the hot water supplied to the shower is ultimately discharged into the sewage system. By harnessing the primary energy from wastewater, we can effectively conserve heat energy and reduce the overall expenditure associated with hot water. The objective of this article is to explore the utilization of heat recovery from domestic wastewater as a means to enhance the energy efficiency of residential buildings.
•Vulvar tumors, divided into high risk (hr) HPV(+) and hrHPV(−) groups, were screened for mutations in 50 genes by NGS.•Mutations were detected at comparable frequencies in the two tumor ...groups.•Mechanisms of two routes of VSCC pathogenesis may be similar despite being initiated from different premalignant lesions.•Most of the identified mutations may activate the PI3K/AKT/mTOR pathway.•The confirmed contribution of mTOR protein to vulvar cancer progression points towards putative therapeutic targets.
Vulvar squamous cell carcinoma (VSCC) constitutes over 90% of vulvar cancer. Its pathogenesis can follow two different pathways; high risk human papillomavirus (hrHPV)-dependent and HPV-independent. Due to the rarity of VSCC, molecular mechanisms underlying VSCC development remain largely unknown. The study aimed to identify pathogenic mutations implicated in the two pathways of VSCC development.
Using next generation sequencing, 81 VSCC tumors, 52 hrHPV(+) and 29 hrHPV(−), were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific).
Mutations of TP53 (46% and 41%, of hrHPV(+) and hrHPV(−) cases respectively) and CDKN2A (p16) (25% and 21%, of hrHPV(+) and hrHPV(−) cases respectively) were the most common genetic alterations identified in VSCC tumors. Further mutations were identified in PIK3CA, FBXW7, HRAS, FGFR3, STK11, AKT1, SMAD4, FLT3, JAK3, GNAQ, and PTEN, albeit at low frequencies. Some of the identified mutations may activate the PI3K/AKT/mTOR pathway. The activation of mTOR was confirmed in the vast majority of VSCC samples by immunohistochemical staining.
Detecting pathogenic mutations in 13/50 genes examined at comparable frequencies in hrHPV(+) and hrHPV(−) tumors suggest that genetic mechanisms of the two routes of VSCC pathogenesis may be similar, despite being initiated from different premalignant lesions. Importantly, our data provide a rationale for new anti-VSCC therapies targeting the PI3K/AKT/mTOR pathway.
Sewage sludge is a very complex system, with solids and water. It is generated as waste from wastewater treatment. Sewage sludge is used to fertilize agricultural and forest areas and to rehabilitate ...devastated areas. It is a good organic fertilizer because it contains significant amounts of nutrients beneficial for plant development and humus-forming substances. The composition of sludge from municipal wastewater treatment plants is similar to soil organic matter, therefore it can be used to improve the physicochemical properties of soil, increasing its sorption capacity. Research material was collected in the Swietokrzyskie and Mazowieckie Voivodships. Sewage sludge was collected from the wastewater treatment plants in Sitkowka Nowiny (Sitkowka) and Kunow, as well as high-quality agricultural soil from Opatowiec and sandy-clay soil from Jastrzebie. Research was carried out on the sorption of heavy metals (Cd, Cr, Cu, Pb, Ni, Zn) by mixtures of sewage sludge with soil. The calculations were made for the concentrations of heavy metals in sewage sludge, soil, and sewage sludge–soil mixtures. The geoaccumulation index (Igeo) and the risk assessment code (RAC) were calculated. Increased sorption capacity was demonstrated in samples with a predominance of sewage sludge. It was shown that heavy metals from sewage sludge, after mixing with soil, changed their form from immobile to mobile.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid ...receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and
-cyclodextrin (
-CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with
-CD. The effect of using FA in QDs-
-CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs-
-CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs-
-CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QD
-
-CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.
The global scientific community is intensively promoting energy-plus buildings. Following the leading world trends, this paper presents a new energy-plus building concept—elevational earth-sheltered ...buildings with three different types of horizontal overhang photovoltaic-integrated panels: wooden support columns covered with clay tiles, steel pipes as support columns covered with sheet steel, and concrete support columns with concrete coverage. In this instance, the specific multi-numerical case study building model for the city of Kragujevac (located in central Serbia with favorable climatic conditions) was performed over 7 months (from 1 October to 30 April), taking into account the soil temperature, the effects of solar shading, the performance of the heating system—a ground source heat pump—and the characteristics of the artificial and automatic lighting control system. The simulation results show that the optimal depth of a horizontal overhang (energy-plus status) depends on the occupant’s habits, in addition to meteorological conditions. The presented methodology can be used for any other location, both in Europe and the world.
In hypertrophic cardiomyopathy (HCM) patients, left ventricular (LV) maximal wall thickness (MWT) is one of the most important factors determining sudden cardiac death (SCD) risk. In a large ...unselected sample of HCM patients, we aimed to simulate what changes would occur in the calculated SCD risk according to the European HCM Risk-SCD calculator when MWT measured using echocardiography was changed to MWT measured using MRI. All consecutive patients with HCM who underwent cardiac MRI were included. MWT measured with echocardiography and MRI were compared, and 5-year SCD risk according to the HCM Risk-SCD calculator was computed using four different models. The final population included 673 patients 389 (57.8%) males, median age 50 years, interquartile range (36-60). The median MWT was lower measured by echocardiography than by MRI 20 (17-24) mm vs 21 (18-24) mm; p < 0.0001. There was agreement between echocardiography and MRI in the measurement of maximal LV wall thickness in 96 patients (14.3%). The largest differences between echo and MRI were - 13 mm and + 9 mm. The differences in MWT by echocardiography and MRI translated to a maximal difference of 8.33% in the absolute 5-year risk of SCD, i.e., the echocardiography-based risk was 8.33% lower than the MRI-based estimates. Interestingly, 13.7% of patients would have been reclassified into different SCD risk categories if MRI had been used to measure MWT instead of echocardiography. In conclusion, although there was high general intermodality agreement between echocardiography and MRI in the MWT measurements, the differences in MWT translated to significant differences in the 5-year risk of SCD.
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