Search Results (41)

Background: While epicardial adipose tissue (EAT) is a known predictor of adverse cardiovascular outcomes, lipomatous hypertrophy of the interatrial septum (LHIS) is composed of metabolically active fat such as brown adipose tissue, which may exert a different effect. This study investigates the coronary atherosclerosis profile in patients with LHIS using CTA, compared with a propensity score-matched control group. Methods: A total of 142 patients were included (n = 71 with LHIS and n = 71 controls) and propensity score-matched for age, gender, BMI, and the major CV risk factors (matching level, <0.05). CTA imaging parameters included HRP, coronary stenosis severity (CADRADS), and CAC score. Results: The mean age was 60.9 years +/− 10.6, there were nine (6.3%) women, and the mean BMI is 28.04 kg/m² +/− 4.99. HRP prevalence was significantly lower in LHIS patients vs. controls (21.1% vs. 40.8%; p < 0.011), while CAC (p = 0.827) and CADRADS (p = 0.329) were not different, and there was no difference in the obstructive disease rate. There was no difference in lipid panels (cholesterol, LDL, HDL, TG) and statin intake rate. Conclusions: HRP prevalence is lower in patients with LHIS than controls, while coronary stenosis severity and CAC score are not different. Clinical relevance: LHIS may serve as imaging biomarker for reversed CV risk. Full article

Background: Huntington’s Disease (HD) remains without disease-modifying treatments, with existing therapies primarily targeting chorea symptoms and offering limited benefits. This study aims to identify druggable genes and potential biomarkers for HD, focusing on using RNA-Seq analysis to uncover molecular targets and improve clinical trial outcomes. Methods: We reanalyzed transcriptomic data from six independent studies comparing cortex samples of HD patients and healthy controls. The Propensity Score Matching (PSM) algorithm was applied to match cases and controls by age. Differential expression analysis (DEA) coupled with machine learning algorithms were coupled to identify differentially expressed genes (DEGs) and potential biomarkers in HD. Results: Our analysis identified 5834 DEGs, including 394 putative druggable genes involved in processes like neuroinflammation, metal ion dysregulation, and blood–brain barrier dysfunction. These genes’ expression levels correlated with CAG repeat length, disease onset, and progression. We also identified FTH1 as a promising biomarker for HD, with its expression downregulated in the prefrontal cortex and upregulated in peripheral blood in a CAG repeat-dependent manner. Conclusions: This study highlights the potential of FTH1 as both a biomarker and a therapeutic target for HD. Advanced bioinformatics approaches like RNA-Seq and PSM are crucial for uncovering novel targets in HD, paving the way for better therapeutic interventions and improved clinical trial outcomes. Further validation of FTH1′s role is needed to confirm its utility in HD. Full article

Parkinson’s disease and related synucleinopathies, including dementia with Lewy bodies and multiple system atrophy, are characterised by the pathological aggregation of the α-synuclein (aSyn) protein in neuronal and glial cells, leading to cellular dysfunction and neurodegeneration. This review synthesizes knowledge of aSyn biology, including its structure, aggregation mechanisms, cellular interactions, and systemic influences. We highlight the structural diversity of aSyn aggregates, ranging from oligomers to fibrils, their strain-like properties, and their prion-like propagation. While the role of prion-like mechanisms in disease progression remains a topic of ongoing debate, these processes may contribute to the clinical heterogeneity of synucleinopathies. Dysregulation of protein clearance pathways, including chaperone-mediated autophagy and the ubiquitin–proteasome system, exacerbates aSyn accumulation, while post-translational modifications influence its toxicity and aggregation propensity. Emerging evidence suggests that immune responses and alterations in the gut microbiome are key modulators of aSyn pathology, linking peripheral processes—particularly those of intestinal origin—to central neurodegeneration. Advances in biomarker development, such as cerebrospinal fluid assays, post-translationally modified aSyn, and real-time quaking-induced conversion technology, hold promise for early diagnosis and disease monitoring. Furthermore, positron emission tomography imaging and conformation-specific antibodies offer innovative tools for visualising and targeting aSyn pathology in vivo. Despite significant progress, challenges remain in accurately modelling human synucleinopathies, as existing animal and cellular models capture only specific aspects of the disease. This review underscores the need for more reliable aSyn biomarkers to facilitate the development of effective treatments. Achieving this goal requires an interdisciplinary approach integrating genetic, epigenetic, and environmental insights. Full article

Osteosarcoma (OSA) is a naturally occurring malignant bone tumor in both humans and canines that is characterized by aggressive local behavior and a high propensity for metastasis. Despite advances in diagnostic methods and therapies, long-term survival rates have remained stagnant, underscoring the great need for the development of biomarkers serving in the prognosis and diagnosis of OSA across species. Biomarkers, molecular indicators of disease presence or progression, are pivotal tools in oncology, offering the potential to determine risk stratification, guide targeted therapies, and monitor treatment response. This review provides an in-depth analysis of the current landscape of OSA biomarkers, highlighting diagnostic and prognostic markers identified across species. We highlighted the role of biomarkers, including protein, cellular, metabolic, imaging, genetic, and epigenetic markers, in osteosarcoma diagnosis and prognosis and categorized them across multiple domains. Furthermore, this review explores the utility of the canine model in osteosarcoma research, emphasizing its relevance to human OSA due to comparable diagnostic approaches, prognostic indicators, and clinical manifestations. With this review, we aim to demonstrate that integrating biomarker research across species can deepen the understanding of osteosarcoma pathogenesis and advance knowledge of its underlying biology, ultimately paving the way for precision medicine strategies that benefit both human and veterinary oncology. Full article

Albuminuria is a sensitive biomarker of kidney dysfunction, and the albumin/creatinine ratio (ACR) is an essential measure for monitoring diabetic kidney disease (DKD). Abnormal levels can indicate a propensity for progressive renal failure and other complications such as cardiovascular diseases. This study employed UV/Visible spectroscopy to analyze aqueous urine samples spiked with bovine serum albumin (BSA) and creatinine at clinically relevant concentrations (0–30 mg/L for albumin and 600–1800 mg/L for creatinine) using a multivariate method. UV/Visible spectra of co-spiked samples recorded in triplicate revealed distinct bands at 229 nm and 249 nm, corresponding to BSA and creatinine, respectively, alongside other amino acid bands. Partial Least Squares Regression (PLS-R) analysis for BSA yielded a Root Mean Square Error of Calibration (RMSEC) and Cross-Validation (RMSECV) values of 66.93 and 73.92 mg/L, respectively. For creatinine, RMSEC and RMSECV values were 244.32 and 275.65 mg/L, respectively. Prediction models for both BSA and creatinine compared to ELISA demonstrated a robust performance with R²_PRED values of 0.96 and 0.95, respectively, indicating strong model reliability. The Limit of Detection (LOD) for co-spiked samples was 19.82 mg/L for BSA and 58.43 mg/L for creatinine. The significance of the achieved Limit of Detection (LOD) lies in its ability to measure concentrations well below the normal physiological ranges of 0–30 mg/L for albumin and 600–1800 mg/L for creatinine. These results demonstrate the proof of concept of applying an UV/Visible-spectroscopy-based method as a rapid, cost-effective point-of-care (PoC) tool for ACR measurements, offering promising applications in the early diagnosis, monitoring, and prognosis of diabetic kidney disease and associated cardiovascular complications. The next stage will involve a pilot trial to evaluate the technology’s potential using clinical patients. Full article

Background: Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. Methods: We enrolled 182 elderly COVID-19 patients from the Chinese PLA General Hospital between November 2022 and April 2023, categorizing them based on progression to respiratory failure requiring mechanical ventilation (defined as severe progression). Olink proteomic analysis was performed on admission serum from 40 propensity score-matched samples, with differentially expressed proteins (DEPs) validated by cytometric bead array (CBA) in 178 patients. To predict severe progression, a model was developed using a 70% training set and validated on a 30% validation set. LASSO regression screened features followed by logistic regression and receiver operating characteristic (ROC) analysis to optimize the model by incrementally incorporating features ranked by random forest importance. Results: Elderly patients progressing to severe COVID-19 exhibited early immune dysregulation, including neutrophilia, lymphopenia, monocytopenia, elevated procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as coagulation dysfunction and multi-organ injury. Proteomics identified a set of biomarkers, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and revealed disruptions in signaling pathways, including the mTOR and VEGF signaling pathways. The optimal predictive model, which incorporated PCT, IL-6, monocyte percentage, lymphocyte count, and TRAIL, achieved an area under curve (AUC) of 0.870 (0.729–1.000) during validation. TRAIL levels negatively correlated with fibrinogen (p < 0.05). Conclusions: Elderly COVID-19 patients with severe progression demonstrate early immune dysregulation, hyperinflammation, coagulation dysfunction, and multi-organ injury. The model we proposed effectively predicts disease progression in elderly COVID-19 patients, providing potential biomarkers for early clinical risk stratification in this vulnerable population. Full article

Background: Liver cirrhosis is often accompanied by metabolic dysfunction. Circulating β-hydroxybutyrate (BHB), the most abundant ketone body, is an emerging metabolic biomarker of mitochondrial dysfunction. Methods: In this prospective observational study, we evaluated plasma BHB concentrations in patients with cirrhosis compared to the general population and investigated their association with all-cause mortality in cirrhosis. Plasma BHB, measured by nuclear magnetic resonance spectroscopy, was compared between 125 patients with cirrhosis on the waiting list for liver transplantation (TransplantLines cohort study; NCT03272841) with 125 propensity-score-matched participants from the population-dwelling PREVEND cohort. Associations of BHB with all-cause mortality were established by tertile-based log-rank tests and Cox regression analyses. A generalized additive model was fitted to assess a potential non-linear association between BHB and mortality. Results: Patients with cirrhosis had lower plasma BHB concentrations than matched PREVEND participants (111.5 µmol/L vs. 138.4 µmol/L, p = 0.02). During 133 (interquartile range 42–375) days of follow up, 27 patients died. All-cause mortality was lowest in the middle BHB tertile and highest in the upper BHB tertile (p < 0.001 by log-rank test). A non-linear, J-shaped association between BHB levels and mortality risk was found with a higher risk of death with the highest and lowest BHB levels. In Cox regression analyses, adjusted for age, sex, MELD score, diabetes, and HDL cholesterol, mortality was highest in the highest BHB tertile (T3 vs. T2 HR: 7.6, 95% CI: 2.3–25.6, p < 0.001). Mortality also tended to be higher in the lowest vs. the middle (T1 vs. T2 HR: 3.5, 95% CI: 0.9–11.7, p = 0.06). Sensitivity analyses, excluding diabetic patients and those with metabolic dysfunction-associated steatotic liver disease, confirmed the robustness of these findings. Conclusion: BHB levels exhibit a J-shaped association with the risk of death in patients with liver cirrhosis. The highest circulating BHB levels are independently associated with increased mortality risk, potentially reflecting underlying metabolic dysregulation. Future studies are necessary to validate the utility of BHB as a prognostic target in cirrhosis. Full article

Background/Objectives: Patients with acute myeloid leukemia (AML) have a higher propensity for adverse cardiovascular outcomes, primarily due to the toxic effects of chemotherapeutic agents. The purpose of this systematic review is to explore the association of acute myeloid leukemia treatment with adverse cardiovascular events. Methods: We systematically screened the literature for studies providing comparative data on cardiovascular toxicities in patients treated for acute myeloid leukemia. After the initial search, 3649 papers were screened and a final total number of 46 were included for the review process. Results: Common chemotherapeutic agents used in AML may cause cardiovascular (CV) toxicities. A plethora of pathophysiological mechanisms are incriminated for these effects. Drug combinations may increase the risk in a synergistic way. In addition, common mutations of AML, personal history of previous cardiovascular disease and impaired heart function carry an increased complication risk. Biomarkers, as well as multimodality imaging, may be used for the early detection of cardiovascular toxicities. Conclusions: Increased risks of CV toxicity and comorbidities are observed among AML patients. With all the available diagnostic modalities, early detection and CV prevention strategies can improve the patient’s prognosis and quality of life. Full article

The clinical effectiveness of generic and brand-name cefepime in real-world settings remains unclear. Given the potential implications for healthcare costs and patient outcomes, this study aims to compare the efficacy and safety of these two formulations. We conducted a multicenter, retrospective cohort study (2017–2022), enrolling adults who received either generic or brand-name cefepime as initial monotherapy for at least three consecutive days. Demographics, comorbidities, disease severity, infection sites, cefepime dosage, and serial laboratory data were analyzed. Propensity score matching was employed to adjust key confounding variables. A total of 2370 patients were included, 877 receiving generic and 1493 receiving brand-name cefepime. After matching, no significant differences were observed in primary (in-hospital mortality, p = 0.841) or secondary outcomes (30-day mortality, readmission, length of stay, ICU stay, and incidence of seizures; all p > 0.05). Biomarker trends and clinical recovery patterns were comparable across groups. Receiving the maximal dosage or not did not alter outcomes among both groups. Generic cefepime showed comparable efficacy and safety to brand-name cefepime, offering a cost-effective alternative without compromising therapeutic outcomes. Full article

miRNAs are small non-coding RNA molecules that play critical roles in the regulation of gene expression and have been closely associated with various diseases, including cancer. These molecules significantly influence the cell cycle of tumor cells and control programmed cell death (apoptosis). Currently, research on miRNAs has become a major focus in developing cancer therapies. Osteosarcoma, a malignant neoplasm predominantly occurring during adolescence and later in life, is characterized by a high propensity for metastasis. This review explores the role of miRNAs in the initiation and progression of cancer, highlighting their potential as predictive biomarkers for disease. It discusses the mechanisms by which natural products modulate miRNA activity to influence apoptosis, ferroptosis, and autophagy in osteosarcoma cells, aiming to identify new strategies for osteosarcoma treatment. Recent studies on how natural products regulate miRNAs to reduce tumor cell resistance to chemotherapy are also reviewed. Furthermore, the review elaborates on how natural products regulate m6A modifications to influence miRNA expression, thereby exerting antitumor effects. In this process, interactions between m6A modifications and miRNAs have been identified, with both jointly influencing tumorigenesis and cancer progression, offering a new perspective in osteosarcoma treatment. These approaches could help uncover novel regulatory mechanisms in osteosarcoma pathways and provide a theoretical foundation for developing new drugs and identifying novel therapeutic targets. Full article

Background: Coronary heart disease is the most common cause of death worldwide. It is responsible for almost a third of deaths in patients over the age of 35. Various biomarkers are currently being studied in detail for their value in predicting postoperative mortality in patients undergoing CABG. Aim: The aim of this study is to analyze the predictive value of certain blood morphological parameters in CABG and off-pump coronary artery bypass grafting (OPCAB). Methods: A total of 520 patients who underwent surgery in two consecutive years and underwent CABG (404) or OPCAB (116) were included in this retrospective study. Gender, age, comorbidities, five-year survival rate, detailed information on hospitalization, surgery, intensive care unit parameters and preoperative blood samples from the cubital vein were recorded. Inverse propensity treatment weighting was applied to adjust for confounding factors at baseline. Results: No differences were found between OPCAB and CABG as an isolated comparison. In the standardized population, patients with abnormal lymphocyte counts had an increased risk of death at one-year and five-year follow-up. In the standardized population, abnormal red blood cell distribution width (RDW-SD), neutrocyte-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were associated with increased mortality in each period analyzed. Conclusions: Abnormal PLR, RDW-SD and NLR are associated with increased early and late mortality in patients undergoing CABG and OPCAB. Abnormal lymphocytes are only associated with increased late mortality. Full article

Wastewater-based epidemiology (WBE) evaluates the health status, environmental exposure, and lifestyle habits of community inhabitants through the investigation of chemical or biological markers present in urban wastewater systems. This approach is frequently employed in discerning drug abuse, disease prevalence, and the presence of environmental contaminants. To comprehend the current state and developmental trajectories in WBE research, the current study utilizes the source literature of the Web of Science Core Collection (WOSCC) database. Implementing the Bibliometrix toolkit in R language and employing CiteSpace and VOSviewer for bibliometric analysis, this investigative pursuit effectuates an all-encompassing evaluation of the WBE literature, traversing a substantial time span of 16 years, encompassing 2008 through 2023. The results of this bibliometric analysis illuminate annual propensities and disciplinary distribution related to WBE research, while discerning the most impactful and prolific contributors, including authors, institutions, countries, and scholarly journals. The onset of the COVID-19 pandemic has engendered the expedited progression of WBE, leading to a substantial escalation in research endeavors in the past three years. By meticulously evaluating highly-cited publications, co-occurrence network of keywords, and keyword burst analysis, it is concluded that the research hotspots in this field focus on the monitoring of illicit drugs, psychoactive substances, and viruses in sewage. Subsequent investigations possess the capacity to propel the advancement of emerging methodologies for biomarker identification and analytical techniques. By concurrently integrating big data technologies (including artificial intelligence and cloud computing) with epidemiological and clinical data sets, a more expansive, precise, and efficacious rendition of WBE research can be realized. Full article

Huntington’s disease (HD) is a chronic, inherited neurodegenerative condition marked by chorea, dementia, and changes in personality. The primary cause of HD is a mutation characterized by the expansion of a triplet repeat (CAG) within the huntingtin gene located on chromosome 4. Despite substantial progress in elucidating the molecular and cellular mechanisms of HD, an effective treatment for this disorder is not available so far. In recent years, researchers have been interested in studying cerebrospinal fluid (CSF) as a source of biomarkers that could aid in the diagnosis and therapeutic development of this disorder. Immunoglobulin heavy constant gamma 1 (IGHG1) is one of the CSF proteins found to increase significantly in HD. Considering this, it is reasonable to study the potential involvement of deleterious mutations in IGHG1 in the pathogenesis of this disorder. In this study, we explored the potential impact of deleterious mutations on IGHG1 and their subsequent association with HD. We evaluated 126 single-point amino acid substitutions for their impact on the structure and functionality of the IGHG1 protein while exploiting multiple computational resources such as SIFT, PolyPhen-2, FATHMM, SNPs&Go mCSM, DynaMut2, MAESTROweb, PremPS, MutPred2, and PhD-SNP. The sequence- and structure-based tools highlighted 10 amino acid substitutions that were deleterious and destabilizing. Subsequently, out of these 10 mutations, eight variants (Y32C, Y32D, P34S, V39E, C83R, C83Y, V85M, and H87Q) were identified as pathogenic by disease phenotype predictors. Finally, two pathogenic variants (Y32C and P34S) were found to reduce the solubility of the protein, suggesting their propensity to form protein aggregates. These variants also exhibited higher residual frustration within the protein structure. Considering these findings, the study hypothesized that the identified variants of IGHG1 may compromise its function and potentially contribute to HD pathogenesis. Full article

Circular RNAs (circRNAs) are stable, enclosed, non-coding RNA molecules with dynamic regulatory propensity. Their biogenesis involves a back-splicing process, forming a highly stable and operational RNA molecule. Dysregulated circRNA expression can drive carcinogenic and tumorigenic transformation through the orchestration of epigenetic modifications via extensive RNA and protein-binding domains. These multi-ranged functional capabilities have unveiled extensive identification of previously unknown molecular and cellular patterns of cancer cells. Reliable circRNA expression patterns can aid in early disease detection and provide criteria for genome-specific personalized medicine. Studies described in this review have revealed the novelty of circRNAs and their biological ss as prognostic and diagnostic biomarkers. Full article

Concurrent chemo-radiotherapy (CCRT) is linked with accelerated disease progression and early death (ED) in various cancers. This study aimed to assess the association of plasma levels of exosomal non-coding ribonucleic acid (RNA) (ncRNA) and blood cell dynamics with ED prediction in patients with cervical cancer undergoing CCRT. Using propensity score matching, a comparison of complete blood counts (CBCs) was performed among 370 CCRT-treated patients. Differences in ncRNA and messenger RNA (mRNA) expression before and after CCRT in 84 samples from 42 patients (cohort 2) were represented as logarithmic fold change (log₂FC). Networks were constructed to link the CBCs to the RNAs whose expression correlated with ED. From the key RNAs selected using multiple regression of all RNA combinations in the network, CBC dynamics-associated ncRNAs were functionally characterized using an enrichment analysis. Cohort 1 (120 patients) exhibited a correlation between elevated absolute neutrophil counts (ANC) and ED. Cohort 2 exhibited a prevalence of microRNA (miR)-574-3p and long intergenic non-protein coding (LINC)01003 ncRNA, whose expression correlated with ANC and hemoglobin values, respectively. Conversely, acyl-coenzyme A thioesterase 9 (ACOT9) mRNA was relevant to all CBC components. An integrative analysis of post-CCRT ncRNA levels and CBC values revealed that the patients with miR-574-3p-LINC01003-ACOT9 log₂FC) < 0 had a better prospect of 30-month disease-specific survival. These findings indicate that miR-574-3p and LINC01003 could serve as ED prognostic biomarkers. Full article