Diffuse idiopathic skeletal hyperostosis in a Roman-period horse from Gerulata (Bratislava-Rusovce, Slovakia): Diagnostic Considerations.

Advancing brain age estimation: normative deviation mapping (NDM) for sensitive detection of pathological aging.

Although asymptomatic or pre-symptomatic Pompe disease is increasingly recognized, early skeletal muscle pathology and the role of residual glycogen at this stage remain unclear. Here, we investigated early muscle pathological changes using human samples and an early-stage Gaa -/- mouse model, focusing on residual glycogen accumulation. Clinical, genetic, imaging, and muscle pathological analyses were performed in an asymptomatic Pompe disease patient carrying a novel GAA variant. Skeletal muscle samples from asymptomatic and symptomatic patients, as well as from early-stage and late-stage Gaa -/- mice, were analyzed using histochemistry, immunohistochemistry, immunofluorescence, and Western blotting to assess residual glycogen accumulation and lysosome-associated pathways. We identified a novel mutation, c.361C > T, in an asymptomatic Pompe disease patient. Despite the lack of symptoms, residual glycogen accumulated in muscle lysosomes. Immunohistochemistry showed positive glycogenin expression, while LAMP1 and LC3 were negative, suggesting early glycogenin detection. Western blot revealed increased glycogenin and STBD1, with mild LAMP1 and LC3 upregulation. In 1-month-old Gaa -/- mice, glycogenin, LAMP1, STBD1, and LC3 were all upregulated. Furthermore, immunofluorescence further showed glycogenin/LAMP1 double-positive muscle fibers in both the patient and mice. Our study shows that key pathological changes in Pompe disease occur during the asymptomatic stage, with early lysosomal accumulation of residual glycogen. This suggests residual glycogen may serve as a biomarker of early disease activity and a potential target for early intervention, informing disease monitoring and the timing of enzyme replacement therapy (ERT). Further studies are needed to validate its clinical utility and explore strategies for early clearance.

MRI can detect the most significant pathological changes of muscle-fat replacement and muscle edema in muscular dystrophies. MRI-derived texture analysis is superior to conventional MRI for identifying pathological changes in muscular dystrophies. Furthermore, the combination of selected radiomics features and clinical biomarkers can enhance the diagnostic accuracy for muscular dystrophies. Muscular dystrophies are difficult to discriminate from their mimickers, so further research is warranted to identify the optimal feature combination and validate the performance of the combined model in myopathies prone to misdiagnosis. This study evaluated the diagnostic accuracy of radiomics features and clinical biomarkers in differentiating muscular dystrophies from their mimickers in a cohort of 161 myopathy patients using machine learning techniques. Multiple machine learning algorithms were jointly applied to screen robust features. The results showed that the combined nomogram exhibited better performance than the individual model using clinical or radiomic features, achieving an AUC of 0.955 in the training set and 0.923 in the validation set. Decision curve analysis confirmed the clinical utility of the nomogram. This multiparametric approach, combining texture features from MRI T1-weighted sequences and STIR sequences with clinical biomarkers (age, gender, and creatine kinase), significantly enhanced the discriminative power. The better performance of the nomogram compared with expert evaluations demonstrated its potential application in distinguishing muscular dystrophies from their mimickers.

Linggan Wuwei Jiangxin Decoction attenuates chronic obstructive pulmonary disease via modulation of the AGE/RAGE signaling pathway.

Hip osteoarthritis (HOA) is the most common hip joint disorder, accounting for approximately 27.9% of all cases of osteoarthritis (OA), often leading to total hip replacement (THR). In the last decades, femoroacetabular impingement (FAI) has been addressed as a significant etiological factor in the development of early-onset HOA, especially in young adults with non-dysplastic hips. FAI has been found to cause damage to all joint tissues, cartilage, labrum, and subchondral bone, thus underlining the importance of an early diagnosis and intervention to prevent progression to end-stage disease. This review aims to provide a comprehensive overview of the biochemical, morphological, and cellular alterations occurring in hip joint tissues in the presence of FAI. Understanding the early pathological changes is of crucial importance as they often precede radiographic signs of disease and may serve as valuable biomarkers for early detection and management of FAI and peri-arthritic conditions to delay or prevent the need for THR in younger populations.

Eupalinolide B prevents cerebral ischemia-reperfusion injury via the PI3K/Akt/GSK3β(Ser9) signaling pathway.

SARS-CoV-2 has precipitated a global health crisis. The Main Protease (Mpro) represents a validated pharmacological target. A series of benzothiazole-based derivatives was designed, synthesized, and evaluated as Mpro inhibitors. The synthesized 5-nitro benzothiazole intermediates (26-29) displayed moderate Mpro inhibition with low to moderate cytotoxicity (CC₅₀=16-83μM in HEK-293 cells). These compounds were subsequently optimized through SAR studies guided by binding site analyses. Lead optimization afforded highly potent derivatives, notably compound 35 (IC50=0.026μM), exhibiting superior potency compared to GC376 and an exceptionally high selectivity index (10,653.8), indicating a favorable potency and safety profile. Acute oral toxicity studies classified compound 35 (LD50=947.6mg/kg BW) and 48 (LD50=274.6mg/kg BW) as Category IV and III toxicants, indicating low acute oral toxicity. Histopathological analysis revealed that the intermediate compound 28 induced hepatic alterations, whereas the final SAR-optimized compound 35 exhibited preserved liver architecture with no apparent pathological changes. Molecular Docking analyses revealed that these benzothiazole derivatives effectively occupied the Mpro active site sub-pocket through stable H-bonding and hydrophobic interactions, thereby facilitating catalytic dyad engagement and pocket adaptability. Covalent docking of compound 35 indicated favorable binding and putative covalent interaction with Cys145. MD simulations confirmed that compound 35 stabilized the protein structure with enhanced compactness, stable interactions, and reduced conformational fluctuations compared to the apo protein. Collectively, these findings highlight benzothiazole-based scaffolds as promising SARS-CoV-2 Mpro inhibitors.

Structural characterization and hypoglycemic activity of a novel pectic polysaccharide extracted from Atractylodes lancea rhizome.

Ferroptosis mechanisms in early brain injury after subarachnoid hemorrhage.

Effect of methanolic extract of Salix babylonica on biochemical parameters and gene expression in streptozotocin induced diabetic rat model.

Stratification of the corneal epithelium plays a vital role in protecting the eye from the external stimuli. However, the molecular mechanisms underlying this process are not fully understood. Herein, we show that death-associated protein kinase 1 (DAPK1) is markedly up-regulated during corneal epithelial development. Exploiting Dapk1 knockout mice, we show that depletion of DAPK1 results in corneal opacity and significant thickening of the corneal epithelium. Immunofluorescence staining using epithelial-specific markers reveals that DAPK1 deficiency causes the loss of corneal epithelial properties and the appearance of epidermal-like pathological changes. Further investigation shows that DAPK1 deficiency disrupts corneal epithelial stratification and impairs epithelial cell junctions due to the generation of excessive suprabasal cells through abnormal cell division. Therefore, this study demonstrates a critical role for DAPK1 in the control of corneal epithelial development, indicating DAPK1 as a potential therapeutic target for corneal diseases.

Despite the high prevalence of neoplastic diseases in dogs, tumour-cell embolism is poorly documented. This study aimed to characterise the presence and pathological features of distant blood vascular tumour-cell emboli (TCE) in dogs submitted for necropsy. TCE were histologically confirmed in 31/528 dogs (5.9%) that died or were euthanized due to neoplastic disease, most frequently mammary carcinomas (17/31, 54.8%). In 15/31 dogs (48.4%), TCE were associated with secondary macroscopic lesions, such as haemorrhage, whereas in 16/31 dogs (51.6%), there was no clear association with additional pathological changes. TCE were most commonly observed in the lungs (25/31), kidneys (9/31), adrenals (5/31), brain (5/31), and myocardium (5/31). Macroscopic pulmonary changes included petechiae or suffusions (8/31), and TCE-associated haemorrhages were also observed in the myocardium (4/31), kidneys (2/31), adrenals (2/31), brain (2/31), and gastrointestinal serosae (2/31). Histological lesions associated with TCE included haemorrhage (18/31), thrombosis (11/31), oedema (8/31), infarcts (7/31), and intimal proliferation and perivascular fibrosis (4/31). Taken together, these findings suggest that blood vascular TCE may be more prevalent in dogs than currently recognised and reinforce the importance of careful pathological evaluation for their detection. The clinical, macroscopic, and microscopic features described herein provide a practical framework for recognising TCE in veterinary pathology and underscore the need for further studies addressing their pathogenesis, clinical significance, and impact on disease progression in dogs.

Exploring the role and potential mechanisms of SIK1 in cartilage damage in osteoarthritis based on metabolomics.

Astragalus polysaccharide ameliorates neuroinflammation in EAE mice by modulating microglial autophagy to reduce lipid droplet accumulation.

Inhibition of sebum production and pro-inflammatory mediators by QDF hydrogel reduces acne symptoms in mice model.

Integrative multi-omics profiling implicates purine metabolism and the PI3K-Akt pathway in radiation-induced lung injury.

Analysis of pathological histochemical characteristics of yak pancreas induced by Fasciola hepatica.

Peripheral cannabinoid receptor activation attenuates frostbite-induced chronic pain via modulation of TRP channels, neuroinflammation, and autophagy.

Kawasaki disease (KD) is an acute systemic vasculitis causing coronary artery lesions (CAL). Paeoniflorin (PF) exerts anti-inflammatory and antioxidant properties, but its role in KD remains unclear. This study aims to elucidate the effects of PF on CAL and the underlying regulatory mechanisms. C57BL/6J mice were induced by Lactobacillus casei cell wall extract (LCWE) to establish a KD mouse model. Inflammatory infiltration and pathological changes of cardiac tissue in mice was evaluated by hematoxylin eosin staining. Oxidative damage of mice was evaluated by measuring protein carbonyl, 8-hydroxy-2'-deoxyguanosine, malondialdehyde and 4-hydroxynonenal (4-HNE). Superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase 4 was measured to evaluate antioxidant levels in mice. Inflammation levels was assessed by measuring tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Apoptosis of cardiac tissues was detected by TUNEL assay. The underlying mechanism was determined by RNA-sequencing. Results showed that PF inhibited inflammatory infiltration and apoptosis of cardiac tissues, as well as oxidative damage and inflammation in KD mouse model, but enhanced antioxidant levels in KD mouse model. Mechanically, PF inhibited cytochrome P450 family 2 subfamily E member 1 (CYP2E1) expression but activated NRF2 pathway in KD mouse model. CYP2E1 overexpression and ML385 (a NRF2 inhibitor) reversed the therapeutic effects of PF on KD mouse model. Moreover, CYP2E1 knockdown restored the therapeutic effects of PF inhibited by ML385 on KD mouse model. Collectively, our findings demonstrated that PF alleviated CAL in KD by activating NRF2 pathway and inhibiting CYP2E1 expression. These results may provide a theoretical basis for the potential use of PF as a therapeutic agent for KD associated with CAL.