Due to its great medical and pharmaceutical importance, honey bee venom is considered to be well characterized both chemically and in terms of biomedical activity. However, this study shows that our ...knowledge of the composition and antimicrobial properties of
venom is incomplete. In this work, the composition of volatile and extractive components of dry and fresh bee venom (BV) was determined by GC-MS, as well as antimicrobial activity against seven types of pathogenic microorganisms. One-hundred and forty-nine organic C
-C
compounds of different classes were found in the volatile secretions of the studied BV samples. One-hundred and fifty-two organic C
-C
compounds were registered in ether extracts, and 201 compounds were identified in methanol extracts. More than half of these compounds are new to BV. In microbiological tests involving four species of pathogenic Gram-positive and two species of Gram-negative bacteria, as well as one species of pathogenic fungi, the values of the minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were determined for samples of dry BV, as well as ether and methanol extracts from it. Gram-positive bacteria show the greatest sensitivity to the action of all tested drugs. The minimum MIC values for Gram-positive bacteria in the range of 0.12-7.63 ng mL
were recorded for whole BV, while for the methanol extract they were 0.49-125 ng mL
. The ether extracts had a weaker effect on the tested bacteria (MIC values 31.25-500 ng mL
). Interestingly,
was more sensitive (MIC 7.63-500 ng mL
) to the action of bee venom compared to
(MIC ≥ 500 ng mL
). The results of the tests carried out indicate that the antimicrobial effect of BV is associated with the presence of not only peptides, such as melittin, but also low molecular weight metabolites.
The vegetation of the Canary Islands is characterized by a large number of endemic species confined to different altitudinal levels. It can be assumed that these circumstances determine the ...characteristic features of the chemical composition of local beekeeping products, including propolis. We report, for the first time, the chemical composition of propolis from Tenerife (Canary Islands). The volatile emissions of three propolis samples collected from different apiaries are represented by 162 C
-C
compounds, of which 144 were identified using the HS-SPME/GC-MS technique. The main group of volatiles, consisting of 72 compounds, is formed by terpenoids, which account for 42-68% of the total ion current (TIC) of the chromatograms. The next most numerous groups are formed by C
-C
alkanes and alkenes (6-32% TIC) and aliphatic C
-C
carbonyl compounds (7-20% TIC). The volatile emissions also contain C
-C
aliphatic acids and C
-C
alcohols, as well as their esters. Peaks of 138 organic C
-C
compounds were recorded in the chromatograms of the ether extracts of the studied propolis. Terpene compounds form the most numerous group, but their number and content in different samples is within very wide limits (9-63% TIC), which is probably due to the origin of the samples from apiaries located at different altitudes. A peculiarity of the chemical composition of the extractive substances is the almost complete absence of phenylcarboxylic acids and flavonoids, characteristic of
propolis from different regions of Eurasia and North America. Aromatic compounds of propolis from Tenerife are represented by a group of nine isomeric furofuranoid lignans, as well as alkyl- and alkenyl-substituted derivatives of salicylic acid and resorcinol.
Machine learning models predicting the bioactivity of chemical compounds belong nowadays to the standard tools of cheminformaticians and computational medicinal chemists. Multi-task and federated ...learning are promising machine learning approaches that allow privacy-preserving usage of large amounts of data from diverse sources, which is crucial for achieving good generalization and high-performance results. Using large, real world data sets from six pharmaceutical companies, here we investigate different strategies for averaging weighted task loss functions to train multi-task bioactivity classification models. The weighting strategies shall be suitable for federated learning and ensure that learning efforts are well distributed even if data are diverse. Comparing several approaches using weights that depend on the number of sub-tasks per assay, task size, and class balance, respectively, we find that a simple sub-task weighting approach leads to robust model performance for all investigated data sets and is especially suited for federated learning.
Tinea gladiatorum (TG) is a fungal skin infection that occurs among wrestlers and other contact sport athletes with a varied prevalence rate. The most common causative factor responsible as well for ...local outbreaks of the infection is an anthropophilic dermatophyte species—Trichophyton tonsurans (T. tonsurans). The purpose of this study was to gather current data about TG, including epidemiology, possible diagnosing methods, clinical features, treatment approaches, and potential prevention techniques. We also performed a systematic review of studies describing TG incidence. The prevalence of the disease varied from 2.4% up to 100%. That wide range of variability forces medical practitioners to update knowledge about TG and points to the fact that it still may be a diagnostic and therapeutic challenge. Spreading awareness among athletes and trainers is one of the most important preventive steps.
Psoriasis (Ps) is a chronic, inflammatory skin disease characterized by thickened, red and scaly plaques. Systemic inflammation associated with psoriasis results in an increased risk of death due to ...the development of psoriasis-associated comorbidities such as cardiovascular disease (CVD) and metabolic syndrome. Although the cardiometabolic features in psoriasis are clinically well described, the underlying molecular mechanisms linking these comorbidities remain poorly understood. Generation of induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells (PBMCs) and skin fibroblasts (SFs) of psoriatic patients provides a novel approach to investigate the pathway by which cutaneous inflammation promotes CV complications in this disorder.
Hand eczema (HE) is a frequent chronic inflammatory dermatosis. Itch and pain are considered two of the most common and burdensome symptoms of the disease. Yet, the data related to these symptoms are ...still limited. The aim of this study was to evaluate characteristics of itch and pain in adults suffering from HE.
The study group comprised 100 adult HE patients. An original questionnaire designed by the authors was used to survey the patients. It included questions regarding demographic characteristics such as the duration of the disease, exacerbation count, past diagnostics and treatment, as well as atopic predispositions. Additionally, the itch and pain intensity (numerical rating scale-NRS) during '3 days prior to the study' and the 'entire disease' period was implemented. The clinical assessment of the disease severity was performed according to two specific measurement instruments: Investigator Global Assessment for Chronic Hand Eczema (IGA-CHE) scale and Hand Eczema Severity Index (HECSI). To assess patient quality of life (QoL), the DLQI tool was used and to determine the level of stigmatization and for its impact on patients' life the 6-Item Stigmatization Scale (6-ISS) was employed.
Within the period of 3 days prior to the examination, itch was reported by 81.0% of patients (
= 81), whereas 53.0% (
= 53) of them experienced pain. Both symptoms were reported more frequently in females (itch:
= 0.022; pain:
= 0.033). When sexes were compared, females reached higher scores in both IGA-CHE and HECSI. Itch and pain intensity correlated positively with disease severity. The intensity of itch and pain significantly influences HE patients' QoL. A positive correlation between the 6-ISS score and the intensity of itch in the 'last 3 days' period was revealed (r = 0.221;
= 0.027).
Itch and pain are common symptoms in HE patients, significantly contributing to the feeling of stigmatization. Providing characteristics of itch and pain may improve HE management. Symptom-decreasing treatment would definitely have a positive influence on patients' well-being.
Atopic dermatitis (AD) is characterized by exacerbations and remissions of eczematous skin, underlain by impaired skin barrier and aberrant Th2-type and Th-22 cytokine production. A number of ...allergens, in particular contact with fur animals, may aggravate the disease. This study seeks to define the influence of having a regular contact with a pet cat at home on the severity of symptoms and signs of AD. We addressed the issue using the SCORing Atopic Dermatitis (SCORAD) and visual analog (VAS) scores to assess the intensity of pruritus and by measuring the blood content of specific IgE and IL-4, IL-13, and IL-22 cytokines. The study group consisted of 47 adult patients suffering from AD since childhood, 18 of whom declared having regular contact with a cat and the remaining 29 who denied it. There also was a control group consisted of 16 healthy volunteers with no AD signs. The SCORAD and VAS scores were significantly higher in patients in contact with a cat than in those without it (median SCORAD 61.0 vs. 50.4 and VAS 9.0 vs. 4.0 points, respectively). The sIgE of a majority of patients (94.4%) in contact with a cat was in Class V-VI, compared with just a few patients (3.4%) with no such contact, having sIgE in the same classes (p < 0.001). Significant correlations were revealed between SCORAD and VAS scores and the class level of serum sIgE value. In addition, IL-22 was a single elevated cytokine, only in the patients in contact with a cat, and it correlated with pruritus severity. The results of the study underline the need to beware of the cat fur allergen, and they stress forethought and caution in acquiring and keeping a pet cat by patients suffering from AD.
Background: Hand eczema (HE) is a chronic inflammatory disease with a high prevalence, negatively influencing patients’ quality of life (QoL). It may also affect patients’ psychological status. The ...aim of this study was to assess and characterize the psychological burden of HE, its influence on patients’ QoL, and the presence and severity of anxiety and depressive disorders in HE patients. Methods: The study group consisted of 100 adult HE individuals. To assess the severity of the disease, two instruments were used: the Investigator Global Assessment for Chronic Hand Eczema (IGA-CHE) scale and the Hand Eczema Severity Index (HECSI). Assessment of patients’ quality of life (QoL) was obtained with the use of the DLQI tool. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires were employed to assess depression and anxiety, respectively, as well as a modified version of the Hospital Anxiety and Depression Scale (HADS-M). Results: The mean DLQI value for the whole group reached 11.62 ± 6.35 points (13.27 ± 6.67 points in females and 9.15 ± 4.95 points in males; p = 0.023). A decrease in QoL correlated positively with the severity of the disease and the severity of itch and pain. In 17 patients (17%), a possible diagnosis of depressive disorder was found. Patients scoring higher results on the PHQ-9 and HADS-M depression (D) questionnaires reported greater intensity of the itch (r = 0.363, p < 0.001, and r = 0.237, p = 0.017, respectively) and the pain (r = 0.445, p < 0.001, and r = 0.287, p = 0.004, respectively). The anxiety disorder might possibly be diagnosed in 25% of patients (n = 25). This study revealed a positive correlation between the severity of the anxiety symptoms, measured with the use of both GAD-7 and HADS-M anxiety (A) tools, and the intensity of the pain (r = 0.248, p = 0.013, and r = 0.342, p = 0.001, respectively). The severity of depressive and anxiety symptoms correlated positively with the severity of the disease. Conclusions: The psychosocial burden of HE is an undeniable phenomenon. The disorder influences patients’ QoL and may cause mental disturbances such as depression and anxiety disorders.
In a drug discovery setting, pharmaceutical companies own substantial but confidential datasets. The MELLODDY project developed a privacy-preserving federated machine learning solution and deployed ...it at an unprecedented scale. Each partner built models for their own private assays that benefitted from a shared representation. Established predictive performance metrics such as AUC ROC or AUC PR are constrained to unseen labeled chemical space and cannot gage performance gains in unlabeled chemical space. Federated learning indirectly extends labeled space, but in a privacy-preserving context, a partner cannot use this label extension for performance assessment. Metrics that estimate uncertainty on a prediction can be calculated even where no label is known. Practically, the chemical space covered with predictions above an uncertainty threshold, reflects the applicability domain of a model. After establishing a link to established performance metrics, we propose the efficiency from the conformal prediction framework (‘conformal efficiency’) as a proxy to the applicability domain size. A documented extension of the applicability domain would qualify as a tangible benefit from federated learning. In interim assessments, MELLODDY partners reported a median increase in conformal efficiency of the federated over the single-partner model of 5.5% (with increases up to 9.7%). Subject to distributional conditions, that efficiency increase can be directly interpreted as the expected increase in conformal i.e. low uncertainty predictions. In conclusion, we present the first indication that privacy-preserving federated machine learning across massive drug-discovery datasets from ten pharma partners indeed extends the applicability domain of property prediction models.
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The
gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external ...genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA) was impaired, explaining the patient's steroid profile. Abiraterone could not bind and inhibit the 17α-hydroxylase activity of the CYP17A1-V366M mutant. Molecular dynamics (MD) simulations showed that V366M creates a "one-way valve" and suggests a mechanism for dual activities of human CYP17A1 where, after the conversion of pregnenolone to 17OH-pregnenolone, the product exits the active site and re-enters for conversion to dehydroepiandrosterone. The V366M mutant also explained the effectiveness of the anti-prostate cancer drug abiraterone as a potent inhibitor of CYP17A1 by binding tightly at the active site in the WT enzyme. The V366M is the first human mutation to be described at the active site of CYP17A1 that causes isolated 17,20 lyase deficiency. Knowledge about the specificity of CYP17A1 activities is of importance for the development of treatments for polycystic ovary syndrome and inhibitors for prostate cancer therapy.
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