Pharmacological and phytochemical insights on the pancreatic ß-cell modulation by Angelica L. roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica roots are a significant source of traditional medicines for various cultures around the northern hemisphere, from indigenous communities in North America to Japan. Among its many applications, the roots are used to treat type 2 diabetes mellitus; however, this application is not mentioned often. Ethnopharmacological studies have reported the use of A. japonica var. hirsutiflora, A. furcijuga, A. shikokiana, and A. keiskei to treat diabetes symptoms, and further reports have demonstrated the three angelica roots, i.e., A. japonica var. hirsutiflora, A. reflexa, and A. dahurica, exhibit insulin secretagogue activity. AIM OF THE STUDY: This study aimed to phytochemically characterize and compare angelica roots monographed in the European Pharmacopeia 11th, isolate major plant metabolites, and assess extracts and isolates' capability to modulate pancreatic ß-cell function. MATERIALS AND METHODS: Root extracts of Angelica archangelica, Angelica dahurica, Angelica biserrata, and Angelica sinensis were phytochemically profiled using liquid chromatography method coupled with mass spectrometry. Based on this analysis, simple and furanocoumarins were isolated using chromatography techniques. Extracts (1.6-50 µg/mL) and isolated compounds (5-40 µmol/L) were studied for their ability to modulate insulin secretion in the rat insulinoma INS-1 pancreatic ß-cell model. Insulin was quantified by the homogeneous time-resolved fluorescence method. RESULTS: Forty-one secondary metabolites, mostly coumarins, were identified in angelica root extracts. A. archangelica, A. dahurica, and A. biserrata root extracts at concentration of 12.5-50 µg/mL potentiated glucose-induced insulin secretion, which correlated with their high coumarin content. Subsequently, 23 coumarins were isolated from these roots and screened using the same protocol. Coumarins substituted with the isoprenyl group were found to be responsible for the extracts' insulinotropic effect. CONCLUSIONS: Insulinotropic effects of three pharmacopeial angelica roots were found, the metabolite profiles and pharmacological activities of the roots were correlated, and key structures responsible for the modulation of pancreatic ß-cell function were identified. These findings may have implications for the traditional use of angelica roots in treating diabetes. Active plant metabolites may also become lead structures in the search for new antidiabetic treatments.

Processivity and specificity of histone acetylation by the male-specific lethal complex.

Acetylation of lysine 16 of histone H4 (H4K16ac) stands out among the histone modifications, because it decompacts the chromatin fiber. The metazoan acetyltransferase MOF (KAT8) regulates transcription through H4K16 acetylation. Antibody-based studies had yielded inconclusive results about the selectivity of MOF to acetylate the H4 N-terminus. We used targeted mass spectrometry to examine the activity of MOF in the male-specific lethal core (4-MSL) complex on nucleosome array substrates. This complex is part of the Dosage Compensation Complex (DCC) that activates X-chromosomal genes in male Drosophila. During short reaction times, MOF acetylated H4K16 efficiently and with excellent selectivity. Upon longer incubation, the enzyme progressively acetylated lysines 12, 8 and 5, leading to a mixture of oligo-acetylated H4. Mathematical modeling suggests that MOF recognizes and acetylates H4K16 with high selectivity, but remains substrate-bound and continues to acetylate more N-terminal H4 lysines in a processive manner. The 4-MSL complex lacks non-coding roX RNA, a critical component of the DCC. Remarkably, addition of RNA to the reaction non-specifically suppressed H4 oligo-acetylation in favor of specific H4K16 acetylation. Because RNA destabilizes the MSL-nucleosome interaction in vitro we speculate that RNA accelerates enzyme-substrate turn-over in vivo, thus limiting the processivity of MOF, thereby increasing specific H4K16 acetylation.

Genetic, clinical and imaging implications of a noncompaction phenotype population with preserved ejection fraction.

Introduction: The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF. Methods: We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered "red flags". Results: Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found. Discussion: The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography. The aspects of right ventricular volumes and function investigated with 3D echocardiography in a large cohort of left ventricular noncompaction morphology (LVNC) population remains unclear. The objective of our research was to study the left (LV) and right (RV) ventricular parameters using 3D echocardiography and analyze the clinical features of a LVNC population with preserved LV ejection fraction (EF > 50 %) in comparison with healthy controls (HC). We selected 41 LVNC subjects with preserved LV function (EF: 52.91 ± 3 %, male n = 26) and without any comorbidities and compared them with an age and sex-matched HC. Three dimensional endocardial contours were evaluated to determine the following LV and RV parameters: end-diastolic (EDV) and end-systolic (ESV) volumes, stroke volume, EF, LV global longitudinal and circumferential strain and RV septal and free wall longitudinal strain. Regarding the clinical characteristics, the family involvement had a notable proportion, accounting for 51%. The EF and strain values of the LVNC population were significantly decreased in both RV and LV compared to HC. Although the LV volumes of the LVNC group were significantly elevated, the RV volumetric parameters did not differ significantly compared to controls. We found significant correlations between LV and RV volumetric and functional parameters and linear regression models showed that LV EDV and LV ESV determined the RV volumetric values. While the alteration and relationship of the RV parameters may represent the potential of biventricular involvement, clinical characteristics of the LVNC group underlines the necessity of monitoring this population, even with preserved EF.

Evaluation of the reliability and educational quality of YouTube™ videos on sport nutrition topics.

BACKGROUND: YouTube is one of the most widespread social media channels, which is of growing importance in science communication and health education. The validity of medical and health-related information available on YouTube cannot be assured, and videos often contain potentially misleading or inaccurate information. Communication on sport nutrition may have a profound effect on the change in nutrition behavior among athletes, so evidence-based nutrition information must reach athletes. The main goal of the research is to evaluate the quality, reliability, and applicability of sports nutrition YouTube videos as educational material for athletes. METHODS: A descriptive cross-sectional design was applied, and a systematic search was performed on YouTube. The quality and reliability of the videos were evaluated by applying the most frequently used and highly reliable scoring systems in the literature (e.g., DISCERN, Global Quality Score, and JAMA criteria) and a sports nutrition-specific scoring system (SNSS). Descriptive statistical analyses, two-sample t-test, Spearman correlation, Kruskal - Wallis, and Mann - Whitney U test were used to evaluate the results. A total of 114 YouTube videos met the inclusion criteria. RESULTS: In 25% of the videos, the sports nutrition information was presented by a dietitian, while in two-thirds, coaches and athletes and other professionals shared sports nutrition knowledge. In terms of video content, the three most common topics were nutrition and health (33%), special diets (21%), and the training diet (17%). For the majority of the videos that received low GQS, JAMAS, DISCERN, and SNSS scores, the accuracy and quality of the analyzed YouTube videos on sports nutrition were inadequate. Videos uploaded by dietitians achieved significantly higher DISCERN, JAMAS, GQS, and SNSS scores. The GQS, SNSS, and DISCERN scores of videos from sports organizations, nonprofit organizations, and independent user sources were lower compared to videos uploaded by academic and professional organizations. Popular sport nutrition videos among users that contain personal stories or the experiences of athletes were deemed less reliable by experts or showed lower educational quality. Henceforth, we found a negative correlation between video popularity and JAMAS, GQS, and SNSS scores. CONCLUSION: This study revealed that sports nutrition videos on the YouTube video platform show low accuracy and reliability. Professionals working with athletes need to consider misconceptions from sports nutrition videos in their nutrition counseling practice. Due to the popularity of the videos, professionals and professional organizations could use YouTube as an online educational tool to increase the nutrition knowledge of athletes.

Structural basis of RNA-induced autoregulation of the DExH-type RNA helicase maleless.

RNA unwinding by DExH-type helicases underlies most RNA metabolism and function. It remains unresolved if and how the basic unwinding reaction of helicases is regulated by auxiliary domains. We explored the interplay between the RecA and auxiliary domains of the RNA helicase maleless (MLE) from Drosophila using structural and functional studies. We discovered that MLE exists in a dsRNA-bound open conformation and that the auxiliary dsRBD2 domain aligns the substrate RNA with the accessible helicase tunnel. In an ATP-dependent manner, dsRBD2 associates with the helicase module, leading to tunnel closure around ssRNA. Furthermore, our structures provide a rationale for blunt-ended dsRNA unwinding and 3'-5' translocation by MLE. Structure-based MLE mutations confirm the functional relevance of our model for RNA unwinding. Our findings contribute to our understanding of the fundamental mechanics of auxiliary domains in DExH helicase MLE, which serves as a model for its human ortholog and potential therapeutic target, DHX9/RHA.

Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts.

Tumors are intricate ecosystems where cancer cells and non-malignant stromal cells, including cancer-associated fibroblasts (CAFs), engage in complex communication. In this study, we investigated the interaction between poorly (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts. We explored various communication channels, including soluble factors, metabolites, extracellular vesicles (EVs), and miRNAs. Co-culture with HLE cells induced LX2 to produce higher levels of laminin ß1, type IV collagen, and CD44, with pronounced syndecan-1 shedding. Conversely, in HuH7/LX2 co-culture, fibronectin, thrombospondin-1, type IV collagen, and cell surface syndecan-1 were dominant matrix components. Integrins α6ß4 and α6ß1 were upregulated in HLE, while α5ß1 and αVß1 were increased in HuH7. HLE-stimulated LX2 produced excess MMP-2 and 9, whereas HuH7-stimulated LX2 produced excess MMP-1. LX2 activated MAPK and Wnt signaling in hepatoma cells, and conversely, hepatoma-derived EVs upregulated MAPK and Wnt in LX2 cells. LX2-derived EVs induced over tenfold upregulation of SPOCK1/testican-1 in hepatoma EV cargo. We also identified liver cancer-specific miRNAs in hepatoma EVs, with potential implications for early diagnosis. In summary, our study reveals tumor type-dependent communication between hepatoma cells and fibroblasts, shedding light on potential implications for tumor progression. However, the clinical relevance of liver cancer-specific miRNAs requires further investigation.

Characteristics of the right ventricle in left ventricular noncompaction with reduced ejection fraction in the light of dilated cardiomyopathy.

BACKGROUND: Reports of left ventricular noncompaction (LVNC) rarely include descriptions of the right ventricle (RV). This study aimed to describe the characteristics of the RV in LVNC patients with reduced LV function (LVNC-R) compared with patients with dilated cardiomyopathy (DCM) and subjects with LVNC with normal left ventricular ejection fraction (LV-EF) (LVNC-N). METHODS: Forty-four LVNC-R patients, 44 LVNC-N participants, and 31 DCM patients were included in this retrospective study (LV-EF: LVNC-R: 33.4±10.2%; LVNC-N: 65.0±5.9%; DCM: 34.6±7.9%). Each group was divided into two subgroups by the amount of RV trabeculation. RESULTS: There was no difference in the RV-EF between the groups, and the RV trabecular mass correlated positively with the RV volume and negatively with the RV-EF in all the groups. All the measured parameters were comparable between the groups with decreased LV function. The hypertrabeculated RV subgroups showed significantly higher RV volumes and lower RV-EF only in the decreased-LV-function groups. The correlation of LV and RV trabeculation was observed only in the LVNC-N group, while LV trabeculation correlated with RV volumes in both noncompacted groups. Both decreased-LV-function groups had worse RV strain values than the LVNC-N group; however, RV strain values correlated with RV trabeculation predominantly in the LVNC-R group. CONCLUSIONS: The presence and characteristics of RV hypertrabeculation and the correlations between LV trabeculation and RV parameters raise the possibility of RV involvement in noncompaction; moreover, RV strain values might be helpful in the early detection of RV function deterioration.

[Thromboembolic complications associated to malignant diseases]. / A malignus betegségekhez társuló tromboembóliás szövodmények.

Cancers are known to increase the tendency for thrombosis, both on the venous and arterial side, which to this day is an important factor in the management of oncology patients. Malignant disease is an independent risk factor for developing venous thromboembolism (VTE). Thromboembolic complications in addition to the disease worsen prognosis and are accompanied by significant morbidity and mortality. VTE is the second most common cause of death in cancer after disease progression. Tumors are characterized by hypercoagulability, in addition to which venous stasis and endothelial damage also occur in cancer patients promoting increased clotting. Treatment of cancer-associated thrombosis is often complex; therefore, it is important to identify patients who benefit from primary thromboprophylaxis. The importance of cancer-associated thrombosis is indisputable in everyday oncology. We briefly summarize the frequency and characteristics of their occurrence, the underlying mechanisms, risk factors, clinical appearance, laboratory diagnostics, and the possibilities of prevention and treatment.

BMP-induced non-canonical signaling is upregulated during autophagy-mediated regeneration in inflamed mesothelial cells.

Previously, we showed that after Freund's adjuvant-induced peritonitis, rat mesothelial cells regain their epithelial phenotype through mesenchymal-epithelial transition (MET) accompanied by autophagy. Since bone morphogenetic proteins (BMPs) are well-known MET-inducers, we were interested in the potential expression of BMPs and BMP-induced pathways. Although mesothelial cells expressed lower amounts of BMP7, its level in the peritoneal cavity and mesothelial synthesis of BMP4 were significantly increased during inflammation. BMPR1A and BMPR2 were also significantly expressed. Expression of transforming growth factor beta-activated kinase (TAK1) and c-Jun NH2-terminal kinases (JNK1-JNK2) were more intense than that of phosphorylated Mothers Against Decapentaplegic homolog 1/5 (p-SMAD1/5), confirming that the non-canonical pathway of BMPs prevailed in our model. JNK signaling through B-cell lymphoma-2 (Bcl-2) can contribute to Beclin-1 activation. We demonstrated that TAK1-JNK-Bcl-2 signaling was upregulated simultaneously with the autophagy-mediated regeneration. A further goal of our study was to prove the regenerative role of autophagy after inflammation. We used a specific inhibitor, bafilomycin A1 (BafA1), and found that BafA1 treatment decreased the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3B) and resulted in morphological signs of cell death in inflamed mesothelial cells indicating that if autophagy is arrested, regeneration turns into cell death and consequently, mesothelial cells die.

Different methods, different results? Threshold-based versus conventional contouring techniques in clinical practice.

BACKGROUND: The quantitative differences of left and right ventricular (LV, RV) parameters of using different cardiac MRI (CMR) post-processing techniques and their clinical impact are less studied. We aimed to assess the differences and their clinical impact between the conventional contouring (CC) and the threshold-based (TB) methods using 70% and 50% thresholds in different hypertrabeculated conditions. METHODS: This retrospective study included 30 dilated cardiomyopathy, 30 left ventricular non-compaction (LVNC), 30 arrhythmogenic cardiomyopathy patients, 30 healthy athletes and 30 healthy volunteers. All participants underwent CMR imaging on 1.5 T. Cine sequences were used to derive measures of the cardiac volumes, function, total muscle mass (TMi) and trabeculae and papillary muscle mass (TPMi) using CC and TB segmentation methods. RESULTS: Comparing the CC and the 70% and 50% threshold TB methods, the LV and RV volumes were significantly lower, the ejection fraction (EF) and the TMi were significantly higher with the TB methods. Between the two threshold setups, only TPMi was significantly higher with the 70% threshold. Regarding the clinical benefits, the LVNC was the only group in whom all the diagnostic and therapeutic decisions and risk stratification were influenced using the TB method. Diagnostic changes occurred in three-quarters of the population, and all the cardiomyopathy groups were affected regarding the decision-making about pharmaco- and device therapy. CONCLUSIONS: Using the TB method, only TPMi was significantly higher with the 70% threshold than the 50% setup, and both of them differed significantly from the CC technique, with relevant clinical impacts in all patient groups.

Role of Phytohormones in Biomass and Polyphenol Accumulation in Salvia bulleyana In Vitro Culture.

Salvia bulleyana is a plant native to the Chinese Yunnan Province. This species has been used in traditional Chinese medicine as a substitute for Danshen (the roots of Salvia miltiorrhiza). The aim of our study was to establish an effective system for propagating S. bulleyana shoots to obtain large amounts of material rich in bioactive compounds. Phytohormones were used to regulate shoot growth and regeneration potential and influence plant secondary metabolism. The shoot tips were incubated on a Murashige and Skoog agar medium supplemented with 0.1 or 0.5 mg/L IAA (indole-3-acetic acid) and the cytokinins benzylaminopurine (BAP), meta-topoline (M-T), 6-benzylaminopurine riboside (RBAP), N-benzyl-9-(2-tetrahydropyranyl)-adenine (BPA) or kinetin, (K) at concentrations of 0.5, 1 or 2 mg/L. It was observed that the type and concentration of growth regulator significantly influenced the regeneration potential of S. bulleyana shoots. The highest multiplication rate was obtained when 0.1 mg/L IAA and 2 mg/L BPA were used. Under these conditions, 100% of shoot tips formed buds and almost seven buds/shoot per explant were obtained after five weeks. Meanwhile, the highest biomass was found for shoots growing on a medium supplemented with 0.1 mg/L IAA and 1 mg/L M-T: 1.2 g of fresh weight and 0.17 g of dry weight. However, a medium with 0.1 mg/L IAA and 2 mg/L RBAP was most favorable for bioactive phenolic acid content, with a total polyphenol level (37.7 mg/g dw) 4.5 times higher than in shoots grown on medium without growth regulators (8.23 mg/g dw). Finally, optimal conditions were selected by TOPSIS (technique for order of preference by similarity to the ideal solution); the culture of S. bulleyana grown on an MS medium containing 0.1 mg/L IAA and 1 mg/L M-T was found to be the most efficient for polyphenol accumulation and can be used for the production of medicinally relevant compounds.

Bio-Guided Isolation of Compounds from Fraxinus excelsior Leaves with Anti-Inflammatory Activity.

Inflammation is the first physiological defence mechanism against external and internal stimuli. The prolonged or inappropriate response of the immune system may lead to the persistent inflammatory response that can potentially become a basis for chronic diseases e.g., asthma, type II diabetes or cancer. An important role in the alleviation of inflammatory processes, as an adjunct to traditional pharmacological therapy, is attributed to phytotherapy, especially to raw materials with a long tradition of use, e.g., ash leaves. Despite their long-term use in phytotherapy, the specific mechanisms of action have not been confirmed in a sufficient number of biological or clinical studies. The aim of the study is a detailed phytochemical analysis of infusion and its fractions, isolation of pure compounds from the leaves of Fraxinus excelsior and evaluation of their effect on the secretion of anti-inflammatory cytokines (TNF-α, IL-6) and IL-10 receptor expression in an in vitro model of monocyte/macrophage cells isolated from peripheral blood. Methods: Phytochemical analysis was carried out by the UHPLC-DAD-ESI-MS/MS method. Monocytes/macrophages were isolated from human peripheral blood using density gradient centrifugation on Pancoll. After 24 h incubation with tested fractions/subfractions and pure compounds, cells or their supernatants were studied, respectively, on IL-10 receptor expression by flow cytometry and IL-6, TNF-α, IL-1ß secretion by the ELISA test. Results were presented with respect to Lipopolysaccharide (LPS) control and positive control with dexamethasone. Results: The infusion, 20% and 50% methanolic fractions and their subfractions, as well as their dominating compounds, e.g., ligstroside, formoside and oleoacteoside isolated from the leaves, show the ability to increase the IL-10 receptor expression on the surface of monocyte/macrophage cells, stimulated by LPS, and to decrease the secretion of pro-inflammatory cytokines, e.g., TNF-α, IL-6.

Constituents of Pulicaria inuloides and Cytotoxic Activities of Two Methoxylated Flavonols.

Plants of the genus Pulicaria are known for providing traditional medicines, spices, herbal teas, and insect deterrents. Pulicaria inuloides (Poir.). DC. is one of the less chemically studied species within the genus. Hydroalcoholic extracts from roots and aerial parts of P. inuloides were analyzed using the UHPLC-PAD-MSn technique and revealed the presence of six caffeoylquinic and eleven caffeoylhexaric conjugates together with hydroxykaempferol dimethyl ether and quercetagetin trimethyl ether. Moreover, constituents of chloroform extract from the whole P. inuloides plants were isolated and identified by spectroscopic methods. One new and four known caryophyllene derivatives, three thymol derivatives, and four polymethoxylated flavonols were found in the analyzed extract. The structure of the new compound was established by spectroscopic methods (HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY). The cytotoxicity of 6-Hydroxykaempferol 3,7-dimethyl ether and quercetagetin 3,7,3'-trimethyl ether (chrysosplenol C), which are major flavonols isolated from the plant, were tested on prostate epithelial cells (PNT2), prostate cancer cells (DU145 and PC3), human keratinocytes (HaCaT), and melanoma cells (HTB140 and A375). Both flavonols demonstrated moderate cytotoxic activity against PC3 cells (IC50 = 59.5 µM and 46.6 µM, respectively). The remaining cell lines were less affected (IC50 > 150 µM).

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

LC-DAD-ESI-MS/MS and NMR Analysis of Conifer Wood Specialized Metabolites.

Many species from the Pinaceae family have been recognized as a rich source of lignans, flavonoids, and other polyphenolics. The great common occurrence of conifers in Europe, as well as their use in the wood industry, makes both plant material and industrial waste material easily accessible and inexpensive. This is a promising prognosis for both discovery of new active compounds as well as for finding new applications for wood and its industry waste products. This study aimed to analyze and phytochemically profile 13 wood extracts of the Pinaceae family species, endemic or introduced in Polish flora, using the LC-DAD-ESI-MS/MS method and compare their respective metabolite profiles. Branch wood methanolic extracts were phytochemically profiled. Lignans, stilbenes, flavonoids, diterpenes, procyanidins, and other compounds were detected, with a considerable variety of chemical content among distinct species. Norway spruce (Picea abies (L.) H.Karst.) branch wood was the most abundant source of stilbenes, European larch (Larix decidua Mill.) mostly contained flavonoids, while silver fir (Abies alba Mill.) was rich in lignans. Furthermore, 10 lignans were isolated from the studied material. Our findings confirm that wood industry waste materials, such as conifer branches, can be a potent source of different phytochemicals, with the plant matrix being relatively simple, facilitating future isolation of target compounds.

Time perception at resting state and during active motion: The role of anxiety and depression.

BACKGROUND: Time perception and motion intensity are interrelated factors that may influence symptom expression and severity in case of various psychiatric conditions, including anxiety and depression. AIMS: The present study aimed to 1) explore the associations between the intensity of physical activity, time perception, impulsivity, anxiety and depressive symptoms, and to 2) investigate the extent to which resting state motion intensity can be used to identify the assessed psychiatric conditions. METHODS: 20 healthy controls and 20 psychiatric patients (with either anxiety or depression-related diagnoses) were included in the study and filled out a questionnaire consisting of validated anxiety, depression and impulsivity measures. Time perception was measured by a computerized time production task, whereas motion intensity was analyzed by a motion capture and analysis software. Respondents were randomly assigned to an experimental (with active motion task) and non-experimental group (resting state conditions). Both subgroups were repeatedly assessed, in order to explore changes in motion intensity, time perception and psychiatric symptom levels. RESULTS: Random forest regression analysis identified the level of impulsivity, depression and anxiety as the strongest predictors of resting state motion intensity, while a path analysis model indicated that controls and psychiatric patients show different pathways regarding the connection between motion intensity changes, time production ratio alterations and symptom reduction. CONCLUSIONS: Our study implies the importance of distinguishing between clinical and subclinical severity of psychiatric symptoms when considering the association between motion intensity, time perception, anxiety and depression. Potential transdiagnostic relevance of resting state motion intensity is also addressed.

Extraction Techniques and Analytical Methods for Isolation and Characterization of Lignans.

Lignans are a group of natural polyphenols present in medicinal plants and in plants which are a part of the human diet for which more and more pharmacological activities, such as antimicrobial, anti-inflammatory, hypoglycemic, and cytoprotective, are being reported. However, it is their cytotoxic activities that are best understood and which have shed light on this group. Two anticancer drugs, etoposide, and teniposide, were derived from a potent cytotoxic agent-podophyllotoxin from the roots of Podophyllum peltatum. The evidence from clinical and observational studies suggests that human microbiota metabolites (enterolactone, enterodiol) of dietary lignans (secoisolariciresinol, pinoresinol, lariciresinol, matairesinol, syringaresinol, medioresinol, and sesamin) are associated with a reduced risk of some hormone-dependent cancers. The biological in vitro, pharmacological in vivo investigations, and clinical studies demand significant amounts of pure compounds, as well as the use of well-defined and standardized extracts. That is why proper extract preparation, optimization of lignan extraction, and identification are crucial steps in the development of lignan use in medicine. This review focuses on lignan extraction, purification, fractionation, separation, and isolation methods, as well as on chromatographic, spectrometric, and spectroscopic techniques for their qualitative and quantitative analysis.

Cardiorespiratory fitness status of elite handball referees in Hungary.

In various team sports, such as handball, referees work on the court by continuously moving with the players. Therefore, their physical fitness also has an impact on their reaction time, which could affect their professional decisions. The cardiorespiratory fitness status of healthy Hungarian elite handball referees was examined via body composition analysis and vita maxima cardiopulmonary exercise testing with lactate measurements. One hundred referees were examined (age: 29.0 ± 7.9 years; male: 64.0%; training: 4.3 ± 2.0 hours/week; ratio of former elite handball players: 39.0%; 51.0% first and 49.0% second division referees of the Hungarian National Handball Leagues). A resting heart rate (HR) of 79.0 ± 12.6 BPM was measured. On the basis of the body composition analysis the fat-free mass index proved to be 19.9 ± 2.6 kg/m2. The referees achieved a maximal oxygen uptake (V̇O2max) of 44.6 ± 6.1 ml/kg/min, with a maximal HR of 187.2 ± 11.1 BPM (which was 98.1 ± 4.6% of their calculated maximal HR) and a peak lactate of 9.2 ± 3.2 mmol/l at 557.1 ± 168.3 sec on our continuous speed, increasing slope treadmill protocol. Second division referees were younger, on a weekly average they trained more, achieved higher treadmill exercise time (respectively, 463.8 ± 131.9 vs 658.4 ± 143.9 sec, p < 0.001) and anaerobic threshold time (respectively, 265.8 ± 100.9 vs 348.2 ± 117.1 sec, p < 0.001), while the two different divisional referees had similar V̇O2max values. Regarding our physical fitness measurements, huge individual differences were observed between the referees (exercise time range: 259.0-939.0 sec, V̇O2max range: 25.3-62.4 ml/kg/min). Since it can affect their performance as referees, individual training planning, regular physical fitness measurements, and strict selection methods are suggested.