Elevated Markers Research Articles

Hormone Replacement Therapy Relieves Periodontitis by Inhibiting Alveolar Bone Loss and Inflammation.

Hormone replacement therapy (HRT) is a commonly used strategy for treating menopausal symptoms, while its relation with periodontitis remains unclear. This study aimed to explore the potential effects of HRT on periodontitis, mainly in aspects of bone loss and inflammation. The alveolar bone height (ABH), alveolar bone thickness (ABT), and bone mineral density (BMD) were measured in menopausal women with periodontitis who had received HRT or had not received HRT by cone beam computed tomography. Based on a rat model of periodontitis, the alveolar bone loss was evaluated by micro-computed tomography and bone-related biochemical markers. The expression/levels of inflammatory markers were measured to reflect periodontal inflammation. Although the differences were not all significant in each premolars/molars, the mesial/distal ABH and buccal/lingual ABT were lower, and the mesial/distal BMD was higher in patients in the HRT group than those in the control group. In a rat model of periodontitis, the alveolar bone loss was relieved by HRT. Additionally, HRT significantly weakened the elevation of inflammatory markers, including TNF-α, IL-1β, and IL-6 in periodontitis rats. HRT contributes to the remission of periodontitis by inhibiting alveolar bone loss and inflammation.

Hepatoprotective effects of ethanolic extract of Corallocarpus epigaeus roots on nitrobenzene-induced liver injury in Wistar rats

ABSTRACT This study examined the potential of Corallocarpus epigaeus ethanolic root extract to combat free radicals using DPPH, FRAP, hydroxyl radical, hydrogen peroxide, and nitric oxide scavenging assays. Rats were initially exposed to a single oral dose of nitrobenzene (50 mg kg−1 body weight), followed by a 15-d oral regimen of the ethanolic root extract of C. epigaeus at 200 mg kg−1 body weight. The assessment of serum liver marker enzymes (AST, ALT, and ALP), lipid peroxidation levels, antioxidant enzyme activities, and histopathological examinations of liver tissues were carried out. The C. epigaeus ethanolic root extract demonstrated antioxidant properties and contained flavonoids, tannins, carotenoids, lycopene, and phenolic compounds. In Nitrobenzene-induced rats, elevated serum markers and increased liver lipid peroxidation were observed that were normalized by the extract. It also increased antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Histopathological analysis confirmed the hepatoprotective effects of the extract.

Association between depression and anxiety and inability to achieve remission in rheumatoid arthritis and psoriatic arthritis.

To investigate the association between depression and anxiety and the inability to achieve remission in rheumatoid arthritis(RA) and psoriatic arthritis(PsA) patients. In addition, the association between depressive and anxiety symptoms and disease activity components were explored. 400 RA and 367 PsA patients from the tREACH and DEPAR were included, respectively. Patients had a possible depression or anxiety disorder if they scored >7 on the Hospital Anxiety and Depression Scale(HADS). Remission was defined as DAS44<1.6 in RA and DAPSA≤4 in PsA. Mixed models were used to assess the association between depression/anxiety, at any timepoint during 2 years, and remission during 2 years, and to explore which disease activity components are most influenced by depression/anxiety. At baseline, 20% of RA patients had a possible depression and 30% a possible anxiety disorder. In PsA this was 18% and 23%. After adjustment for concurrent anxiety symptoms depression was associated with a lower odds of achieving remission during 2 years of follow-up (OR 0.45(95%CI 0.25-0.80) for RA and OR 0.24(95%CI 0.08-0.71) for PsA). Anxiety was not associated with remission after adjustment for concurrent depression symptoms.The presence of depression/anxiety was associated with higher tender joint count, worse general health, more pain and slightly elevated inflammation markers, but not with more swollen joints in both RA and PsA. The presence of depressive symptoms in RA and PsA patients at baseline or during follow-up was associated with a lower likelihood of achieving remission. Healthcare professionals should, therefore, be aware of symptoms of depression.

NLRP3 inflammasome activation contributes to acute liver injury caused by CVA6 infection in mice

BackgroundCoxsackievirus (CV) A6 has emerged as an important causative agent in global outbreaks of hand, foot, and mouth disease (HFMD), which typically presents as a mild illness with a large generalized rash, herpes. However, some patients can develop encephalitis, pneumonia, myocarditis and liver injury. Our previous study took the view that CVA6 could replicate in mouse liver, leading to acute liver injury; however, the precise underlying mechanism remains elusive.Methods10-day-old wild-type (WT, C57BL/6J) and NLRP3 knock-out (KO) mice were intraperitoneal (i.p.) inoculated with a lethal dose of the CVA6 strain. The muscle homogenate supernatant from normal mice was used to inoculate mock-infected mice. At 5 days post infection (dpi), the mouse liver was taken out for histopathological analyses and molecular biology experiments.ResultsOur in vivo experiments demonstrated that CVA6 caused severe liver injury in mice, as evidenced by pathological changes in liver slices, elevated liver injury markers (e.g., AST, ALT, LDH) and pro-inflammatory cytokines (e.g., IL-6, MCP-1, TNF-α, IL-1β). Further results revealed the activation of NLRP3 inflammasome characterized by the increase in the expression of NLRP3, Cleaved-Casp-1 (p20), mature IL-1β and IL-18. Importantly, upon CVA6 infection, NLRP3 KO mice exhibited attenuated pathological damage and reduced levels of pro-inflammatory cytokines production (e.g., TNF-α and IL-1β) compared with WT mice. Finally, increased levels of blood ALT, AST, LDH were strongly correlated with the severity of CVA6 patients.ConclusionCollectively, our findings suggest that the activation of NLRP3 inflammasome is involved in CVA6 infection-induced acute liver injury, providing novel insights into CVA6 infection associated adverse clinical outcomes.

Chemopreventive potential of goniothalamin in diethylnitrosamine-induced hepatocellular carcinoma through the suppression of P13K/AKT signalling pathway.

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.

Analysis of Serum and Synovial Inflammatory Markers in Periprosthetic Joint Infections: A Narrative Review.

Periprosthetic joint infection (PJI) is considered a rare but devastating complication after total joint arthroplasty (TJA). The problem lies in the fact that there is a paucity of "gold standard" diagnostic tests that make the diagnosis of PJI extremely challenging. Recently, there have been increasing evidence-based guidelines that have been introduced to standardise the approach to a patient with a suspected PJI. Diagnosing a case of PJI traditionally involves initial screening for elevated serum inflammation markers C-reactive protein (CRP) (mg/dL) and erythrocyte sedimentation rate (ESR), and aspiration remains the sole confirmatory investigation. However, several factors would affect the values of the aforementioned markers, such as gender, age, and the presence of inflammatory circumstances. Serum D-dimer that detects fibrinolytic activities during infection has high sensitivity, but the specificity was not persuasive as it would elevate during other conditions, such as venous thromboembolism. Therefore, there is also a need for a simultaneous and secondary marker. There are also several synovial biomarkers, including ESR, CRP, alpha-defensin, and synovial fluid leukocyte count and differential for the detection of PJI. In this narrative review, we want to sum up the serum and inflammatory markers that have been introduced so far for detecting PJI.

Vanillic acid ameliorates diethyl phthalate and bisphenol S-induced oxidative stress and neuroinflammation in the hippocampus of experimental rats.

Long-term adverse effects on human health are caused by exogenous compounds that alter the functions of biological systems, especially neuroendocrine disruptors like diethyl phthalate (DEP) and bisphenol S (BPS). Although vanillic acid (VA) has pertinent neuropharmacological characteristics, its effect against DEP + BPS-induced neurotoxicity has not been explored. This study proposed that VA may offer protection against the neurotoxicity caused by DEP + BPS. Thirty male Wistar rats were randomly distributed across five groups: a control group receiving DMSO, a group exposed to a mixture of BPS and DEP, two BPS + DEP-exposed groups treated with VA at doses of 25 mg/kg or 50 mg/kg, and a nonexposed group treated with 50 mg VA/kg. After 21 days, the hippocampal tissues were processed for biochemical analyses. Our results indicate that exposure to DEP + BPS upregulated neurosignaling mediators (NTPDase, ADA, MAO-A, and Ca2+), inhibited others (AChE and Ca2+/Mg2+-ATPase), decreased hippocampus antioxidants (GSH, GPx, CAT, and SOD), and elevated markers of oxidative stress/damage (NO, H2O2, MDA, and AOPP). AR, BAX, TNF-α, BAK1, and IL-1β expressions were upregulated, while IL-10 and BDNF expressions were downregulated. NF-κB and caspase-3/9 pathways were also upregulated. Co-treatment with vanillic acid remarkably precluded these neurotoxic outcomes by improving neurosignaling, augmenting antioxidant status, abrogating oxidative damage, inflammation (TNF-α, IL-1β), and apoptosis (BAX, BAK1, caspase-3/9). Vanillic acid also restored IL-10 and BDNF levels, thereby exhibiting neuroprotective effects, corroborated by histological examinations. We posit vanillic acid as a safe and effective therapeutic agent against neurotoxicity occasioned by exposure to neuroendocrine disruptors.

Patients with crush syndrome and kidney disease: lessons learned from the earthquake in Kahramanmaraş, Türkiye

This study investigated in-hospital outcomes and related factors in patients diagnosed with postearthquake crush syndrome after the earthquakes in Kahramanmaraş, Türkiye. One thousand twenty-four adult patients diagnosed with crush syndrome were analyzed. Data on demographic characteristics, clinical presentation, laboratory values, treatments, and outcomes were collected. A total of 9.8% of patients died during their hospital stay. Nonsurvivors were generally older, more likely to have preexisting chronic kidney disease, and faced more severe injuries and complications, including hypotension-shock, arrhythmias, elevated markers of renal dysfunction, and higher rates of acute kidney injury (AKI) and compartment syndrome. In addition, intensive care unit needs were higher. Multivariate analysis confirmed that age, injury severity, shock, high potassium, uric acid, and lactate levels on admission, development of AKI, compartment syndrome, and intensive care unit admission were significant predictors of mortality. Better disaster preparedness and improved health care infrastructure could be potential explanations for improved in-hospital mortality in the current era, as compared to previous earthquakes.

Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents

Viral infections can lead to platelet activation and hemostatic complications. However, the extent to which platelet reactivity remains altered after convalescence, contributing to long-term health impairments as observed after COVID-19 is not yet fully understood. Therefore, we conducted a cohort study (DRKS00025217) to determine platelet function in individuals convalesced from mild COVID-19. Assays were performed ex vivo with blood from convalescents at 2–15 weeks and 6–10 months after convalescence, focusing on platelet aggregation, activation markers, and thrombin formation. In addition, two other potentially relevant factors for platelet function were examined: the immunomodulatory mediator sphingosine-1-phosphate (S1P) and the platelet expression of the transporter MRP4 (ABCC4). Our findings indicate that robust platelet functions, including platelet aggregation determined by light transmission aggregometry, and thrombin formation, were not altered in convalescents compared to matched control individuals. However, an elevation in subtle platelet activation markers, such as P-selectin surface expression and activation of glycoprotein IIb/IIIa, was observed 2–15 weeks after convalescence. This was accompanied by an increased expression of MRP4 in platelets and significantly elevated levels of S1P in platelet-poor plasma. Our findings suggest increased platelet sensitization and a pro-inflammatory state even after convalescence from mild COVID-19, pointing toward MRP4 and S1P as associated factors.

A comprehensive meta-analysis of in vitro studies on polycystic ovary syndrome cell lines

Introduction: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. In vitro studies using PCOS cell lines have been instrumental in understanding the pathophysiology and identifying potential therapeutic targets. This meta-analysis aims to synthesize and evaluate the existing literature on PCOS cell line research. Methods: A systematic search of PubMed, Scopus, and Web of Science databases up to January 2024, using relevant keywords and medical subject headings. Inclusion criteria were original research articles in English, focusing on PCOS cell lines and reporting quantitative data. Data extraction included study design, cell line model, outcomes, and main findings. Results: A total of 48 studies met the inclusion criteria, involving human granulosa-derived (KGN, COV434), theca-derived (HsTE-1, HsTE-10), and ovarian surface epithelial (IOSE-80) cell lines. These studies focused on the evaluation of hormonal imbalances, insulin resistance, and inflammation. The meta-analysis revealed that PCOS cell lines exhibited increased androgen production, elevated insulin resistance markers, and pro-inflammatory cytokine expression compared to control cell lines. Conclusion: In vitro studies using PCOS cell lines have provided valuable insights into the molecular mechanisms underlying PCOS pathogenesis. These cell lines serve as valuable tools for understanding the complex interplay between hormonal dysregulation, insulin resistance, and inflammation.

Combining Chemotherapy Agents and Autophagy Modulators for Enhanced Breast Cancer Cell Death

Purpose: Autophagy, governed by genes with dual roles in cell death and survival, plays a crucial role in cancer persistence. Arsenic trioxide (ATO), carboplatin (CP), and cyclophosphamide (CY) are used to treat various cancers. ATO impedes cell proliferation and triggers apoptosis in cancer cells. CP, a platinum-based drug, damages cancer cell DNA, while CY acts as an alkylating agent, disrupting cell proliferation. This study investigates the combined effects of ATO, CP, and CY on inducing apoptosis and modulating autophagy in triple-negative breast cancer (TNBC) cell lines, BT-20 and MDA-MB-231. Methods: The cytotoxic effects of ATO, CP, and CY, alone and in combination, were evaluated using the MTT assay on BT-20 and MDA-MB-231 cells. Apoptosis and cell cycle progression were analyzed by annexin-V FITC/PI staining and flow cytometry. Gene expression of autophagy- and apoptosis-related markers, including Beclin 1, LC3, caspase 3, and BCL2, was quantified using RT-PCR. Data were analyzed using GraphPad Prism 4.0 with one-way ANOVA followed by Dunnett's test. Results: The The combination of ATO, CP, and CY significantly reduced cell viability and enhanced apoptosis, evidenced by increased caspase-3 activity and reduced BCL2 expression. Cell cycle arrest in the G1 phase was observed, alongside elevated autophagy markers Beclin 1 and LC3. Conclusion: The combination of ATO, CP, and CY induces synergistic effects in promoting apoptosis and autophagy in TNBC cell lines. These findings suggest that this combination therapy could be a promising approach to enhancing treatment efficacy in aggressive breast cancers, offering new insights into potential therapeutic strategies.

Synergistic Effects of Fructose and Food Preservatives on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): From Gut Microbiome Alterations to Hepatic Gene Expression

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of MASLD. Methods: We utilized a human microbiota-associated mouse model, administering 10% fructose with or without preservatives for 11 weeks. Liver histology, hepatic gene expression (microarray analysis), biochemical markers, cytokine profiles, intestinal permeability, and gut microbiome composition (16S rRNA and Internal Transcribed Spacer (ITS) sequencing) were evaluated. Results: Fructose and potassium sorbate synergistically induced liver pathology characterized by increased steatosis, inflammation and fibrosis. These histological changes were associated with elevated liver function markers and altered lipid profiles. The treatments also induced significant changes in both the bacterial and fungal communities and disrupted intestinal barrier function, leading to increased pro-inflammatory responses in the mesenteric lymph nodes. Liver gene expression analysis revealed a wide range of transcriptional changes induced by fructose and modulated by the preservative. Key genes involved in lipid metabolism, oxidative stress, and inflammatory responses were affected. Conclusions: Our findings highlight the complex interactions between dietary components, gut microbiota, and host metabolism in the development of MASLD. The study identifies potential risks associated with the combined consumption of fructose and preservatives, particularly potassium sorbate. Our data reveal new mechanisms that are involved in the development of MASLD and open up a new avenue for the prevention and treatment of MASLD through dietary interventions and the modulation of the microbiome.

The Impact of Chemokine-Like Receptor 1 Gene Knockout on Lipopolysaccharide-Induced Epididymo-Orchitis in Mice.

This comprehensive study delved into the pivotal function of chemokine-like receptor 1 (CMKLR1) in lipopolysaccharide (LPS)-triggered epididymo-orchitis in mice. Upon LPS exposure, wild-type (WT) mice exhibited marked elevations in serum pro-inflammatory markers, including G-CSF, IL-6, and RANTES, along with heightened levels of TNF-α and IL-6 in testicular and epididymal tissues, which accompanied by pronounced structural damage within the testicular tissue and a concurrent decline in serum testosterone, estradiol (E2) levels, and testicular steroid synthetase expression. Remarkably, Cmklr1 gene ablation intensified the pro-inflammatory response in the serum (especially IFN-γ), testes, and epididymis of epididymo-orchitis models. Furthermore, Cmklr1 deficiency uniquely induced structural alterations within the epididymis, which is absent in the WT model. This genetic manipulation also exacerbated the decline in serum testosterone and E2 levels and testicular steroid synthase activity. While chemerin levels were significantly diminished in WT epididymo-orchitis models, Cmklr1 knockout had no discernible effect on chemerin expression in the model. In addition, a noteworthy observation was the elevation of the serum low density lipoprotein/high density lipoprotein (LDL/HDL) ratio in Cmklr1-deficient mice. Collectively, these findings underscore that the lack of chemerin/CMKLR1 signaling axis could potentially worsen the symptoms during LPS-induced epididymo-orchitis, highlighting its potential as a therapeutic target in related pathologies.

Hyperexpression of PTAFR and PF4 as Possible Platelet Risk Biomarkers in Patients With COVID-19.

SARS-CoV-2 infection presents different severity levels that suggest the influence of genetic factors on the clinical outcome of the disease. In cases of severe COVID-19, the presence of elevated coagulation markers, increased platelet activation and aggregation and the risk of thrombotic complications are described. Given the participation of these cells in several serious viral infections and their negative role when associated with a prothrombotic response, it is important to understand the mechanistic role of SARS-CoV-2 in platelet physiology. This study evaluated the hyperexpression of platelet-activating factor receptor (PTAFR) and platelet factor 4 (PF4) in unvaccinated and hospitalized patients with COVID-19. The study included 43 COVID-19 patients stratified according to WHO guidelines. Subsequently, the expression of the PTAFR and PF4 genes were evaluated using the real-time quantitative PCR and their possible correlation with the severity of the disease and clinical variables including hospitalization, outcome, sex, age and laboratory parameters (platelet count, INR and D-dimer). The analysis demonstrated a significant (p<0.05) hyperexpression of these genes COVID-19 patients (n=43) compared to healthy controls. Expression of these genes in patients was not statistically significant (p>0.05) different between patients stratified according to clinical variables. The expression of PTAFR and PF4 suggests an important molecular pathway in the pathophysiology of the disease and may be valuable platelet biomarkers to indicate increased risk in patients with COVID-19 who require hospital care, contributing to personalized intervention strategies and improving their clinical management.

Pathogenic mechanism and therapeutic intervention of impaired N7-methylguanosine (m7G) tRNA modification

Mutations modification enzymes including the tRNA N7-methylguanosine (m7G) methyltransferase complex component WDR4 were frequently found in patients with neural disorders, while the pathogenic mechanism and therapeutic intervention strategies are poorly explored. In this study, we revealed that patient-derived WDR4 mutation leads to temporal and cell-type-specific neural degeneration, and directly causes neural developmental disorders in mice. Mechanistically, WDR4 point mutation disrupts the interaction between WDR4 and METTL1 and accelerates METTL1 protein degradation. We further uncovered that impaired tRNA m7G modification caused by Wdr4 mutation decreases the mRNA translation of genes involved in mTOR pathway, leading to elevated endoplasmic reticulum stress markers, and increases neural cell apoptosis. Importantly, treatment with stress-attenuating drug Tauroursodeoxycholate (TUDCA) significantly decreases neural cell death and improves neural functions of the Wdr4 mutated mice. Moreover, adeno-associated virus mediated transduction of wild-type WDR4 restores METTL1 protein level and tRNA m7G modification in the mouse brain, and achieves long-lasting therapeutic effect in Wdr4 mutated mice. Most importantly, we further demonstrated that both TUDCA treatment and WDR4 restoration significantly improve the survival and functions of human iPSCs-derived neuron stem cells that harbor the patient's WDR4 mutation. Overall, our study uncovers molecular insights underlying WDR4 mutation in the pathogenesis of neural diseases and develops two promising therapeutic strategies for treatment of neural diseases caused by impaired tRNA modifications.

Myocarditis in the modern era: analysing the impact of high-sensitivity troponin &amp; C-reactive protein in predicting the extent of myocarditis and LV systolic dysfunction on cardiac magnetic resonance

Abstract Background The diagnostic yield of acute myocarditis has improved considerably since the advent of high-sensitivity troponin (hs-Tn) assays and adoption of the 2018 Lake Louise criteria for cardiac magnetic resonance (CMR)-based imaging for myocardial oedema and injury (1). Yet, a seminal 1997 study, predating these technological advances, remains widely cited for highlighting an absence of troponin rise in two-thirds of myocarditis cases (2). We hypothesize that all cases of myocarditis exhibit hs-Tn rise. However, whether such elevations in hs-Tn or inflammatory markers correlate with the extent of myocardial injury and left ventricular systolic dysfunction (LVSD) on CMR remain unclear. To provide insight into this, we examined a contemporary cohort of cases between 2019-2023. Methods Two authors independently conducted case-notes reviews to verify the diagnosis of myocarditis. CMR findings were stratified into regional (e.g. inferolateral) and global myocarditis (e.g. subepicardial LGE in all segments). This classification aimed to explore potential correlations with LVSD severity, peak hs-Tn and other inflammatory markers. Receiver operating characteristics (ROC) curves was calculated to determine any cut-off value for predicting CMR findings and adverse patient outcomes. Results 103 inpatients were clinically coded as ‘myocarditis’ upon discharge, but subsequent CMR (within 4 weeks) reclassified 23 patients into other causes (Figure 1). Analysis of the myocarditis cohort revealed a predominantly male population (76%) with median age 53, commonly presenting with chest pain without a viral prodrome (Figure 2A-D). Elevated hs-Tn levels were observed universally, with a median peak hs-TnT of 610ng/L (IQR 1081.5ng/L) and hs-TnI of 3820ng/L (IQR 12416ng/L). In contrast, peak CRP ranged between 2mg/L (normal) and 600mg/L. Global myocarditis was detected in 11/80 patients (13.8%); however, this finding did not correlate with adverse patient outcomes which included all-cause mortality (9.6%) and cardiac re-admissions within 12 months (9.6%, namely for chest pains). No arrhythmic deaths were noted. COVID was present in 4% on admission. CRP cut-off of 140mg/L predicted the occurrence of global myocarditis with a sensitivity of 72.7% and specificity of 87.0% (AUC 0.74, 95% CI 0.52-0.96, p=0.014) (Figure 2E). However, neither hs-Tn or CRP levels correlated with the degree of LVSD (Figure 2F) or adverse outcomes. This is likely limited by the small sample. Conclusion Although all cases of myocarditis exhibited raised hs-Tn, this did not correlate with the degree of LV systolic impairment on CMR. Myocarditis with regional LV involvement can have normal CRP levels, while a CRP cut-off &amp;gt;140mg/L may predict the occurrence of global myocarditis. However, CMR stratification into regional and global was not associated with adverse patient outcome within 12 months. A larger sample size is required to verify this finding, including longer term follow-ups.Flowchart of patients included in studyMain findings

Integrated plasma proteomics and myocardial tissue transcriptomics reveal elevated fibrosis markers in arrhythmogenic cardiomyopathy patients

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is characterized by myocardial fibrofatty replacement and ventricular arrhythmias, with potential progression to heart failure. This study aims to identify ACM-specific biomarkers for improved prognosis and possible treatment strategies. Methods RNA sequencing and transcriptome analyses were performed in cardiomyocytes of 10 ACM patients, 10 dilated cardiomyopathy patients and 10 healthy controls. Analyses were performed using liquid chromatography and mass spectrometry. Additionally, plasma protein expression was assessed in 38 ACM patients and 24 healthy controls using the Proximity Extension Assay (Olink®). A standardized bicycle exercise test was performed in 11 ACM patients and controls and blood was obtained before and after exercise. Results Myocardial tissue transcriptomics identified several upregulated molecules associated with extracellular matrix formation and immune response in ACM. Plasma protein sequencing revealed upregulation of proteins involved in metabolic pathways, inflammation, and fibrosis. Integration of these analyses identified key soluble profibrotic markers such as Fibulin-3, Endostatin and C-X-C motif chemokine 10 (CXCL10) in plasma of ACM patients. After exercise, Fibulin-3 levels increased in ACM patients compared to controls. These findings were further validated using enzyme-linked immunosorbent assay (ELISA). Conclusion This comprehensive analysis revealed distinct proteomic and transcriptomic signatures in ACM patients' plasma and cardiomyocytes. The integrative analysis identified several upregulated profibrotic markers in ACM. Our Findings may advance diagnostic and prognostic strategies and offer potential therapeutic targets.

Permanent and persistent atrial fibrillation are independent risk factors of mortality after severe COVID-19

Abstract Background New coronavirus disease (COVID-19), pandemic infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), had a deep global influence on morbidity and mortality profile. Comorbidities, especially cardiovascular diseases were identified to strongly modify the clinical course of COVID-19. However, the prognostic role of incident or prevalent atrial fibrillation has not been fully explained. Purpose The aim of this study was to evaluate the association between atrial fibrillation and outcomes following hospitalization in patients with severe COVID-19. Methods We analyzed 199 patients (72 female, median age 70 years) with severe COVID-19 hospitalized between November 2020 and February 2021, due to SARS-CoV-2 infection. Study cohort included 68 patients with a history of AF (34 patients with paroxysmal AF, 19 with permanent AF, 15 patients with persistent AF) and 51 patients presented with AF during hospitalization. Results Overall mortality during 90 days from the admission to hospital was 41% (n=82). Non-survivors were older, had significantly elevated inflammation markers (CRP, WBC, procalcitonin, IL-6), NT-proBNP and D-dimer on the first day of hospitalization, lower left ventricular ejection fraction and worse kidney function as compared to those who stayed alive during the follow-up. Among the hospitalized patients with COVID-19, a history of AF and the presence of AF during hospitalization contributed to higher mortality, p=0.001. The patients with permanent and persistent AF were at the greatest risk of death, p&amp;lt;0.001. In multivariate analysis, taking into account whether the patients had a history of AF, the subtypes of AF (paroxysmal, permanent, persistent) and whether the AF was present during hospitalization to identify the independent risk factors of death in the study period, we found that AF was related to worse prognosis and persistent or permanent form represented an independent predictor of mortality, p=0.035. Conclusions Different clinical presentations of AF have varying impact on survival in severe COVID-19. Mortality in hospitalized patients with severe COVID-19 was higher among patients with history of AF, especially with persistent and permanent type of AF, and with AF present during hospitalization.Figure.Survival depending on the type o.

Assessment of Artemisia campestris L. Leaf Extract Effects on Polycystic Ovarian Syndrome in Rats, Antioxidant and α-Amylase Inhibition Activities.

Polycystic Ovarian Syndrome (PCOS) is characterized by metabolic and reproductive dysfunction, often associated with elevated oxidative stress markers in the bloodstream. This study examines the potential antioxidant properties and α-amylase inhibitory activity of Artemisia campestris leaves extract (Artemisia campestris L) and its effects on rats with induced PCOS. Estradiol valerate was administered to ten mature Wistar rats to induce PCOS, while a control group consisted of five mature Wistar rats. Following a 16-day induction period, the rats were categorized into three groups: a control group, a PCOS group, and an experimental group receiving 200 mg/kg body weight of A. campestris L. extract orally for 15 days. Serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured using the ELISA technique. The group treated with A. campestris L. extract exhibited significantly reduced LH levels compared to the PCOS group. Histomorphometric analysis indicated notable changes in follicle counts and the thickness of the theca layer. These findings suggest a significant alleviation of PCOS symptoms, potentially linked to the effects of A. campestris L. on oxidative stress pathways. Furthermore, aqueous extracts of A. campestris L. displayed potent in vitro inhibition of α-amylase, with an IC50 value of 2.418 µg/mL.

The Role of HE4 in the Follow-Up of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—CEEGOG OX-01 Study

Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4’s role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values’ accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III–IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3–4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.