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Extracellular vesicles (EVs) are lipid bilayer-delimited particles. According to their size and synthesis pathway, EVs can be classified into exosomes, ectosomes (microvesicles), and apoptotic bodies. Extracellular vesicles are of great interest to the scientific community due to their role in cell-to-cell communication and their drug-carrying abilities. The study aims to show opportunities for the application of EVs as drug transporters by considering techniques applicable for loading EVs, current limitations, and the uniqueness of this idea compared to other drug transporters. In addition, EVs have therapeutic potential in anticancer therapy (especially in glioblastoma, pancreatic cancer, and breast cancer).
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Micropartículas Derivadas de Células , Exosomas , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Exosomas/metabolismo , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Bacteria are the source of many bioactive compounds, including polymers with various physiological functions and the potential for medical applications. Pyomelanin from Pseudomonas aeruginosa, a nonfermenting Gram-negative bacterium, is a black-brown negatively charged extracellular polymer of homogentisic acid produced during L-tyrosine catabolism. Due to its chemical properties and the presence of active functional groups, pyomelanin is a candidate for the development of new antioxidant, antimicrobial and immunomodulatory formulations. This work aimed to obtain bacterial water-soluble (Pyosol), water-insoluble (Pyoinsol) and synthetic (sPyo) pyomelanin variants and characterize their chemical structure, thermosensitivity and biosafety in vitro and in vivo (Galleria mallonella). FTIR analysis showed that aromatic ring connections in the polymer chains were dominant in Pyosol and sPyo, whereas Pyoinsol had fewer Car-Car links between rings. The differences in chemical structure influence the solubility of various forms of pyomelanins, their thermal stability and biological activity. Pyosol and Pyoinsol showed higher biological safety than sPyo. The obtained results qualify Pyosol and Pyoinsol for evaluation of their antimicrobial, immunomodulatory and proregenerative activities.
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Melaninas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/metabolismo , Melaninas/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismoRESUMEN
Equiseti herba has been traditionally indicated in bacterial diseases of the efferent urinary tract or bad healing wounds in many regions worldwide. Most of the plant material used for medical purposes comes from collections of wild growing plants. The European Pharmacopoeia requires that Equiseti herba should consist of a minimum of 95% Equisetum arvense and a maximum of 5% foreign ingredients. This includes Equisetum palustre, which is known for its potentially toxic alkaloid palustrine. However, both Equisetum species are quite common, look morphologically very similar, and share similar habitats, hence, are therefore often confused. Recently, several structurally related Equisetum alkaloids have been identified in E. palustre but not in E. arvense. We have established a hydrophilic interaction liquid chromatography HPLC-ESI-MS/MS method for the detection of these E. palustre-specific Equisetum alkaloids in order to quantify the contamination of Equiseti herba (E. arvense) by E. palustre plant material. In a second, independent approach, the results of the HPLC-MS/MS analysis were confirmed by scanning electron microscopy, looking for the species-specific characteristics of the stoma apparatus of E. palustre. Thirty-four Equiseti herba products obtained from different pharmacies, drug stores, supermarkets, and web stores were analyzed. The majority of the products (26 out of 34) were Equisetum alkaloid positive, with contents ranging from 0.29â-â21.7 mg of Equisetum alkaloids/kg (d.âw.). In addition, the transfer of Equisetum alkaloids into tea infusions was investigated, demonstrating a 42 to 60% transfer rate for cold and hot water extraction of Equisetum alkaloid-contaminated Equiseti herba, respectively.
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Alcaloides , Equisetum , Alcaloides/análisis , Biomarcadores , Cromatografía Líquida de Alta Presión/métodos , Equisetum/química , Extractos Vegetales , Espectrometría de Masas en Tándem/métodosRESUMEN
New hydroxy- and anilinoindanone derivatives 3 and 4 were synthesized starting from 3-hydroxybenzo[e]isoindolinone 1 via the addition of alkyllithium (s-BuLi, n-BuLi, MeLi or i-PrLi) to the carbonyl group, followed by lactam ring opening and, finally, an intramolecular cyclization leading to target compounds. The same starting material was used for the preparation of the new benzo[f]phthalazinone derivatives 12-16 through multi-step reactions. The target derivative 16 was obtained from the corresponding bromolactam 15 by the Buchwald-Hartwig amination. Structures of the obtained compounds were confirmed by the NMR spectra.
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Indanos , Isoindoles , Isoindoles/química , CiclizaciónRESUMEN
Amino- and polyaminophthalazinones were synthesized by the palladium-catalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L-929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported.
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In the original version of this article [1], published on 8 November 2018, there was an error in the name of the 2nd author.
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BACKGROUND: A crucial step in image fusion for intraoperative guidance during endovascular procedures is the registration of preoperative computed tomography angiography (CTA) with intraoperative Cone Beam CT (CBCT). Automatic tools for image registration facilitate the 3D image guidance workflow. However their performance is not always satisfactory. The aim of this study is to assess the accuracy of a new fully automatic, feature-based algorithm for 3D3D registration of CTA to CBCT. METHODS: The feature-based algorithm was tested on clinical image datasets from 14 patients undergoing complex endovascular aortic repair. Deviations in Euclidian distances between vascular as well as bony landmarks were measured and compared to an intensity-based, normalized mutual information algorithm. RESULTS: The results for the feature-based algorithm showed that the median 3D registration error between the anatomical landmarks of CBCT and CT images was less than 3 mm. The feature-based algorithm showed significantly better accuracy compared to the intensity-based algorithm (p < 0.001). CONCLUSION: A feature-based algorithm for 3D image registration is presented.
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Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Angiografía por Tomografía Computarizada/métodos , Tomografía Computarizada de Haz Cónico/métodos , Anciano , Anciano de 80 o más Años , Algoritmos , Procedimientos Endovasculares , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Periodo Preoperatorio , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: In accordance with the European guidelines on rhinosinusitis and nasal polyps (EPOS 2012), CT is used as the main imaging modality for the assessment intensity of inflammatory lesions.The aim of this study was to measure the differences in the assessment of inflammatory changes in the paranasal sinuses due to different parameters of width (W) and length (L) of the CT window. MATERIAL/METHODS: A retrospective analysis included 44 CT scans of the paranasal sinuses that were performed in adults. All studies were characterized by the presence of inflammatory changes in at least one of the sinuses.Measurements of the same inflammatory lesions were performed sequentially with different CT windows. The results were statistically analyzed. RESULTS: A statistically significant difference was observed between the average measurements that were performed with the use CT windows dedicated for the sinuses and head. A downward trend in the measured values and a shift towards soft tissue values was observed with decreasing window parameters. CONCLUSIONS: A major cause of inaccurate examinations of pathological changes in the paranasal sinuses may be due to selection of unsuitable CT windows. Therefore, in order to avoid missing inflammatory lesions in the paranasal sinuses, it is reasonable to use CT windows dedicated for the sinuses or bones.
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Objectives: This study aimed to find if a relationship exists between antero-posterior malocclusions and the level of musculoskeletal disorders in adults, including body posture and static foot analysis. Methods: In all, 420 participants were recruited through convenience sampling (Kraków University students and patients of a local dentist's practice). Following general medical interviews, dental examinations and consideration of inclusion and exclusion criteria, 90 healthy volunteers (ages 19-35) were enrolled and assigned to three groups (n = 30) based on occlusion type (Angle's molar Class I, II or III). The research procedure involved occlusion and temporomandibular disorder assessment conducted by a dental specialist. Comprehensive morphological measurements of body asymmetry were performed using the Videography 2D package and FreeSTEP software, which calculated the parameters determined from anterior, posterior and lateral projection photos. Foot loading distribution was analyzed using the FreeMED baropodometric platform. Results: Significant differences were demonstrated in the positioning of the head, cervical and lumbar spine in the sagittal plane among individuals with the analyzed occlusal classes (p < 0.05). Individuals with Angle's Class II exhibited significantly greater forward head positions and greater depths of cervical and lumbar lordosis compared with individuals with Class III or Class I. Those with overbites had higher forefoot loading. The Class III individuals exhibited greater L-R displacement, indicating a larger angle of displacement of the centers of the right and left feet relative to the lower edge of the measurement platform, suggesting pelvic rotation. Conclusions: An inclination for concurrent occurrences of malocclusions and posture deviations in the sagittal plane was observed. An interdisciplinary approach involving dentistry and physiotherapy specialists which utilizes tools for comprehensive posture assessment is crucial for diagnosing and treating such conditions.
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Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation.
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Background: There is still an ongoing debate about the role of the craniomandibular system, including occlusal conditions, on postural stability. This study aims to assess the role of antero-posterior malocclusion on postural control and plantar pressure distribution during standing and walking. Methods: 90 healthy volunteers (aged 19 to 35) were qualified for the study. The subjects were assigned to three groups, depending on the occlusion type. Each group (Angle Class I, II and III) consisted of 30 people. The research procedure included a clinical occlusal assessment performed by a dentist. Postural control measurements were carried out using a force platform by measuring plantar pressure distribution during standing (six trials with and without visual control) and walking test conditions. Results: The tendency to shift the CoP forward is demonstrated by Angle Class II subjects and backwards by Class I and III subjects (p < 0.001). Individuals with a malocclusion demonstrated significantly higher selected stabilographic parameters while standing on both feet (with eyes open and closed) and during the single-leg test with eyes open (p < 0.05). The analysis of the dynamic test results showed no significant correlations between Angle Classes and the selected gait parameters. Conclusions: Analyses conducted among individuals with malocclusions showed the impact of occlusion on static postural stability. In order to diagnose and effectively treat malocclusion, a multidisciplinary approach with the participation of dentists and physiotherapy specialists is necessary, with the use of stabilometric and kinematic posture assessments.
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Oclusión Dental , Maloclusión , Humanos , Adulto , Marcha , Postura , Posición de Pie , Equilibrio PosturalRESUMEN
The role of the microbiome in the pathogenesis and treatment of asthma is significant. The purpose of this article is to show the interplay between asthma and the microbiome, and main areas that require further research are also highlighted. The literature search was conducted using the PubMed database. After a screening process of studies published before May 2023, a total of 128 articles were selected in our paper. The pre-treatment bronchial microbiome in asthmatic patients plays a role in their responsiveness to treatment. Gut microbiota and its dysbiosis can contribute to immune system modulation and the development of asthma. The association between the microbiome and asthma is complex. Further research is necessary to clarify which factors might moderate that relationship. An appropriate gut microbiome and its intestinal metabolites are a protective factor for asthma development. Prebiotics and certain dietary strategies may have a prophylactic or therapeutic effect, but more research is needed to establish final conclusions. Although the evidence regarding probiotics is ambiguous, and most meta-analyses do not support the use of probiotic intake to reduce asthma, several of the most recent studies have provided promising effects. Further studies should focus on the investigation of specific strains and the examination of their mechanistic and genetic aspects.
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Amphotericin B (AmB) is a life-saving and widely used antifungal antibiotic, but its therapeutic applicability is limited due to severe side effects. Here, we report that the formulation of the drug based on a complex with albumin (BSA) is highly effective against Candida albicans at relatively low concentrations, which implies lower toxicity to patients. This was also concluded based on the comparison with antifungal activities of other popular commercial formulations of the drug, such as Fungizone and AmBisome. Several molecular spectroscopy and imaging techniques, e.g., fluorescence lifetime imaging microscopy (FLIM), were applied to understand the phenomenon of enhanced antifungal activity of the AmB-BSA complex. The results show that the drug molecules bound to the protein remain mostly monomeric and are most likely bound in the pocket responsible for the capture of small molecules by this transport protein. The results of molecular imaging of single complex particles indicate that in most cases, the antibiotic-protein stoichiometry is 1:1. All of the analyses of the AmB-BSA system exclude the presence of the antibiotic aggregates potentially toxic to patients. Cell imaging shows that BSA-bound AmB molecules can readily bind to fungal cell membranes, unlike drug molecules present in the aqueous phase, which are effectively retained by the cell wall barrier. The advantages and prospects of pharmacological use of AmB complexed with proteins are discussed.
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Anfotericina B , Antifúngicos , Antifúngicos/farmacología , Antifúngicos/química , Anfotericina B/farmacología , Anfotericina B/química , Candida albicans , Albúminas , Antibacterianos/farmacologíaRESUMEN
BACKGROUND This report describes a 63-year-old Polish man presenting with COVID-19 (Coronavirus Disease 2019) pneumonia in early 2020, before vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were available. Nine weeks following recovery from the initial infection, he tested positive again for SARS-CoV-2. CASE REPORT Man, age 63, was admitted to the Military Institute of Medicine on March 12, 2020, with body temperature 40°C, a cough, and breathlessness. On March 12, 2020, SARS-CoV-2 RNA was found in a nasopharynx smear. A chest X-ray (RTG) showed discrete areas of interstitial densities. On June 13, 2020, after 32 days of hospitalization and 2 negative real-time polymerase chain rection (RT-PCR) test results, patient was released home in good general condition. On July 23, 2020 he reported to the emergency room with fever of 39°C and general weakness. A nasopharynx smear confirmed SARS-CoV-2 infection. On admission, the patient was in moderately good condition with auscultatory changes typical for pneumonia on both sides of the chest. On the seventh day of hospitalization, the patient was transported to the Intensive Care Unit (ICU) due to drastic deterioration in respiratory function. Respiratory support with non-invasive high-flow oxygen therapy (Opti-Flow) was used. On August 20, 2020, after negative RT-PCR test results, he was discharged in good general condition. CONCLUSIONS This case of COVID-19 pneumonia presented early in the COVID-19 pandemic of 2020, and the laboratory diagnosis of the initial and subsequent SARS-CoV-2 infection relied on the laboratory methods available at that time. However, several cases of repeat SARS-CoV-2 infection have been described before the development of vaccines in late 2020.
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COVID-19 , Neumonía , Hospitalización , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía/diagnóstico , ARN Viral , Reinfección , SARS-CoV-2 , Estados UnidosRESUMEN
Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive method in oncological diagnosis. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of systemic cancers?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). Changes in salivary metabolome were most commonly determined in patients with breast cancer, gastrointestinal cancers, and lung cancer. Most studies involved unstimulated whole saliva as the diagnostic material, evaluated by different spectroscopic methods. Among the found saliva metabolites, the alterations in the metabolic pathways of amino acids and polyamines were most frequently observed, which showed significant predictive values in oncological diagnostics. The most frequently encountered risks of bias were the absence of data regarding blinding, sample size justification, and randomisation. In conclusion, salivary metabolites seem to be potentially reliable for detecting the most common systemic cancers. However, further research is desirable to confirm these outcomes and to detect new potential metabolic biomarkers in saliva.
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(1) Background: There is a constant search for new prognostic factors that would allow us to accurately determine the prognosis, select the type of treatment, and monitor the patient diagnosed with uveal melanoma in a minimally invasive and easily accessible way. Therefore, we decided to evaluate the prognostic role of its pigmentation in a clinical assessment. (2) Methods: The pigmentation of 154 uveal melanomas was assessed by indirect ophthalmoscopy. Two groups of tumours were identified: amelanotic and pigmented. The statistical relationships between these two groups and clinical, pathological parameters and the long-term survival rate were analyzed. (3) Results: There were 16.9% amelanotic tumours among all and they occurred in younger patients (p = 0.022). In pigmented melanomas, unfavourable prognostic features such as: epithelioid cells (p = 0.0013), extrascleral extension (p = 0.027), macronucleoli (p = 0.0065), and the absence of BAP1 expression (p = 0.029) were statistically more frequently observed. Kaplan−Meier analysis demonstrated significantly better overall (p = 0.017) and disease-free (p < 0.001) survival rates for patients with amelanotic tumours. However, this relationship was statistically significant for lower stage tumours (AJCC stage II), and was not present in larger and more advanced stages (AJCC stage III). (4) Conclusions: The results obtained suggested that the presence of pigmentation in uveal melanoma by indirect ophthalmoscopy was associated with a worse prognosis, compared to amelanotic lesions. These findings could be useful in the choice of therapeutic and follow-up options in the future.
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Ciprofloxacin is a chemotherapeutic agent mainly used in the treatment of the pulmonary and urinary tract infections but is also known for its anticancer properties. The aim of these study was to check the anticancer effect of ciprofloxacin on selected five cell lines. Human non-small cell lung cancer line A549, human hepatocellular carcinoma line HepG2, human and mouse melanoma lines (A375.S2 and B16) and rat glioblastoma line C6 were used for evaluation of cytotoxic properties of ciprofloxacin (in concentration range: 10-1000 microg/mL). Viability was established using trypan blue assay and MTT. Ciprofloxacin induced morphological changes and decreased viability of A549 cells in a concentration and time dependent manner. In case of A375.S2 and B16 cell lines, cytotoxicyty of ciprofloxacin was observed but we were not able to eradicate all cells from A375.S2 and B16 cultures. HepG2 line was sensitive to ciprofloxacin, but this effect was independent from concentration and incubation time. The C6 cells were insensitive to ciprofloxacin. Our results showed that ciprofloxacin can be potentially used for the experimental adjunctive therapy of lung cancer.
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Ciprofloxacina/farmacología , Neoplasias/patología , Animales , Antineoplásicos/farmacología , Neoplasias Encefálicas/patología , Carcinoma Hepatocelular/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Forma de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glioblastoma/patología , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Melanoma Experimental/patología , Ratones , Ratas , Factores de TiempoRESUMEN
The COVID-19 pandemic has undoubtedly affected education at all levels, including medical and dental education. Our study aimed to assess the effectiveness of the blended learning in conservative dentistry with endodontics. The students had theoretical classes in a remote form (using the e-learning portal and Teams communicator) and practical classes with the participation of patients in the appropriate sanitary regime. The author's survey was conducted among fourth-year dental students. The online questionnaire consisted of 5 parts: self-evaluation, evaluation of theoretical e-learning classes, evaluation of practical clinical classes, evaluation of safety, and evaluation of performed blended learning. The majority of respondents declared that their learning effectiveness increased during the pandemic. Most surveyed students preferred remote learning in asynchronous form (e-learning portals) to synchronous form (virtual meetings in real-time). All respondents described the provided personal protective equipment as sufficient or even as excessive. Our students were very satisfied with the proposed blended-learning model and would like to continue it even after the pandemic has ended. Among the advantages, they particularly mentioned the increase in efficiency and the individualised pace of learning, while the disadvantage was the limitation of social contacts. The appropriate use of modern technology can effectively revolutionise dental education.
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COVID-19 , Educación a Distancia , Endodoncia , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Pyrethroids are chemical insecticides that are widely used to control pests. Entomopathogenic fungi are considered environmentally safe alternatives to these compounds. Pyrethroids and entomopathogenic fungi not only co-exist in the environment but can also be applied together in pest control. They are often found in contact with each other, and thus, it seems important to understand their interactions at the cellular level. In this study, we analyzed whether pyrethroids could influence the phospholipid profile of Beauveria bassiana and whether membrane changes are one of the mechanisms by which these fungi adapt to unfavorable environmental conditions. The results of our study revealed that pyrethroids changed the phospholipid profile and increased the cell membrane permeability of B. bassiana, which enabled them to enter and accumulate within the fungal cells, resulting in oxidative stress. Pyrethroids influenced the amount of neutral lipids, caused a decrease in sodium content, and also temporarily lowered the level of the secondary metabolite oosporein in the studied fungi. These findings indicate that the effect of pyrethroids on entomopathogenic fungi may be more complex than originally thought and that lipidomic studies can aid in fully understanding the influence of these chemicals on the mentioned group of fungi.
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Beauveria/efectos de los fármacos , Piretrinas/efectos adversos , Beauveria/metabolismo , Agentes de Control Biológico , Permeabilidad de la Membrana Celular/efectos de los fármacos , Insecticidas/efectos adversos , Lipidómica , Estrés Oxidativo , Fosfolípidos/metabolismoRESUMEN
Not required for Clinical Vignette.