Search Results (1,253)

This study aimed to elucidate the oncogenic role of FOXA1(forkhead box A1) in ovarian cancer and to evaluate its potential as both a therapeutic target and a diagnostic biomarker. We further investigated whether FOXA1 inhibition could enhance responsiveness to immune checkpoint blockade and overcome chemoresistance. A total of seventy-six ovarian tissue samples were analyzed, including nine normal, thirty-four benign, and thirty-three malignant specimens. IHC (immunohistochemistry) staining was performed to assess FOXA1 expression and its correlation with tumor stage. Functional studies were conducted using FOXA1 siRNA in SK-OV3 and HEYA8 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following FOXA1 silencing. Quantitative RT-PCR was used to measure the expression of FOXA1 and EMT (epithelial–mesenchymal transition)-related genes. The effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were also examined. IHC analysis revealed significant differences in FOXA1 expression among normal, benign, and malignant tissues, with levels correlating with tumor stage. FOXA1 silencing significantly reduced proliferation and decreased migration and invasion by 60–80%, accompanied by marked downregulation of EMT-related genes. Moreover, FOXA1 inhibition enhanced atezolizumab responsiveness and reduced carboplatin resistance in ovarian cancer cells. In summary, FOXA1 acts as an oncogenic driver in ovarian cancer, promoting proliferation, invasion, and EMT activation. Its overexpression correlates with disease progression, supporting its potential as a biomarker and therapeutic target. Targeting FOXA1 could enhance immunotherapy efficacy and help overcome chemoresistance in ovarian cancer. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants associated with neurotoxicity and increased risk of neurodegenerative diseases. PCB 153, a highly abundant non-coplanar congener, bioaccumulates in human tissues and impairs homeostasis. This study investigated the transcriptomic effects of PCB 153 (2,2′,4,4′,5,5′-Hexachlorobiphenyl) in retinoic acid (RA)-differentiated SH-SY5Y neuronal cells to identify early, sub-cytotoxic molecular alterations. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after 24 h exposure to increasing PCB 153 concentrations. RNA-Seq was performed on cells treated with 5 μM PCB 153, the highest non-cytotoxic dose. Sequencing reads were quality-filtered, aligned to the human genome, and analyzed with DESeq2. Functional enrichment was conducted using Gene Ontologies and KEGG pathways. Western blot analyses were performed to assess protein level changes in selected targets. RNA-Seq identified 1882 significantly altered genes (q-value < 0.05). Gene Ontology analysis revealed strong enrichment of proteasome-related terms, with most proteasomal subunits displaying coordinated upregulation. KEGG analysis further showed significant enrichment of Alzheimer’s (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), and other neurodegenerative disease pathways. These findings indicate that PCB 153 triggers a pronounced proteostatic response in neuron-like cells, suggesting early disruption of protein homeostasis that may contribute to mechanisms associated with neurodegeneration. Full article

Objectives: This systematic review aimed to evaluate the effectiveness of currently available methods for the diagnosis and monitoring of skeletal, dental, and soft tissue changes, as well as the adequacy of follow-up protocols, in adolescents and adults treated with miniscrew-assisted rapid palatal expansion (MARPE). Materials and Methods: This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive electronic literature search was performed across five databases (PubMed, Scopus, Embase, Cochrane, and Web of Science) to identify prospective and retrospective clinical studies evaluating dental, periodontal, and alveolar bone outcomes associated with MARPE in late adolescent and adult patients. Study selection, data extraction, and risk of bias assessment were independently performed by two reviewers. Risk of bias was assessed using the ROBINS-I tool for non-randomized studies and the RoB 2 tool for randomized studies. The certainty of the evidence was evaluated using the GRADE approach. Owing to substantial methodological heterogeneity and limited follow-up duration, a structured qualitative (narrative) synthesis of the results was performed. Results: A total of 20 studies were included in the systematic review. The reported adverse events primarily involved hard and soft tissues and were identified using cone-beam computed tomography (CBCT), clinical and periodontal examination, panoramic and cephalometric radiography, and digital dental casts. Dental effects, including dental tipping, were frequently reported across the included studies. Alveolar bone loss was reported in 11 studies, buccal alveolar bone dehiscence in 3 studies, and failure of palatal suture opening in 6 studies. In most of the included studies, follow-up was either not reported or limited. Conclusions: The MARPE technique appears to be potentially effective in achieving transverse maxillary expansion in late adolescent and adult patients. However, the included studies report possible adverse events affecting periodontal and alveolar bone tissues, such as alveolar bone thinning and gingival hypertrophy, the assessment of which requires an integrated diagnostic approach combining CBCT imaging with clinical and periodontal examination. Overall, the certainty of the available evidence was low to very low, mainly due to a high risk of bias, methodological heterogeneity, and limited or absent follow-up in most studies. Therefore, the results should be interpreted with caution. Well-designed prospective controlled studies with standardized protocols and long-term follow-up are needed to conclusively evaluate the safety and long-term clinical stability of the MARPE technique. Full article

Salinity stress represents a critical environmental constraint that significantly limits the development of tilapia aquaculture in brackish water environments. Its substantial impacts on fundamental physiological processes in fish, particularly osmotic balance, energy metabolism, and antioxidant defense mechanisms, have become a major scientific concern in aquaculture research. To systematically elucidate the molecular mechanisms underlying the response of genetically improved farmed tilapia (Oreochromis niloticus) to salinity stress and to test the hypothesis that it adapts through metabolic reprogramming for energy reallocation under such conditions, this study employed an integrated transcriptomic and metabolomic approach. Through a rigorously controlled experimental design with freshwater (0‰) as the control group and brackish water (24‰) as the experimental group, we conducted a comprehensive analysis of dynamic changes in gene expression profiles and metabolite spectra in the liver tissues of experimental fish. The study yielded the following key findings: First, salinity stress significantly suppressed growth performance indicators, including body weight and length, while simultaneously inducing extensive transcriptomic restructuring and profound metabolic remodeling in liver tissue. A total of 1529 differentially expressed genes (including 399 up-regulated and 1130 down-regulated genes) and 127 significantly differential metabolites were identified. Second, the organism achieved strategic reallocation of energy resources through coordinated suppression of multiple energy-consuming anabolic pathways, particularly steroid biosynthesis and fatty acid metabolism, with the remarkable down-regulation of Fasn, a key gene in the fatty acid synthesis pathway, being especially prominent. Energy-sensing and metabolic homeostasis regulatory networks played a central coordinating role in this process, guiding the organism through metabolic reprogramming by regulating downstream metabolic nodes. From a multi-omics integrative perspective, this study provides in-depth insights into the sophisticated metabolic remodeling and energy allocation strategies employed by GIFT to cope with salinity stress. These findings, particularly the suppression of fatty acid biosynthesis and the reprogramming of glycolysis/gluconeogenesis pathways, not only elucidate the molecular mechanisms by which teleosts achieve environmental adaptation through energy reallocation, but also provide actionable molecular targets for the selective breeding of salinity-resilient tilapia strains. Full article

Objective: This study compares the brain protective effects of L-borneolum and its main components (a combined application of L-borneol and L-camphor) on the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). It also makes clear the intrinsic regulatory mechanisms that link the neuroprotective effects of these compounds on IS to the blood-brain barrier (BBB), based on network pharmacology predictions. Furthermore, the study investigates the relationship between these compounds and the Major Facilitator Superfamily Domain-containing Protein 2A (MFSD2A)/Caveolin-1 (Cav-1) signaling axis. Methods: The MCAO/R model in rats was established to evaluate the therapeutic effect of L-borneolum (200 mg/kg) and its main components combination of L-borneol and L-camphor (6:4 ratio, 200 mg/kg). Neurological scores, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed to evaluate the neurological damage in the rats. Cerebral blood flow Doppler was applied to monitor the cerebral blood flow changes. Immunofluorescence analysis of albumin leakage and transmission electron microscopy (TEM) were conducted to evaluate blood-brain barrier (BBB) integrity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the optimal drug concentration. Trans-epithelial electrical resistance (TEER) and horseradish peroxidase (HRP) assays were employed to confirm the successful establishment of an in vitro BBB co-culture model. Network pharmacology was utilized to predict the biological processes, molecular functions, and cellular components involved in the treatment of ischemic stroke (IS) by the main components of L-borneolum (L-borneol and L-camphor). Finally, immunofluorescence, real-time fluorescent quantitative PCR (RT-qPCR) and western blot analyses were performed to detect the expression of Major Facilitator Superfamily Domain Containing 2A (MFSD2A), caveolin-1 (CAV-1), sterol regulatory element-binding protein 1 (SREBP1) in brain tissue and hCMEC/D3 cells. Results: Network pharmacology prediction indicated that L-borneolum and its main components (L-borneol and L-camphor) in the treatment of IS are likely associated with vesicle transport and neuroprotection. Treatment of IS with L-borneolum and its main components significantly decreased neurological function scores and cerebral infarction area, while alleviating pathological morphological changes and increasing the number of Nissl bodies in the hippocampus. Additionally, it improved cerebral blood flow, reduced albumin leakage, and decreased vesicle counts in the brain. The trans-epithelial electrical resistance (TEER) of the co-culture model stabilized on the fifth day after co-culture, and the permeability to horseradish peroxidase (HRP) in the co-culture model was significantly lower than that of the blank chamber at this time. RT-qPCR and Western blot results demonstrated that, compared to the model group, the expression of SREBP1 and MFSD2A significantly increased, while the expression of Cav-1 decreased. Conclusions: L-borneolum and its main components combination (L-borneol/L-camphor, 6:4 ratio) may exert a protective effect in rats with IS by improving BBB transport function through modulation of the MFSD2A/Cav-1 signaling pathway. Full article

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion. Full article

Background/Objectives: This retrospective study evaluated and compared the cephalometric effects of an elastodontic bioactivator and conventional high-pull headgear in growing patients with hyperdivergent Class II malocclusion. Methods: Patients aged 7–11 years were divided into two groups according to the appliance used for the orthodontic treatment performed: elastodontic device (ED) and high-pull headgear (HPHD). Cephalometric measurements were recorded at baseline (T0) and after 18 months of treatment (T1). The data were subjected to statistical analysis, descriptive statistics were calculated, and an ANOVA test and post hoc Tukey test were performed (repeated measures correction was applied for intragroup comparisons). Linear regressions were conducted. Significance was predetermined as p < 0.05 for all the tests performed. Results: 40 patients were included, 20 belonging to the ED group and 20 to the HPHD group. Both groups showed a significant increase in SNB (p < 0.05), suggesting favorable mandibular positional changes. SNA and ANB did not show significant intra- or intergroup variations (p > 0.05). Regarding vertical skeletal parameters, no significant intra- or intergroup changes were observed at T0 and T1, indicating that both devices preserved vertical stability without worsening the hyperdivergent pattern. Dentoalveolar and soft-tissue effects were limited. Conclusions: Both ED and HPHD are effective in managing hyperdivergent Class II growing patients. The two appliances provide comparable improvements in mandibular positioning. Both devices seem to preserve vertical skeletal dimensions, avoiding further mandibular clockwise rotation. Both appliances are associated with minimal undesirable effects on the soft tissues. Full article

Cadmium (Cd) drastically inhibits plant growth and metabolism, whereas arbuscular mycorrhizal (AM) fungi can enhance plant Cd tolerance through metabolic regulation. To clarify tissue-specific responses, we conducted a pot experiment combined with GC-MS to examine how AM fungi influence root and leaf metabolism of ryegrass (Lolium perenne L.) under different Cd levels. Root and leaf metabolomes diverged substantially in composition and function. In total, 83 metabolites were identified in roots, mainly phenolics, amines, and sugars associated with carbon–nitrogen metabolism and stress-defense pathways, whereas 75 metabolites were identified in leaves, largely related to photosynthetic metabolism. Roots were more sensitive to Cd, showing significant metabolic alterations at Cd ≥ 5 mg·kg⁻¹, including disruption of galactose metabolism, while leaves exhibited notable changes only at Cd ≥ 100 mg·kg⁻¹, with suppression of citrate, L-aspartate, and starch and sucrose metabolism. AM fungi modulated plant metabolism more strongly under Cd stress. Specifically, AM fungi restored Cd-suppressed galactose and glyoxylate/dicarboxylate metabolism in roots, enhanced starch and sucrose metabolism and amino acid pathways in leaves, and increased stress-related amino acids and organic acids in both tissues. Overall, AM fungi substantially alleviated Cd-induced metabolic inhibition, particularly at Cd ≥ 50 mg·kg⁻¹, providing mechanistic insight into AM-enhanced Cd tolerance and supporting the application of AM symbiosis in remediation of Cd-contaminated soils. Full article

Nanoplastics (NPs) pose significant risks due to their small size and ability to penetrate biological tissues. However, the molecular pathways and cellular mechanisms affected by NP exposure in marine teleosts remain poorly understood, especially in tropical reef fishes. This study examined the impact of short-term (7 days) waterborne exposure of 100 nm-carboxyl-modified polystyrene NPs on the false clownfish (Amphiprion ocellaris) exposed at two daily concentrations: low (20 µg/L, environmentally relevant) and high (2000 µg/L). A multidisciplinary approach, including biochemical and transcriptomic analyses, was conducted to assess toxic effects. Biochemical assays revealed limited changes in antioxidant defenses (CAT, GR, GST, TOSC). However, the Integrated Biomarker Response index (IBRv2i) suggested a compromised physiological condition, supported by transcriptomic data. Transcriptomic profiling revealed 409 significantly differentially expressed genes (DEGs) in the high-concentration and 354 DEGs in the low-concentration groups, with 120 shared DEGs mostly upregulated and indicative of a core molecular response. Collectively, the transcriptional profile of the low-concentration group resembled an early-warning, energy-reallocation strategy aimed at preserving essential sensory functions while minimizing expendable functions. The high-concentration group amplified the shared stress signature and recruited an additional 289 unique genes, resulting in pronounced enrichment of Gene Ontology terms related to “muscle contraction”, “oxygen transport”, “hydrogen-peroxide catabolism”, and “extracellular-matrix”. This study demonstrates that PS-NP exposure can alter gene expression and physiology in juvenile reef fish, even at environmentally relevant concentrations. Molecular responses varied with concentrations highlighting the role of exposure level in influencing biological systems and potential long-term impacts of NP pollution in marine environments. Full article

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota–liver–brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis’s connection to dementia or cognitive impairment. Full article

Brachycephalic obstructive airway syndrome is a group of abnormalities that primarily affect the upper respiratory tract, particularly in dogs—especially in English and French bulldogs, pugs, and Boston terriers. The description and the consequences of these anomalies are well known. We performed a detailed histopathological analysis of soft palate samples taken from brachycephalic dogs with BOAS III. We examined the impact of the severity and composition of inflammatory infiltrates on individual histological structures, such as mucosal membrane, serosal and mucosal glands, and muscles. The study was conducted on 50 samples of soft palate tissue collected from pugs and French bulldogs. The sections were then stained with haematoxylin and eosin (HE) and Masson–Goldner trichrome. In general, both lymphocytic and plasmocytic inflammation were observed. Plasmacytic inflammation was more commonly associated with more advanced changes, including glandular fibrosis, muscle degeneration, and waxy necrosis of the muscles. Therefore, inflammatory infiltration—particularly plasmocytic infiltration—is associated with more severe clinical symptoms and a poorer prognosis in BOAS III dogs. Full article

Low back pain (LBP) represents a major societal and economic burden, with annual costs in the United States estimated at $90–134.5 billion. LBP disproportionately impacts postmenopausal women relative to age-matched men, suggesting a role for sex-specific biological factors. Although the mechanisms underlying this disparity are not fully understood, hormonal imbalance during menopause may contribute to LBP pathophysiology. This narrative review aimed to elucidate the impact of menopause on LBP, with emphasis on hormonal effects on spinal tissues and systemic processes. A literature search was conducted, followed by screening of titles, abstracts, and full texts of original clinical studies, preclinical research using human or animal samples, and relevant reviews. Rigour and reproducibility were evaluated using the ARRIVE Guidelines and the Modified Downs & Black Checklist. Evidence indicates that menopause is associated with changes in intervertebral discs, facet joint, ligamentum flavum, skeletal muscle, sympathetic innervation, and systemic systems such as the gut microbiome. However, most findings are correlational rather than causal. Evidence supporting hormone replacement therapy for LBP remains inconclusive, whereas exercise and other treatments, including parathyroid hormones, show more consistent benefits. Future studies should focus on causal mechanisms and adhere to rigour guidelines to improve translational potential. Full article

Background/Objectives: Geometric morphometric analysis (GMA) is a statistical method that captures and quantifies shape variation. This study aimed to assess hard and soft tissue shape variations and changes following orthodontic treatment in Class III skeletal malocclusion using GMA. Methods: A retrospective study was conducted on 84 lateral cephalometric radiographs (pre-treatment and near-end treatment) of Class III patients aged 16–40 years (ANB < 2°). Thirty-five landmarks were digitized in Cartesian coordinates using MorphoJ software for shape analysis. Results: The sample included 62% females and 38% males, with a mean age of 24.7 ± 5.2 years. Vertical dimension variations (hypodivergent to hyperdivergent) contributed most to shape changes PC1 (23.35%), followed by anteroposterior variations PC2 (13.51%). Gender significantly influenced hard and soft tissue variation with 30.91%SS (F = 56.99, p < 0.0001). Males had significantly larger and longer ramus, body of the mandible, alveolar height, LAFH, TAFH and upper lip length. (PD: 0.026, p < 0.05). Significant shape changes were seen in the mandible (PD = 0.018, p < 0.05). SNB increased by 0.41° (from 81.73° ± 3.67°), and ANB improved by 0.46° but remained Class III (−0.33° ± 1.82°). Lower anterior facial height increased by 1.78 mm (p < 0.05). The lower incisors retroclined significantly (from 92° ± 8.56° to 87° ± 6.96°, p < 0.05), while the interincisal angle increased by 5.9°. Upper incisors remained procline (118° ± 11°, p > 0.05). Upper lip length increased by 0.4 mm (p < 0.05). Conclusions: Vertical and anteroposterior shape variations are notable within Class III malocclusion. Post-treatment changes in both hard and soft tissues indicate that orthodontic camouflage can enhance facial esthetics and skeletal balance. GMA provides objective quantification and visualization of these treatment-related craniofacial changes. Full article

Acute lung injury may occur after cardiac arrest (CA), with innate immunity likely playing an important role in lung inflammation after CA. This study aimed to survey serial changes in the toll-like receptor (TLR) 4 signaling pathway in post-resuscitation lung injury in CA rats. A randomized animal study was conducted in rats with CA followed by successful cardiopulmonary resuscitation (CPR). The expression of TLR4 pathway biomarkers was analyzed and compared to the sham controls at different time points after CA with CPR. Lung tissues were collected for histological analysis to assess structural damage. Bronchoalveolar lavage fluid (BALF) was analyzed to quantify inflammatory cytokines and to assess changes in regulatory B cells (Bregs) and regulatory T cells (Tregs). Histological examination revealed marked pulmonary hemorrhage and structural injury shortly after CA. CA with CPR increased myeloid differentiation factor 88 (MyD88) mRNA and protein expression compared to controls at 2 h after CA. Cytokine analysis of BALF showed elevated IFN-γ, interleukin (IL)-1α, IL-1β, IL-2, IL-6, and IL-10 at 2 h after CA. A reduction in Bregs was noted at 2 h, whereas Tregs transiently increased between 2 and 4 h but declined at 6 h after CA. The MyD88-dependent signaling pathway appears to be rapidly activated in rats with CA after CPR, which may contribute to the early pulmonary inflammation observed as soon as 2 h after CA. Full article