Search Results (2,178)

Background/Objectives: Pediatric intussusception, a condition where part of the intestine telescopes into an adjacent segment, predominantly affects children aged 6–18 months. Prompt diagnosis and management are crucial to prevent serious complications such as ischemia or necrosis. This systematic review aims to comprehensively evaluate and synthesize existing research on predictive and prognostic biomarkers associated with pediatric intussusception that can aid in early diagnosis, severity assessment, outcome prediction, and treatment. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science using specific MeSH and free-text terms related to intussusception, biomarkers, and the pediatric population. The review followed PRISMA guidelines, with independent screening, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. A total of 47 studies, mostly retrospective cohorts from diverse countries, with over 20,000 patients, were included. Results: The studies identified numerous biomarkers associated with disease severity, including hematological markers and indices (e.g., WBC counts and neutrophil-to-lymphocyte ratio), inflammatory markers (CRP and cytokines), biochemical markers (serum lactate, D-dimer, and electrolytes), and novel molecular markers (I-FABP, MCP-1, and transfer RNA fragments). Elevated inflammatory markers and derived ratios consistently predicted bowel necrosis, ischemia, and need for surgery. Biochemical markers like serum lactate and D-dimer correlated with ischemic severity. Emerging molecular biomarkers show promise for early, non-invasive risk stratification. However, heterogeneity in study designs, assay methods, and cutoff values currently limits immediate clinical application. Conclusions: Biomarker research offers valuable tools for improving pediatric intussusception management, with the potential to enhance early diagnosis and outcome prediction. While traditional markers are useful, novel molecular and protein biomarkers hold promise for more specific and rapid assessment. Validation through multicenter, prospective studies and standardized protocols is essential before routine implementation. Integrating biomarkers with clinical and imaging data could refine decision-making, ultimately reducing morbidity and improving prognosis in affected children. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues. Methods: The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R⁺ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643’s impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R⁺ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR. Results: WY14643 decreased inflammatory markers such as CD45R⁺IFN-γ⁺, CD45R⁺IL-6⁺, CD45R⁺iNOS⁺, CD45R⁺MCP-1⁺, CD45R⁺IL-1α⁺, CD45R⁺IL-2⁺, CD45R⁺Notch1⁺, CD45R⁺Notch3⁺, CD45R⁺GITR⁺, and CD45R⁺NF-κB p65⁺ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney. Conclusions: This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis. Full article

Background/Objectives: Atopic dermatitis (AD)-related skin inflammation involves the release of cytokines and chemokines from keratinocytes; therefore, keratinocyte-based models are widely used to evaluate the anti-inflammatory potential of botanical extracts. This study examined the relationship between phytochemical profiles and anti-inflammatory potential of baobab fruit 30% and 70% ethanol extracts (BE-30 and BE-70, respectively) in a TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocyte model. Methods: The anti-inflammatory effects of both extracts were evaluated by measuring cytokine and chemokine secretion in TI-stimulated HaCaT cells. Phytochemical characterization was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and targeted high-performance liquid chromatography (HPLC). Results: Both extracts were non-cytotoxic. TI-stimulation markedly increased interleukin (IL)-6, IL-8 and monocyte chemotactic protein (MCP)-1 secretion, while BE-30 and BE-70 significantly reduced all three mediators in a dose-dependent manner. At comparable doses, BE-70 exhibited greater inhibition than BE-30. BE-30 showed a non-monotonic IL-8 response at low concentrations, whereas BE-70 consistently reduced IL-8 in a dose-dependent manner. LC–MS/MS profiling revealed a polyphenol-rich composition, including flavonol glycosides and related phenolic compounds. HPLC confirmed the presence of four marker analytes (procyanidin B2, epicatechin, rutin and tiliroside), which were enriched in BE-70. The content of these four polyphenols was 1.94-fold higher in BE-70. Conclusions: Baobab fruit extracts exhibit anti-inflammatory activity associated with polyphenols. These findings suggest that they could be used as analytical standards and in dermatological applications. Full article

To explore the appropriate supplementation rate of yeast culture (YC) in Kazakh sheep during fattening, the effects of different YC supplementation rates on rumen fermentation parameters and microbial community were studied through in vitro rumen fluid fermentation experiments. A 0.40 g high-concentrate diet was used as the fermentation substrate, and five groups were added with YC at 0% (CK), 1.25% (YC1), 2.5% (YC2), 3.75% (YC3) and 5% (YC4) of dietary dry matter, respectively. Anaerobic fermentation was carried out for 48 h in 60 mL fermentation broth. The results showed that the 48 h GP and microbial crude protein (MCP) concentration in all YC supplementation groups were significantly higher than those in the CK group (p < 0.05). The concentrations of total volatile fatty acids (TVFA) and propionate in the YC1 and YC2 groups were significantly increased and the A/P ratio in the two groups was significantly decreased (p < 0.05). The Multi-factor Comprehensive Evaluation Index (MFAEI) calculation indicated that 1.25% was appropriate. The YC1 and YC2 groups significantly increased the richness and diversity of rumen bacterial communities (Chao1 and Shannon indices, p < 0.05), and significantly increased the relative abundance of Bacteroidota and NK4A214_group (p < 0.05), while significantly decreasing the relative abundance of the potential pathogenic bacterium Campylobacter (p < 0.05). Ustilago abundance was significantly suppressed in all the YC-supplemented groups (p < 0.05). The most effective YC supplementation rate among the tested doses was 1.25% according to the MFAEI and key microbial indicators. The results suggest that dietary supplementation of 1.25% YC (dry matter basis) may beneficially modulate rumen fermentation parameters under in vitro conditions, providing a reference for further in vivo studies on its application in fattening Kazakh sheep. Full article

COVID-19 perturbs the renin-angiotensin system (RAAS) and inflammatory pathways, shaping disease severity. Soluble ACE2 (sACE2) and angiotensin II (Ang II) are central regulators of vascular and immune homeostasis. We profiled plasma from COVID-19 patients and controls using ELISA, together with 48 cytokine profiling and clinical data. Both sACE2 and Ang II were significantly elevated in patients. Increased Ang II was associated with oxygen supplementation and dyspnea, and negatively correlated with IL-3, whereas sACE2 correlated with IL-13 and FGF. Comorbidities modulated cytokine expression: diabetes mellitus was linked to reduced LIF and MCP-1, hypertension to decreased LIF and increased IP-10, and obesity to elevated IL-12p70. Age correlated with TNF and HGF, and reduced oxygen saturation was associated with lower LIF. These findings reveal that acute COVID-19 disrupts RAAS and amplifies immune dysregulation, with Ang II emerging as a pivotal mediator of respiratory compromise and inflammatory imbalance, underscoring its potential as a biomarker and therapeutic relevance. Full article

Nabkhas are a common type of biogenic aeolian landform in arid and semi-arid regions. Their morphological characteristics, surface sediment grain size composition, and spatial distribution patterns can, to some extent, be associated with the interactions between vegetation and the aeolian environment. In this study, nabkhas formed around Caragana tibetica shrubs in the desert steppe of Damao Banner, Inner Mongolia, were selected as the research object. Based on field investigations, UAV image identification, grain size analysis, and spatial point pattern analysis, the characteristics of nabkhas were comparatively analyzed among a control plot without shrubs (CK) and three shrub-covered plots: a low coverage plot (LCP), a medium coverage plot (MCP), and a high coverage plot (HCP). The results showed that (1) some morphological parameters of nabkhas varied among plots with different vegetation cover, but the responses of various indicators were not entirely consistent. The MCP exhibited relatively higher values in indicators such as shrub long axis (L_g), short axis (W_g), and windward slope length (L_y). (2) The surface sediments of nabkhas were mainly composed of silt and fine sand, followed by very fine sand. Compared with the CK, the silt content was generally lower in the shrub-covered plots, whereas the contents of fine sand and very fine sand were higher. The mean grain size (Mz, Φ value) tended to decrease, while the skewness (SK_G) and kurtosis (K_G) tended to increase, and the sorting coefficient (σ_G) showed relatively limited variation. (3) In the LCP, MCP, and HCP, the fractal dimension (D) was significantly positively correlated with the Mz and σ_G (p < 0.05), and significantly negatively correlated with the SK_G and K_G (p < 0.01), suggesting that the D may be associated with variations in sediment grain size structure. (4) Overall, the nabkhas around Caragana tibetica shrubs exhibited a spatial distribution pattern characterized by aggregation at small scales and randomness at large scales, with small-scale clustering being more evident in the MCP and HCP. In general, nabkhas around Caragana tibetica shrubs under different vegetation cover conditions showed observable differences in morphological characteristics, surface sediment grain size composition, and spatial distribution patterns, providing a comparative case reference for the study of nabkhas in desert steppe areas. Full article

Interactions between alcohol and nutrition play an important role in the development and progression of alcohol-associated liver disease (ALD). Although dietary cholesterol was shown to exacerbate fatty liver and liver injury in alcohol-fed mice, findings regarding the combined effect of dietary cholesterol and heavy alcohol drinking on cholesterol homeostasis remain controversial. Ezetimibe has been widely used as a cholesterol-lowering drug in hypercholesterolemic subjects. It is not fully understood whether ezetimibe blunts the adverse effect of cholesterol on lipid and biliary bile acid metabolism in alcohol-exposed mice. In the current study, wild-type mice were subjected to NIAAA alcohol feeding model. Dietary cholesterol (0.2%, w/v) and ezetimibe (0.001%, w/v) were added to the liquid diets. Cholesterol and triglyceride contents in the liver and circulation were determined. Biliary bile acid composition, as well as hepatic and circulating inflammatory markers were analyzed. We found that ezetimibe protected mice from the synergistic effects of dietary cholesterol and alcohol on hepatic triglyceride accumulation, which was accompanied by enhanced expression of genes involved in hepatic beta oxidation. Dietary cholesterol caused great increases in liver cholesterol content and dramatic reductions in the expression of hepatic cholesterol biosynthetic genes in both control- and alcohol-fed mice. These changes were normalized by ezetimibe treatment. Ezetimibe attenuated dietary cholesterol-induced elevations in total biliary bile acids. Moreover, mice fed a diet containing both cholesterol and alcohol exhibited increased expression of monocyte chemoattractant protein 1 (Mcp1) and tumor necrosis factor alpha (Tnfα) in the distal small intestine. Collectively, our findings indicate that ezetimibe effectively mitigates the adverse effects of dietary cholesterol and alcohol consumption on hepatic lipid accumulation and liver injury. Full article

Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES, CXCL12/SDF-1a, CCL7/MCP-3, CCL2/MCP-1, CXCL1/GROa, and the eotaxin family, contribute to the development and/or exacerbation of inflammation, which is a common feature of numerous skin diseases as well as metabolic syndrome. The pathological and molecular connections between chronic inflammatory skin diseases and metabolic syndrome are increasingly recognized as being driven by shared inflammatory pathways, oxidative stress, and adipokine dysregulation. While systemic inflammation acts as a common thread, the precise mechanisms for some conditions remain partially understood. Nevertheless, the exact pathological and molecular connections between skin diseases (i.e., psoriasis, atopic dermatitis, pemphigus vulgaris, acute and chronic spontaneous urticaria, bullous pemphigoid, squamous cell carcinoma, alopecia areata, systemic sclerosis, discoid lupus erythematosus, diffuse large B-cell lymphoma) and metabolic syndrome are not yet fully understood. This narrative review summarizes the robust association between various chronic inflammatory skin diseases and metabolic syndrome in the context of pro-inflammatory chemokines. Full article

In recent years, Large Language Models (LLMs) have demonstrated strong capabilities in contextual reasoning and knowledge retrieval. However, their application in industrial domains is limited by concerns regarding data security, reliance on cloud infrastructure, and high operational costs. To address these challenges, this study proposes the use of the Model Context Protocol (MCP) as a middleware framework that enables the deployment of offline-operable Small Language Models (SLMs) for industrial data processing. MCP facilitates structured interaction between SLMs and external resources (e.g., databases, APIs, and processors), allowing secure and controlled data access without exposing proprietary systems. As illustrated in the proposed framework, user input is first processed by the SLM (Qwen-7B) for intent determination. When external data is required, MCP coordinates the invocation of relevant resources and integrates the returned results into the model. The SLM then generates the final response. This approach enables SLMs to perform local computation for contextual analysis and decision support while maintaining low computational requirements and full data locality. The proposed system eliminates dependence on cloud-based LLM services and enhances security and cost efficiency. Experimental results demonstrate that the MCP-based architecture provides a practical and effective solution for deploying intelligent assistants in industrial environments without relying on large-scale external AI services. Full article

Traditional fuzzy decision-making often relies on manual expert calibration, which is labor-intensive and susceptible to subjective bias. This study addresses these limitations by proposing a novel framework that transforms the intrinsic probabilistic outputs of Large Language Models (LLMs) into Triangular Fuzzy Numbers (TFNs). We introduce a multi-temperature sampling strategy coupled with weighted quantile aggregation and an adaptive interval adjustment mechanism to systematically map model stochasticity to fuzzy possibility distributions. Empirical validation on a structured prototype dataset demonstrates that the proposed method achieves high consistency with expert consensus, with GPT-4.2 exhibiting superior central accuracy and Gemini-2.5 excelling in uncertainty coverage. Furthermore, in complex unstructured scenarios involving business public opinion, the integration of Model Context Protocol (MCP) and Retrieval-Augmented Generation (RAG) significantly corrects cognitive biases and converges uncertainty boundaries. This research establishes a rigorous pathway from generative AI probabilities to fuzzy decision theory, offering a robust automated solution for quantitative risk assessment and intelligent decision support. Full article

Aims. To investigate the relationship between ultrasound (US)-detected parenchymal abnormalities in the major salivary glands (MSG), joint and tendon inflammation, and systemic disease activity in patients with primary Sjögren’s syndrome (pSS). Patients and methods. This cross-sectional, multicenter study enrolled 60 patients with pSS and 20 healthy controls (HCs). Systemic disease activity was evaluated using the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), while symptom burden was assessed with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). MSG evaluation included bilateral gray-scale (GS) and power Doppler (PDUS) assessment of the parotid and submandibular glands using a semi-quantitative 0–3 scoring system. Musculoskeletal ultrasound (MSUS) assessment comprised bilateral examination of the wrists, second to fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, the fourth extensor wrist compartment, and the flexor tendons of the second to fifth fingers for GS and PD-detected synovitis and tenosynovitis, also scored semi-quantitatively. Recorded outcomes included GS and PD synovitis scores, total synovitis score, tenosynovitis score, GS and PD glandular scores, and total glandular score. Results. Synovitis was most frequently detected in the wrists, followed by the second PIP joint. Subclinical synovitis—defined as a GSUS synovitis score > 0 in a joint without clinical swelling—was detected in 66.7% (n = 28) of patients with pSS. No significant correlations were found between joint US scores and salivary gland US scores. ESSPRI showed moderate positive correlations with both the GS synovitis score (p = 0.002) and the total synovitis score (p = 0.003), as well as significant positive correlations with all salivary gland US scores: GS (p < 0.001), PD (p = 0.002), and total glandular score (p < 0.001). ESSDAI demonstrated only a weak positive correlation with the GS salivary gland score (p = 0.030). Conclusions. In patients with pSS, the extent of US-detected MSG parenchymal abnormalities does not reflect systemic disease activity and does not correlate with US-detected joint synovitis. In contrast, patient-reported symptom burden is associated with both joint inflammation and MSG parenchymal changes on US. Larger studies are needed to further define the role of salivary gland and joint US in evaluating disease activity in pSS. Full article

Background and objectives: Occupational and environmental inhalation exposures, including high-aspect-ratio carbon nanotubes, can trigger pulmonary fibrosis (PF). The relationship between exposure-specific fibrogenic pathways (granulomatous inflammation versus diffuse epithelial injury) and lung microbiome dysbiosis remains incompletely understood. We therefore compared lung microbiome alterations in rat PF models induced by multi-walled carbon nanotubes (MWCNTs) and bleomycin. Materials and Methods: Female Wistar rats received a single intratracheal instillation of vehicle, MWCNTs (750 μg/rat), or bleomycin (1 mg/rat). At day 28, fibrosis and inflammation were evaluated by histopathology and bronchoalveolar lavage fluid (BALF) profiling. Lung microbial communities were characterized by 16S rRNA gene sequencing (V3–V4). Seventeen lung samples passed stringent quality control and were analyzed (control n = 5; bleomycin n = 7; MWCNT n = 5). Results: Both agents induced PF with increased profibrotic signaling, but with distinct pathological signatures: MWCNTs produced localized granulomatous lesions and a robust neutrophilic response (25% of BALF cells), whereas bleomycin caused diffuse interstitial remodeling. Bleomycin increased microbial richness (alpha diversity; p < 0.05) and significantly shifted community structure (beta diversity; p < 0.05), while MWCNT exposure showed comparatively limited changes in global diversity. The relative abundance of Pseudogracilibacillus (including P. marinus) was higher in the bleomycin group than in controls, whereas Facklamia tabacinasalis and Corynebacterium maris were more abundant in the MWCNT group. Across samples, Proteobacteria abundance was inversely correlated with BALF TGF-β, MCP-1, and neutrophil proportion. At the species level, Pseudogracilibacillus marinus was positively correlated with BALF TGF-β, while Facklamia tabacinasalis and Corynebacterium maris were positively correlated with MCP-1, CINC-3, and neutrophil proportion (Spearman; p < 0.05). Conclusions: Mechanistically distinct fibrogenic exposures generate exposure-linked lung microbiome signatures that track with host inflammatory and profibrotic responses. These signatures may support biomarker development for environmentally and occupationally relevant PF and motivate longitudinal and functional studies to clarify causality. Full article

Members of Marseilleviridae, a family of icosahedral giant viruses, have been identified worldwide in all types of environments. The virion shows a characteristic internal membrane extrusion at the five-fold vertices of the capsid, but its structural details need to be elucidated. We now report the 4.4 Å cryo-electron microscopy structure of the melbournevirus capsid by using a block-based reconstruction approach. Results: An atomic model of the major capsid protein (MCP) shows a unique cup structure on the trimer that accommodates additional proteins. A polyalanine model of the Penton base protein shows internally extended N- and C-terminals, which indirectly connect to the internal membrane extrusion. The Marseilleviruses share the same orientational organization of the MCPs as previously reported for other giant viruses, but the unique minor capsid protein components named Scaffold may be alternatively utilized to control the dimensions of the capsid during assembly as the tape measure protein. Full article

Leucine-rich-repeat kinase 2 (LRRK2) is a multidomain protein highly expressed in immune cells and implicated in the regulation of immune functions including immune signaling, cytokine release and autophagy. LRRK2 is one of the therapeutic targets in Parkinson’s Disease (PD). Aberrant activation of LRRK2 can also contribute to intestinal inflammation, mainly in inflammatory bowel disease (IBD). Hence the modulation of LRRK2 may influence gut inflammation providing an improvement in disease outcomes. Over the years, microRNAs (miRNAs) have acquired much attention thanks to their potential as therapeutic targets in several pathological conditions, including inflammatory disorders. In this study, we aimed to examine the ability of miR-369-3p in the modulation of autophagy targeting LRRK2 expression. Bioinformatics analysis revealed that Lrrk2 is a target gene of miR-369-3p, and LRRK2 expression was increased in ulcerative colitis patients compared with that in a healthy control. In in vitro analysis, we validated that mimic transfection with miR-369-3p in Raw264.7 significantly reduced the expression of LRRK2 both in basal and inflammatory conditions. Moreover, the inhibition of LRRK2 limited the nuclear translocation of Nuclear factor kappa B (NF-κB) induced by lipopolysaccharide (LPS) stimulation. In turn, we found that, in inflammatory conditions, the intracellular increase in miR-369-3p precluded the inhibition of autophagy by LRRK2 by restoring autophagy marker light chain 3 (LC3)II/I ratio, BECLIN-1 and decreasing p62 expression. Furthermore, we detected that the upregulation of miR-369-3p decreased the release of pro-inflammatory mediators Tumor necrosis factor (TNF), C-C motif ligand 2/Monocyte chemoattractant protein-1 (CCL2/MCP-1), C-C motif ligand 3/Macrophage inflammatory protein-1 alpha (CCL3/MIP-1α) and C-C motif ligand 5/Regulated on activation, normal T-cell expressed and secreted (CCL5/RANTES) and increased the anti-inflammatory cytokine interleukin 10 (IL-10) in response to LPS. This study supports the anti-inflammatory potential of miR-369-3p in immune cells and suggests the potential of miR-369-3p as a therapeutic agent in the treatment of acute intestinal inflammatory conditions such as ulcerative colitis. Full article

Graphene oxide (GO) is a promising nanocarrier for the delivery of oligonucleotides. It offers a high loading capacity, efficient cellular uptake, and surface functionalization. MicroRNA-21 (miR-21) is a well-characterized oncomiR commonly overexpressed in hepatocellular carcinoma (HCC). In HCC, miR-21 contributes to tumor progression, inflammation, and angiogenesis. In a previous in vitro study, we showed that GO alone induces the upregulation of pro-inflammatory and tumor-related genes in HepG2 cells. However, conjugation with an antisense miR-21 (GO-antisense miRNA 21) reverses this effect, suggesting a potential therapeutic application. This study aims to evaluate the antitumor and anti-angiogenic efficacy of the GO-antisense miR-21 nanosystem in ovo using the chick embryo chorioallantoic membrane (CAM) model. Fertilized chicken eggs (n = 4 per group) were randomized into untreated, GO-treated, and GO–antisense miR-21-treated cohorts. A dose of 200 μL (GO 10.0 µg/mL: antisense miR-21 5.0 pmol/mL) was administered intratumorally. Tumor size, volume, and vascularization were monitored through stereomicroscopy and histological analysis. The expression of inflammatory and tumor-associated genes (IL-8, MCP-1, TIMP-2, ICAM-1 and NF-kB) was assessed by quantitative PCR. Given its prominent response, IL-8 protein expression was further analyzed via immunofluorescence. To evaluate tumor-specific delivery, FITC-labeled GO was tracked by confocal microscopy. Our data revealed that treatment with unfunctionalized graphene oxide (GO) unexpectedly promoted tumor vascularization and led to a significant increase in tumor weight. This was accompanied by upregulation of inflammatory markers. In contrast, GO-antisense miR-21 significantly reduced the tumor volume and vessel density. It also successfully downregulated all target genes. Confocal imaging demonstrated preferential accumulation of the nanosystem within the tumor mass. Our results highlight the dual anti-inflammatory and anti-angiogenic effects of GO-antisense miRNA 21 in ovo and support its potential as a targeted nanoplatform for HCC treatment. Full article