Search Results (3,295)

Usp21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of Usp21 dysfunction remain incompletely understood. In this study, we generated Usp21 knockout (KO) mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol (T-CHOL) and free fatty acid (FFA) in Usp21 KO mice compared to wild-type (WT) mice. Next, we performed RNA-sequencing (RNA-seq) to identify genes that Usp21 regulates. The results highlighted several candidate genes based on their biological relevance, and their expression levels were validated by RT-qPCR. The Usp21 KO mice exhibited significant elevations in the expression of the genes Fabp7, Nlrc5, and Ppargc1a, which play an important role in lipid metabolism, compared to WT. These data suggest that Usp21 may play roles in lipid metabolism in association with Fabp7, Nlrc5 and Ppargc1a. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single-nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was significantly associated with hypercholesterolemia. These data suggest that Usp21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in adolescents with obesity and is linked to insulin resistance and cardiovascular disease (CVD). Pancreas steatosis might be associated with MASLD and early CVD. Imaging-based analyses of these associations have not been studied extensively in children. Objectives: To assess the reproducibility of liver and pancreatic steatosis and volume measurement on MRI in adolescents with obesity and MASLD and their association with homeostatic model assessment of insulin resistance (HOMA-IR) and subclinical vascular changes on ultrasound. Methods: This is an observational study on adolescents with MASLD and obesity. Hepatic and pancreatic steatosis, volume, and abdominal fat were assessed using magnetic resonance spectroscopy and proton density fat fraction. Reproducibility of these measurements was performed. Vascular markers included non-invasive vascular elastography (NIVE), carotid artery intima-media thickness (IMT), and pericardial fat thickness. Fasting blood tests measured the HOMA-IR. Bivariate correlation and simple linear regression were performed using SPSS. Results: We obtained 23 participants aged 12 to 17 years (78.3% male). Measurements were reproducible [ICC 0.807–0.998]. Liver steatosis was positively correlated with HOMA-IR (p = 0.015). Pancreas steatosis was positively correlated with HOMA-IR (p = 0.02), IMT/diameter (p = 0.002), and pericardial fat (p = 0.03). Liver steatosis was not significantly correlated with pancreas steatosis nor vascular markers. There were negative associations between NIVE metrics and visceral abdominal fat (p = 0.009) and intraperitoneal fat (p = 0.047). Conclusions: Liver and pancreas steatosis measurements on MRI are reproducible. In this exploratory study, adolescents with obesity and MASLD, pancreas steatosis, and pancreas volume show association with subclinical CVD markers. Visceral and intraperitoneal abdominal fat show association with increased vascular stiffness, suggesting a potential role of imaging-based cardiovascular risk assessment in this population if validated. These preliminary findings require validation in larger, diverse prospective cohorts. Full article

Magnesium alloy represents a typical category of biodegradable medical materials. However, the poor corrosion resistance and rapid degradation have significantly hindered the clinical adoption of magnesium alloy implants. This paper puts forward a method to improve the corrosion resistance of magnesium alloy by using an Fe-based composite coating. The microstructure and composition of the coating were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive spectroscopy (EDS). The corrosion resistance was evaluated through potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurements conducted in simulated body fluid, while the degradation behavior of the samples was evaluated by examining the hydrogen evolution volume and corrosion morphology during immersion tests. The results indicate that the composite coating exhibits a dual-layer structure, consisting of an amorphous carbon–fluorine transition layer and an iron-rich surface layer. After coating treatment, the corrosion current density of magnesium alloy decreased from 1.38 × 10⁻⁴ to 3.41 × 10⁻⁶ A/cm². Throughout a 28-day immersion period, the composite-coated sample demonstrated a remarkably low hydrogen evolution rate and maintained a smooth, intact surface. Furthermore, hemolysis and platelet adhesion tests confirmed the outstanding blood compatibility of the composite-coated magnesium alloy, showing an ultralow hemolysis rate of 0.1% and minimal platelet adhesion with well-preserved morphology. Full article

Background: Maple syrup urine disease (MSUD) is a genetic disorder caused by mutations in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, leading to toxic buildup of branched-chain amino acids (BCAAs) and their ketoacid derivatives. While newborn screening (NBS) and molecular testing are standard diagnostic tools, they face challenges such as delayed results and false positives. Untargeted metabolomics has emerged as a complementary approach, offering comprehensive metabolic profiling and potential for novel biomarker discovery. We previously applied untargeted metabolomics to neonates with MSUD, identifying distinct metabolic signatures. Objective: This follow-up study investigates metabolic changes and biomarkers in pediatric MSUD patients and explores shared dysregulated metabolites between neonatal and pediatric MSUD. Methods: Dried blood spot (DBS) samples from pediatric MSUD patients (n = 14) and matched healthy controls (n = 14) were analyzed using LC/MS-based untargeted metabolomics. Results: In pediatric MSUD, 3716 metabolites were upregulated and 4038 downregulated relative to controls. Among 1080 dysregulated endogenous metabolites, notable biomarkers included uric acid, hypoxanthine, and bilirubin diglucuronide. Affected pathways included sphingolipid, glycerophospholipid, purine, pyrimidine, nicotinate, and nicotinamide metabolism, and steroid hormone biosynthesis. Seventy-two metabolites overlapped with neonatal MSUD cases, some exhibiting inverse trends between age groups. Conclusion: Untargeted metabolomics reveals that the metabolic profiling of MCUD pediatric patients different from that of their controls. Also, there are valuable age-specific and shared metabolic alterations in MSUD, enhancing the understanding of disease progression in MSUD patients. This supports its utility in improving diagnostic precision and developing personalized treatment strategies across developmental stages. Full article

Clusterin plays an important role in carcinogenesis and serves as an important diagnostic biomarker of various clinical conditions. This work describes an application of a surface-enhanced Raman scattering (SERS)-based immunoassay using Al foil substrate that has the potential for the detection of clusterin. We first optimized the parameters of the assay using anti-human IgG/human IgG (hIgG) as a model antibody/antigen system using various substrates based on Au film, Si, Al tape and Al foil. Among the tested substrates, Al foil exhibited better performance, when assay of human IgG on Al foil demonstrated a detection limit of 2 pM and a semi logarithmic trend range from 10 pM to 1000 pM. Afterwards, the same SERS immunoassay method was implemented for detection of clusterin and resulted in a good semi-logarithmic calibration line with a high R² value of 0.99, which was obtained in the range from 1 ng/mL to 1000 ng/mL. The low detection limit for clusterin antigen was found to be 3 ng/mL, which is better than most LODs for clusterin reported in the literature and also nearly 4 orders of magnitude lower than possible concentrations of clusterin in human blood. Moreover, the assay requires a relatively low volume of sample (10 μL). Overall, the assay performance demonstrates the significant potential of SERS on Al foil as a low-cost/high-availability substrate for sensing and biosensing, including detection of cancer biomarkers. Full article

Effective treatment of central nervous system (CNS) infections remains a major challenge, as most therapeutic agents do not efficiently cross the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). Coumarin derivatives are of particular interest due to their broad pharmacological activity, favorable safety profile, and potential to penetrate biological barriers. Eight novel coumarin-based peptidomimetics functionalized with trifluoromethyl or methyl scaffolds were synthesized and evaluated as antimicrobial agents with the ability to cross the blood–brain barrier. Antimicrobial activity of the investigated compounds was tested against Staphylococcus aureus and multiple Escherichia coli strains (K12, R2, R3, R4) using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Cytotoxicity was assessed in vitro in BALB/c-3T3 mouse fibroblasts and αT3-1 pituitary gonadotrope cells using the MTT assay. In vivo studies were performed in sheep to assess transfer of the compounds from blood to cerebrospinal fluid (CSF). All synthesized derivatives demonstrated antimicrobial activity and acceptable cytotoxicity, comparable to those of clinically used antibiotics. CF₃-modified coumarin peptidomimetics show promise as antimicrobial agents with the potential to penetrate the BBB/BCSFB. These findings support further investigation of coumarin-based scaffolds as a platform for the development of novel therapeutics for CNS infections. Full article

Background/Objectives: Excessive alcohol consumption leads to hangovers, which cause discomfort and reduce work efficiency, resulting in socioeconomic losses. Theracurmin, known for its antioxidant and hepatoprotective properties, may help mitigate these effects. We evaluated the efficacy and safety of two Theracurmin-based products in alleviating hangover symptoms in humans. Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted in 27 healthy adults, with a balanced distribution of men and women. Two formulations were tested: Ready Q, containing Theracurmin, Hovenia dulcis Thunb. extract powder, and L-glutathione yeast extract; and Theracurmin, containing only Theracurmin. The products were administered on designated visit days, followed by an alcohol challenge 30 min after administration. Blood and breath alcohol profiles were assessed 15 h post-consumption, and participants completed a hangover symptom questionnaire. Results: Compared to placebo, Ready Q resulted in a significantly lower area under the curve (AUC) for serum alcohol concentration (−94.92 mg·h/dL [−170.91, −18.93]), as well as lower AUC (−8.441 mg·h/dL [−11.713, −5.169]) for serum acetaldehyde. Theracurmin showed similar effects, with reduced AUC (−117.21 mg·h/dL [−194.20, −40.22]) for serum alcohol concentration, and lower AUC (−8.161 mg·h/dL [−12.597, −3.725]) for corrected serum acetaldehyde levels. Conclusions: These findings suggest that both products effectively enhance alcohol metabolism in healthy adults, underscoring their potential as interventions for alleviating alcohol hangovers. Full article

Microphysiological systems (MPSs) have emerged as alternatives to animal testing in drug development, following the FDA Modernization Act 2.0. Double-layer channel-type MPS chips with porous membranes are widely used for modeling various organs, including the intestines, blood–brain barrier, renal tubules, and lungs. However, these chips faced challenges owing to optical interference caused by light scattering from the porous membrane, which hinders cell observation. Trans-epithelial electrical resistance (TEER) measurement offers a non-invasive method for assessing barrier integrity in these chips. However, existing electrode-integrated MPS chips for TEER measurement have non-uniform current densities, leading to compromised measurement accuracy. Additionally, chips made from polydimethylsiloxane have been associated with drug absorption issues. This study developed an electrode-integrated MPS chip for TEER measurement with a uniform current distribution and minimal drug absorption. Through a finite element method simulation, electrode patterns were optimized and incorporated into a polyethylene terephthalate (PET)-based chip. The device was fabricated by laminating PET films, porous membranes, and patterned gold electrodes. The chip’s performance was evaluated using a perfused Caco-2 intestinal model. TEER levels increased and peaked on day 5 when cells formed a monolayer, and then they decreased with the development of villi-like structures. Concurrently, capacitance increased, indicating microvilli formation. Exposure to staurosporine resulted in a dose-dependent reduction in TEER, which was validated by immunostaining, indicating a disruption of the tight junction. This study presents a TEER measurement MPS platform with a uniform current density and reduced drug absorption, thereby enhancing TEER measurement reliability. This system effectively monitors barrier integrity and drug responses, demonstrating its potential for non-animal drug-testing applications. Full article

African swine fever (ASF) remains a major threat to swine production in Central Luzon, Philippines. This study assessed ASF detection and farm-level risk factors in Central Luzon using a risk-based surveillance framework. Pooled blood samples from five pigs per farm were collected in 277 farms across seven provinces and tested by real-time PCR. The analysis yielded an apparent farm-level prevalence of 26.7% (95% CI: 21.6–32.3), defined by one pooled 5-pig blood sample per farm. However, these values reflect risk-based surveillance outcomes rather than population-representative prevalence. Detection varied by province, with high rates in Bataan (80.5%) and Nueva Ecija (55.0%), moderate detection in Zambales (24.3%), lower detection in Pampanga (5.0%) and Tarlac (20.0%), and no positives in Aurora or Bulacan. Survey data were available for 201 farms. Firth-penalized logistic regression identified the absence of perimeter fencing as the only statistically significant predictor of ASFV detection. Veterinary oversight and consultancy showed protective but non-significant trends. These results highlight structural and professional biosecurity gaps, emphasizing the need for expanded veterinary outreach, fencing support, and training to mitigate ASF risk in smallholder-dominated production systems. Full article

Background/Objectives: Type 2 diabetes (T2D) is a pressing public health challenge in the United States (U.S.). Community-based diabetes education programs equip individuals with T2D with the knowledge and skills to improve dietary behaviors, build confidence, and better manage their condition to reduce complications. However, few studies evaluate self-care adherence and self-efficacy together. This study examined participant adherence to diabetes self-care practices and confidence in managing diabetes through a community-based education program. Methods: Do Well, Be Well with Diabetes (DWBWD) is a 5-week program focused on reinforcing the best practices in diabetes management through dietary practices, physical activity, and gaining self-confidence in managing T2D. The program was evaluated among 137 participants across 14 Texas counties using pre- and post-surveys that assessed the number of days per week participants engaged in diabetes self-care practices, as well as their confidence in performing these behaviors (rated on a scale from 1 = not at all confident to 5 = extremely confident). Results: Participants were mostly male (75.9%), White (60.6%), and over 65 years (58.4%). Most participants had T2D (57.7%) or prediabetes (27.0%). Compared to the program entry, participants reported improvements (p < 0.001) in self-care practices, as reflected by their mean differences (MD), including following a healthful eating plan (MD −1.46), consuming five servings of fruit and vegetables (MD −0.87), spacing carbohydrate intake evenly throughout the day (MD −1.64), engaging in at least 30 min of daily physical activity (MD −0.74), testing blood glucose (MD −1.08), and checking their feet (MD −1.09). Confidence in performing all self-care behaviors significantly improved (p < 0.001), with MDs between −0.53 and −1.13, indicating higher post-program scores. Conclusions: Participation in the DWBWD program increased confidence in diabetes management and enhanced engagement in key health behaviors associated with reducing diabetes complications. Full article

Liquid biopsies promise major advantages for cancer screening and diagnosis. By detecting biomarkers in peripheral blood samples, liquid biopsies reduce the need for invasive techniques and provide important genetic information integral to the emerging molecular classification of cancers. Unfortunately, the concentrations of most biomarkers, particularly circulating tumour nucleic acids, are vanishingly small—beyond the sensitivity and specificity of most assays. Clustered Regularly Interspaced Short Palindromic Repeats diagnostics (herein labelled ‘CRISPR-Dx’) use gene editing tools to detect, rather than modify, nucleic acids with extremely high specificity. These tools are commonly combined with isothermal nucleic acid amplification to also achieve sensitivities comparable to high-performance laboratory-based techniques, such as digital PCR. CRISPR assays, however, are inherently well suited to adaptation for point-of-care (POC) use, and unlike antigen-based POC assays, are significantly easier and faster to develop. In this review, we summarise current CRISPR-Dx platforms and their analytical potential for cancer biomarker discovery, with an emphasis on enhancing early diagnosis, disease monitoring, point-of-care testing, and supporting cancer therapy. Full article

 COVID-19 infection is often accompanied by psychological symptoms, which may persist long after the end of the infection (long COVID). The symptoms include fatigue, cognitive impairment, and anxiety. The reason for these long-term effects is currently unclear. Therapeutic approaches have included cognitive rehabilitation therapy, physical activity, and serotonin reuptake inhibitors (SSRIs) if depression co-exists. The neuropsychological evaluation of subjects with suspected cognitive issues is essential for the correct diagnosis. Most of the COVID-19 studies used the Montreal Cognitive Assessment (MoCA) or the Mini Mental State Examination (MMSE). However, MoCA scores can be confusing if not interpreted correctly. For this reason, we have developed an original technique to map cognitive domains and motor performance on various brain areas in COVID-19 patients aiming at improving the follow-up of long-COVID-19 symptoms. To this end, we retrospectively reanalyzed data from a cohort of 40 patients hospitalized for COVID-19 without requiring intubation or hemodialysis. Cognitive function was tested during hospitalization and six months after. Global cognitive function and cognitive domains were retrieved using MoCA tests. Laboratory data were retrieved regarding kidney function, electrolytes, acid–base, blood pressure, TC score, and P/F ratio. The dimensionality of cognitive functions was represented over cortical brain structures using a transformation matrix derived from fMRI data from the literature and the Cerebroviz mapping tool. Memory function was linearly dependent on the P/F ratio. We also used the UMAP method to reduce the dimensionality of the data and represent them in low-dimensional space. Six months after hospitalization, no cases of severe cognitive deficit persisted, and the number of moderate cognitive deficits reduced from 14% to 4%. Most cognitive domains (visuospatial abilities, executive functions, attention, working memory, spatial–temporal orientation) improved over time, except for long-term memory and language skills, which remained reduced or slightly decreased. The Cerebroviz algorithm helps to visualize which brain regions might be involved in the process. Many patients with COVID-19 continue to suffer from a subclinical cognitive deficit, particularly in the memory and language domains. Cerebroviz’s representation of the results provides a new tool for visually representing the data.  Full article

Background/Objectives: Hepatitis B virus (HBV) remains a persistent challenge for transfusion safety. Although testing for hepatitis B surface antigen (HBsAg) and nucleic acid testing (NAT) reduces transmission risk, antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis B surface antigen (anti-HBs) provide additional insight into past infection and vaccine-induced immunity. We aimed to determine their seroprevalence among blood donors in southern Croatia and assess associations with age, occupation, and time since vaccination. Methods: This cross-sectional study was conducted between February and November 2024 at two regional transfusion centers in southern Croatia. A total of 1008 voluntary blood donors, all HBsAg- and NAT-negative, were tested for anti-HBc and anti-HBs using chemiluminescent microparticle immunoassay. Demographic and vaccination data were collected through verified medical records. Results: Anti-HBc was detected in 0.5% of donors, exclusively among the unvaccinated. Protective anti-HBs levels were found in 38.1% overall and 70.6% of vaccinated donors, with significant declines by age and more than 15 years post-vaccination (p = 0.024). Healthcare workers showed higher seroprotection than non-healthcare donors (67.0% vs. 35.1%; p < 0.001), although one-third still lacked protective levels. Conclusions: HBV exposure was rare, but waning vaccine-induced immunity was evident, with protective anti-HBs levels in 70.6% of vaccinated donors, declining with age and time since vaccination. These findings highlight the need for periodic monitoring of anti-HBs and targeted booster strategies, especially in older and occupationally exposed groups. HBsAg and NAT provide a high level of transfusion safety, while the role of routine anti-HBc testing in this low-endemic context should be carefully evaluated in view of its potential benefits and drawbacks. Donor-based surveillance is a valuable tool for evaluating long-term vaccine effectiveness and guiding public health policy. Full article

Background: Bisphenols (BPs) are present in medical instruments, plastic containers, and personal care products (PCPs). Bisphenol A has been replaced by its alternatives, bisphenol S, F, AF, and B. Due to the awareness of their toxicity, mixed exposure to these alternatives at the regional level has been given less attention; there is a need to study this area of research. This meta-analysis examined the exposure of urinary bisphenol A and its metabolites to blood Hypothalamic–Pituitary–Thyroid axis hormones (HPT axis hormones) in pregnant women and adult males and females. We searched Embase, PubMed, Web of Science, Cochrane Library, and CINAHL until 8 January 2025, yielding 4588 articles using the PECO framework. Quality assessment was done using AHRQ: Agency for Healthcare Research and Quality for cross-sectional and NOS: Newcastle Ottawa Scale for cohort studies, with combined exposure evaluated using random and fixed-effect models. The I² test assessed heterogeneity. We included eighteen studies for the final analysis. Fixed-effect model estimates revealed that BPA is negatively associated with thyroid-stimulating hormone (TSH) in female and male adults (β = −0.02; 95% CI = −0.04 to −0.01); (β = −0.08; 95% CI = −0.14 to −0.02). In Females, BPA was positively associated with free thyroxine, FT4 (β = 0.001, 95% CI, 0.001 to 0.001). In the male group, BPA was negatively associated with FT4 (β = −0.001, 95% CI, −0.001 to −0.001). As per pregnant women, there was no association found between exposure to bisphenols and total Thyroxine (TT4), FT4, and TSH in both trimesters (β = 0.010, 95% CI = −0.030 to 0.050); (β = 0.001, 95% CI = −0.010 to 0.010); (β = −0.001, 95% CI = −0.010 to 0.001), respectively, for early pregnancy. Bisphenols can significantly influence HPT axis hormones in adult males, females, and pregnant women. Gender-based studies were observed, concluding that adult females are more affected by bisphenol exposures than adult males. The subgroup analysis based on the regions did not reveal any associations. Full article

Iron overload-driven liver fibrosis is a major concern in β-thalassaemia patients, but non-invasive or minimally invasive biomarkers for fibrosis staging remain limited. This study evaluated five plasma microRNAs (let-7a, miR-21, miR-29a, miR-34a, and miR-122) as potential markers for distinguishing liver fibrosis stages in β-thalassaemia. Plasma samples from 40 patients with fibrosis stages F0–F1 to F4 were analysed using RT-qPCR, normalised against the arithmetic mean of reference miRNAs miR-16 and miR-221. Expression levels of candidate miRNAs showed no statistically significant variation across stages, and logistic regression and ROC analyses revealed fair discriminatory performance for individual miRNAs and their combinations in selected stage comparisons. Notably, while for the discrimination of different fibrosis stages all five candidate miRNAs tested showed fair area-under-the-curve values between 0.7 and 0.8 individually and up to 0.917 in combination, none of these findings reached statistical significance. These results suggest that while the selected set of miRNAs reflects liver injury, its performance for precise fibrosis staging in β-thalassaemia is limited. A key cause for the low discriminatory power of these miRNAs may be the overall change of the blood miRNA transcriptome in haemoglobinopathies. The results indicate the need for validation in larger cohorts based on larger miRNA panels or the use of alternative source materials to improve diagnostic performance. Full article