Histology and histopathology最新文献

Muscle weakness is a common issue following anterior cruciate ligament (ACL) reconstruction and is closely linked to muscle atrophy. Preventing or reducing this atrophy is a key goal of rehabilitation. This review summarizes current knowledge on muscle atrophy after ACL reconstruction, including its spatial distribution, time course, underlying mechanisms, and potential interventions. Atrophy affects multiple lower limb muscles and may be influenced by the type of graft used. Tendon harvesting appears to negatively impact the muscle belly of the donor muscle, while atrophy may also occur in the contralateral limb independently of graft harvesting. Muscle atrophy is often already present before surgery and tends to worsen postoperatively. Although partial recovery may occur, long-term deficits are frequently observed. At the muscle fiber level, evidence is inconsistent regarding which fiber types are more vulnerable to atrophy. A transient shift toward faster fiber types has been reported after surgery. On the cellular and molecular level, satellite cell depletion via apoptosis may hinder muscle regrowth and thereby contribute to persistent muscle atrophy. Concurrently, increased expression of myostatin, atrogin-1, and muscle RING-finger-1, along with postoperative inflammation, may promote protein degradation, further exacerbating muscle atrophy. Rehabilitation strategies that involve early immobilization or non-weight bearing may exacerbate atrophy. Interventions such as eccentric training, neuromuscular electrical stimulation, blood flow restriction training, pharmacological agents, and nutritional support demonstrate potential, but no definitive treatment has been established. Future studies using appropriate animal models to clarify the molecular mechanisms of muscle atrophy will be crucial for developing effective therapies.

Objective: Hepatic sinusoidal obstruction syndrome (HSOS) is a disease characterized by damage to hepatic sinusoidal endothelial cells (HSECs). This research investigates the role and regulatory pathway of PU box-binding protein (PU.1) in the progression of HSOS.

Methods: We established an in vivo HSOS model through peritoneal administration of monocrotaline (MCT). Primary murine HSECs were isolated and treated with various concentrations of MCT to establish an in vitro HSOS model. PU.1 knockdown was achieved using lentiviral shRNA constructs, and its impact on oxidative stress, PTBP1 expression, β-catenin mRNA stability, and Wnt/β-catenin signaling was evaluated through kits, RT-qPCR, and western blot. Dual-luciferase and chromatin immunoprecipitation assays were conducted to assess the interaction between PU.1 and the PTBP1 promoter. The molecular association between PTBP1 and β-catenin mRNA was confirmed through RNA pull-down and RIP assays.

Results: PU.1 was upregulated in MCT-induced HSOS, contributing to elevated oxidative stress and activation of the Wnt/β-catenin pathway. PU.1 directly enhanced PTBP1 transcription, which stabilized β-catenin mRNA and sustained Wnt/β-catenin signaling. PU.1 knockdown alleviated oxidative stress, reduced liver damage, and disrupted the PTBP1-β-catenin interaction, leading to Wnt/β-catenin activity inhibition. Overexpression of PTBP1 reversed the protective effects of PU.1 knockdown, reinstating oxidative stress and reactivating Wnt/β-catenin signaling.

Conclusion: PU.1 facilitated HSOS pathogenesis by promoting the transcriptional activity of PTBP1 and activating the Wnt/β-catenin pathway. Targeting PU.1 can serve as a promising therapeutic strategy for reducing oxidative stress and liver damage in HSOS.

Aim: To investigate the clinicopathological features, immunophenotype, diagnosis, and prognosis of invasive carcinoma originating from microglandular adenosis.

Methods: Two cases of invasive carcinoma originating from microadenosis were analyzed in the Department of Pathology of the Ruijin Hospital affiliated with the Medical College of Shanghai Jiaotong University. Histopathological morphology, immunohistochemical staining, and prognosis were observed.

Results: (1) Histopathological morphology: microscopically, the tumor showed small clusters and nests of infiltrative growth; a few areas showed tubules, and some eosinophilic secretions were observed in the lumen. (2) Immunohistochemistry and molecular genetics: Case 1 was partly positive for S-100, positive for SOX-10, and negative for ER, PR, and HER2 (2+). The result of HER2 gene amplification was negative. Breast and liver tissue lesions in Case 2 were positive for S-100 and SOX-10 but negative for ER and HER2. PR was positive in the liver lesions but showed moderate to strong expression in approximately 80% of the staining. Myoepithelial markers (p63 and calponin) showed loss of myoepithelium around the nests of invasive cancers. TP53 (R213Ter) showed somatic gene variations, and no exon amplification or deletion was detected in BRCA1/2.

Conclusion: Invasive carcinoma originating from microadenosis has the same immunophenotype as microadenosis, and its prognosis is difficult to determine.

Background: Myocardial ischemia-reperfusion injury (MIRI) is a major contributor to myocardial infarction and leads to significant myocardial dysfunction. Mitochondria, crucial for cellular energy production, are particularly susceptible to damage during ischemia/reperfusion (I/R) events. Carbon monoxide-releasing molecule-3 (CORM-3), a water-soluble compound that releases carbon monoxide (CO), has demonstrated multiple protective effects against I/R injury. Mitochondria are recognized as selective targets for CO's protective actions in cells.

Purpose: This study aimed to explore whether CORM-3 mitigates cardiomyocyte injury during hypoxia/reoxygenation (H/R) by regulating the mitochondrial-mediated apoptosis pathway and mitochondrial respiration.

Methods: Neonatal rat cardiomyocytes were cultured and randomly assigned into four groups: control group, H/R group (hypoxia for three hours followed by reoxygenation for six hours), CORM-3 group, and inactivated CORM-3 (iCORM-3) group. CORM-3 and iCORM-3 (12.5 µmol/L) were administered at the onset of hypoxia. Mitochondrial ultrastructure was assessed using transmission electron microscopy. The protein levels of caspase-3, caspase-9, mitochondrial cytochrome c, and cytosolic cytochrome c were analyzed via western blot. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were measured by flow cytometry. ATP levels were quantified using an ATP Assay Kit, and mitochondrial respiratory chain complex IV activity was determined using a cytochrome oxidase activity colorimetric assay kit.

Results: CORM-3 effectively reduced myocardial mitochondrial structural damage induced by H/R and downregulated the expression of caspase-3, caspase-9, and cytosolic cytochrome c. Moreover, CORM-3 inhibited cytochrome c release from mitochondria and enhanced mitochondrial membrane potential. Additionally, CORM-3 diminished ROS production and increased the activity of mitochondrial respiratory complex IV in cardiomyocytes. CORM-3 also alleviated the decline in ATP levels following H/R. The protective effects were lost when using inactivated CORM-3 (iCORM-3), suggesting that CO is the active mediator.

Conclusion: The results indicate that CORM-3 effectively alleviates myocardial injury during H/R by inhibiting mitochondria-mediated apoptosis and enhancing mitochondrial respiratory function.

The objective of this study was to investigate the protective effect of electroacupuncture (EA) preconditioning on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The changes in inflammatory factors and total protein content in bronchoalveolar lavage fluid (BALF) were quantified using enzyme-linked immunosorbent assay (ELISA) and bicinchoninic acid assay (BCA). Hematoxylin and eosin (H&E) staining was employed to assess the extent of lung injury, while Ly-6G immunohistochemistry was used to examine the infiltration of inflammatory cells. Western blot analysis was employed to detect the expression of TRPV4 and proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway. In comparison with the sham-operated group, the model group demonstrated an elevated production of inflammatory factors in the BALF, augmented total protein content, elevated lung injury score, increased number of Ly-6G-positive cells, upregulation of TRPV4 expression in the lung, and enhanced p38 phosphorylation. The aforementioned pathological changes were significantly improved by EA preconditioning. Furthermore, the protective effect of EA preconditioning on ALI mice was verified by the use of GSK1016790A, an agonist of TRPV4, which demonstrated that this effect is exerted through the TRPV4-mediated p38 MAPK signaling pathway.

Background: Pediatric ulcerative colitis (UC) is an inflammatory bowel disease characterized by dysregulated immune responses and intestinal inflammation, often more severe than adult-onset UC. Th17 cells play a crucial role in UC pathogenesis but the mechanisms regulating their differentiation and recruitment in pediatric UC remain incompletely understood.

Methods: Transcriptomic analysis of pediatric UC patients and weighted gene co-expression network analysis (WGCNA) were performed to identify key dysregulated genes. The functional role of the candidate gene ITGAX was investigated using in vitro Th17 differentiation assays with siRNA knockdown and an in vivo dextran sodium sulfate (DSS)-induced UC mouse model with intrarectal siRNA administration.

Results: WGCNA identified ITGAX, SOCS3, CXCL1, CASP1, and CXCL11 as core upregulated genes in pediatric UC, with ITGAX being a novel candidate regulator of Th17 cells. ITGAX knockdown in naive CD4⁺ T cells impaired Th17 differentiation and IL-17A production in vitro. In the DSS-induced UC mouse model, intrarectal ITGAX siRNA ameliorated colonic inflammation and ulceration, suppressed IL-17A levels, and selectively reduced the expansion of IFNγ-IL-17⁺ Th17 cells in the colon.

Conclusion: ITGAX is a key promoter of Th17-cell differentiation and expansion, contributing to the pathogenesis of pediatric UC. Targeting ITGAX may represent a potential therapeutic strategy for pediatric UC by modulating aberrant Th17 responses.

Objective: Effective preventive measures for radiotherapy and chemotherapy-induced esophagitis are currently lacking. This study aims to investigate the local impact of chemotherapeutic agents on normal esophageal tissue and assess the cytoprotective effects of amifostine against chemotherapy-induced esophageal injury.

Methods: Twenty-four New Zealand white rabbits were randomly assigned to the control group, which only received saline; the cisplatin (DDP) group, which received 0.25 mg/ml of the chemotherapeutic drug (DDP); and the combined treatment group, which received pre-treatment with 0.8 mg/ml amifostine followed by 0.25 mg/ml DDP. Each group consisted of eight rabbits. A custom-made balloon device for targeted esophageal drug delivery was inserted into the esophagus, followed by the infusion of DDP and/or amifostine into the created space. After six days, rabbits were euthanized, and esophageal specimens were examined for mucosal damage.

Results: Macroscopically, compared with the control group, the DDP group exhibited significant thickening, edema, mucosal ulceration, and congestion in the infused esophageal region. Conversely, the combined treatment group showed mild thickening and a smooth or mildly congested mucosal surface. Microscopically, the DDP group displayed extensive mucosal detachment, edema, dilated submucosal blood vessels, and substantial infiltration of inflammatory cells. The combined treatment group exhibited partial mucosal detachment and moderate inflammatory cell infiltration in the submucosal and muscular layers, with few inflammatory cells in the muscle layer.

Conclusion: This study provided evidence that damage caused by the local infusion of DDP might be reduced by pre-treatment of the cytoprotective agent amifostine.

Introduction: A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), a metalloproteinase involved in extracellular matrix (ECM) degradation, is implicated in several pathological conditions. This study evaluated ADAMTS4 in leprosy skin lesions.

Methods: In total, 519 skin samples were selected, including 20 healthy controls (HC) and 499 samples with leprosy skin lesions. Leprosy lesions were divided into tuberculoid range "T" (n=95), lepromatous range "L" (n=115), type 1 reaction (n=120), type 2 reaction (n=128), and lesions in regression (n=41). Following standardization with an anti-ADAMTS4 marker, all samples were subjected to immunohistochemistry (IHC). Marker expression in cells or tissues with moderate or intense staining intensity (2+ or 3+) was considered positive, and the absence of or weak expression (0 or 1+) was considered negative.

Results: ADAMTS4 was expressed in several cells involved in the inflammatory processes of leprosy, particularly macrophages and fibroblasts, and in different skin tissues affected by leprosy lesions. Marker expression was remarkable in different tissues affected by leprosy lesions compared with the control group.

Conclusion: ADAMTS4 expression in different leprosy lesions and their reaction phenomena suggest its contribution to disease progression and reactive inflammatory amplification, indicating ADAMTS4 as a potential biomarker and therapeutic target in leprosy.

Phosphodiesterase 10A (PDE10A), located on cytoband 6q27, acts as a haploinsufficient tumor suppressor in glioblastoma, where its loss drives aggressive tumor behavior and is associated with a proneural-to-mesenchymal (PN-MES) shift. Leveraging bioinformatic analyses of The Cancer Genome Atlas (TCGA) pan-cancer dataset, we identified gastrointestinal carcinomas, specifically stomach adenocarcinoma and colon adenocarcinoma, as cancers where 6q27/PDE10A loss is prognostic. In both stomach adenocarcinoma and colon adenocarcinoma, PDE10A loss was associated with reduced overall survival (OS) and progression-free survival (PFS). Additionally, PDE10A loss correlated with increased lymphatic invasion and higher AJCC pathologic nodal stage in colon adenocarcinoma. In an independent institutional cohort, immunohistochemical analysis showed lower PDE10A expression in metastatic colon adenocarcinomas compared to primary tumors. Furthermore, PDE10A loss and decreased protein expression corresponded with an epithelial-to-mesenchymal transition (EMT) phenotype in both cohorts, consistent with the known PN-MES shift observed in glioblastoma. In summary, PDE10A loss in colon adenocarcinoma is associated with decreased OS and PFS, more frequent lymphatic invasion, higher pathologic nodal stage, metastatic disease, and an EMT phenotype.

Background: Menstrual stoppage, follicular dysplasia, and hypergonadotropic hypoestrogenism in women under forty are among the symptoms of premature ovarian failure (POF). This study aimed to explore the role and mechanism of amygdalin on ovarian function in a POF mouse model.

Methods: A POF mouse model was established via injection of D-galactose (D-gal), followed by amygdalin treatment. Histological staining of ovarian tissues was applied to determine follicular development and granulosa cell apoptosis. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) were measured in ovarian tissues. Enzyme-linked immunosorbent assay was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), anti-Müllerian hormone (AMH), and reactive oxygen species (ROS) in serum, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in ovaries.

Results: D-gal increased levels of FSH, LH, ROS, MDA, TNF-α, IL-1β, IL-6, Bax, atretic follicles, and granulosa cell apoptosis, and decreased P, E2, AMH, SOD, GSH-px, Bcl-2, and primordial, primary, secondary, and total follicles (p<0.01). Amygdalin with different concentrations reversed the effects of D-gal on mice (p<0.05).

Conclusion: Amygdalin improved ovarian function in POF mice through inhibiting oxidative stress, inflammation, and granulosa cell apoptosis. These results suggested that amygdalin may be a potential antioxidant for POF treatment.