Histology and histopathology最新文献

Background and purpose: Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Polygonum multiflorum Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process.

Methods: The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing.

Results: TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent.

Conclusion: TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.

Huntington's disease (HD) is a devastating, autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Among the major pathological hallmarks of HD are mutant huntingtin aggregation, white matter loss and reactive astrogliosis, which together contribute to neuronal dysfunction and death, particularly in the striatum and cortex. Recent studies in HD mouse models have identified a specialized astrocyte subtype that clusters around white matter bundles originating from the secondary cortex and passing through the striatum. While the functional role of these astrocytes remains unclear, they express Glial Fibrillary Acidic Protein (GFAP), a marker typically associated with both fibrous and reactive astrocytes. The discovery of this white matter-associated astrocyte subtype, along with other astrocytic subtypes differing between grey and white matter, underscores the complexity of glial responses in HD. Accurate identification and interpretation of these glial populations are crucial for understanding disease mechanisms and progression. Given the overlapping expression profiles of commonly used astrocyte markers like GFAP, the careful selection and application of both astrocyte and white matter markers in histopathological analyses are essential to advance our understanding of how glial cells contribute to HD pathology. In this review we discuss different histopathological approaches to assess the roles of glia in HD, emphasizing the need for standardized approaches and critical evaluation of marker specificity.

Background: Rheumatoid arthritis can affect extra-articular organs such as the liver, and the problem of drug-induced liver injury caused by traditional antirheumatic drugs for improving the condition cannot be ignored. This study aims to investigate the therapeutic effects of resveratrol (Res) on hepatic inflammation and oxidative stress in mice with collagen-induced arthritis (CIA) and to elucidate the relationship between the regulatory mechanisms of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway.

Methods: In this study, we used chicken type II collagen in combination with complete Freund's adjuvant to induce arthritis in a mouse model, and Res was administered by tube feeding to detect the serum biochemical liver function and inflammation levels, oxidative stress, and apoptosis in the livers of mice. An in vitro cellular model of liver inflammation and oxidative stress was established by treating mouse primary hepatocytes (MPHs) with tumor necrosis factor-α (TNF-α) and H₂O₂. The intrinsic mechanism of Res in attenuating hepatic inflammation and oxidative stress in CIA mice was explored by treating MPHs with an Nrf2 inhibitor and Keap1 overexpression plasmid.

Results: Res significantly reduced the levels of inflammation and oxidative stress in liver tissues of CIA mice as well as in MPHs treated with TNF-α and H₂O₂ and activated the Nrf2/Keap1 signaling pathway. Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression, which promoted apoptosis.

Conclusion: This study demonstrated the intrinsic mechanism of Res of attenuating hepatic inflammation and oxidative stress in CIA mice through the Nrf2/Keap1 pathway, which provides a new idea for finding hepatoprotective treatments for rheumatoid arthritis.

Objectives: Kidney stones are a frequent urinary system disorder. Lysimachia christinae Hance is an accepted herb in traditional Chinese medicine for treating kidney stones. However, the effects and mechanisms of Lysimachia christinae Hance aqueous extract (LCH) are yet to be elucidated.

Methods: The function of the aqueous extract of LCH was assessed using kidney stone rat models induced by 1% ethylene glycol+2% NH4Cl. Additionally, an in vitro model of human renal tubular epithelial cells (HK-2) treated with calcium oxalate was used.

Results: Resultantly, the treatment of aqueous extract of LCH at different concentrations or LCH+LY294002 (PI3K-specific inhibitor) showed significant improvement in inorganic ions and renal pathological injury in nephrolithiasis rats. Besides, consistent with the in vivo assay, LCH-containing serum increased cell viability and inhibited oxidative stress and deposition of Ca²⁺ in HK-2 cells, while the influences of LCH-containing serum were attenuated. Mechanistically, the aqueous extract of LCH and LCH-containing serum also promoted Nrf2 and HO-1 levels and inhibited the phosphorylated expression levels of PI3K, AKT, and mTOR.

Conclusion: This study shows that LCH ameliorates the kidney damage in kidney stone rats and HK-2 cells. The mechanism of LCH in treating kidney stones is related to the activation of the Nrf2/HO-1 axis and the inhibition of the PI3K/Akt/mTOR pathway.

This study aimed to explore the beneficial effects and underlying protection mechanism of Tanshinone IIA (TSIIA) in diabetic cardiomyopathy (DCM) from the perspectives of mitophagy and mitochondrial integrity. Here, we found that TSIIA significantly increased STZ-induced body weight (L-TSIIA, 299.5 vs. 276.3; H-TSIIA, 308.3 vs. 276.3) and reduced blood glucose concentration (H-TSIIA, 16.1 vs. 21.5). Meanwhile, TSIIA effectively restored the function and morphology of myocardial tissue in diabetes mellitus (DM) rats. Further, TSIIA has been confirmed to have a protective effect on the ultrastructure and function of myocardial mitochondria, which was achieved through activation of mitophagy, as evidenced by enhanced co-localization of LC3 and COX IV (H-TSIIA, 88188.0 vs. 14829.0). Mechanistically, TSIIA alleviated DCM via activation of the PINK1/Parkin axis, increasing PINK1 (H-TSIIA, 0.5 vs. 0.2), Parkin (H-TSIIA, 0.6 vs. 0.3), Beclin-1 (H-TSIIA, 0.6 vs. 0.2) and LC3II/I (H-TSIIA, 0.5 vs. 0.3) expression, as well as decreasing p62 (H-TSIIA, 1.4 vs. 3.6) expression. This study provided a novel insight into the protective effect of TSIIA in DCM and revealed, for the first time, that TSIIA could noticeably improve STZ-induced DCM by enhancing PINK1-Parkin dependent mitophagy.

Chronic kidney disease (CKD), histologically defined by glomerulosclerosis, tubular atrophy, interstitial fibrosis, and capillary rarefaction, represents a profound challenge in cellular pathology. This review synthesizes recent advances to position Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as a master regulator of maladaptive cellular remodeling in CKD. We delineate the compartment-specific histopathological roles of ROCK2, demonstrating its function as a central signaling integrator that transduces mechanical, metabolic, and inflammatory stimuli into a convergent profibrotic phenotype. At the cellular level, ROCK2 activation drives podocyte foot process effacement and mesangial matrix expansion in the glomerulus, induces metabolic reprogramming and transcriptional dysregulation in tubular epithelia, disrupts endothelial junctional integrity in the microvasculature, and promotes myofibroblast transdifferentiation and immune-mediated scarring in the interstitium. Therapeutically, isoform-selective ROCK2 inhibition with agents like belumosudil demonstrates compelling efficacy in preclinical models, attenuating hallmark histopathological lesions. Translating these findings requires biomarker-driven patient stratification and innovative kidney-targeted delivery systems to maximize effectiveness and minimize systemic effects. Future research must ultrastructurally localize ROCK2 within human kidney niches, delineate its cell-type-specific effector networks, and validate its role as a therapeutic target to halt or reverse the characteristic microscopical progression of CKD.

This review summarizes the current evidence on the expression and prognostic significance of acyl-CoA dehydrogenase long-chain (ACADL) and minichromosome maintenance 2 (MCM2) in meningiomas. Meningiomas, which comprise approximately 41% of intracranial tumors, are classified by the World Health Organization into 15 histological subtypes and three grades of malignancy. However, owing to the biological heterogeneity within tumors of the same grade, alternative classifications based on molecular features have been proposed. One of these classifies meningiomas into four prognostically relevant molecular groups: immunogenic, benign NF2-wildtype, hypermetabolic, and proliferative. The latter two groups have the worst clinical outcomes and are enriched in ACADL and MCM2 expression, suggesting their potential as immunohistochemical surrogates. A revision of the current literature on the expression of these markers in meningiomas indicates their likely unsuitability as surrogates for molecular groups. However, MCM2 expression was consistently associated with aggressive histopathological features and reduced recurrence-free survival, emerging as a promising independent prognostic marker. ACADL also showed negative prognostic relevance, but with limited data, predominantly in grade 2 meningiomas. Both markers correlated with higher WHO grades but lacked standardized assessment criteria, limiting their clinical application. While ACADL and MCM2 immunoexpression does not reliably substitute molecular classification, MCM2, in particular, holds potential for routine prognostic use pending further validation and standardization of immunohistochemical protocols.

Aldose reductase (AR), the rate-limiting enzyme of the polyol pathway, converts glucose to sorbitol using NADPH and becomes markedly overactive under hyperglycemic conditions. Its widespread expression in ocular tissues links AR to numerous eye disorders through sorbitol accumulation, microglial activation, NADPH depletion, oxidative stress, and increased formation of advanced glycation end products. These mechanisms contribute to the development of diabetic retinopathy, cataract, glaucoma, and other optic neuropathies, conditions that affect a large portion of the population and carry a substantial risk of progressing to vision loss if left untreated. The central involvement of AR in these processes has driven extensive development of aldose reductase inhibitors (ARIs), which reduce sorbitol buildup, oxidative stress, VEGF expression, and microglial activation. Thus, clarifying the functions of AR and therapeutically targeting this pathway remains essential for advancing strategies to prevent or slow the progression of ocular disease.

Squamous papilloma (SP) of the external ear is a rare benign neoplasm, with limited research on its associated human papillomavirus (HPV) infections and pathologic features. This study aims to provide a comprehensive analysis of the largest case series of external ear SP from Southwest China. We retrospectively collected 88 cases diagnosed with SP in the external ear canal, of which 85 (97%) were located in the external auditory canal and 3 (3%) on the auricle. We investigated the clinical, pathological, and HPV-typing characteristics using Polymerase chain reaction (PCR) and reverse dot blot (RDB) hybridization. Our series included 74 males and 14 females, with a median age of 62.5 years (range: 5-91 years). The predominant HPV type was HPV-6 (59/62, 95.2%), followed by high-risk types HPV-16 (4/62, 6.5%), HPV-52 (2/62, 3.2%), and HPV-58 (1/62, 1.6%). Histologically, all cases demonstrated typical features of SP, including koilocytes, hyperkeratosis, and basal/parabasal hyperplasia. Additionally, co-infection with multiple HPV types was observed in four cases. Notably, high-risk HPV types were detected in seven cases, all of which were completely excised with no recurrence during follow-up. This study suggests regional variations in HPV-subtype distribution and highlights potential environmental factors contributing to the prevalence of SP in Southwest China.

Background: Postoperative cognitive dysfunction (POCD) is a common and serious complication in older adult patients. While the tyrosine kinase ABL1 has been implicated in neurodegenerative diseases, its specific role in POCD remains unexplored. This study aims to investigate whether ABL1 influences POCD in aged mice by regulating microglial autophagy and neuroinflammation via the mTOR/ULK1 pathway.

Methods: An aged mouse model of POCD was established, and ABL1 silencing and 3-Methyladenine (3-MA) were used to intervene in mice. The Novel Object Recognition Test (NORT) assessment and water maze experiment were conducted. qRT-PCR quantified the mRNA levels of inflammatory cytokines, hippocampal damage was assessed by immunofluorescence, and western blot analyzed the protein expression of autophagy-related genes and the mTOR/ULK1 pathway. Co-Immunoprecipitation (CO-IP) was used to detect the binding of ABL1 to mTOR. In vitro experiments used microglial cells, where ABL1 silencing and rapamycin (Rapa) were used to construct a cellular model and conduct relevant cell experiments.

Results: ABL1 silencing or 3-MA rescued cognitive deficits in aged POCD mice, concurrently mitigating neuroinflammation, microglial activation, and aberrant autophagy in the hippocampus. We established ABL1 as a direct binding partner of mTOR. Silencing ABL1 activated the mTOR pathway, leading to ULK1 inhibition and suppression of autophagic activity. Consistent with these in vivo results, ABL1 knockdown in microglia attenuated pro-inflammatory responses, inhibited autophagy, and conferred protection against neuronal damage.

Conclusions: ABL1 exacerbates POCD in aged mice by promoting microglial autophagy and neuroinflammation through the mTOR/ULK1 signaling pathway. Targeted inhibition of ABL1 may represent a novel therapeutic strategy for preventing or treating POCD.