Search Results (243)

Liver disease encompasses a wide range of conditions, each requiring tailored therapeutic approaches. This review describes and critically discusses treatments with robust evidence for improving liver health. Ursodeoxycholic acid (UDCA) is a drug approved by the Food and Drug Administration of the USA to treat primary biliary cholangitis (PBC). In addition, UDCA has been demonstrated to protect against metabolic dysfunction-associated steatohepatitis, fibrosis, and drug-induced liver injury (DILI). The mechanism of action of UDCA has been attributed not only to decreasing the effects of toxic bile acids but also to protecting mitochondrial integrity and function, as well as to antioxidant, anti-inflammatory, and anti-apoptotic activities. UDCA can scavenge reactive oxygen species (ROS) and activate the nuclear factor-E2-related factor-2 (Nrf2) pathway, thereby exerting antioxidant activity. The anti-inflammatory activity of UDCA is associated with its ability to inhibit the nuclear factor-κB pathway. Pirfenidone is a well-recognized antifibrotic drug for the treatment of idiopathic pulmonary fibrosis; its effects on liver fibrosis have also been demonstrated. Pirfenidone exerts anti-inflammatory effects by attenuating the nucleotide-binding oligomerization domain-like receptor 3 inflammasome signaling pathway. The antioxidant actions of pirfenidone are associated with its ability to upregulate the Nrf2 pathway. Both the anti-inflammatory and antioxidant properties of pirfenidone act together to attenuate lung and liver fibrosis, decreasing transforming growth factor-β levels, inhibiting profibrogenic hepatic stellate cell activation, and increasing extracellular matrix degradation. Methyltransferases utilize S-adenosyl-L-methionine (SAM) as a methyl donor for most transmethylation reactions in the body. SAM increases reduced glutathione (GSH) levels, exerting important antioxidant effects. Evidence indicates that SAM prevents fibrosis and attenuates hepatocellular carcinoma development, improving patient survival. N-acetylcysteine (NAC) is a precursor to L-cysteine and GSH and is used in clinical settings to treat cancer, nephropathy, heart disease, pulmonary fibrosis, polycystic ovary syndrome, and influenza. Regarding the liver, NAC is the most accepted treatment for DILI, especially after paracetamol overdose. Owing to its antioxidant and anti-inflammatory actions, NAC has been successfully used to treat chronic liver injuries, including hepatosteatosis and fibrosis. Therefore, ursodeoxycholic acid, pirfenidone, S-adenosyl-L-methionine, and N-acetylcysteine could represent therapeutic strategies for the treatment of liver pathologies. Full article

Soil provides essential ecosystem services and is pivotal for achieving multiple United Nations (UN) Sustainable Development Goals amid growing population pressures and resource demands. In arid to semi-arid regions such as Maio Island (Cape Verde), nutrient-poor soils and unsustainable land-use practices increase agricultural vulnerability, while volcanic geochemistry introduces elements that are not human friendly, further challenging environmental quality and long-term sustainability. Assessing soil (physical–chemical–biological) condition is therefore crucial for informed environmental and land-use planning. Here, Maio’s topsoil was evaluated using protocols adapted from Santiago, the largest Cape Verdean island. Estimated Background Values (EBVs) indicated naturally elevated V, Cr, Ni, Co, and Cu concentrations, consistent with mafic volcanic terrains. Robust Principal Component Analysis (rPCA) revealed geochemical groupings linked to volcanic–sedimentary units, with the dominant component (PC1) defined by Co–V–Cu–Mn–Ni versus As–Cd. Environmental Risk Indices (ERIs) and Multi-Element ERIs (ME–ERIs) quantified elemental enrichment relative to international land-use standards (residential and agricultural) and subsequently to Maio’s EBVs. The highest exceedances were observed for Cr, Co, Ni, V, and Cu, whereas As, Cd, Hg, Pb, and Zn fell within thresholds. The EBV-based assessment identified fewer exceedances than stricter international guidelines, though a few multi-element “hotspots” persist, highlighting potential land-use constraints and the need for preventive management. Overall, the integrated EBV/ERI/ME–ERI framework establishes an environmental geochemical baseline for Maio and offers a screening tool applicable across the entire archipelago. Full article

Background/Objectives: There is high demand for Anshenbunao syrup (ABS) in Chinese medicine owing to its steady therapeutic efficacy for insomnia and neurasthenia. However, it contains a substantial proportion of Polygoni Multiflori Radix Praeparata (PMRP), which is associated with reported cases of drug-induced liver injury (DILI). Here, we aim to establish an integrated approach combining PK screening with a dual-model toxicity verification system to systematically identify liver injury components (from high to low concentrations and from direct to idiosyncratic hepatotoxicity) to accurately uncover diverse potential hepatotoxicity markers. Methods: A sensitive UPLC-MS/MS method was used to accurately quantify the components in plasma at the ng/mL level and conduct a pharmacokinetic analysis. Rat models were used to evaluate exposure levels of the eight active constituents and three major metabolites after a single oral gavage dose of 10 mL/kg ABS and identify the quality markers. The early-stage and high-throughput assessment of direct and idiosyncratic hepatotoxicity was conducted in vitro utilizing HepG2 cells. After the administration of the quality markers (0.01–80 μM), CCK-8 was used to detect cell viability on both normal and susceptible cells, and the latter was induced by lipopolysaccharide. Results: As a result, seven quality markers were screened based on their contents and exposure levels in rat plasma by UPLC–MS/MS, including emodin (EM), liquiritin (LI), 2,3,5,4′–Tetrahydroxystilbene–2–O–β–D–glucoside (TSG), icariin, emodin–8–O–β–D–glucoside, baohuoside I (BA), and 18β–glycyrrhetinic acid (GTA). Moreover, the half maximal inhibitory concentration values of both normal cells and the lipopolysaccharide-induced immune stress liver injury cells were fitted within the concentration range of 0.01–80 μM, based on which, EM, BA, and GTA were identified as the principal hepatotoxic constituents in ABS at elevated concentrations. This study is the first to demonstrate that TSG, EM, LI, and GTA exhibit synergistic cytotoxicity in LPS-sensitized hepatocytes at clinically relevant concentrations, whereas EM was also a direct hepatotoxic component. Given that TSG is one of the major ingredients in ABS, the underappreciated idiosyncratic hepatotoxicity could elevate the risk of adverse clinical outcomes. Conclusions: In conclusion, this study effectively identifies hepatotoxic constituents in ABS and evaluates their hazards under immune stress and toxicity profiles in clinical concentrations, which also provides a robust foundation for the awareness of PMRP-induced DILI due to ABS. Full article

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease that causes substantial morbidity and social exclusion. Global efforts under the World Health Organization’s Global Programme to Eliminate Lymphatic Filariasis have markedly reduced prevalence, and several Pacific Island Countries and Territories (PICTs) have achieved elimination of the disease as a public health problem. However, post-validation surveillance (PVS), essential for detecting resurgence and enabling early response, has rarely been implemented, and barriers to its delivery remain poorly understood. We used two complementary qualitative approaches to identify systemic barriers and enablers to LF PVS in PICTs. First, we conducted a Nominal Group Technique followed by a structured expert elicitation involving program managers and technical staff. Data were analysed thematically and triangulated across sources. Participants identified 70 challenges which were consolidated into ten thematic domains. Pertinent barriers relate to limited leadership understanding of LF and surveillance options, inconsistent technical and financial support, and a lack of context-appropriate operational guidance. Additional challenges included limited field-ready diagnostics, procurement delays, the absence of formal mandates, and low community engagement. Enablers included embedding PVS within existing health services, leveraging trusted community networks, strengthening regional frameworks, and co-developing practical tools with countries. Sustaining LF elimination in the Pacific will require political commitment, regional collaboration, and integrated, programmatic approaches informed by recent PVS experience. Full article

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease targeted by the World Health Organization (WHO) for global elimination as a public health problem. Sixteen Pacific Island countries and territories were historically endemic, and eight have now met the WHO criteria for elimination as a public health problem. Elimination as a public health problem does not imply zero transmission. Rather, it denotes that LF prevalence has been reduced below a defined threshold at which community transmission can be sustained. Following validation of elimination, the WHO recommends post-validation surveillance (PVS) to detect potential re-emergence of LF as a public health problem. However, implementing PVS is challenging in Small Island Developing States with dispersed populations, limited workforce capacity, resource constraints, and competing health priorities. The ‘Voices and Visions: Building Partnerships for Integrated Serosurveillance of LF and Other Infectious Diseases in the Pacific Islands’ meeting was held in Brisbane, Australia, from 8–10 July 2025. Fifty-one delegates, including Pacific LF programme managers, WHO representatives, global health partners, and academic researchers, reviewed regional PVS progress, discussed the newly released WHO guidelines for the implementation, monitoring, and evaluation of PVS, planned for PVS implementation, and explored novel multiplex bead assay (MBA) serological analysis methods to strengthen regional coordination for its development as a public health tool. Five broad themes emerged. First, the new WHO Monitoring and Epidemiological Assessment of Mass Drug Administration in the Global Programme to Eliminate Lymphatic Filariasis: A Manual for National Elimination Programmes, 2nd edn needs to be operationalised to meet decision-making needs across diverse Pacific settings. Second, integrating LF-PVS with existing surveys and health service activities could improve efficiency and long-term sustainability. Third, regional coordination and alignment of funding cycles will require high-level collaboration. Fourth, community engagement is essential to strengthen demand for PVS. Finally, while at an early stage and with further evidence needed, MBA laboratory methods hold promise for cost-effective, feasible integrated multi-pathogen serosurveillance. Full article

Acetaminophen (APAP) overdose is a major global cause of drug-induced liver injury (DILI), and the rising incidence of APAP-induced hepatotoxicity has raised substantial concern in the medical community, highlighting an urgent need for effective therapeutic approaches. Coptidis Rhizoma alkaloids (CRAs) have shown hepatoprotective effects in multiple hepatic disease models. This study aimed to investigate the therapeutic efficacy and the underlying mechanisms of CRA in acetaminophen (APAP)-induced acute liver injury. After identifying 18 alkaloid components in CRA, we employed an integrated strategy of untargeted metabolomics and network pharmacological analysis to investigate the underlying mechanisms. The potential mechanisms were subsequently validated through histopathological examination and molecular biology assays. Our results showed that CRA exerted dose-dependent protection against APAP-induced liver injury in vitro and in vivo. This protective effect was mediated by enhanced hepatic glutathione (GSH) biosynthesis via increased intracellular cysteine (Cys) availability. In the mouse model, hepatic Cys and GSH levels were increased by 2.2-fold and 1.8-fold, respectively, relative to the model group, which consequently attenuated oxidative stress damage. Furthermore, CRA suppressed APAP-induced activation of ERK and NF-κB, reducing the phosphorylation levels by 39.2% and 38.0%, respectively. Accordingly, it also downregulated the subsequent expression of inflammatory mediators in the TNF signaling pathway. These findings provide crucial mechanistic insights into the hepatoprotective role of CRA against APAP-induced toxicity, establishing a valuable foundation for developing novel therapeutic or preventive strategies for APAP-induced liver injury. Full article

Background: Drug-induced liver injury (DILI), a major type of adverse drug reaction, has become one of the leading causes of acute liver injury and liver failure worldwide. Its clinical significance lies not only in acute hepatocyte necrosis and functional failure but also in its role as a key initiating factor for liver cancer progression. Therefore, early diagnosis of DILI is of great importance. Methods: This study employed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) to perform widely targeted metabolomics analysis on acetaminophen (APAP)-induced liver injury mice and healthy mice. Results: UPLC-QTRAP-MS/MS identified 41 differentially expressed metabolites primarily involved in glycerophospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and glutathione metabolism pathways. The significant elevation of serum and hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) confirmed the successful establishment of the drug-induced liver injury (DILI) model. ROC curve analysis indicated 11 metabolites with AUC values exceeding 0.90 as potential biomarkers, including (R)-2-Hydroxybutyric acid, Glu-Gln, γ-Glu-Gln, 2-Methyllactic acid, L-Serine, Hyodeoxycholic acid, 3-Epideoxycholic acid, and Glycochenodeoxycholic acid 7-sulfate. Conclusions: We propose that these differential metabolites may serve as candidate biomarkers for DILI. Our findings provide a novel metabolomic signature derived directly from the injured tissue and offer a theoretical foundation for further research into early diagnosis of drug-induced liver injury. Full article

The urgency of research into innovation and digital marketing is driven by growing competition within the tourism industry, which demands greater destination visibility (DV) and tourist engagement (TE). At the same time, Areia Branca Beach, a prominent destination in Timor-Leste, has not been managed optimally to support sustainable tourism. Furthermore, the utilisation of governance innovation and digital marketing—particularly the integration of content marketing (CM), immersive technology (IT), and digital data analytics (DDA)—remains limited and has yet to be substantiated by robust empirical evidence at the scale of a developing destination. This study aims to investigate the role of DDA in the causality between CM and IT in influencing DV and TE. A quantitative approach was employed, using moderated regression analysis (MRA) to test the empirical relationships between the variables. Primary data were collected through face-to-face field surveys of tourists who had visited Areia Branca Beach, located northeast of Dili, Timor-Leste, on at least two occasions. The study adopted simple random sampling (SRS) with a finite population correction (FPC). A total of 364 tourists were selected to assess their perceptions using a structured questionnaire. The study reveals four main findings. First, CM significantly affects DDA and DV. Second, IT influences DDA, but not TE. Third, DDA significantly affects both DV and TE. Fourth, DDA moderates the effect of CM on DV and the effect of IT on TE. The findings underscore that the collaborative governance concept, through governance and marketing innovations, is not yet optimal for shaping sustainable tourism. Finally, future academic and practical policy implications require more in-depth exploration to emphasise the enhancement of resource management capacity genuinely needed in the subjects studied, beyond governance and digital marketing innovations within the sustainable tourism framework. Full article

Ataúro Island, located in the inner Banda Arc, provides a natural laboratory to investigate the interplay between magmatic evolution, hydrothermal circulation, and near-surface weathering in an active arc–continent collision setting. This study presents the first systematic island-wide geochemical baseline for Ataúro Island, based on multi-element analyses of stream sediments integrated with updated geological, structural, and hydromorphological information. Compositional Data Analysis (CoDA–CLR–PCA), combined with anomaly mapping and spatial overlays, defines a coherent three-tier geochemical framework comprising: (i) a lithogenic component dominated by Fe–Ti–Mg–Ni–Co–Cr, reflecting the geochemical signature of basaltic to andesitic volcanic rocks; (ii) a hydrothermal component characterized by Ag–As–Sb–S–Au associations spatially linked to structurally controlled zones; and (iii) an oxidative–supergene component marked by Fe–V–Zn redistribution along drainage convergence areas. These domains are defined strictly on geochemical criteria and represent geochemical process domains rather than proven metallogenic provinces. Rare earth element (REE) systematics further constrain the geotectonic setting and indicate that the primary geochemical patterns are largely controlled by lithological and magmatic differentiation processes. Spatial integration of geochemical patterns with fault architecture highlights the importance of NW–SE and NE–SW structural corridors in focusing hydrothermal fluid circulation and associated metal dispersion. The identified Ag–As–Sb–Au associations are interpreted as epithermal-style hydrothermal geochemical enrichment and exploration-relevant geochemical footprints, rather than as evidence of confirmed or economic mineralization. Overall, Ataúro Island emerges as a compact natural analogue of post-arc geochemical system evolution in the eastern Banda Arc, where lithogenic background, hydrothermal fluid–rock interaction, and early supergene processes are superimposed. The integrated geochemical framework presented here provides a robust baseline for future targeted investigations aimed at distinguishing lithogenic from hydrothermal contributions and evaluating the potential significance of the identified geochemical enrichments. Full article

Objective: The aim of this study was to assess the association between the Lung Immune Prognostic Index (LIPI) measured at diagnosis and both event-free survival (EFS) and overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). Methods: This retrospective cohort included patients diagnosed with stage III NSCLC between September 2022 and July 2024, all of whom had a minimum follow-up duration of six months. LIPI was calculated using the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase levels at diagnosis. Clinical, demographic, and treatment-related data were systematically collected. Survival outcomes were estimated using the Kaplan–Meier approach, while factors associated with prognosis were examined through Cox proportional hazards models. Results: The study population consisted of 68 patients, predominantly male (86.8%), with a mean age of 63.4 ± 8.7 years. According to the Lung Immune Prognostic Index classification, 29 patients (42.6%) were categorized as having a good score, 27 (39.7%) as intermediate, and 12 (17.6%) as poor. During a median follow-up of 15.4 months, a total of 40 progressions and 22 deaths occurred. Median EFS was 17.7, 9.4, and 5.8 months for good, intermediate, and poor LIPI groups, respectively (p < 0.001). Median OS was 25.7 months in the good LIPI group, was not reached in the intermediate group due to insufficient events, and was 6.7 months in the poor group (p < 0.001). In multivariate Cox analysis, poor LIPI was independently associated with inferior survival (EFS: HR = 2.87, 95% CI: 1.85–4.46, p < 0.001; OS: HR = 2.59, 95% CI: 1.40–4.78, p = 0.002). Conclusions: LIPI calculated at diagnosis is an independent prognostic factor for both EFS and OS in stage III NSCLC. Validation in larger, prospective cohorts is warranted to further define its prognostic role in stage III NSCLC. Full article

Drug-induced liver injury (DILI) remains one of the most challenging adverse drug reactions in clinical practice, particularly in its idiosyncratic form, which is not dose-dependent and is largely driven by host-specific immune and genetic factors. Recent genomic studies have revealed strong associations between certain human leukocyte antigen (HLA) alleles and susceptibility to DILI, supporting an immunogenetic mechanism in which drug or metabolite–protein adducts act as neoantigens, triggering aberrant T-cell activation and hepatocellular injury. This review summarizes current evidence on the contribution of HLA polymorphisms to the pathogenesis of idiosyncratic DILI, highlighting allele-specific risk patterns, such as HLA-B*57:01 associated with flucloxacillin, HLA-DRB1*15:01–DQB1*06:02 in amoxicillin–clavulanate, and HLA-B*35:02 in minocycline-induced liver injury. Furthermore, ethnic variability and allele-haplotype interactions are discussed as potential modulators of susceptibility and clinical phenotype. By integrating genetic and immunological insights, the identification of HLA signatures offers promising tools for precision medicine, enabling earlier identification of at-risk individuals and improved prevention of severe hepatotoxic reactions. Full article

Acute liver injury during pregnancy is rare and predominantly associated with pregnancy-related conditions including acute fatty liver of pregnancy; Hemolysis, Elevated Liver Enzymes and Low Platelets syndrome; intrahepatic cholestasis of pregnancy; and preeclampsia. Drug-induced liver injury (DILI) is a less common and often overlooked cause of acute liver injury in pregnant patients. A literature search on acute liver injury during pregnancy and therapeutic plasma exchange was conducted, revealing the most common causative factors and syndromes. A 39-year-old woman was diagnosed with acute liver injury in the 23rd week of her third pregnancy and, upon extensive differential diagnoses, a suspicion of DILI occurred after the use of methyldopa. Methyldopa, the drug of choice for the treatment of hypertensive disorders of pregnancy, has a high safety profile for the developing fetus and is well tolerated by pregnant women, yet, in susceptible individuals, a hepatotoxic effect may occur. The drug was discontinued and symptomatic treatment with ursodeoxycholic acid and prednisone was implemented with marginal effect. Upon a multidisciplinary joint consultation, plasmapheresis procedures were introduced, granting a significant improvement in the patient’s liver function and enabling the continuation of the pregnancy. Plasmapheresis treatment was safely and effectively used for the first time in the therapeutic process in a pregnant patient with DILI. Interdisciplinary cooperation of specialists with gastroenterology, nephrology, and obstetrics expertise is crucial to achieving a timely diagnosis and begin effective treatment for pregnant patients with acute liver injury. Full article

Identifying road surface cracks by semantic segmentation is a difficult problem. This is because segmentation typically detects objects by area, whereas cracks are string-like. Conventional loss functions such as Binary Cross-Entropy (BCE), Dice, and IoU often fail to capture the fine, elongated features of cracks, as they rely on pixel-level, area-based overlap, leading to suboptimal performance. To address this, we investigate one of the skeleton-based losses, the Centerline Dice (clDice) loss, which emphasizes the preservation of tubular structures via soft skeletonization. We improve road crack segmentation by combining clDice with conventional loss functions, systematically evaluating its role by varying the weight parameter and skeletonization iterations. Experiments are conducted on the EdmCrack600 and CrackForest datasets using two segmentation models: a customized CNN-based U-Net++ and a transformer-based SegFormer. Performance is evaluated using the Dice coefficient, IoU, clDice, and Hausdorff Distance. Results show that combining clDice and IoU loss with customized U-Net++ achieves superior performance. Compared to a standard BCE baseline, it improves the Dice coefficient by 4.9 and 2.8 percentage points on EdmCrack600 and CrackForest and improves the clDice score by 3.9 and 1.7 percentage points. These results highlight improved segmentation of thin, linear cracks, supporting practical advancements in road monitoring and segmentation of linear structures. Full article

Background: Numerous protocols exist concerning the decellularization of the esophagus, a potential alternative to the classical surgical approach for the reconstruction of the digestive tract after esophagectomy. This systematic literature review (SLR) aimed to provide an overview of the effectiveness of the current protocols. Methods: This SLR was conducted in PubMed, EMBASE, and Scopus until September 2025. Study selection, data extraction, and quality assessment were performed by two independent reviewers according to the inclusion/exclusion criteria. Results: A total of 2494 references were screened after removing duplicates. Among these references, 26 articles were included. The large majority of studies (24/26) used Sodium Dodecyl Sulfate (SDS) or Sodium DeoxyCholate (SDC), and the most common physical method was the cannulation of the esophagus (17/26). The animal model was very heterogenous. All protocols except one showed no residual cell nuclei, with only 5/19 papers confirming a satisfactory residual amount of DNA. The assessment of the extracellular matrix (ECM)—mostly qualitative—revealed global preservation but with a systematic loss of glycosaminoglycans (GAGs). Conclusions: The decellularization of the esophagus is feasible, but the definition of the optimal protocol to achieve this goal remains difficult because of the important heterogeneity among the different studies. Full article

Portugal contributed to the global diffusion of sweetpotato (Ipomoea batatas L. Lam.). Although it is of minor importance on the Portuguese mainland, it is one of the most common crops in the Azores and Madeira archipelagos and is highly relevant in the Portuguese ex-colonies Mozambique and Timor-Leste. We analyzed the genetic diversity and population structure of sweetpotato from these five geographic provenances using twelve nuclear simple sequence repeat (SSR) markers. We studied 45 accessions, 15 of which were collected from farmers’ fields in these five regions and 30 of which are held at “Banco de Germoplasma de Moçambique”. The SSR markers showed a high level of polymorphism and a high number of alleles per locus. Population structure analyses using Bayesian clustering (STRUCTURE) grouped accessions from farmers’ fields into two groups and divided samples of “Banco de Germoplasma de Moçambique” into three groups. A principal coordinate analysis (PCoA), based on the Bruvo distance, supported the population structure analysis. Concerning the genebank accessions, the two analyses indicated three clusters, all of them containing Mozambican landraces. From our results, it may be concluded that sweetpotato populations from the three countries do not share a common genetic background, despite the shared history of the countries. Full article