Histology and histopathology最新文献

Background: Increasing attention has been attracted to the application of human umbilical cord-derived mesenchymal stem cells (HUCMSCs) in the cell therapy of various diabetic complications, including diabetic retinopathy (DR). Lysophosphatidylcholine (LPC) has been reported to induce cell apoptosis and an inflammatory response. The present study aimed to investigate the mechanism of HUCMSCs in high glucose (HG)-treated retinal microvascular endothelial cells (RMECs) and the effect of LPC on this mechanism.

Methods: To mimic DR in vitro, RMECs were treated with HG. Flow cytometry analysis was used to identify HUCMSCs and the expression of their surface markers. The apoptosis of RMECs was also accessed using flow cytometry analysis. A CCK-8 assay was performed to measure the viability of RMECs. ELISA was used to detect the concentration of inflammatory cytokines (TNF-α, IL-6, and IL-1β) in RMECs. The protein expression of tight junction proteins in RMECs was examined using western blot analysis.

Results: HUCMSCs were identified to present positive markers (CD105, CD73, and CD90) and loss of negative markers (CD45, CD34, and HLA-DR). In RMECs, HG significantly induced a decrease in cell viability and an increase in cell apoptosis and tight junction proteins. Moreover, HG treatment promoted the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and facilitated oxidative stress. However, these dysregulated cellular behaviors were alleviated by the treatment of the culture medium of HUCMSCs. Furthermore, LPC treatment reversed the effect of HUCMSCs on HG-induced RMEC injury and impaired the blood-retinal barrier. Moreover, the effect of HUCMSCs on the inflammatory response and oxidative stress of RMEC was also neutralized by LPC treatment.

Conclusion: LPC reverses the effects of HUCMSCs on HG-induced RMEC dysfunction, impaired blood-retinal barrier, inflammation, and oxidative stress.

Objective: Endometrial cancer (EC) is a common gynecologic malignancy with high morbidity and mortality. Kinesin Family member 22 (KIF22) is regarded as a critical oncogene, but its functions in EC progression remained elusive. Hence, this research elucidated the role of KIF22 in EC development and studied the possible mechanism.

Methods: KIF22 expression in EC and the relationship with the overall survival of EC cases were determined by GEPIA and online K-M plotter. After transfection with sh-KIF22, cell viability and invasion were evaluated utilizing CCK-8 and Transwell assays. The content of IFN-γ, IL-2, and TNF-α was assessed utilizing an ELISA assay. The protein levels of p-STAT3, STAT3, and PD-L1 were examined using western blot. A xenograft tumor was constructed to assess tumor growth.

Results: KIF22 was elevated in EC, with high KIF22 levels presenting poor overall survival. Additionally, silenced KIF22 restrained EC cell viability, invasion ability, and STAT3/PD-L1 pathway, enhanced the viability of CD8+ T cells, and elevated the levels of IFN-γ, IL-2, and TNF-α. Moreover, the rescue assay revealed that STAT3 overexpression counteracted the inhibitory effect of silenced KIF22 on EC cell proliferation, invasion and immune escape. Furthermore, silenced KIF22 repressed EC tumor growth and p-STAT3 and PD-L1 levels, and elevated the IFN-γ level in vivo.

Conclusion: The findings demonstrated that KIF22 was elevated in EC and correlated with a poor prognosis. Silenced KIF22 repressed cell proliferation, invasion, and immune escape via suppressing the STAT3/PD-L1 pathway in EC.

In many mammals, accessory gland secretions are ejaculated into the female reproductive tract, along with sperm, and the prostates and seminal vesicles are the main glands responsible for these secretions. Cauda epididymal sperm can efficiently fertilize eggs in vitro; however, we found that seminal vesicle secretions improved sperm fertilization rates in vivo by artificial insemination. Furthermore, using the seminal vesicle-removed mice, other studies have shown that seminal vesicle secretions contribute to embryogenesis and offspring health by regulating the environment in the female reproductive tract. These results indicate the significance of accessory gland secretions in fertilization and development in vivo. More than 700 proteins are present in the accessory glands, and genome editing accelerates the functional analysis of these proteins at the individual level. For example, some studies reported results from phenotypic analyses of genetically modified mice that were different from those of in vitro experiments. In this review, we discuss the current findings on the effects of accessory gland secretions on male fertility and the future prospects.

Renal tumors encompass a diverse group of neoplasms with distinct, morphological, and molecular features. Recent research has highlighted the stimulator of interferon genes (STING) pathway as a key player in tumorigenesis, immune modulation, and autophagy across various renal tumor histotypes. This review explores the biological, diagnostic, prognostic, and therapeutic implications of STING in both epithelial and mesenchymal renal neoplasms. In clear cell renal cell carcinoma, STING expression correlates with aggressive histological features and poor clinical outcomes, suggesting a role in immune evasion and tumor progression. Similarly, in fumarate hydratase-deficient renal cell carcinoma, STING activation, driven by mitochondrial dysfunction and fumarate accumulation, aligns with PD-L1 expression and tumoral inflammatory infiltrate, supporting its potential function as a predictive biomarker of immunotherapy response. In renal perivascular epithelioid cell (PEC) proliferations, widespread STING expression is linked to autophagy regulation and mTOR pathway interaction, offering novel therapeutic insights. The dual role of STING in promoting or suppressing inflammation underscores the therapeutic potential of both agonists and antagonists of this pathway, depending on the specific tumor entity. Moreover, STING's interplay with interferons and cytokines, such as IL-6 and IFNγ, further supports its relevance in modulating immune responses and treatment efficacy. Despite current limitations, accumulating evidence places STING as a promising biomarker and therapeutic target in numerous renal tumors. Future studies are warranted to clarify its mechanistic roles and optimize its clinical application across renal tumor subtypes.

Left untreated, life threatening urinary tract conditions such as urinary retention and overactive bladder syndrome affect a significant portion of the world's population. To alleviate these conditions, medical devices are introduced to patient care plans. Understanding medical device interactions with the urethra is necessary for innovation and improved urethral health in users. Human models are important for mapping these interactions, but viable tissue samples can be expensive, scarce and difficult to obtain. Animal models have become an alternate approach to human models. However, selecting the appropriate animal model for comparison can vary depending on the methods utilized. Due to their similarities to human, porcine models are emerging for lower urinary tract studies. To achieve various testing modalities of tissue, preparation may differ into native or opened tissue. This study looks at the effects of preparing tissue in a native or opened fashion and provides additional data justifying a male porcine model in lieu of humans using scanning electron microscopy, standard histological microscopy, and immunohistochemistry.

Background: Heart failure remains a leading cause of mortality worldwide with limited therapeutic options. Xinyang Tablet (XYT), a clinically used traditional Chinese medicine, demonstrates cardioprotective effects, but its mechanisms against cardiac hypertrophy remain unclear. This study aimed to elucidate the therapeutic mechanisms of XYT in heart failure with a focus on oxidative stress and hypertrophy pathways.

Methods: Pressure-overload heart failure was induced by transverse aortic constriction (TAC) in mice. Cardiac function was assessed via histology (hematoxylin-eosin [H&E], Masson's trichrome), oxidative stress markers (dihydroethidium [DHE] staining, superoxide dismutase [SOD]/malondialdehyde [MDA]/glutathione peroxidase [GSH-Px] assays), and molecular analyses. In vitro, angiotensin II (AngII)-treated HL-1 cardiomyocytes evaluated hypertrophy and oxidative stress responses. Multiomic approaches, including ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), network pharmacology, RNA sequencing (RNA-seq), and single-cell RNA sequencing (scRNA-seq), identified XYT's bioactive compounds and hub targets, validated by AKT inhibitor (MK-2206) experiments.

Results: XYT attenuated TAC-induced cardiac hypertrophy and fibrosis, reducing heart volume, cardiomyocyte cross-sectional area, and fibrotic markers (collagen type I alpha 1 [COL1A1]/collagen type III alpha 1 [COL3A1]). XYT suppressed oxidative stress by decreasing reactive oxygen species (ROS)/NADPH oxidase 2 (NOX2)/NOX4 while increasing superoxide dismutase 2 (SOD2)/GSH-Px in vivo and in vitro. Bioinformatics identified 18 hub genes (e.g., histone deacetylase 2 [HDAC2], SOD2) and enriched phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)/oxidative stress pathways. XYT inhibited HDAC2/AKT/glycogen synthase kinase-3β (GSK-3β) phosphorylation, while AKT inhibition with MK-2206 mimicked XYT's protective effects.

Conclusion: XYT ameliorates heart failure by targeting HDAC2 to suppress AKT/GSK-3β signaling, mitigating oxidative stress, cardiac hypertrophy, and fibrosis, providing mechanistic evidence for clinical translation.

Metastasis of colorectal cancer (CRC) is the main cause of CRC-related mortality. FAM107A is widely expressed in various normal tissues. However, few studies have revealed the biological function of FAM107A in epithelial-mesenchymal transition (EMT) in human cancer cells, and the related molecular mechanisms and signaling cascades are completely unknown. Here, we found that FAM107A was abnormally expressed in human CRC tissues and cell lines. Further research has shown that overexpression of FAM107A through transfection weakened the expression level of EMT-related markers. In addition, our research results indicated that upregulation of FAM107A inhibited the AKT signaling cascade in human CRC cells, while AKT activators restored activation of p50, indicating that FAM107A may regulate EMT through AKT activation of p50. Our results suggest that FAM107A could be a potential target for the treatment of CRC.

The growth of colorectal cancer (CRC) can be affected by cholesterol (CHO), which may inhibit the efficacy of oxaliplatin (OXA). A high-fat diet can upregulate phosphorylation by sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1) and promote tumour cell proliferation. Moreover, S1P activates signal transducer and activator of transcription 3 (STAT3), which plays a critical role in tumour cell proliferation. Knockdown of arginine-specific single ADP ribosyltransferase 1 (ART1) can delay the growth of CRC and promote the inhibitory effect of OXA on CRC cell proliferation. Consequently, in a high-CHO environment, this study aims to investigate the impact of ART1 knockdown in CRC cells treated with OXA and on the growth of transplanted tumours in mice in vivo.

Acute exposure to seizurogenic chemicals, such as organophosphates (OPs) or domoic acid (kainate analogue), can trigger status epilepticus (SE), marked by central (seizures) and, with OPs, peripheral effects due to irreversible inhibition of acetylcholinesterase (AChE). The initial seizurogenic activity in the brain initiates a cascade of molecular and cellular changes, known as epileptogenesis, the process by which epilepsy develops. Among the several signaling pathways involved in epileptogenesis, this review discusses the roles of the Src family of tyrosine kinases (SFK), especially Fyn kinase, and inducible nitric oxide synthase (iNOS) mediated mechanisms. Both signaling molecules are upregulated following initial seizures and persist for a long time, contributing to neuroinflammation, elevated levels of reactive oxygen and nitrogen species (ROS/RNS), and proinflammatory cytokines, as well as neurodegeneration and spontaneously recurring seizures. Epilepsy is a progressive disease associated with unprovoked seizures and cognitive decline. While the current standard of care can alleviate symptoms and reduce mortality, they do not address long-term neurological consequences. In this review, we discuss preclinical testing of two CNS-targeted drugs, iNOS and SFK inhibitors 1400W and Saracatinib (SAR; AZD0530), respectively, as potential disease-modifiers.

Background: 1,25-Dihydroxyvitamin D3 (1,25(OH)₂D₃) is a physiologically active form of vitamin D. Our study investigated the renoprotective functions of 1,25(OH)₂D₃ in diabetic nephropathy (DN) progression and its underlying mechanism targeting the ROS/TXNIP/NLRP3 inflammasome pathway.

Methods: DN was induced in Wistar rats via high-fat diet (4 weeks) and streptozotocin injection (30 mg/kg, i.p.); hyperglycemic rats were randomized into DN and DN + 1,25(OH)₂D₃ (16 μg/kg, 12 weeks) groups. Rat mesangial HBZY-1 cells were maintained under normal glucose (5.5 mM), high glucose (25 mM), high glucose plus 1,25(OH)₂D₃ (1-50 nM), or high glucose plus N-acetylcysteine (NAC, 10 mM). Cell viability was assessed by the CCK-8 assay. Oxidative stress parameters (ROS via DCFH-DA fluorescence, MDA content, SOD activity) and pyroptosis markers (LDH release, PI/Hoechst 33342 nuclear staining) were quantified. Renal histopathology was performed using PAS and Masson trichrome staining. Biochemical analyses included serum creatinine, urea nitrogen, and 24-h urinary protein quantification. Molecular profiling encompassed ELISA (IL-1β, IL-6, TNF-α, IL-18, fibronectin, collagen IV), RT-qPCR (NOX2, NOX4, NLRP3, ASC), western blotting (TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, collagen IV, fibronectin, laminin), and TXNIP immunofluorescence.

Results: 1,25(OH)₂D₃ significantly attenuated high glucose-induced pathological alterations in HBZY-1 cells, including ROS overproduction, TXNIP upregulation, NLRP3 inflammasome activation, oxidative stress, inflammation, extracellular matrix (ECM) deposition, and pyroptotic cell death. Consistently, 1,25(OH)₂D₃ suppressed ROS/TXNIP/NLRP3/caspase-1 signaling, ameliorated renal dysfunction, and mitigated histopathological damage in DN rats.

Conclusion: 1,25(OH)₂D₃ confers renoprotection in DN by inhibiting the ROS/TXNIP/NLRP3 inflammasome axis, thereby suppressing oxidative stress, inflammatory cytokine production, ECM accumulation, and pyroptotic cell death in glomerular mesangial cells and renal tissues.