Cholesterol, the essential building block of cellular membranes, has proven to be a useful tool for increasing the biocompatibility and bioavailability of drug delivery systems in cancer treatment. Resveratrol, a natural polyphenolic compound with promising anticancer properties, faces significant limitations due to its low solubility and bioavailability, hindering its clinical utility. Therefore, in the present study, we aimed to design cholesterol-functionalized cyclodextrin nanosponges (Chol-NSs) with a tunable cholesterol content to optimize resveratrol encapsulation and delivery. Both formulations, free carbonyl diimidazole (CDI) NSs and functionalized Chol-NSs, demonstrated high drug loading and encapsulation efficiency. In vitro experiments revealed that cholesterol incorporation significantly improved the cellular uptake of nanocarriers and potentiated the cytotoxic effects of resveratrol on breast cancer cells. Importantly, both free CDI NSs and functionalized Chol-NSs, even at varying cholesterol percentages, demonstrated a safe profile against both fibroblast and breast cancer cell lines. These results indicate that cholesterol-functionalized nanosponges represent a promising platform for the effective and safe delivery of natural compounds in cancer therapy.
- Klíčová slova
- cholesterol, crosslinked polymer, drug delivery, functionalization, nanosponge,
- MeSH
- antitumorózní látky aplikace a dávkování farmakokinetika MeSH
- biologická dostupnost MeSH
- buňky 3T3 MeSH
- cholesterol * chemie MeSH
- cyklodextriny * chemie MeSH
- imidazoly chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- myši MeSH
- nádory prsu * farmakoterapie patologie MeSH
- nanostruktury * chemie MeSH
- příprava léků metody MeSH
- resveratrol * aplikace a dávkování farmakokinetika MeSH
- systémy cílené aplikace léků * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky MeSH
- cholesterol * MeSH
- cyklodextriny * MeSH
- imidazoly MeSH
- N,N-carbonyldiimidazole MeSH Prohlížeč
- resveratrol * MeSH
Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine.
- Klíčová slova
- cathelicidins, clinical trials, peptide formulations, recombinant production, resistance mechanism, skin drug delivery, wound healing,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The widespread use of antimicrobial drugs has contributed to the increasing trace levels of contaminants in the environment, posing an environmental problem and a challenge to modern-day medicine seeking advanced solutions. Nanofiltration is one such breakthrough solution for the selective removal of antibiotics from wastewater due to their high efficiency, scalability, and versatility. This study examines the separation of antibiotics (sulfamethoxazole (SMX), trimethoprim (TMP), and metformin (MET), respectively) using commercially available membranes with an emphasis on AFC membranes (AFC 30 and AFC 80). Thus, we evaluate their efficacy, performance, and applicability in wastewater treatment processes. The data for characterizing the structural parameters of the NF membranes were determined from an uncharged organic solute rejection experiment, and the effect of various operating conditions on the retention of solutes was evaluated. All experimental data were collected using a laboratory-scale nanofiltration unit and HPLC, and rejection percentages were determined using analytical measurements. The results obtained allowed for the determination of the radius of the membrane pores using the Steric Hindrance Pore (SHP) model, resulting in values of 0.353 and 0.268 nm for the AFC 30 and AFC 80 membranes, respectively. Additionally, higher transmembrane pressure and feed flow were observed to lead to an increased rejection of antibiotics. AFC 30 demonstrated a rejection of 94% for SMX, 87% for TMP, and 87% for MET, while AFC 80 exhibited a rejection of 99.5% for SMX, 97.5% for TMP, and 98% for MET. The sieving effect appears to be the primary separation mechanism for AFC 30, as lower feed-flow rates were observed to intensify concentration polarization, thereby compromising rejection efficiency. On the contrary, AFC 80 experienced less concentration polarization due to its smaller pore sizes, effectively preventing pore clogging. Membrane performance was evaluated using the Spiegler-Kedem-Katchalsky model, based on irreversible thermodynamics, which effectively explained the mechanism of solute transport of antibiotics through the AFC 30 and AFC 80 membranes in the NF process.
- Klíčová slova
- SHP model, Spiegler–Kedem model, antibiotics, nanofiltration, rejection,
- Publikační typ
- časopisecké články MeSH
Glycosphingolipids (GSL) are a highly heterogeneous class of lipids representing the majority of the sphingolipid category. GSL are fundamental constituents of cellular membranes that have key roles in various biological processes, such as cellular signaling, recognition, and adhesion. Understanding the structural complexity of GSL is pivotal for unraveling their functional significance in a biological context, specifically their crucial role in the pathophysiology of various diseases. Mass spectrometry (MS) has emerged as a versatile and indispensable tool for the structural elucidation of GSL enabling a deeper understanding of their complex molecular structures and their key roles in cellular dynamics and patholophysiology. Here, we provide a thorough overview of MS techniques tailored for the analysis of GSL, emphasizing their utility in probing GSL intricate structures to advance our understanding of the functional relevance of GSL in health and disease. The application of tandem MS using diverse fragmentation techniques, including novel ion activation methodologies, in studying glycan sequences, linkage positions, and fatty acid composition is extensively discussed. Finally, we address current challenges, such as the detection of low-abundance species and the interpretation of complex spectra, and offer insights into potential solutions and future directions by improving MS instrumentation for enhanced sensitivity and resolution, developing novel ionization techniques, or integrating MS with other analytical approaches for comprehensive GSL characterization.
- Klíčová slova
- Derivatization, Fragmentation, Glycosphingolipids, Liquid chromatography, Mass spectrometry, Structural elucidation,
- MeSH
- glykosfingolipidy * chemie analýza MeSH
- hmotnostní spektrometrie * metody MeSH
- lidé MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- glykosfingolipidy * MeSH
BACKGROUND: A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors. METHODS: In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry. RESULTS: Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status. CONCLUSION: The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors.
- Klíčová slova
- Aspartate-β-hydroxylase, Head and neck cancer, Human papillomavirus, Hypoxia, Prognosis,
- Publikační typ
- časopisecké články MeSH
The main goal of this research is to investigate the effectiveness of graphitic carbon nitride (g-C3N4, g-CN) in both bulk and nanosheet forms, which have been surface-modified with silver nanoparticles (Ag NPs), as photocatalysts for the degradation of acid orange 7 (AO7), a model dye. The photodegradation of AO7 dye molecules in water was used to test the potential photocatalytic properties of these powder materials under two different lamps with wavelengths of 368 nm (UV light) and 420 nm (VIS light). To produce Ag NPs (Ag content 0.5, 1.5, and 3 wt%) on the g-CN materials, a new synthesis route based on a wet and low-temperature method was proposed, eliminating the need for reducing agents. The photodegradation activity of the samples increased with increasing silver content, with the best photocatalytic performances achieved for bulk g-CN samples and nanosheet silver-modified samples (with the highest content of 3 wt% Ag) under UV light, i.e., more than 75% and 78%, respectively. The VIS-induced photocatalytic activity of both examined series was higher than that of UV. The highest activities of 92% and 98% were achieved for the 1.5% Ag-modified g-CN bulk and nanosheet materials. This research presents an innovative, affordable, and environmentally friendly chemical approach to synthesizing photocatalysts that can be used for degrading organic pollutants in wastewater treatment.
- Klíčová slova
- Acid orange 7, Ag nanoparticles, Graphitic carbon nitride, Photocatalytic degradation, g-C3N4,
- Publikační typ
- časopisecké články MeSH
Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.
- Klíčová slova
- A. thaliana, cell biology, centremeres, centromeric histone, chromosomes, gene expression, meiosis, micronuclei, spindle assembly checkpoint,
- MeSH
- Arabidopsis * genetika metabolismus MeSH
- centromera metabolismus MeSH
- histony metabolismus MeSH
- kinetochory metabolismus MeSH
- meióza MeSH
- reakce na tepelný šok MeSH
- rostliny genetika MeSH
- segregace chromozomů MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- histony MeSH
The white truffle (Tuber magnatum Picco.; WT) is the most expensive and arguably also the most delicious species within the genus Tuber. Due to its hidden belowground life cycle, complex host symbiosis, and yet unknown distribution, cultivation of the enigmatic species has only recently been achieved at some plantations in France. A sustainable production of WTs under future climate change, however, requires a better ecological understanding of the species' natural occurrence. Here, we combine information from truffle hunters with a literature review to assess the climatic, edaphic, geographic, and symbiotic characteristics of 231 reported WT sites in southeast Europe. Our meta-study shows that 75% of the WT sites are located outside the species' most famous harvest region, the Piedmont in northern Italy. Spanning a wide geographic range from ~ 37° N in Sicily to ~ 47° N in Hungary, and elevations between sea level in the north and 1000 m asl in the south, all WT sites are characterised by mean winter temperatures > 0.4 °C and summer precipitation totals of ~ 50 mm. Often formed during past flood or landslide events, current soil conditions of the WT sites exhibit pH levels between 6.4 and 8.7, high macroporosity, and a cation exchange capacity of ~ 17 meq/100 g. At least 26 potential host species from 12 genera were reported at the WT sites, with Populus alba and Quercus cerris accounting for 23.5% of all plant species. We expect our findings to contribute to a sustainable WT industry under changing environmental and economic conditions.
- Klíčová slova
- Ectomycorrhiza, Environmental change, Fungi, Global warming, Non-woody forest products, Truffle cultivation,
- MeSH
- Ascomycota * MeSH
- mykorhiza * MeSH
- půda MeSH
- symbióza MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- půda MeSH
PURPOSE: Fecal immunochemical test (FIT) once a year or colonoscopy once in 10 years is the option approved for colorectal cancer (CRC) screening for asymptomatic individuals aged ≥ 50 years in the Czech Republic. We analyzed participation in the screening program to determine possible improvements. METHODS: In this observational cross-sectional study, data were collected from 4044 randomly chosen individuals from the Czech population (1866 men, 2178 women) aged ≥ 50 years by questionnaires. Individuals who underwent colonoscopy within the last 10 years or/and FIT within the last 2 years were classified as participants in the screening. RESULTS: 1050 individuals underwent FIT, 464 colonoscopy, and 558 underwent both. Adjusted for age, gender, and education, a higher chance of participation in the screening was observed in groups of non-smokers (OR = 1.25; CI 1.05-1.48), ex-smokers (OR = 1.51; CI 1.26-1.83), consuming smoked meat products less than once a week (OR = 1.26; CI 1.09-1.45), practicing physical activity at least once a week (OR = 1.25; CI 1.03-1.51), hospitalized in the past 12 months (OR = 1.73; CI 1.47-2.05), or consulting a general practitioner (GP) in the past 12 months (OR = 2.26; CI 1.87-2.74). The chance of participation of individuals having a risk factor for CRC (obesity, smoking, diabetes, low physical activity, alcohol drinking) was not higher compared to those without the risk factors. CONCLUSION: Individuals with a tendency to a healthy lifestyle or being in recent contact with the healthcare system by various means, mainly visiting a GP, had a higher participation in the screening for CRC. Among groups with an increased risk for CRC, higher participation was not shown.
- Klíčová slova
- Alcohol drinking, Diabetes, Obesity, Physical activity, Screening, Smoking,
- MeSH
- časná detekce nádoru * MeSH
- kolonoskopie MeSH
- kolorektální nádory * diagnóza epidemiologie prevence a kontrola MeSH
- lidé MeSH
- plošný screening MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm2 were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated. If the wound healed less than 20% of the baseline size after 6 weeks, the patient was transferred to the AM group (35 patients, 43 wounds). Weekly visits included an assessment of the patient's condition, photo documentation, wound debridement, and dressing. Quality of life and the pain degree were subjectively reported by patients. After SOC, 7 wounds were healed completely, 1 defect partially, and 28 defects remained unhealed. AM application led to the complete closure of 24 wounds, partial healing occurred in 10, and 9 remained unhealed. The degree of pain and the quality of life improved significantly in all patients after AM application. This study demonstrates the effectiveness of cryopreserved AM grafts in the healing of NHW of polymorbid patients and associated pain reduction.
- Klíčová slova
- cryopreserved amniotic membrane, nonhealing wounds, pain, polymorbid patients,
- Publikační typ
- časopisecké články MeSH
