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Background: Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients. Methods: A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data. Results: The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium–glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass. Conclusions: The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.

Background and Objectives: Rheumatoid arthritis (RA) patients experience sarcopenia and decreased muscle mass and handgrip strength, leading to decreased quality of life and disability. The prevalence of RA varies across regions. This study aimed to evaluate the factors associated with RA in Croatian regional centres and explore correlations between clinical parameters and muscle strength. Materials and Methods: Included in this study were 267 stable RA patients from four Croatian clinical centres. The patients’ mean age was 60.4 ± 12.0 years, with 12.7% of them being male. For each study participant, information was gathered on their anthropometric characteristics, clinical and laboratory indicators, quality of life, disease activity, and sociodemographics. Results: The main results showed that in the female RA participants, the significant positive predictors are weight, height, exercise, VAS, and haemoglobin level. The negative predictors are the use of conventional synthetic disease-modifying anti-rheumatic drugs, the use of biological disease-modifying anti-rheumatic drugs, the number of tender joints, the number of swollen joints, the estimated sedimentation rate, the C-reactive protein, the disease activity score, the parameters of the EQ5D, and being prescribed with three or more medications. In the male RA participants, significant predictors of muscle strength are only weight, height, and anxiety/depression difficulties, according to the EQ5D. Conclusions: This study showed correlations between muscle strength and the parameters of disease activity, inflammation parameters, health-related quality of life, therapy, and exercise in the female RA participants in Croatia.

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Abstract The essential oils from the Centaurea genus are well known for their pharmacological properties. The most abundant and dominant chemical components in Centaurea essential oils are ß-caryophyllene, hexadecanoic acid, spathulenol, pentacosane, caryophyllene oxide, and phytol. However, whether these dominant components are the key drivers for observed antimicrobial activity remains unclear. Thus, the aim of this study was dual. Here we provide comprehensive, literature-based data to correlate the chemical compounds in Centaurea essential oils with the tested antimicrobial activity. Secondly, we characterized the essential oil of Centaurea triumfettii All. squarrose knapweed using coupled system gas chromatography–mass spectrometry and tested its phytochemicals for antimicrobial activity against E. coli and S. epidermis using disc diffusion assay and monitoring their growth in Muller Hinton broth. The most abundant compounds in C. triumfettii essential oil were hexadecanoic acid (11.1%), spathulenol (10.8%), longifolene (8.8%), germacrene D (8.4%), aromadendrene oxide (6.0%) and linoleic acid (5.3%). Based on our analysis of literature data from other Centaurea essential oils, they were positively correlated with antimicrobial activity. Using an agar disk diffusion method, tested chemical constituents did not show experimental evidence to support this positive correlation to antimicrobial activity when we tested them as pure components. The antibacterial effect of essential oil constituents may be related to a complex synergistic, rather than a single component as suggested by performed network pharmacology analysis, underlying the theoretical interactions between the essential oil phytochemicals listed as potentially responsible for antimicrobial activity and should be confirmed in further in-depth studies. This is the first report on the comparative analysis of Centaurea essential oils with good antimicrobial activity, as well as the first analysis of chemical components of the essential oil from C. triumfettii and the first report of antimicrobial activity of the representative, pure components: aromadendrene, germacrene D, spathulenol, longifolene, and the mixture of selected chemical compounds. This work contributes to the body of knowledge on the genus Centaurea and C. triumfettii species.

Abstract The aim of this cross-sectional study was to determine the associations between the Mediterranean diet (MeDi), nutritional status parameters, muscle strength, and periodontal status in Dalmatian kidney transplant recipients (KTRs). 89 KTRs were included in this analysis, 40 (45%) women, with a mean age of 61 years (IQR = 13) and a mean time since kidney transplantation of 5 years (IQR = 6.6). An OHIP-14 questionnaire and questionnaire-based periodontal history were obtained from all participants, a comprehensive periodontal examination was performed. Body composition data, anthropometric and clinical parameters were collected for each study participant. The Mediterranean Diet Serving Score (MDSS) was used to assess MeDi adherence, and handgrip strength was measured with a hand dynamometer. Our results showed low adherence to MeDi in KTRs (28%) and almost 50% of KTRs suffer from severe forms of periodontitis. We also found a low OHIP-14 score and poor oral hygiene habits. KTRs with a less severe form of periodontitis had higher muscle mass and handgrip strength. MDSS score was associated with a higher number of teeth, and everyday cereal intake was inversely associated with the periodontitis stage. Our results demonstrate the associations between nutritional status, muscle strength, dietary habits, and periodontal health in Dalmatian KTRs.

Adropin is a secretory peptide that regulates glucose, lipid, and protein metabolism, which is closely related to obesity, insulin resistance, dyslipidemia, and atherogenesis. The serum adropin level is related to sex and depends upon nutritional preferences. This study aims to determine the association between serum adropin levels and body composition parameters in kidney transplant recipients (KTRs), especially emphasizing sex differences. Our case–control study involved 59 KTRs (28 postmenopausal women and 31 men) who were divided into two groups according to sex, and each group of those KTRs was further divided into higher or lower adropin values than the mean value in each sex group. Univariate regression showed a negative association of adropin levels with most anthropometric and body composition parameters in men’s KTRs. Contrary to this, the serum adropin level was negatively associated only with phase angle in postmenopausal female KTRs. Multivariate regression showed that skeletal muscle mass and phase angle were the only negative predictors in women’s KTRs, whereas in men, negative predictors were BMI and body water. These findings imply that adropin could have a different impact on metabolic homeostasis in KTRs regarding sex and could be considered a negative predictor of body composition in KTRs.

Background: The aim of the current systematic review was to summarize and evaluate the overall advantages of lung ultrasonography (LUS) examination using high-resolution computed tomography (HRCT) as a reference standard in assessing the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients. Methods: Databases PubMed, Scopus, and Web of Science were searched for studies evaluating LUSs in ILD assessments including SSc patients on 1 February 2023. In assessing risk of bias and applicability, the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used. A meta-analysis was performed and the mean specificity, sensitivity, and diagnostic odds ratio (DOR) with a 95% confidence interval (CI) were obtained. In addition, in a bivariate meta-analysis, the summary receiver operating characteristic (SROC) curve area was additionally calculated. Results: Nine studies with a total of 888 participants entered the meta-analysis. A meta-analysis was also performed without one study that used pleural irregularity to assess the diagnostic accuracy of LUSs using B-lines (with a total of 868 participants). Overall sensitivity and specificity did not differ significantly, with only the analysis of the B-lines having a specificity of 0.61 (95% CI 0.44–0.85) and a sensitivity of 0.93 (95% CI 0.89–0.98). The diagnostic odds ratio of univariate analysis of the eight studies using the B-lines as a criterion for ILD diagnosis was 45.32 (95% CI 17.88–114.89). The AUC value of the SROC curve was 0.912 (and 0.917 in consideration of all nine studies), which indicates high sensitivity and a low false-positive rate for the majority of the included studies. Conclusions: LUS examination proved to be a valuable tool in discerning which SSc patients should receive additional HRCT scans to detect ILD and therefore reduces the doses of ionizing radiation exposure in SSc patients. However, further studies are needed to achieve consensus in scoring and the evaluation methodology of LUS examination.

Colorectal cancer (CRC) is the third most frequent cancer type in both males and females, with about 35% of patients being diagnosed in stage IV metastatic disease. Despite advancements in treatment, life expectancy in patients with metastatic disease is still not satisfying. Due to frequent drug resistance during conventional and targeted cancer treatments, the development and testing of multi-target therapies is an important research field. Medicinal mushrooms specific isolated compounds as well as complex extract mixtures have been studied in depth, and many mushroom species have been proven to be non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. In this study, we have performed a tandem mass tags qualitative and quantitative proteomic analyses of CT26.WT colon cancer tumor tissues from Balb/c mice treated with the studied medicinal mushroom extract mixture, with or without 5-fluorouracil. Besides significantly improved survival, obtained results reveal that Agarikon.1 alone, and in combination with 5-fluorouracil exert their anticancer effects by affecting several fundamental processes important in CRC progression. Bioinformatic analysis of up- and downregulated proteins revealed that ribosomal biogenesis and translation is downregulated in treatment groups, while the unfolded protein response (UPR), lipid metabolism and tricarboxylic acid cycle (TCA) are upregulated. Moreover, we found that many known clinical biomarkers and protein clusters important in CRC progression and prognosis are affected, which are a good basis for an expanded translational study of the herein presented treatment.

The present study evaluated for the first time changes in the saliva proteome in bitches with pyometra through a high-throughput quantitative proteomic analysis. The aims were to explore whether saliva composition could reflect the physiopathological changes occurring in canine pyometra and to identify potential biomarkers of the disease. Saliva samples from six healthy (H) and six bitches with pyometra (P) were analyzed using tandem mass tags–based approach. Additionally, 15 samples were used for the validation of changes in haptoglobin (Hp) concentration in saliva of dogs with pyometra. Proteomic analysis quantified 707 proteins in saliva. Comparison of the two groups revealed 16 unique proteins significantly modulated in saliva, with S100A calcium-binding protein 12 (S100A12), vimentin, and Hp the most up-regulated in canine pyometra. According to PANTHER (Protein Analysis Through Evolutionary Relationships) classification tool, these proteins are mainly related to proinflammatory mediators, acute-phase proteins, and sepsis. In conclusion, it can be stated that there are changes in various proteins in saliva in canine pyometra reflecting different physiopathological changes occurring in this disease. These proteins could be a source of potential non-invasive biomarkers for this disease that should be confirmed in future studies.

The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p

The response of pathophysiological research to emerging epidemics often occurs after the epidemic and, as a consequence, has little to no impact on improving patient outcomes or on developing high-quality evidence to inform clinical management strategies during the epidemic. Rapid and informed guidance of epidemic (research) responses to severe infectious disease outbreaks requires quick compilation and integration of existing pathophysiological knowledge. As a case study we chose the Zika virus (ZIKV) outbreak that started in 2015 to develop a proof-of-concept knowledge repository. To extract data from available sources and build a computationally tractable and comprehensive molecular interaction map we applied generic knowledge management software for literature mining, expert knowledge curation, data integration, reporting and visualization. A multi-disciplinary team of experts, including clinicians, virologists, bioinformaticians and knowledge management specialists, followed a pre-defined workflow for rapid integration and evaluation of available evidence. While conventional approaches usually require months to comb through the existing literature, the initial ZIKV KnowledgeBase (ZIKA KB) was completed within a few weeks. Recently we updated the ZIKA KB with additional curated data from the large amount of literature published since 2016 and made it publicly available through a web interface together with a step-by-step guide to ensure reproducibility of the described use case. In addition, a detailed online user manual is provided to enable the ZIKV research community to generate hypotheses, share knowledge, identify knowledge gaps, and interactively explore and interpret data. A workflow for rapid response during outbreaks was generated, validated and refined and is also made available. The process described here can be used for timely structuring of pathophysiological knowledge for future threats. The resulting structured biological knowledge is a helpful tool for computational data analysis and generation of predictive models and opens new avenues for infectious disease research. ZIKV Knowledgebase is available at www.zikaknowledgebase.eu.

A year after the initial outbreak, the COVID-19 pandemic caused by SARS-CoV-2 virus remains a serious threat to global health, while current treatment options are insufficient to bring major improvements. The aim of this study is to identify repurposable drug candidates with a potential to reverse transcriptomic alterations in the host cells infected by SARS-CoV-2. We have developed a rational computational pipeline to filter publicly available transcriptomic datasets of SARS-CoV-2-infected biosamples based on their responsiveness to the virus, to generate a list of relevant differentially expressed genes, and to identify drug candidates for repurposing using LINCS connectivity map. Pathway enrichment analysis was performed to place the results into biological context. We identified 37 structurally heterogeneous drug candidates and revealed several biological processes as druggable pathways. These pathways include metabolic and biosynthetic processes, cellular developmental processes, immune response and signaling pathways, with steroid metabolic process being targeted by half of the drug candidates. The pipeline developed in this study integrates biological knowledge with rational study design and can be adapted for future more comprehensive studies. Our findings support further investigations of some drugs currently in clinical trials, such as itraconazole and imatinib, and suggest 31 previously unexplored drugs as treatment options for COVID-19.

This study aims to evaluate the changes in salivary and serum proteomes that occur in canine diabetes mellitus type-1 (DM) through a high-throughput quantitative proteomic analysis. The proteomes of 10 paired serum and saliva samples from healthy controls (HC group, n = 5) and dogs with untreated DM (DM group, n = 5) were analyzed using Tandem Mass Tags (TMT)-based proteomic approach. Additionally, 24 serum samples from healthy controls and untreated DM were used to validate haptoglobin in serum. The TMT analysis quantified 767 and 389 proteins in saliva and serum, respectively. Of those, 16 unique proteins in serum and 26 in saliva were differently represented between DM and HC groups. The verification of haptoglobin in serum was in concordance with the proteomic data. Our results pointed out changes in both saliva and serum proteomes that reflect different physiopathological changes in dogs with DM. Although some of the proteins identified here, such as malate dehydrogenase or glyceraldehyde-3-phosphate dehydrogenase, were previously related with DM in dogs, most of the proteins modulated in serum and saliva are described in canine DM for the first time and could be a source of potential biomarkers of the disease. Additionally, the molecular function, biological process, pathways and protein class of the differential proteins were revealed, which could improve the understanding of the disease’s pathological mechanisms.