Histology and histopathology最新文献

The use of tissues of porcine origin has gained significant momentum in the scientific community due to their anatomical and physiological resemblance to human tissues. This review provides a comprehensive overview of the key biological features of porcine ocular structures, including the cornea, conjunctiva, and associated tissues, in comparison to their human counterparts. Additionally, this review outlined the ex vivo applications of these tissues in the study of different biological processes and the simulation of pathological conditions. By highlighting the potential of porcine ocular surface tissues as cost-effective, ethically appropriate, and reliable models, this review underscores their value in advancing eye and vision research.

Orchidectomy and estrogenization of the male represent a procedure that is applicable in sex reassignment or in prostate cancer therapy. This approach has an influence on the hypothalamic-pituitary-adrenal axis and thus affects cardiovascular function and metabolism. We utilized orchidectomized rats to evaluate the effects of estradiol on the structure and hormonal output of the adrenal gland. Adult Wistar rats were divided into sham-operated (SO; n=7), orchidectomized (Orx; n=7), and estradiol-treated orchidectomized (Orx+E; n=7) groups. Estradiol-dipropionate (0.625 mg/kg b.m.) was administered subcutaneously for three weeks, while the SO and Orx groups received vehicle alone. Set objectives were achieved using histochemistry/immunohistochemistry, stereology, and immunoassays. In Orx+E rats, the hormonal milieu was characterized by decreased testosterone and increased ACTH, compared with the Orx group. Also, orchidectomy and estradiol treatment provoked a significant increase in adrenal cortex volume and volume of ZF per se, with increased cell and nuclei volumes in all three adrenocortical zones (ZG, ZF, and ZR), in comparison with Orx rats. Concentrations of aldosterone in blood, as well as corticosterone in blood and adrenal tissue were increased, while circulating DHEA was decreased (with increased immunoexpression of adrenocortical CYP 17 enzyme), all in Orx+E compared with Orx animals. The wide zonal distribution of VEGF and the pronounced blood supply within the ZF of Orx+E animals acted to support the synthesis and secretion of corticosteroids. These results seem cautionary in the context of young male estrogenization, given the negative impact of high mineralocorticoids and glucocorticoids on cardiovascular function and metabolism.

Introduction: Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, with a low five-year survival rate of less than 10%. Transforming growth factor β regulator 4 (TBRG4) is differentially expressed in PC tissues, but its specific functions and regulatory role in PC have not been clarified.

Methods: TBRG4 mRNA expression in PC cells was measured by qRT-PCR. Protein levels of TBRG4, key markers related to the epithelial-mesenchymal transition (EMT) process, and factors related to the TGF-β/smad3 pathway were quantified by western blot. The migratory and invasive abilities of PC cells were evaluated by wound healing and Transwell assays, respectively. Spearman's correlation analysis was performed to analyze the expression correlation between TBRG4 and TGF-β1 (or SMAD3). Xenograft mouse models were established to explore the in vivo role of TBRG4.

Results: The mRNA and protein expression of TBRG4 were elevated in PC cells. TBRG4 knockdown repressed PC cell migration, invasion, and the EMT process. Moreover, TBRG4 activated TGF-β/smad3 signaling in PC cells and positively correlated with TGF-β1 (or SMAD3) expression in PC tissues based on bioinformatics analysis. Furthermore, SRI-011381 (an agonist of TGF-β1) counteracted the inhibitory influence of TBRG4 knockdown on PC cellular behaviors, and SB431542 (an inhibitor of the TGF-β type I receptor) treatment countervailed the promoting influence of TBRG4 overexpression on PC cell invasion, migration, and EMT. Results of in vivo assays verified that TBRG4 silencing inhibited tumorigenesis and TGF-β/smad3 signaling.

Conclusion: The silencing of TBRG4 inhibits PC cell invasion, migration, EMT, and tumorigenesis by inactivating TGF-β/smad3 signaling.

Autism spectrum disorder (ASD) is a globally recognized neurodevelopmental condition characterized by repetitive and restrictive behavior, persistent deficits in social interaction and communication, mental disturbances, etc., affecting approximately 1 in 100 children worldwide. A combination of genetic and environmental factors is involved in the etiopathogenesis of the disease, but specific biomarkers have not yet been identified. Due to the lack of clinical evidence, fluctuations in symptoms, and difficulties in in-vitro and in-vivo modeling, developing medications for ASD is quite difficult. Although several drugs are used to treat autism, only risperidone and aripiprazole have received FDA approval in the United States. Epidemiological studies have suggested that maternal exposure to valproic acid (VPA), acetaminophen, propionic acid, and metals, such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg), may contribute to the development of various neurodevelopmental disorders. Pathological targets directly implicated in the disease include excitatory-inhibitory (E/A) imbalance, hyperserotonemia, GSK-3 inhibition, and Akt pathway activation. However, while a combination of pharmacotherapy, behavioral, and nutritional/dietary interventions has been found to be the most effective conventional therapy to date, many patients have chosen to implement particular dietary supplements for reducing ASD symptoms. In this review, we briefly describe various pathological targets and their roles in the pathophysiology of ASD and treatment strategies, including some future research directions.

Testicular cryopreservation has been highlighted as a promising alternative for preserving male fertility and can be applied to restore spermatogenesis in prepubertal individuals or cancer patients, preserve biologically valuable genotypes, and in studies on reproductive physiology or toxicity of various substances. This review presents an analysis of the technical aspects and applications of testicular cryopreservation, examining the contributions of important studies in this area and discussing the different factors that can impact the efficiency of the technique. Testicular fragments can be obtained from living or dead individuals, at any age and reproductive stage, through orchiectomy or biopsy. Among the methods used for processing, slow freezing and vitrification in open or closed systems stand out. However, factors such as species, age, medium used, cryoprotectants, and cryopreservation method can influence the viability of the testis after heating. To obtain sperm, the testes can be cultured in vitro or in vivo and the recovered gametes applied in assisted reproduction techniques. However, in some species, mainly wild animals and humans, this is still a limitation to be overcome.

Bacground: Breast phyllodes tumors (BPTs) are difficult to differentiate from other tumor types. In-depth research is needed due to the insufficient description of the amine oxidase protein family, particularly in BPTs.

Objective: This study investigated the expression and clinical implications of amine oxidase-related proteins in BPTs.

Methods: Tissue microarrays were constructed (n=181), and amine oxidase-related proteins of monoamine oxidase (MAO) A, MAOB, lysyl oxidase (LOX), and primary-amine oxidase 3 (AOC3) were assessed using immunohistochemical staining. Staining patterns of these proteins were compared and analyzed with clinicopathologic parameters.

Results: In all, 149, 27, and 5 cases were classified as benign, borderline, and malignant, respectively. A higher grade of BPT was associated with increased MAOB (P<0.001), LOX (P=0.035), and AOC3 (P<0.001) expression. BPT cases with tumor recurrence and distant metastasis had higher proportions of MAOB positivity in stromal components (P=0.002 and 0.018, respectively). During follow-up, there was a significant association between MAOB positivity in the stromal component and shorter disease-free survival (DFS) (P=0.001) as well as overall survival (P=0.003). Moreover, MAOB positivity emerged as an independent factor for shorter DFS (hazard ratio: 4.253, 95% confidence interval: 1.034-17.49, P=0.045).

Conclusions: Higher MAOB, LOX, and AOC3 expression were observed in higher-grade BPTs, and MAOB expression was identified as a significant prognostic factor.

Background: Cancer-associated fibroblasts (CAFs) play important roles in tumor microenvironments. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a potential cancer therapy target. This study aimed to explore the expression of PYCR1 in glioma-associated CAFs and analyze the effects of PYCR1 expression in CAFs on the proliferation of C6 glioma.

Methods: A rat glioma model was induced by injecting C6 cells in the right caudate putamen via a microliter syringe. After 14 days, tumor tissues were collected, and the levels of COL1A1 and PYCR1 were measured by immunohistochemistry. The colocalization of fibroblast activation protein α (FAP) and PYCR1 in tissues was measured by double-immunofluorescence. The CAFs were labeled by FAP and isolated from the tumor tissues using a fluorescence-activated cell sorting (FACS) machine. The isolated CAFs were further separated into CAFs with different PYCR1 expressions using the FACS machine. CAFs with different PYCR1 expressions were respectively cocultured with C6 cells or MUVECs for 48h using a Transwell permeable support. The invasion and proliferation of C6 cells were measured using a Transwell assay and colony formation assay, and the angiogenesis of MUVECs was measured using a Tube formation assay. The expression of COL1A1 and PYCR1 proteins in C6 cells and VEGF-A and EGF proteins in MUVECs was measured by western blotting. PYCR1 silencing in C6 cells was induced by PYCR1 siRNA transfection, the effects of which on the proliferation of C6 cells were measured using a wound healing assay, a Transwell assay, and western blotting.

Results: The PYCR1 and COL1A1 upregulation co-occurred in the rat glioma, and PYCR1 was expressed in CAFs. The CAF coculture enhanced the invasion and proliferation of C6 cells and the angiogenesis of MUVECs. Meanwhile, the levels of COL1A1 protein in C6 cells, and the levels of VEGF-A and EGF proteins in MUVECs were increased after CAF coculture. Moreover, the effects of CAF coculture were increased with PYCR1 expression in the CAF. Silencing PYCR1 suppressed the migration and invasion of C6 cells, and decreased the levels of COL1A1 and VEGF-A proteins in C6 cells.

Conclusions: PYCR1 is expressed in glioma-associated CAFs, and promotes the proliferation of C6 cells and angiogenesis of MUVECs, suggesting that targeting PYCR1 may be a therapeutic strategy for glioma.

Mast cells, which originate from the bone marrow, possess the ability to secrete a diverse array of active molecules. These molecules include mediators (histamine, heparin), which have been identified for decades and are stored in specific granules, as well as small molecules generated instantaneously in response to stimulation (membrane lipid derivatives, nitric oxide), and a multitude of multifunctional cytokines that are secreted constitutively. Activated mast cells participate in the regulation of the local immune response and exert control over critical events of inflammation and healing with the assistance of a vast array of mediators. The involvement of these cell types in inflammatory states suggests that mast cells may function as sentinels that activate local immune processes in response to various types of stimuli and the entry of antigens. Moreover, due to their proximity to nerve fibers and reactivity to a variety of neurotransmitters, mast cells are among the cells that may facilitate local neuroimmune interactions. With this in mind, it is necessary to consider their participation in the repair of injuries in both acute and chronic conditions.

Retinal ischemia is a fundamental pathologic condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, age-related macular degeneration, and other eye diseases. Extensive inflammation, redox imbalance, apoptosis, and abnormal vascular formation in retinal ischemia could lead to visual impairments. Developing or finding effective treatments is urgently needed to protect the eye against retinal ischemia and related damage. To address the demand, we have searched for promising therapeutic molecular targets in the eye (e.g., hypoxia-inducible factor [HIF], peroxisome proliferator-activated receptor-alpha [PPARα], and nicotinamide adenine dinucleotide [NAD⁺]), and found that modulations of each molecular target might protect the eye against retinal ischemic damage in terms of complex pathologic mechanisms. In the current article, we review and update the therapeutic evidence of modulation of HIF, PPARα, or NAD⁺ and discuss future directions for developing promising drugs based on these molecular targets. This summary urges research to obtain more solid evidence of each molecular target in retinal ischemic diseases.

Purpose: Our previous study demonstrated that NRF3 (NFE2L3, Nuclear Factor-erythroid 2-related factor 3) could suppress cell metastasis and proliferation in breast cancer. In this study, we investigated the mechanisms underlying its function in breast cancer.

Methods: In the present study, NRF3 expression and its clinical characteristics in breast cancer were analyzed using public datasets and clinical specimens. After breast cancer cells were overexpressed NRF3, FACS was used to detect the intracellular ROS levels. The migration and invasion activities of NRF3-ectopic expressed breast cancer cells were determined by transwell assay. To validate the role of ROS/ERK axis in the inhibitory effect of NRF3 in cell metastasis, ROS scavenger NAC was also included.

Results: We found that NRF3 mRNA was highly expressed, while NRF3 protein was extremely lowly expressed in breast cancer tissues compared with their normal counterparts, and low level NRF3 was associated with poorer prognosis in patients with triple negative breast cancer (TNBC). More interestingly, overexpression of NRF3 protein significantly increased cellular ROS production and dramatically decreased p-ERK level and cell migration in TNBC cells. Mechanistically, NRF3 protein was found to be mutually regulated by valosin-containing protein (VCP). Strikingly, VCP-knockdown dramatically increased NRF3 protein expression, but NRF3-knockin also decreased VCP expression in return. Moreover, antioxidant NAC treatment effectively increased the level of p-ERK and VCP expression, as well as cell migration and invasion abilities of TNBC cells.

Conclusion: NRF3, a tumor suppressor downregulated by VCP, could attenuate cell metastasis in TNBC cells by increasing cellular ROS accumulation and subsequently inhibiting the ERK phosphorylation.