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Designing and the anticancer activity of chitosan and chitosan oligosaccharide lactate nanobeads loaded with Biginelli hybrid
No full textThis study focuses on the designing and characterization, and anticancer evaluation of chitosan-based nanoparticles (NPs) loaded (enriched) with a Biginelli hybrid compound (BH). NPs based on chitosan (CH) or chitosan oligosaccharide lactate (CHOL), are carefully designed to encapsulate a tetrahydropyrimidine derivative (BH) with already proven anticancer properties. The formulations were evaluated for their physicochemical properties, including particle size distribution and morphology, using techniques such as infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The cytotoxicity profiles were assessed on different cancer cell lines, showing a higher selectivity towards HeLa and A549 cells related to BH. BH-CH showed better cytotoxic profile related to BH-CHOL NPs. A cell cycle analysis revealed an accumulation of cells in the G2/M phase after a treatment with these NPs, indicating the ability to induce mitotic arrest in cancer cells. In summary, the results underscore the promising application of CH-based natural nanocarriers for the targeted delivery of Biginelli hybrids, showcasing a significant potential for further in vivo testing
New scale measuring willingness to deliver pharmaceutical care to elderly (WPhCareEld scale)
No full textAgeism is the existence of stereotypes, prejudices, and discrimination against the elderly. It is prevalent in the general population, but also among healthcare workers. The aim of this study was to develop and test a new scale for assessing the willingness of pharmacists to offer pharmaceutical care to elderly patients. The study was designed as cross-sectional, testing the reliability of the newly created questionnaire. The questionnaire was prepared through the work of a focus group, following the eight-step method, and administered via the internet. The WPhCareEld scale showed good internal consistency and reliability (Cronbach’s alpha was 0.726) in a sample of community pharmacists, and its factor analysis showed that the scale measures four domains: willingness of community pharmacists to care for elderly patients through direct and indirect communication with prescribers, how the pharmacists value elderly patients, and whether the pharmacists have prejudices against elderly patients. The study confirmed the reliability and internal consistency of the newly designed questionnaire for measuring the willingness of community pharmacists to provide pharmaceutical care to elderly patients
Antimicrobial Activities of Essential Oils of Different Pinus Species from Bosnia and Herzegovina
No full textAbstract: Background/Objectives: The emergence of antimicrobial resistance has urged researchers to explore new antimicrobial agents, such as essential oils (EOs). The aim of this study was to examine chemical composition and antimicrobial activity of the EOs from the needles and green cones of four Pinus species (Pinus mugo Turra., P. nigra J.F., P. syilvestris L., and P. halepensis Miller) from Bosnia and Herzegovina. Methods: Chemical profiles of EOs were assessed by gas chromatography, while microdilution method was used to test their antimicrobial activity. A synergistic action of EOs and gentamicin was investigated by the checkerboard assay. Results: The chemical composition of the tested EOs showed a high percentage of α-pinene, (E)-caryophyllene, limonene, germacrene D, myrcene, and δ-3-carene. EO from green cones of P. sylvestris showed high efficiency against S. aureus and E. faecalis. The MIC of P. nigra cones’ EO was 100 μg/mL against E. coli. The EO of P. halepensis green cones demonstrated the strongest activity against E. faecalis. EOs of P. halepensis needles and green cones exhibited the highest activity against C. albicans. Further, synergistic interaction was detected in combination of the selected EOs/gentamicin toward S. aureus and K. pneumoniae. Conclusions: Among the tested EOs, oils of P. sylvestris cones and P. halepensis cones and needles showed the greatest antimicrobial activity. The same EOs and EO from P. nigra cones displayed synergistic potential in combination with gentamicin, supporting their utilization as antimicrobial agents alone or in combination with antibiotics, which is in line with their ethnopharmacological usage and circular bioeconomy principles
Cardiovascular Risk in Patients with Ankylosing Spondylitis
No full textObjectives: Ankylosing spondylitis (AS) is an autoinflammatory, chronic disease. Patients with AS are at increased risk of cardiovascular disease (CVD). The link between AS and subclinical atherosclerosis is multifactorial and still not completely understood. The aim of this study was to examine the potential associations between carotid intima–media thickness (cIMT) and different cardiometabolic biomarkers in individuals with AS. Methods: A total of 96 patients with AS were prospectively included. cIMT was measured via ultrasonography. Multiple linear regression analysis was used to find the best predictors of cIMT values. Principal component analysis (PCA) was implemented to extract factors that were further tested via binary logistic regression analysis in relation to cIMT. Results: Waist circumference (WC), low-density lipoprotein cholesterol (LDL-c), and the BASDAI score were independently correlated with cIMT in AS patients (p = 0.037, p = 0.060, and p = 0.048, respectively; adjusted R2 = 0.113). PCA extracted four panels of biomarkers, i.e., “haematology–lipid-related factor” (i.e., ferritin, haemoglobin, HDL-c, and triglycerides), “proinflammatory–prothrombotic-related factor” (i.e., platelets, neutrophils, and C-reactive protein), “LDL-c–vitamin-related factor” (i.e., vitamins D and B12, and LDL-c), and “age–glucometabolic-related factor” (i.e., age and HbA1c), in relation to higher cIMT in patients with AS. Among these four clusters, “age–glucometabolic-related factor” was an independent predictor of increased cIMT (p < 0.001). Conclusions: In addition to traditional cardiometabolic risk factors, WC and LDL-c, the disease activity score (BASDAI) is independently related to subclinical atherosclerosis in AS patients. The joint involvement of heterogeneous cardiometabolic risk factors may reflect different pathophysiological processes of subclinical atherosclerosis in patients with AS
A Longitudinal Study of Escherichia coli Clinical Isolates from the Tracheal Aspirates of a Paediatric Patient—Strain Type Similar to Pandemic ST131
No full textEscherichia coli is a Gram-negative bacterium and part of the intestinal microbiota. However, it can cause various diarrhoeal illnesses, i.e., traveller’s diarrhoea, dysentery, and extraintestinal infections when the bacteria are translocated from the intestine to other organs, such as urinary tract infections, abdominal and pelvic infections, pneumonia, bacteraemia, and meningitis. It is also an important pathogen in intensive care units where cross-infection may cause intrahospital spread with serious consequences. Within this study, four E. coli isolates from the tracheal aspirates of a tracheotomised paediatric patient on chronic respiratory support were analysed and compared for antibiotic resistance and virulence potential. Genomes of all four isolates (5381a, 5381b, 5681, 5848) were sequenced using Oxford Nanopore Technology. According to PFGE analysis, the clones of isolates 5681 and 5848 were highly similar, and differ from 5381a and 5381b which were isolated first chronologically. All four E. coli isolates belonged to an unknown sequence type, related to the E. coli ST131, a pandemic clone that is evolving rapidly with increasing levels of antimicrobial resistance. All four E. coli isolates in this study exhibited a multidrug-resistant phenotype as, according to MIC data, they were resistant to ceftriaxone, ciprofloxacin, doxycycline, minocycline, and tetracycline. In addition, principal component analyses revealed that isolates 5681 and 5848, which were recovered later than 5381a and 5381b (two weeks and three weeks, respectively) possessed more complex antibiotic resistance genes and virulence profiles, which is concerning considering the short time period during which the strains were isolated
Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
Get PDFObjective: Chronic obstructive pulmonary disease (COPD) is multi-factorial disorder which
results from environmental influences and genetic factors. We aimed to investigate whether
methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with
COPD development and severity in Serbian adult population.
Methods: The study included 155 patients with COPD and 134 healthy volunteers. Genotyping
was determined performing home-made polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxi-
dized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxi-
dized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was
presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g).
Results: Frequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients
and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in geno-
type or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was signifi-
cantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-
Elastase) was significantly lower in COPD patients than in the control group. In COPD group,
increased level of OxyA1ATwas present in G allele carriers who were smokers relative to G allele
carriers who were not smokers. In the smoker group of patients with severe and very severe
COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes.
Conclusion: These findings suggest that MSRA rs10903323 gene polymorphism is probably not a
risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized
A1AT in COPD-smokers, and in severe form of COPD
Chemometrically-aided general approach to novel adsorbents studies: Case study on the adsorption of pharmaceuticals by the carbonized Ailanthus altissima leaves
No full textA chemometrically based approach was applied to select the most efficient drug adsorbent among the biochars obtained from the novel feedstock, the leaves of the invasive plant (Ailanthus altissima). The representative target adsorbates (atenolol, paracetamol, ketorolac and tetracycline) were selected on the basis of their physicochemical properties to cover a wide chemical space, which is the usual analytical challenge. Their adsorption was investigated using design of experiments as a comprehensive approach to optimise the performance of the adsorption system, rationalise the procedure and overcome common drawbacks. Among the response surface designs, the central composite design was selected as it allows the identification of important experimental factors (solid-to-liquid ratio, pH, ionic strength) and their interactions, and allows the selection of optimal experimental conditions to maximise adsorption performance. The biochars were prepared by pyrolysis at 500 °C and 800 °C (BC-500 and BC-800) and the ZnCl2-activated biochars were prepared at 650 °C and 800 °C (AcBC-650 and AcBC-800). The FTIR spectra revealed that increasing the pyrolysis temperature without activator decreases the intensity of all bands, while activation preserves functional groups, as evidenced by the spectra of AcBC-650 and AcBC-800. High temperatures during activation promoted the development of an efficient surface area, with the maximum observed for AcBC-800 reaching 347 m2 g−1. AcBC-800 was found to be the most efficient adsorbent with removal efficiencies of 34.1, 51.3, 55.9 and 38.2 % for atenolol, paracetamol, ketorolac and tetracycline, respectively. The models describing the relationship between the removal efficiency of AcBC-800 and the experimental factors studied, showed satisfactory predictive ability (predicted R2 > 0.8) and no significant lack-of-fit was observed. The results obtained, including the mathematical models, the properties of the adsorbates and the adsorbents, clearly indicate that the adsorption mechanisms of activated biochars are mainly based on hydrophobic interactions, pore filling and hydrogen bonding
Biohemija i laboratorijska dijagnostika gojaznosti
Get PDFUntil now, a lot of research has been carried out which significantly helped in
understanding and solving the problem of obesity. Despite this, there has been an upward in
obesity trend at the global level. The role of laboratory diagnostics in the field of obesity is of
great importance to doctors for establishing a diagnosis and monitoring the effects of therapy.
Determining biochemical parameters also contributes to practical usefulness in the prevention of
this disease, and prevention of consequent complications. Routinely available biochemical
analyses are usually used to diagnose and monitor the effects of obesity therapy. The initial
association related to laboratory analyses refers to parameters of lipid status, but there are a variety
of routine laboratory parameters that can help in understanding and monitoring obesity from
different angles. Timely and adequate management of obesity is also of interest from an economic
aspect. For this reason, the topic of this research is to summarize the latest aspects of the concept
of obesity, specifically from the point of view of biochemistry and laboratory diagnostics. Taking
into account the complexity of this disease, it is important to point out the future perspectives and
challenges that inevitably arise before both laboratory professionals and healthcare providers in
general.Do sada je sprovedeno dosta istraživanja koja su značajno pomogla u sagledavanju i rešavanju problema gojaznosti. I pored toga, gojaznost ima trend porasta na globalnom nivou. Uloga laboratorijske dijagnostike u oblasti gojaznosti je od velikog značaja lekarima za postavljanje dijagnoze i praćenje efekata terapije. Određivanje biohemijskih parametara takođe doprinosi praktičnoj korisnosti u prevenciji ovog oboljenja, kao i predupređenju posledičnih komplikacija. Obično se za postavljanje dijagnoze i praćenje efekata terapije gojaznosti određuju rutinski dostupne biohemijske analize. Prvobitna asocijacija vezana za laboratorijske analize odnosi se na parametre lipidnog statusa, ali jako je veliki broj rutinskih analiza koje mogu pomoći u sagledavanju i praćenju gojaznosti iz različitih uglova. Dodatno, pravovremeno i adekvatno upravljanje gojaznošću je od interesa i sa ekonomskog aspekta. Iz tog razloga, tema ovog istraživanja je sumiranje najnovijih aspekata koncepta gojaznosti, posebno sa stanovišta biohemije i laboratorijske dijagnostike. Uzimajući u obzir složenost ove bolesti, važno je ukazati na buduće perspektive i izazove koji se neizbežno javljaju kako pred laboratorijskim stručnjacima, tako i pred zdravstvenim radnicima uopšte
Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation
Get PDFNotwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine
Osnovni principi otkrivanja oštećenja DNK pomoću alkalnog komet testa
Get PDFThe Comet assay is a highly sensitive and rapid method for detecting DNA damage at the
level of individual cells. It measures single-stranded and double-stranded DNA breaks, alkali-
labile, incomplete excision repair and cross-linking sites. A major advantage of the Comet assay
is its applicability to both proliferating and non-proliferating cells, and it can be performed on all
types of eukaryotic cells. The basic principle of the alkaline Comet assay is to lyse the biological
membranes to release proteins bound to the DNA, followed by a short-term electrophoresis at a
pH above 13. Through this process, the DNA fragments migrate and form a comet-like shape,
which is visualized by staining with a DNA-binding fluorescent dye. The extent of electrophoretic
migration is proportional to the amount of DNA damage. Key advantages of the Comet assay
include sensitivity - the assay can detect low levels of DNA damage, versatility – it can be used
with a small amount of test substance, speed – results are usually available within 24 to 48 hours,
and broad applicability – the method is suitable for numerous purposes, including molecular
epidemiology, occupational exposure studies, environmental biomonitoring, antigenotoxicity
assessments and clinical research. Overall, the Comet assay provides valuable data for a range of
scientific and clinical fields, making it a versatile and powerful tool for assessing DNA damage.Komet test je veoma osetljiva i brza metoda za otkrivanje oštećenja DNK na nivou pojedinačnih ćelija. Meri jednolančane i dvolančane DNK prekide, alkalno labilna mesta, mesta nepotpune ekscizione reparacije i mesta unakrsnog povezivanja. Značajna prednost komet testa je njegova primenjivost na proliferišuće i neproliferišuće ćelije, a može se primeniti na gotovo bilo kom tipu eukariotskih ćelija. Osnovni princip alkalnog komet testa uključuje ugradnju ćelija u agarozni gel praćen lizom ćelijskih membrana i uklanjanjem proteina kako bi se oslobodila ukupna DNK. Zatim se denaturiše DNK i podvrgava elektroforezi, nakon čega se vrši neutralizacija. Ćelije se boje različitim fluorescentnim bojama kako bi se obezbedila vizuelizacija i procena intenziteta nivoa DNK oštećenja koriščenjem fluorescentnog mikroskopa. Stepen elektroforetske migracije DNK vizuelizovane u vidu repa komete je srazmeran količini oštećenja DNK. Ključne prednosti komet testa su osetljivost - test može da otkrije niske nivoe DNK oštećenja, raznovrsnost - može se koristiti sa malom količinom test supstance i na različitim tipovima eukariotskih ćelija, brzina -rezultati su obično dostupni u roku od 24 do 48 sati i široka primenjivost - metoda je pogodna za više namena, uključujući molekularnu epidemiologiju, studije profesionalne izloženosti, biomonitoring životne sredine, procene antigenotoksičnosti i klinička istraživanja. Sve u svemu, komet test pruža vredne podatke u širokom spektru naučnih i kliničkih oblasti, što ga čini moćnim alatom za procenu DNK oštećenja