Search Results (144)

Background/Objectives: Baccharis dracunculifolia DC. is a medicinal plant and the primary botanical source of Brazilian green propolis. This study aimed to characterize the phytochemical profile of its ethanol extract and evaluate its antioxidant, anti-inflammatory, cytotoxic, and acute oral toxicity profiles. Methods: The extract was characterized by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Antioxidant and anti-inflammatory activities were evaluated by complementary in vitro assays, cytotoxicity in NIH/3T3 fibroblasts, and acute oral toxicity according to OECD Guideline 423 in Wistar rats at 300 and 2000 mg/kg. Results: UHPLC-QTOF-MS analysis resulted in the tentative annotation of 54 metabolites, including phenolic acids, flavonoids, caffeoylquinic acid derivatives, diterpenes, glycolipids, and saponins. The extract showed antioxidant activity, with a DPPH IC₅₀ of 0.77 ± 0.009 mg/mL and FRAP reducing capacity of 1.24 ± 0.22 µM ferrous sulfate/mg. Anti-inflammatory activity increased with concentration, reaching 58.60 ± 0.23%, 60.84 ± 0.40%, and 57.89 ± 2.96% inhibition of hemolysis, macrophage spreading, and phagocytosis, respectively, at 600 µg/mL (p < 0.05 vs. negative control). NIH/3T3 viability remained above 70% at all tested concentrations and exposure times. No mortality, treatment-related clinical signs, or significant changes in body weight, hematological and biochemical parameters, relative organ weights, or histopathological findings were observed at doses up to 2000 mg/kg. Conclusions: The B. dracunculifolia ethanol extract exhibited antioxidant and anti-inflammatory activities in vitro, without relevant cytotoxicity under the tested conditions, and showed no evidence of acute oral toxicity at doses up to 2000 mg/kg. Full article

Background: There is limited evidence regarding sarcopenia in Thailand, especially in southern provinces when applying the AWGS-2019 criteria. Objective: The present study aimed to determine the prevalence and independent risk factors of sarcopenia among community-dwelling older adults in Nakhon Si Thammarat. Methods: A cross-sectional study was conducted involving 246 adults aged 60 years or older. Sarcopenia was defined using the AWGS-2019 criteria. Data collection comprised the Mini Nutritional Assessment-Short Form (MNA-SF), Abbreviated Mental Test (AMT), and physical performance assessments. Multivariable logistic regression analysis was performed to identify independent predictors, incorporating both categorical and continuous variables. Results: The prevalence of sarcopenia was 27.64%. Multivariable analysis identified age of ≥80 years or older (AOR = 4.25, 95% CI: 1.12–16.14; p = 0.033) and body mass index (BMI) below 18.5 kg/m² (AOR = 3.58, 95% CI: 1.20–10.65; p = 0.022) as significant risk factors. Protective factors included attainment of secondary education or higher (AOR = 0.12, 95% CI: 0.02–0.78; p = 0.025), BMI of 23.0 kg/m² or greater (AOR = 0.19, 95% CI: 0.09–0.40; p < 0.001), engagement in regular physical activity (AOR = 0.21, 95% CI: 0.08–0.54; p = 0.001), and normal nutritional status (AOR = 0.24, 95% CI: 0.08–0.71; p = 0.010). Further continuous analysis confirmed that each 5-year increase in age significantly increased the risk of sarcopenia (AOR = 1.52, 95% CI: 1.14–2.03; p = 0.005), while each 1 kg/m² increase in BMI was associated with a protective effect (AOR = 0.78, 95% CI: 0.69–0.88; p < 0.001). Conclusions: Sarcopenia is common among older adults in Southern Thailand. Both categorical and continuous analyses identify advanced age as a primary risk factor. In contrast, higher education, optimal body mass index, regular physical activity, and adequate nutrition serve as important protective factors. These results highlight the importance of community-based screening and targeted interventions that address nutritional adequacy and structured exercise to enhance quality of life in this population. Full article

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes following refractory out-of-hospital cardiac arrest (OHCA); however, access is constrained by geography and resources. This study compared two strategies against the current system in Nara Prefecture, Japan: a two-stage hospital model using chest-pain network hospitals as ECPR-initiation sites, and a prehospital ECPR model using physician-staffed ambulances from two extracorporeal membrane oxygenation (ECMO)-ready hospitals. Methods: A geographic information system (GIS)-based simulation was conducted using emergency medical service (EMS) records of witnessed cardiac-origin OHCA cases (2017–2022). Isochrone analyses estimated areas reachable within a 60 min arrest-to-ECMO target. In the two-stage hospital model, patients located within a 15 min transport radius from chest-pain network hospitals were considered geographically covered. In the prehospital ECPR model, a physician-staffed ambulance was assumed to reach arrest sites within a 25 min travel-time radius from ECMO-ready hospitals. The study outcome was geographic coverage, defined as the proportion of cases within each service area; the two strategies were compared using McNemar’s test for paired proportions. Results: Among 1476 included cases, the coverage rate was as follows: current system, 28.7%; two-stage hospital model, 65.2%; prehospital model, 70.4% (p < 0.001). Certain eastern and southern mountainous regions remained outside both coverage areas. Conclusions: Using real-world EMS data, a mobility-focused prehospital ECPR strategy provided broader potential geographic access without requiring additional fixed hospital infrastructure than expanding hospital-based initiation sites. Optimization of prehospital deployment may represent a geographically feasible approach to expanding ECPR access in mixed urban–rural regions, though operational feasibility and cost-effectiveness require further evaluation. Full article

Bitter Melon Leaf Extract (BMLE) possesses potential anticancer and anti-inflammatory properties; however, conventional extraction methods restrict phytochemical yield and bioactivity. Here, we optimized extraction using High-Pressure Processing (HPP) with Box–Behnken Design (BBD) and Response Surface Methodology (RSM). The optimized extract (O-BMLE) demonstrated significantly higher total flavonoid content (27.7 vs. 8.7 mg RE/g) and FRAP antioxidant capacity (96.5 vs. 71.2 μmol TE/g) compared to conventional BMLE. Additionally, O-BMLE exhibited enhanced cytotoxicity (A549 IC₅₀: 58.7 vs. 147 μg/mL) and selectivity (SI: 5.03 vs. 2.60) against A549, HepG2, and SKOV3 cancer cells while showing minimal effects on 3T3-L1 fibroblasts. In LPS-stimulated RAW264.7 macrophages, O-BMLE selectively inhibited JNK phosphorylation without affecting NF-κB phosphorylation, resulting in suppression of iNOS, COX-2, IL-1β, IL-6, and TNF-α expression as well as nitric oxide production. HPLC analysis revealed equivalent momordicine-I levels (~28 mg/g) between extracts. In contrast, HPLC-qTOF-MS profiling revealed that O-BMLE was enriched in stearidonic acid (66% increase in relative abundance), 4-hydroxybenzoic acid (19.5%), monolinolenin, 6-gingerol, and pedunculoside, which are compounds linked to JNK inhibition, antioxidant activity, and cytokine suppression. These results indicate that HPP-BBD/RSM optimization selectively modifies the bitter melon leaf metabolome, thereby enhancing anticancer and anti-inflammatory activities independently of momordicine-I content alone. O-BMLE may therefore serve as a promising candidate for the development of functional foods and nutraceuticals targeting inflammation-associated cancers. Full article

Background/Objectives: Lumbar spinal canal stenosis (LSS) is a major cause of neurological disability and is frequently accompanied by neuropathic pain (NeP). Duloxetine is widely used for NeP, but its clinical role in LSS and the determinants of treatment response remain unclear. This study aimed to identify predictors of duloxetine efficacy in LSS. Methods: We retrospectively analyzed 145 patients with LSS who received duloxetine for ≥3 months (median dose 40 mg) with at least 1-year follow-up. Patients were classified into those with radicular pain or cauda equina syndrome. Treatment response was assessed at 3 months. Stenosis severity was evaluated using the Schizas classification. Multivariable logistic regression analysis was performed to identify independent predictors of duloxetine response in patients with cauda equina syndrome. Results: Duloxetine was effective in 29.4% vs. 52.3% in radicular pain and cauda equina syndrome, respectively. Among patients with cauda equina syndrome, Schizas Grade D was more frequent in responders than non-responders and independently predicted duloxetine response. Nearly 90% of responders had been unresponsive to other NeP medications. A subset of patients with severe stenosis avoided surgery following duloxetine treatment. Conclusions: Duloxetine showed greater efficacy in cauda equina-dominant LSS compared with radicular pain. Paradoxically, more severe spinal canal stenosis tended to be associated with a higher likelihood of response. These findings suggest that neurological phenotype and radiological severity may influence duloxetine responsiveness and support a symptom- and imaging-guided pharmacological management for LSS, although these findings should be interpreted with caution and considered hypothesis-generating given the retrospective study design. Full article

Mitochondrial dysfunctions contribute to the pathogenesis of tauopathies, a group of neurodegenerative diseases with abnormal accumulation of microtubule-associated protein tau. The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated, and activities of complexes I and IV were elevated. Feeding 5-ALA/SFC to tau flies lowers oxidative damage without correcting OXPHOS activities or mitochondrial distribution. 5-ALA/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. These results suggest that 5-ALA/SFC attenuates a neurodegenerative pathway involving tau, mitochondria, and ROS. Full article

Background: Anatomical variations in visceral arteries are not so uncommon (up to 20% of cases in general population), with splenic and hepatic artery anomalies being the most frequently reported. Aberrant arteries may be affected with aneurysmal lesions that are rare but potentially fatal conditions. In their treatment, a comprehensive understanding and knowledge of the underlining anatomical variation are pivotal to prevent potential ischemic complications for the end organ. Methods: A comprehensive literature search on the PubMed, Cochrane and Scopus databases was done using the terms: “anomalous visceral artery aneurysm”, “Aberrant visceral arteries”, and “anomalous origin visceral vessels”. Eligible studies published from inception to 30 June 2024 were identified. Only those that had included the adopted treatment strategies (open, endovascular or hybrid repair) and the related outcomes (mortality, bleeding, end-organ ischemia, lesions of the surrounding organ, need for reintervention) were analyzed to evaluate the safety and efficacy of each approach. A narrative analysis of the indications informing the selection of each interventional treatment, based on individual procedural risks, was also presented. Results: A total of 30 publications describing 36 patients (mean age 48.9 ± 12.8 years, range 22–73 years) with aneurysms involving aberrant visceral arteries were included. Most patients were female (25/36, 69.4%). True aneurysms predominated (with a mean size of 30.5 ± 11.5 mm, range 6–60 mm), being reported in 33/36 (91.7%) patients. Most lesions involved a splenic artery arising from the superior mesenteric artery (27/36, 75.0%). Overall, 26/36 (72.2%) patients were symptomatic upon presentation, most commonly with abdominal or epigastric pain, often associated with nausea or vomiting, back pain or shortness of breath. All patients underwent preoperative Computed angiotomography or subtraction angiography to define the operative strategy. Most cases were managed electively (31/36, 86.1%), but 11.1% (4/36) of cases required urgent intervention (in one case the urgency status was not specified). Overall, 19/36 (52.8%) patients underwent purely endovascular repair, 15/36 (41.7%) were treated with open surgery, and 2/36 (5.6%) had hybrid procedures combining endovascular coiling with laparoscopic splenic artery ligation. Indication for treatment was based on vessel tortuosity, landing zones, and the presence of side branches supplying end organs. Early outcomes were favorable regardless of treatment strategies. A single organ-related complication was reported (1/36, 2.8%) following open/endovascular repair, consisting of mild pancreatitis, which resolved with conservative management. No perioperative or aneurysm-related deaths were reported in any of the included cases. No recurrent aneurysms or late aneurysm-related complications were described during the reported follow-up intervals (mean ≈ 10.5 months, range 1.5–42 months). Conclusions: Aneurysms arising from aberrant visceral arteries present unique challenges because their origin, course, and collateral networks deviate from standard anatomy. Patient selection and detailed anatomic mapping preoperatively are decisive as inadequate imaging or failure to recognize an aberrant origin can lead to the incomplete exclusion or inadvertent sacrifice of critical branches. Understanding the anatomy of visceral arteries and their variations is paramount in clinical practice, particularly when planning interventions for minimizing procedural risks, optimizing outcomes, and preventing potential complications. Contemporary practice favors endovascular repair due to lower perioperative morbidity, but success depends on vessel tortuosity, landing zones, and the presence of important side branches that supply end organs. Full article

With the conclusion of proton–proton collision data-taking in 2025, the ATLAS experiment has now integrated a luminosity exceeding 300 ${\mathrm{fb}}^{-1}$ during the Run 3 period, which began in July 2022 following Long Shutdown 2 (LS2). During LS2, a series of detector upgrades were implemented, including the installation of the New Small Wheel (NSW) in the innermost stations of the Muon Spectrometer end-caps. The ATLAS Muon Spectrometer, the largest muon system ever built at a collider, now comprises both established gaseous detectors—Monitored Drift Tubes, Thin Gap Chambers, and Resistive Plate Chambers—and newer detectors like Micromegas and small-strip TGCs in the NSW. These new systems are now in stable operation following an extensive phase of construction and commissioning, providing enhanced muon tracking and trigger capabilities. This presentation covers the performance of the muon system, focusing on the stability of the established detectors over time, their ability to handle increasing luminosity and associated irradiation levels, and studies on detector aging. Emphasis will be placed on the NSW upgrade, including the strategies adopted for alignment, track reconstruction, and trigger. The performance results presented in this contribution are based on Run 3 data collected up to 2024. Full article

Hepatocellular carcinoma (HCC) exhibits a striking male predominance, particularly in Hepatitis B Virus (HBV) endemic regions. While lifestyle factors and estrogen protection are traditional explanations, they fail to fully account for this disparity. This review elucidates the molecular mechanisms driving this gender gap, focusing on the interplay between the Androgen Receptor (AR), viral replication, and the suppression of NKG2D-mediated immune surveillance. We synthesized experimental and clinical findings linking AR signaling, the viral protein HBx, and the regulation of NKG2D ligands (MICA/MICB). Current evidence identifies a positive feedback loop where AR enhances HBV replication, while HBx amplifies AR activity. Crucially, this axis systematically dismantles innate immunity: AR signaling represses MICA/B transcription via miRNA networks and upregulates ADAM metalloproteases, leading to ligand shedding and the release of soluble MICA (sMICA), effectively blinding Natural Killer (NK) cells. We propose that historical failures of anti-androgen monotherapy likely stemmed from ignoring this immune modulation. Consequently, targeting the AR-NKG2D axis represents a promising strategy to sensitize tumors to immunotherapy, suggesting that future therapeutic approaches should combine AR modulation with immune checkpoint inhibitors or shedding-blockade. Full article

The development of anisotropic gold nanostructures supporting localized surface plasmon (LSP) resonances in the near-infrared (NIR) biological window is of great interest for diagnostic and therapeutic nanotechnologies. Here, we report gold open-shell nanoparticles (AuOSNs), a symmetry-broken nanoshell architecture exhibiting strong NIR surface-enhanced Raman scattering (SERS) activity. AuOSNs were fabricated via a surfactant-free strategy combining bottom-up silica sphere assembly with a simple top-down gold deposition process, without using highly cytotoxic surfactants such as cetyltrimethylammonium bromide (CTAB). Boundary element method (BEM) simulations revealed that the asymmetric open-shell geometry induces NIR LSP resonances with pronounced electromagnetic field localization near the opening edges, depending on excitation configuration. Consistent with these predictions, extinction spectra of AuOSNs dispersed in water showed an LSP resonance peak at ~793 nm, close to the 785 nm excitation wavelength for SERS. In aqueous dispersion, AuOSNs modified with 4-mercaptobenzoic acid (4-MBA) exhibited strong SERS activity with enhancement factors of ~10⁶. Furthermore, polyethylene glycol (PEG)-modified MBA/AuOSNs showed negligible cytotoxicity in vitro. SERS imaging confirmed that PEG/MBA/AuOSNs enable visualization of HeLa cells via characteristic MBA SERS signals. These results demonstrate that surfactant-free AuOSNs provide a biocompatible platform for NIR-excited SERS sensing and cellular imaging, highlighting their potential in plasmonic bioimaging applications. Full article

Background: Ultra-widefield (UWF) images are frequently used for fundus examinations during medical screening. Optos^® generates pseudo-color images using only red and green lasers, which may reduce the visibility of retinal interface lesions. In contrast, Clarus™ incorporates blue light, suggesting potential superiority in epiretinal membrane (ERM) detection. Methods: This retrospective study included 233 patients (408 eyes; 816 UWF images per device) who underwent simultaneous Optos^® and Clarus™ imaging plus optical coherence tomography (OCT) at our institution from March to April 2019. Ten blinded ophthalmologists assessed only the UWF images for ERM presence or absence. Diagnosis was confirmed by fundus examination and OCT. McNemar’s test compared detection accuracy. Results: Clarus™ consistently outperformed Optos^®, with superior sensitivity [median 49% (range 42–70) vs. 14% (4–47); p = 0.002], correct judgment rate [85% (82–90) vs. 78% (44–88); p = 0.010], and lower unassessed rate [6% (2–13) vs. 13% (3–52); p = 0.002]. This superiority held across ERM stages, lens status, and ophthalmologist experience levels. Conclusions: This study demonstrated that Clarus™ significantly outperformed Optos^® in ERM detection accuracy. These results suggest that true-color UWF systems like Clarus™ may be more useful for macular screening in routine practice and health examinations. Full article

Mind–body practices such as meditation, yoga, and martial arts have been suggested to enhance flexible self-experience and psychological well-being. However, few studies have examined short-term effects of contemplative bodywork rooted in traditional martial arts on perception of self–other boundaries and relevant psychological states. The present study employed a three-arm randomized controlled design to examine psychological effects of the Wakame Exercise, a paired body–mind practice derived from a school of martial arts in Japan. Seventy undergraduates were randomly assigned to a 45 min session of wakame exercise (N = 25; 20 females, 5 males; M age = 19.4, SD = 0.64), a control practice, Push-Hand Sumo (N = 25; 15 females, 10 males; M age = 19.5, SD = 1.20), or rest (N = 20; 17 females, 3 males; M age = 19.4, SD = 1.09). Outcomes included nondual awareness, perceived body boundaries, creative attitudes, decentering, and positive/negative affect. The wakame exercise group showed significant increase in nondual awareness (p < 0.001, Cohen’s d = −1.74) and decrease in the salience of perceived body boundaries (p < 0.001, Cohen’s d = 1.25) following practice, which were more apparent than controls. Within the wakame exercise group, nondual awareness was significantly positively correlated with creative attitudes, and higher creative attitudes were associated with greater decentering following practice. These findings suggest that brief paired practices rooted in Eastern martial arts can promote nondual awareness and temporary boundary dissolution, potentially enhancing creativity (Approved by the Ethics Review Committee on Research with Human Subjects of Waseda University, No. 2022–397). Full article

A chimeric protein of heparanase and Ig-Fc was designed as a novel tool to expand the detection of structurally heterogeneous heparan sulfate (HS) and related glycosaminoglycans. The whole mouse heparanase gene was combined with the gene segment encoding the mouse IgG1 hinge-Fc domain. A point mutation E335A was inserted to disable putative HS degradation activity. Chimeric proteins consisted of the latent form of the enzyme devoid of HS degradation activity. The chimeric proteins bound to heparin, N-desulfated heparin, and O-sulfated N-acetylheparosan. Their binding spectrum to glycosaminoglycans differed from that of anti-HS mAb 10E4. The chimeric proteins bound to Kato III and A549 cell lines. The binding was reduced by knocking down EXT1 gene expression. One of the chimeric proteins stained the epidermal cells in the hyperplastic spinous layer of inflamed atopic dermatitis skin and inflammatory cells in the dermis, which were not stained with mAb 10E4. The protein stained a polarized structure on the surface of monocytic U937 and THP1 cells. Similar polarized structures were observed with anti-syndecan-1 antibody staining. The chimeric protein and anti-syndecan-1 antibody precipitated similar sets of proteins that included syndecan-1 from the lysates of U937 cells. These novel chimeric proteins are useful to detect HS abundant in O-sulfation in histochemical, cytochemical, and biochemical studies. Full article

Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas with an extremely rare perineurial subtype. Herein, we present a case of a perineurial MPNST in the cauda equina. Clinically and radiologically, a mass extending from within the spinal canal at the L5 level to outside the intervertebral foramen was identified, raising suspicion of a neurogenic tumor as the primary diagnosis. Computed tomography-guided biopsy suggested an intermediate- to low-grade malignancy; however, a definitive diagnosis could not be established. Two years later, worsening neurological symptoms prompted further imaging, which revealed significant tumor growth and bone invasion. Open biopsy was performed to obtain a definitive diagnosis of perineurial MPNST. MPNSTs lack distinctive imaging features and are generally diagnosed based on a combination of radiological and histopathological findings. Although MPNSTs have a poor prognosis, the perineurial subtype is considered to have a relatively favorable outcome. Given these factors, early diagnosis followed by surgical resection or radiation therapy is recommended. Full article