Search Results (453)

Background/Objectives: Routine liver biopsies play an important role in monitoring liver allografts but carry non-negligible risks. This pilot study assesses the feasibility of dynamic long-axial field-of-view (LAFOV) [¹⁸F]FDG PET/CT as a non-invasive alternative to biopsy. Methods: Liver transplant (LTx) recipients meeting the inclusion criteria of ≥10 months post-transplantation and scheduled routine biopsy were prospectively enrolled, along with healthy controls. All participants underwent dynamic LAFOV [¹⁸F]FDG PET/CT, followed by biopsy in LTx recipients, who were stratified by inflammatory severity using the BANFF score. Hepatic kinetic parameters (K1, k2, k3, k4) and SUVmean/SUVmax were compared using Mann–Whitney U tests. Correlations were assessed using Spearman’s rank correlation. A p-value < 0.05 was considered significant. Analyses were performed in RStudio (version 2024.12.10563). Results: Sixteen LTx recipients (mean age 48.6 years; seven female, nine male) and eight healthy controls (mean age 35.4 years; six female, two male) were included. Healthy controls had mean k3 and k4 values of 0.0037 min⁻¹ ± 0.0003 min⁻¹ and 0.0019 min⁻¹ ± 0.0011 min⁻¹, respectively. LTx recipients showed significantly higher k3 and k4 values, both when including and excluding patients with biopsy-confirmed inflammation. Descriptive comparisons between LTx recipients with and without significant inflammation (n = 3) showed no clear differences. Spearman analysis showed no significant correlations between the BANFF score and kinetic parameters. The strongest degree of correlation was found between BANFF score and k3, indicating a moderate positive but non-significant association (k3: rs = 0.396, p = 0.128). Conclusions: Elevated k3 and k4 values in LTx recipients were not explained by allograft inflammation, suggesting altered FDG kinetics post-transplant. These differences may confound [¹⁸F]FDG PET interpretation. Larger studies are needed to assess the clinical applicability of dynamic LAFOV [¹⁸F]FDG PET/CT. Full article

Endothelial dysfunction, chronic inflammation, immune dysregulation, oxidative stress, mitochondrial dysfunction, and metabolic disturbances collectively contribute to cardiovascular diseases (CVDs) associated with blood stasis patterns. Xuefu Zhuyu Decoction (XFZYD) is widely used clinically for the management of CVDs. Based on serum-exposed prototype profiling in rats, two pharmacology-driven core component sets of XFZYD were defined as the core set for the promotion of blood circulation and the elimination of blood stasis (CPBEB; HSYA, GRo, FA, β-ECD, AMY, ALB, PF) and the core set for the regulation of qi and the relief of pain (CRQRP; LIQ, NR, NAR, ROF, HSD, NHP, LTG, NRG, ISL, FNT, NOB, PD, SSa). CPBEB primarily targets vascular pathology by regulating endothelial dysfunction with dyslipidemia-driven arterial lipid deposition. Mechanistically, CPBEB is associated with improved endothelial function, reduced plaque instability, attenuated chronic inflammation and oxidative stress, normalized lipid and bile acid metabolism, and decreased thrombosis. CRQRP primarily modulates vascular tone and systemic energy metabolism. These effects are linked to enhanced AMPK/SIRT1-driven antioxidant defenses and mitochondrial homeostasis, increased NO/cGMP signaling, coordinated crosstalk among the TLR4/NF-κB, JAK/STAT, NLRP3, and PPAR pathways, and remodeling of the gut microbiota–immune network. In summary, this review integrates modern analytical approaches with network pharmacology and the literature evidence to clarify the material basis underlying XFZYD’s therapeutic effects in CVDs, thereby supporting the modernization and internationalization of traditional Chinese medicine. Full article

Chemokine CXCL1, also known as Gro-α and MGSA, a ligand of CXCR2, is the best-known CXC chemokine in cancer processes, after CXCL8/IL-8 and CXCL12/SDF-1. This paper is the first review on the role of CXCL1 in general molecular processes associated with cancer. It provides a comprehensive overview that allows for an in-depth understanding of the importance of CXCL1 in tumor-related processes. In this review, however, we did not address the clinical aspects of CXCL1, as these were discussed in our previous review articles. The present paper focuses on the involvement of CXCL1 in cancer processes such as proliferation, cancer stem cell (CSC) function, senescence, angiogenesis, lymphangiogenesis, migration and metastasis, and effects on tumor-associated cells such as neutrophils, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs). It also describes the significance of CXCL1 in cancer-associated diseases such as cancer cachexia, cancer-associated immunodeficiency, neuroinflammatory-mediated affective-like behaviors, bone cancer pain, and acute kidney injury. We also present the effects of obesity on CXCL1-related cancer processes. Full article

The Green Oasis (GRO) Project is a targeted urban greening intervention designed to evaluate the environmental and health impacts of compact, high-density plantings in dense built environments. Initiated in downtown Louisville, the project transformed Founders Square, a 0.64-acre sparsely planted park, into a microforest (“Trager Microforest”), a multilayered planting of 119 trees and more than 200 shrubs. The impact of this intervention is being assessed through a randomized crossover study in which participants walk in the microforest and a nearby impervious parking lot. Physiological outcomes include heart rate, heart rate variability, arterial stiffness, and stress biomarkers measured in saliva, urine, and sweat. Environmental conditions are continuously monitored by fixed and mobile weather stations, air pollution sensors, and biodiversity surveys. Baseline assessments were conducted in 2023 and 2024, with post-planting evaluations now underway (2025–). Power calculations indicate adequate sensitivity (n ≈ 40–50) to detect changes in cardiovascular stress responses in participants. Complementary ecological measurements include soil microbiome composition, greenhouse gas fluxes, and avian diversity. This study addresses critical gaps in understanding how small-scale, high-density greening interventions affect cardiovascular resilience, stress physiology, and microclimatic regulation. By integrating environmental, biological, and human health data, GRO establishes a comprehensive framework for evaluating the efficacy of urban microforests as nature-based solutions. The results are expected to inform urban planning, public health strategies, and climate adaptation policies, demonstrating how compact greening interventions can simultaneously mitigate heat, reduce pollution, enhance biodiversity, and promote human wellbeing in dense urban cores. Full article

Ticks are important vectors of bacterial pathogens with veterinary and public health significance. However, information on the diversity of tick-associated bacteria in forest ecosystems of northeastern China remains limited. In this study, 821 questing ticks were collected from Huoshankou National Forest Park in Mudanjiang City, Heilongjiang Province, and identified as Haemaphysalis japonica, Hae. concinna, and Ixodes persulcatus. Molecular screening based on rrs gene amplification detected Anaplasma, Ehrlichia, and Coxiella-like endosymbionts (CLE), which were further characterized using multilocus phylogenetic analyses. Anaplasma bovis was detected in Hae. concinna and exhibited two distinct genotypes. In addition, a potentially novel Anaplasma lineage was identified in I. persulcatus. Phylogenetic analyses based on the rrs, gltA, and groEL genes consistently placed this lineage in a separate clade from currently recognized Anaplasma species. Furthermore, two genetically distinct Ehrlichia lineages were detected in Hae. japonica and Hae. concinna. Two lineages of tick-associated CLE were also characterized using five genetic genes. Overall, these findings demonstrate considerable genetic diversity of tick-associated bacteria in forest ecosystems of northeastern China and expand current understanding of their molecular diversity. Further studies incorporating broader sampling and genome-based analyses will be necessary to clarify their taxonomic status and epidemiological relevance. Full article

The cause of chronic neurological effects associated with Lyme disease (LD) remains unclear. We propose that bacterial extracellular vesicles (BEVs) released by Borrelia burgdorferi, the causative agent of LD, exacerbate spirochete-induced damage and serve as a persistent source of antigenic stimulation. We showed that, over a 10-day period, in vitro cultures of B. burgdorferi B31 produced 38,000 BEVs per spirochete with a distinctive double-membrane structure and median diameter of 143.3 nm. BEVs contained known immunogenic and immunomodulatory molecules such as peptidoglycan, p66, flagellar filament protein (FlaB), basic membrane proteins A/B/D, BdrV, GroEL, CRASP-1, ErpA8, glycerophosphodiester phosphodiesterase, p37, OMS28, p13, OspA/B/C, VlsE, and outer membrane glycolipids (e.g., cholesteryl 6-O acyl beta D galactopyranoside). Chromosome-encoded 16S ribosomal RNA and cp32 plasmid-encoded OspE and terminase genes were also detected in the BEVs. Of the 45 Borrelia proteins identified in the urine of a C3H/HeJ murine model of Lyme disease, 14 were associated with BEVs. In human urine samples, 31 of 289 spirochete proteins detected in patients with either acute Lyme disease or persistent borreliosis post-treatment symptoms, including p66 and FlaB, were also BEV-associated. BEV treatment of HMC3 human microglial cells reduced phagocytic activity and triggered aberrant activation of inflammatory and immunometabolic pathways, including upregulation of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and Toll-like receptor 2 (TLR2) gene expression. BEVs also induced NRF2 nuclear translocation. In conclusion, these findings support that BEVs can amplify spirochete-induced damage and act as antigenic debris, driving dampened phagocytic activity and dysregulated inflammation, with implications for diagnostics and therapeutics targeting vesicle-mediated pathology. Full article

In this paper, we propose a metaheuristic optimization algorithm called Adaptive Gold Rush Optimizer (AGRO), a substantial evolution of the original Gold Rush Optimizer (GRO). Unlike the standard GRO, which relies on fixed probabilities in the strategy selection process, AGRO utilizes a novel adaptive mechanism that prioritizes strategies improving solution quality. This adaptive component, which can be applied to any optimization algorithm with fixed probabilities in the strategy selection, adjusts the probabilities of the three core search strategies of GRO (Migration, Collaboration, and Panning), in real time, rewarding those that successfully improve solution quality. Furthermore, AGRO introduces fundamental modifications to the search equations, eliminating the inherent attraction towards the zero coordinates, while explicitly incorporating objective function values to guide prospectors towards promising regions. Experimental results demonstrate that AGRO is highly competitive against ten state-of-the-art algorithms on the twenty-three classical benchmark functions, the CEC2017, and the CEC2019 datasets, offering robust performance across diverse problem landscapes. Full article

Background/Objectives: Objective and reproducible evaluation of glabellar lines remains challenging, as current clinical assessments rely largely on subjective rating scales and two-dimensional photography, which lack depth information. This study aimed to assess the clinical utility of a laser-based three-dimensional (3D) imaging approach for objective quantitative evaluation of glabellar lines in adults undergoing botulinum toxin treatment. Methods: A laser-based 3D imaging system was used to quantitatively measure glabellar line morphology. System accuracy for area, perimeter, volume, and depth was evaluated using standardized physical models. In a prospective observational study, 31 adults with moderate-to-severe glabellar lines undergoing routine botulinum toxin treatment were assessed at baseline, day 7, and week 4. Quantitative 3D measurements were compared with clinician- and participant-reported severity scores, as well as patient satisfaction and Global Rating of Outcome (GRO) scores. Results: The 3D imaging measurements demonstrated high geometric measurement precision, with errors ≤2% for area, perimeter, and volume, and ≤0.5 mm for depth. Significant reductions in wrinkle depth were observed after treatment. Quantitative 3D measurements showed moderate correlations with clinician-reported scores (r = 0.53–0.54) and participant-reported scores (r = 0.59–0.66). Improvement rates derived from 3D measurements were positively correlated with patient satisfaction and GRO scores. Conclusions: Laser-based 3D imaging provides an objective and quantitative approach for evaluating glabellar lines and treatment response to botulinum toxin. This method may complement conventional clinical assessments and support further validation in larger clinical studies. Full article

We report a rare case of polymicrobial late-onset knee prosthetic joint infection (PJI) caused by Parvimonas micra and Staphylococcus aureus. An 80-year-old woman with multiple comorbidities presented, five years after total knee arthroplasty, with progressive pain and radiographic signs of prosthetic loosening. Synovial fluid analysis revealed marked neutrophilic inflammation, and intraoperative tissue cultures, including sonication fluid yielded both pathogens. Identification was confirmed by MALDI-TOF MS and whole-genome sequencing (WGS). The P. micra strain showed 97.2% identity to reference strain SAMN29629855, and carried virulence genes such as groEL, tufA, clpP, ctrD, srtC4, and gaIE, associated with oxidative stress response, adhesion, immune evasion, and biofilm formation. Resistance genes vanW, vanT, and vanY from the van operon were also detected, though vanA and vanB were absent. The patient underwent a two-stage revision surgery and a 12-week course of pathogen-targeted antimicrobial therapy, with complete resolution of symptoms and no recurrence after 12 months. This case highlights the overlooked pathogenicity of P. micra in chronic PJIs, especially in polymicrobial biofilm-related infections. The integration of WGS provided valuable insights into possible genetic characteristics of virulence determinants of this rare cause of PJI. Full article

Background/Objectives: New guidelines for management of metabolic-dysfunction-associated steatotic liver disease (MASLD) patients recommend an individualized medicine approach mainly targeting patients with fibrotic metabolic-dysfunction-associated steatohepatitis (MASH) and metabolic risk factors for progression of disease. This cohort study reports real-world experience for the individual evaluation and final diagnosis of patients on suspicion of fibrotic MASH according to standardized international criteria. We aimed to identify patients with significant fibrosis (F2–F4). Methods: Adult patients with metabolic syndrome and/or elevated alanine aminotransferases (ALT > 50) referred in a 5-year period (2018–2022) on suspicion of fibrotic MASH were included. Medical history, anthropometric measurements, and routine (blood tests, ultrasound) and specific examinations were applied. Liver biopsy was offered for definite diagnosis and to evaluate MASLD characteristics. Patient demographics and characteristics as well as the absolute number and proportion of patients with definite MASLD and fibrotic MASH are reported. Results: A total of 137 adult patients were included. Ten percent of patients were evaluated without liver biopsy and diagnosed with chronic liver diseases other than MASLD. Liver-biopsied patients (n = 123) had a mean age (SD) of 49 (14) years, and 50% were males. Overweight or obesity was present in 94%, dyslipidemia in 74%, hypertension in 40%, and type 2 diabetes mellitus in 34%. Of all 137 patients, 104 (76%) were diagnosed with definite MASLD and 80 (58%) with definite MASH. A total of 74 (54%) patients had definite fibrotic MASH, while 41 (30%) had significant (F2–4) fibrotic MASH. Eight patients (6%) had cirrhotic (F4) MASH. A multivariate logistic regression analysis indicated that patients with type 2 diabetes, older age, and higher BMI were associated with an apparent increased risk of F2–F4 fibrosis. Conclusions: The majority of referred patients had cardiometabolic–hepatic metabolic risk factors and were diagnosed with definite MASLD. More than half of these were diagnosed with fibrotic MASH. Older age, type 2 diabetes, and higher BMI were apparent risk factors for MASH F2–F4 fibrosis. We conclude that the individual cardiovascular–hepatic risk profile applied supports the new guidelines and may be useful for referral and further evaluation at expert care centers in a real-world setting. Full article

Background: Scrub typhus is commonly misdiagnosed because of nonspecific clinical features and limited data on the performance of diagnostic tests. This study aimed to evaluate the accuracy of commercially available serological and molecular assays for diagnosing scrub typhus. Methods: Adult patients with suspected scrub typhus who visited a tertiary-care hospital in South Korea from July 2022 to December 2024 were prospectively enrolled. Scrub typhus was confirmed by either a positive real-time polymerase chain reaction (PCR) result for Orientia tsutsugamushi or a ≥ four-fold increase in the O. tsutsugamushi-specific total immunoglobulin (Ig) antibody titer on an immunofluorescence assay (IFA). The diagnostic performances of the serial IFA, an immunochromatography-based rapid diagnostic test (ICT), and multiplex real-time PCR targeting the groEL and 47-kDa genes were compared. Results: Among 159 patients, 81 had scrub typhus and 78 did not. The sensitivity and specificity were 64% and 100% for the serial IFA, 75% and 91% for the ICT, and 95% and 100% for multiplex PCR, respectively. The area under the curve was significantly higher for the ICT (0.819) than for the acute-phase IFA (0.743, p = 0.02). Conclusions: Multiplex real-time PCR provided rapid and highly accurate confirmation of scrub typhus, and an acute-phase ICT may be an alternative to a single acute-phase IFA for early clinical decision-making. Full article

NMR spectroscopy enables the study of complex mixtures, including plant extracts. The interpretation of specific ranges of ¹H NMR spectra allows for the determination of polyphenolic compound, sugar, amino acid, and fatty acid profiles. The main goal of ¹H NMR analyses of plant extracts is to identify the unique “fingerprint” of the material being studied. The aim of this study was to determine the metabolomic profile and antioxidant activity of various Lavandula angustifolia (Betty’s Blue, Elizabeth, Hidcote, and Blue Mountain White) and Lavandula × intermedia cultivars (Alba, Grosso, and Gros Bleu) grown in Poland. Modern green chemistry extraction methods (supercritical fluid extraction (SFE) and ultrasound-assisted extraction (UAE)) were used to prepare the lipophilic and hydrophilic extracts, respectively. The secondary metabolite profiles were determined using the diagnostic signals from ¹H NMR and HPLC-DAD analyses. These metabolomic profiles were used to illustrate the differences between the different lavender and lavandin cultivars. The HPLC-DAD analysis revealed that both lavender species have similar polyphenolic profiles but different levels of individual compounds. The extracts from L. angustifolia were characterized by higher phenolic acid and flavonoid contents, while the extracts from L. × intermedia had a higher coumarin content. Diagnostic ¹H NMR signals can be used to verify the authenticity and origin of plant extracts, and identify directions for further research, providing a basis for applications such as in cosmetics. Full article

Heat shock protein (HSP) gene families are known to be expressed preferentially over normal cellular proteins when poultry cells are exposed to environmental stressors. Bordetella avium infection leads to bordetellosis, which is characterized by severe inflammation of the tracheal epithelium, representing a severe stressor for the infected turkey poult. The purpose of this experiment was to examine the expression of HSP60 and HSP70 in the tracheae of B. avium-challenged poults. Tracheae were dissected from five poults per treatment at 7, 11, 14, and 21 days of age, and snap-frozen rings were examined immunohistochemically for the presence of HSP60 and HSP70 using HSP60 and HSP70 monoclonal antibodies (MABs). Infected poults expressed HSP60 predominantly on the apical surface of ciliated epithelial cells and weakly near the nucleus, and HSP70 was expressed only in the cytoplasm. Early in the development of bordetellosis, infected poults expressed more HSP60 and HSP70 than control poults of the same age, but at 14 days after infection, infected birds showed significantly decreased HSP60 proteins, which was associated with loss of tracheal epithelium. With loss of tracheal epithelium, the expression of HSP70 decreased at 11 days in the infected poults, and by day 21, very low levels of the proteins were observed in the infected poults compared to control poults with intact tracheal epithelium. It was concluded that decreased expression of HSP60 was indicative of HSP60 proteins becoming antigenic targets for the host’s immune system since immunologically targeted B. avium cells express GroEL (highly conserved HSP60 family equivalent) and DnaK (highly conserved HSP70 equivalent). The potential targeting of host and pathogen HSP60 by the innate immune system could feasibly facilitate loss of tracheal epithelium during the development of bordetellosis. Full article

Background/Objectives. Antibiotic resistance is an escalating global health concern, highlighting the need for innovative antibacterial strategies beyond traditional drugs. GroEL, a highly conserved bacterial chaperonin essential for protein folding and stress tolerance, represents a promising but underexplored therapeutic target. This study aimed to identify short peptides capable of binding GroEL monomers and potentially altering their function, with the long-term goal of disrupting bacterial survival mechanisms. Methods. A phage display screening of a 12-mer peptide library was performed against purified GroEL monomers, yielding five candidate peptides (G1–G5). Their interactions with GroEL were analyzed through molecular docking and molecular dynamics simulations using three-dimensional GroEL structures (1MNF, 1XCK, 8S32). Stability of binding and interaction profiles were assessed through molecular dynamics-based analyses and MM/GBSA free energy calculations. Results. Peptides G4 and G5 displayed the most stable and energetically favorable interactions, with G4–8S32 showing the strongest binding (−116.68 kcal/mol). These peptides localized near inter-subunit interfaces, suggesting potential interference with GroEL oligomerization or allosteric transitions, which are critical for its biological function. Conclusions. Our findings demonstrate that short peptides can stably bind GroEL and potentially modulate its activity. Peptides G4 and G5 represent at our knowledge the first promising scaffolds for developing a novel class of peptide-based antibacterial agents targeting conserved chaperonin systems. This work introduces a new avenue that warrants further experimental validation. Full article

Diagnosis of rickettsial infections is challenging due to nonspecific clinical symptoms and limitations of current diagnostic methods. Molecular assays allow early detection but are limited by cost and technical demands, whereas conventional serological tests often exhibit cross-reactivity and low sensitivity during the early stages of infection. This study aimed to develop and evaluate a recombinant-antigen sandwich ELISA for improved antibody detection against Rickettsia spp. Three Rickettsia akari proteins, rGroEL, rDnaK, and rA8GP63 (uncharacterized protein), were produced and validated for immunogenicity. The assay was evaluated using 94 patient serum samples, including those with positive, negative, and unknown clinical course. The optimized ELISA demonstrated high reproducibility, with IgG sensitivity of 89.47–95.39% and specificity of 90%. IgM detection, also assessed, showed lower sensitivity (42.11–82.89%) but maintained strong specificity (83.33%). The diagnostic performance was comparable to that of a commercial indirect immunofluorescence assay, with no cross-reactivity detected in sera from patients with unrelated infections. rDnaK and rA8GP63 represent newly explored diagnostic candidates. These findings highlight the potential of this recombinant protein-based ELISA as an accessible, sensitive and specific diagnostic tool, with a meaningful clinical impact for improving the early and accurate detection of rickettsial infections. Full article