Objectives
The aims of this study were to evaluate the radiopacity, compressive strength, setting time, and porosity of white Portland cement (PC) with the addition of bismuth oxide (Bi
2
O
3
), ...zirconium dioxide (ZrO
2
), and ytterbium trifluoride (YbF
3
) after immersion at 37 °C for 7 days in distilled water or phosphate buffer saline.
Materials and methods
Specimens measuring 8 mm in diameter and 1 mm in thickness were fabricated from PC with the addition of 10, 20, and 30 wt% Bi
2
O
3,
ZrO
2
or YbF
3
. ProRoot MTA (Dentsply, Tulsa, OK, USA) and pure PC were used as controls. For radiopacity assessments, specimens were radiographed alongside a tooth slices and an aluminum stepwedge on Extraspeed occlusal dental films (Insight Kodak, Rochester, New York). Mean optical density of each specimen was calculated and used to express radiopacity of the material as an equivalent thickness of aluminum. Compressive strength was measured by using 4-mm diameter and 6-mm high specimens and Universal testing machine. High-pressure mercury intrusion porosimeter (Carlo Erba Porosimeter 2000) was employed to measure the porosity of the specimens. The setting time was measured by using a needle of 100 g in weight. The morphology of specimens was evaluated using a scanning electron microscope (TESCAN Mira3 XMU, USA Inc.). Data were analyzed by one-way ANOVA and post hoc Tukey test (
P
< 0.05).
Results
The PC with the addition of at least 10 wt% Bi
2
O
3
and 20 wt% ZrO
2
or YbF
3
demonstrated greater radiopacity value than the recommended 3 mmAl cut-off. ZrO
2
and YbF
3
increased the compressive strength of PC, but it was not statistically significant (
P
> 0.05), while Bi
2
O
3
decreased it (
P
< 0.05). All radiopacifiers significantly increased the porosity of the experimental cements (
P
< 0.05). Bi
2
O
3
extended the setting time of PC (
P
< 0.05), whilst ZrO
2
and YbF
3
did not significantly affect it (
P
> 0.05).
Conclusions
ZrO
2
and YbF
3
may be used as a suitable alternative to replace Bi
2
O
3
in MTA without influencing its physical properties.
The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of ...adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes.
DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry. Cytotoxicity of ASA at concentrations of 10, 50 and 100 µg/ml was tested by MTT and NR assays. Osteo/odontogenic differentiation was analyzed via alizarin red staining and ALP activity. Quantitative PCR (qPCR) was used for osteo/odontogenic markers’ (DSPP, BMP2, BMP4, BSP, OCN and RUNX2) and c-Myc expression analysis. AMPK inhibition of ASA-induced osteo/odontogenesis was tested by qPCR of selected markers (DSPP, OCN and RUNX2).
Cytotoxicity assays showed that only the highest ASA dose decreased cell viability (89.1 %). The smallest concentration of ASA applied on DPSCs resulted in a remarkable enhancement of osteo/odontogenic differentiation, as judged by increased mineralized nodules’ formation, ALP activity and gene expression of analyzed markers (increase between 2 and 30 folds), compared to untreated cells. ASA also increased DPSCs proliferation. Interestingly, AMPK inhibition per se upregulated DSPP, OCN and RUNX2; the gene upregulation was higher when ASA treatment was also included. c-Myc expression level decreased in cultures treated with ASA, indicating undergoing differentiation processes.
Low concentrations of ASA (corresponding to the standard use in cardiovascular patients), were shown to stimulate osteo/odontogenic differentiation of dental pulp stem cells.
•Low concentration of ASA stimulates osteo/odontogenic differentiation of DPSCs.•Low concentration of ASA increases DPSCs proliferation.•AMPK inhibition upregulates osteo/odontogenenic differentiation of DPSCs.
Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs ...underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC‐specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC‐specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA‐specific mutational signature SBS22, with 68% to 76% AA‐specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC‐specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN‐associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine‐based screening of AAN patients for cancer presence and recurrence.
What's new?
Ingestion of aristolochic acid (AA) via contaminated wheat‐containing food products is a major cause of endemic neuropathy and urologic carcinogenesis in southeastern Europe. Here, using integrated multi‐omics analysis, the authors identified molecular programs underlying upper tract urothelial tumors (UTUC) in patients in Southern Europe with past carcinogenic AA exposure. Analyses reveal associations between 89 miRNAs and 1,862 target mRNAs, with confirmation of UTUC‐specific transcripts at protein level. AA‐specific mutations in UTUC and deleterious mutations were uncovered at both gene and transcript levels. The findings suggest that tumors in the urinary tract can be monitored by urine miRNA signature.
We report the first two cases of familial lecithin:cholesterol acyltransferase (LCAT) deficiency in Croatia with classical clinical and biochemical features.
A 30-year-old man with nephrotic ...syndrome, corneal opacities, hepatosplenomegaly, anemia, low high-density lipoprotein (HDL)-cholesterol levels and arterial hypertension (blood pressure >200/100 mmHg) was admitted to our department. At admission, he had an elevated creatinine serum level (233 μmol/L), proteinuria of 12 g in 24-h urine (g/24 h), 3–7 erythrocytes in urine sediment and notable anemia (hemoglobin level 90 g/l). His HDL-cholesterol was significantly low (0.42 mmol/L). Besides chronic kidney disease (CKD), other secondary causes of hypertension were ruled out. The patient was previously diagnosed with membranous nephropathy and treated unsuccessfully with immunosuppressive agents (steroids, cyclosporine, cyclophosphamide). Re-evaluation of histopathological findings of kidney biopsy revealed massive deposition of lipid material in the glomerular basal membrane and in the mesangial region. His 4-year younger brother was also evaluated due to corneal opacities and new-onset arterial hypertension. Nephrotic range proteinuria with preserved global renal function was determined. He also had very low HDL-cholesterol levels.
Kidney biopsies from both patients were consistent with LCAT deficiency. The disease was confirmed by measurement of LCAT enzyme activity, plasma cholesterol esterification rate, and genetic testing. Two novel missense variants in the LCAT gene (c.496G > A and c.1138T > C) were found.
To our knowledge, the presented cases are the first reported cases of genetic LCAT deficiency in Croatia. Given the clinical presentation, the complete lack of LCAT activity and cholesterol esterification rate, diagnosis of familial LCAT deficiency was made.
•A 30-year-old man presents with nephrotic syndrome and corneal opacities.•Dyslipidemia with very low high-density lipoprotein cholesterol level is determined.•Analysis confirms absent lechitin:cholesterol acyltransferase activity.•Genetic analysis confirms the diagnosis with the two novel gene variants.
Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 ...with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.
•Formulation and evaluation of olopatadine viscous eye drops was performed.•Combination of chitosan and hydroxypropyl guar gum was compatible with the drug.•The drug permeability was estimated using ...HCE-T cell-based models and PAMPA.•MTT assay demonstrated that the tested eye drops were non-toxic and well tolerated.•An ocular itch test on mice was employed for efficacy evaluation.
The aim of this work was the formulation and the comprehensive evaluation of the viscous eye drops using vehicles containing medium chain chitosan (0.5% w/v), hydroxypropyl guar gum (0.25% w/v) and their combination as carriers for olopatadine (0.1% w/v). Physicochemical properties (appearance, clarity, pH, osmolality, viscosity and drug content) of the tested formulations were within acceptable ranges for the ophthalmic preparations, while DSC and FT-IR techniques demonstrated the compatibility between olopatadine and polymers.
The drug permeability was successfully estimated in vitro using both HCE-T cell-based models (Model I and Model II) and the parallel artificial membrane permeability assay (PAMPA), considering the impact of chitosan as a permeation enhancer. The MTT cytotoxicity assay demonstrates that the tested formulations (diluted 10-fold in HBSS pH 5.5) were non-toxic and well tolerated.
An ocular itch test on mice was carried out with the formulation containing the combination of polymers comparable with a commercially available olopatadine eye drops without viscosity enhancers. The tested eye drops produced a slightly higher anti-pruritic/analgesic-like effect than the commercial preparation. It could be assumed that the use of this viscous ophthalmic vehicle due to its advanced mucoadhesive properties and good safety profile is a feasible strategy to improve the efficacy of olopatadine.
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Series of novel dual-sensitive poly(2-hydroxypropyl acrylate/itaconic acid) hydrogels were designed as multifunctional drug delivery system which can provide several advantages including drug ...protection, self-regulated oscillatory release and targeted delivery to a single entity. The hydrogels were synthesized by the free-radical crosslinking copolymerization and evaluated as carriers for hydrophobic drug, Oxaprozin, with specific controlled release properties. Structural, morphological, thermal, surface charge, swelling and antimicrobial properties of the hydrogels were investigated for unloaded and Oxaprozin-loaded samples. Swelling studies demonstrated pH- and temperature-sensitivity of drug-free and drug-loaded P(HPA/IA) hydrogels. The results of swelling and oscillatory swelling, and swelling behavior of drug-free, and drug-loaded hydrogels in simulated gastrointestinal conditions, and in vitro Oxaprozin release studies confirmed these hydrogels as a highly effective colon-specific drug delivery system with excellent performance of long-term controlled release. These unique properties make the P(HPA/IA) hydrogels highly attractive materials for developing multifunctional drug delivery systems.
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•Novel dual-sensitive hydrogels by the free-radical crosslinking polymerization.•Volume phase transition temperatures in physiologically relevant temperature range.•Design of multifunctional drug delivery system.•Overcoming serious side effects of drug in upper gastrointestinal tract.•Long-term controlled release of hydrophobic drug, Oxaprozin.
The mineralogical composition of airborne dust particles is an important but often neglected parameter for several physiochemical processes, such as atmospheric radiative transfer and ocean ...biochemistry. We present the development of the METAL-WRF module for the simulation of the composition of desert dust minerals in atmospheric aerosols. The new development is based on the GOCART-AFWA dust module of WRF-Chem. A new wet deposition scheme has been implemented in the dust module alongside the existing dry deposition scheme. The new model includes separate prognostic fields for nine (9) minerals: illite, kaolinite, smectite, calcite, quartz, feldspar, hematite, gypsum, and phosphorus, derived from the GMINER30 database and also iron derived from the FERRUM30 database. Two regional model sensitivity studies are presented for dust events that occurred in August and December 2017, which include a comparison of the model versus elemental dust composition measurements performed in the North Atlantic (at Izaña Observatory, Tenerife Island) and in the eastern Mediterranean (at Agia Marina Xyliatos station, Cyprus Island). The results indicate the important role of dust minerals, as dominant aerosols, for the greater region of North Africa, South Europe, the North Atlantic, and the Middle East, including the dry and wet depositions away from desert sources. Overall, METAL-WRF was found to be capable of reproducing the relative abundances of the different dust minerals in the atmosphere. In particular, the concentration of iron (Fe), which is an important element for ocean biochemistry and solar absorption, was modeled in good agreement with the corresponding measurements at Izaña Observatory (22% overestimation) and at Agia Marina Xyliatos site (4% overestimation). Further model developments, including the implementation of newer surface mineralogical datasets, e.g., from the NASA-EMIT satellite mission, can be implemented in the model to improve its accuracy.
This research aims to content analyze the literature on innovation in the field of sports in Montenegro to provide a better basis for the establishment of a monitoring system. The research was ...conducted drawing on a pre-established methodology related to the assessment of the level of sports innovation based on 16 defined indicators. Grades were attributed to data found in available scientific articles that were published until 2021, as well as in secondary data sources (Google Scholar, PubMed, Scopus, and Web of Science), such as governmental and nongovernmental reports and online content on Google (N = 18) from the same period. The findings of content analysis indicate that all indicators averaged 2.25 (fair) on a six-point scale, while only one indicator was rated as excellent, five indicators were rated as good, four indicators were rated as fair, and lastly, five indicators were rated as poor. Based on the obtained results, a low level of innovation in the field of sports in Montenegro was determined, and this also applies to innovation indicators individually. These results can be used as an initial step in planning an appropriate strategy development at the national level, which will lead to the improvement of innovation activities and their implementation in the field of sports in Montenegro.
The cereal grains, which represent the cultivated grasses fruits, supply almost half of the total caloric requirements for humans and provide more nourishment compared with any other class of the ...food. Out of many cereals used for food, maize, rice, and wheat are the most important food resources for humans, representing 94% of the total cereals consumption. According to the data of the Republic Institute of Statistics for the year 2018, the harvested areas of corn amount to 906,753 hectares. The production of about 7 million tons was achieved with an average yield of 7.7 t/ha according to the Ministry of Agriculture of the Republic of Serbia. Serbia is still among the ten largest exporters of wheat and corn in the world for the period of 2014/15–2017/18. More precisely, it ranks seventh in the export of corn. Utilization of maize products for food animal nutrition (1000 t) is 491,48, and for industrial processing (1000 t) 278,862 expressed as the total consumption (1000 t) is 769,910. Therefore, a total of 103 samples of maize products were analyzed for the presence of toxins, i.e., tropane alkaloids (TAs). The samples were collected from the retail stores in the Republic of Serbia in 2021 and analyzed for the presence of atropine and scopolamine (33 corn grits, 39 polenta, and 31 semolina samples). Therefore, the Recommendation 2015/976/EU on the monitoring of TAs in food was adopted by the EU Commission to obtain more occurrence data on TAs in food. The monitoring extent, however, is restricted because reliable analytical methods and appropriate sensitivity are limited. There was a limit of 1 g/kg for each atropine and scopolamine in cereals containing millet, sorghum, buckwheat, or their derivatives. All the samples were analyzed by the LC-MS/MS. The LOQ was set at 1.0 μg/kg. Out of the total 103 tested samples, 32 samples (31.1%) were contaminated with atropine and scopolamine in concentrations above the LOQ. The highest concentrations of the studied TAs were observed in a semolina sample-atropine: 58.80 μg/kg, scopolamine: 10.20 μg/kg. The obtained results indicate that the TAs concentrations are above the LOQ which can be considered potential human and animal health hazards.
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