Histology and histopathology最新文献

Under unilateral ureteral obstruction (UUO) in mouse kidneys, comparing proximal and distal tubules and collecting ducts, the distal tubules exhibited the most pronounced dilation and epithelial attenuation. Basal infoldings, typically well-developed in normal distal tubule cells, were infrequently present. Instead, the cell base was predominantly covered by flat-contoured plasma membranes interspersed with clusters of palisade-aligned thin cytoplasmic processes. These processes resembled the mitochondria-free terminal portions of cytoplasmic processes normally enclosed by basal infolding membranes in normal distal tubule cells. Some process clusters were enclosed by internal extensions of adjacent flat-contoured membranes, forming process-containing membranous sacs partially open to the basal interstitial space. Similar membranous bodies were observed deep within the cells, with some opening to intercellular spaces through fusion with lateral cell membranes. These membrane modifications likely represent the morphological sequence of membrane dynamics, providing additional membranes to compensate for the increased basal surface area in dilated tubules. Similarly, the collecting ducts dilated with attenuated epithelia and the basal surfaces were covered by flat-contoured plasma membranes with sparse clusters of palisade-aligned processes, suggesting basal infoldings, which also serve as a membrane supply to basolateral surfaces in these cells. However, membranous sacs containing thin processes were less frequent in collecting duct cells, indicating a less extensive membrane remodeling process compared with distal tubule cells. On the other hand, the proximal tubules exhibited the lowest luminal dilation and epithelial attenuation, and the replacement of the diminished basal infoldings by flat membranes was less frequently encountered.

CD34, once considered solely a hematopoietic stem cell marker, is now recognized as a lineage interface identifying distinct tissue-resident progenitor populations that critically influence cardiac homeostasis and pathological remodeling. It has been applied clinically for CD34-targeted therapies, such as cell-capture stents, G-CSF mobilization, and unselected CD34⁺ cell transplantation. However, they fail to discriminate between reparative and pathogenic subsets. Recent advances in lineage tracing, single-cell genomics, and human tissue studies have made major progress in this research field. It has been reported that (1) non-bone marrow-derived endothelial progenitor cells (EPCs) sustain vascular integrity and promote neovascularization; (2) hematopoietic progenitors give rise to inflammatory monocytes, neutrophils, and dendritic cells, orchestrating immune responses after injury; and (3) resident fibroblast progenitor cells (FPCs) differentiate into myofibroblasts and drive interstitial and perivascular fibrosis. During cardiac remodeling, it seems that all types of CD34⁺ cells were involved. In this Review, we integrate histological, mechanistic, and clinical evidence to delineate the diverse CD34⁺ lineages in cardiac remodeling. We discuss how to refine surface-marker panels for isolating endothelial-committed progenitors and exclusion of inflammatory and fibrogenic subsets during cardiac repair. We propose a paradigm shift from generic CD34⁺ cell enrichment toward lineage-specific therapeutic strategies.

Background: Cerebral ischemia-reperfusion can cause structural changes in brain tissue and disrupt physiological functions. Naoluotong granules (NLT) exhibit significant neuroprotective effects on brain nerve cells and are widely utilized in treating cerebral ischemia-reperfusion injury (CIRI). However, the underlying molecular mechanisms remain elusive.

Methods: The CIRI model was established in vivo, with rats assigned to four groups. 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to evaluate the effects of NLT and AST-IV on neurological function and pathological injury after cerebral ischemia-reperfusion. immunofluorescence, real-time PCR, and Western-blot assays were performed to explore the effects of NLT and AST-IV on the RIP1/NIK/IKKα/NF-κB pathway. The micro-enzyme immunoassay method was applied to examine the expression levels of various factors in each group. To verify the neuroprotective effects of NLT and AST-IV in vitro, an oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cell model was established and treated with the drug-containing serum of NLT and AST-IV.

Results: Necroptosis plays a significant role in the onset and progression of ischemia-reperfusion-induced neural injury. In vivo studies have shown that both NLT and AST-IV improve neurological function scores, reduce infarct volume, and enhance pathological features following MCAO/R. They significantly inhibited the expression of the RIP1/NIK/IKKα/NF-κB pathway, thereby reducing neuronal cell necroptosis. In vitro studies also showed that NLT and AST-IV reduced OGD/R-induced necroptosis.

Conclusions: This study confirms that the significant neuroprotective effects of NLT and AST-IV in alleviating CIRI are related to inhibiting necrosis by suppressing the RIP1/NIK/IKKα/NF-κB pathway.

The extracellular matrix (ECM) plays fundamental roles in modulating tissue structure and function under normal and pathological conditions. ECM composition is an essential consideration for studying cellular microenvironments, as varied composition leads to changes in cell behavior and delivery of therapeutics. Collagen VI is a non-fibrillar collagen that is found in both fibrotic and tumor microenvironments, where it promotes disease progression and suppresses the immune system. In this review, we summarize the contributions of collagen VI to fibrosis and tumor progression, followed by a focus on its ability to modulate the immune system in these contexts. Finally, we explore whether collagen VI could be a suitable therapeutic target for future study. While many studies have demonstrated the importance of collagen VI in disease progression, further studies of its immunomodulation abilities are needed to fully realize its potential as a therapeutic target in fibrosis and the tumor microenvironment.

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder featuring dopaminergic neuron loss, which is associated with mitochondrial dysfunction. Astragalus polysaccharide (APS) extracted from Astragalus membranaceus possesses antioxidant, anti-inflammatory, and neuroprotective properties. APS was previously revealed to exert neuroprotective effects in experimental PD models. However, the underlying mechanism remains poorly understood. Therefore, our study was designed to reveal the molecular mechanism through which APS exerts neuroprotective effects in PD.

Methods: SH-SY5Y cells were treated with 6-hydroxydopamine (6-OHDA) to induce the in vitro model of PD. 6-OHDA-treated SH-SY5Y cells were further transfected with sh-CEND1 and treated with APS to assess whether APS alleviates 6-OHDA-induced neurotoxicity through regulating CEND1. Cell viability, apoptosis, intracellular ROS levels, mitochondrial membrane potential (MMP), and the levels of dopaminergic neuronal markers and mitochondrial biogenesis-related proteins in SH-SY5Y cells were evaluated through a CCK-8 assay, flow cytometry, DCFH-DA staining, JC-1 staining, and western blotting. Finally, CEND1-knockout (CEND1-KO) mice were used to confirm whether APS exhibits the neuroprotective effects via a CEND1-dependent mechanism. Behavior tests, immunohistochemical staining, and western blotting were performed to examine mouse motor dysfunction, neuronal injury, and mitochondrial dysfunction.

Results: 6-OHDA downregulated CEND1 expression in SH-SY5Y cells and PD mice, which, however, was reversed after APS treatment. CEND1 knockdown aggravated while CEND1 overexpression ameliorated 6-OHDA-induced SH-SY5Y cell injury, apoptosis, ROS production, and mitochondrial dysfunction. The preventive effects of CEND1 upregulation against 6-OHDA-induced neuron degeneration and mitochondrial dysfunction were attributed to the activation of the PI3K/AKT and AMPK/SIRT1/PGC-1α signaling pathways. Besides, APS alleviated 6-OHDA-induced SH-SY5Y cell injury and mitochondrial dysfunction, while silencing of CEND1 abrogated the neuroprotective effects of APS in vitro. APS administration successfully improved motor deficits, neuronal injury, and mitochondrial impairments in WT (wild-type) mice, but failed to protect against PD in CEND1-KO mice.

Conclusion: APS exerts its neuroprotective effects in PD by preventing mitochondrial dysfunction through increasing CEND1 expression.

Objective: To investigate the pathological diagnostic value of AHNAK2 in gallbladder carcinoma (GBC), especially in adenocarcinoma (AC).

Methods: Tissue microarrays (TMAs) were constructed from 296 gallbladder tumor cases, comprising 562 cores that included normal/atypical epithelium, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/TIS), and GBC. Immunohistochemical staining for AHNAK2 and IMP3 was performed on these TMAs and another 10 GBC cases, and the sensitivity and specificity of AHNAK2 were assessed across different gallbladder tumor types.

Results: AHNAK2 immunohistochemical expression demonstrated a progressive increase across pathological stages (p<0.001). Among tumor types, AHNAK2 positivity was observed in 67.53% (260/385) of ACs, 97.83% (45/46) of adenosquamous/squamous cell carcinomas (ASC/SCCs), 34.78% (8/23) of neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (NEC/miNEN), but not in areas of NECs, and none in undifferentiated carcinomas (UCs). Importantly, among three grades of well, moderately, and poorly differentiated AC, the positive rate of AHNAK2 decreased from 70.59% (24/34), 70.11% (190/271), to 57.50% (46/80); conversely, IMP3 increased from 58.82%, 78.97% to 83.75%. Given the extremely low positivity rates of AHNAK2 and IMP3 in normal/atypical epithelium, combining these markers significantly improved diagnostic performance, demonstrating 83.73% sensitivity and 91.38% specificity for HGIN/TIS and GBC, achieving sensitivities of 91.18%, 90.77%, and 93.75% across well, moderately, and poorly differentiated ACs.

Conclusion: AHNAK2 demonstrates moderate sensitivity and high specificity in the pathological diagnosis of GBC, particularly for well-differentiated ACs. Combining AHNAK2 with IMP3 significantly enhances diagnostic sensitivity, achieving up to 90% across all AC grades.

Yolkin is an egg yolk-derived protein with immunoregulatory properties. In this work, yolkin was evaluated as a protective agent in endotoxemic BALB/c mice. The mice were pretreated with yolkin either orally in drinking water or intraperitoneally (i.p.) before i.p. injection of E. coli lipopolysaccharide (LPS). Circulating blood leukocyte number, blood cell composition, serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and haptoglobin, as well as histological changes in the spleen and the liver, were examined. Yolkin differentially regulated the values of these parameters, depending on the administration protocol; however, the serum levels of TNF-α and IL-6 were generally decreased, and the level of haptoglobin, an acute-phase protein, was elevated. The pretreatment of mice with yolkin led to improved histological architecture in the investigated organs of endotoxemic mice, particularly in the liver, where yolkin diminished an increased level of vascular permeability and reversed a decreased number of Kupffer cells. These changes were independent of the route of yolkin administration. In conclusion, yolkin proved effective in the amelioration of pathogenic consequences of LPS administration and may be considered a potential protective measure for patients at risk of endotoxemia.

Gestational diabetes mellitus (GDM) refers to a diabetic condition observed in pregnant women, significantly affecting both the health of the mother and the growth of the offspring. G protein-coupled receptor 4 (GPR4) is a receptor widely distributed across various tissues, but its role in GDM remains unclear. Our research aims to investigate the role of GPR4 in GDM and explore the potential therapeutic effects of its antagonist, NE 52-QQ57, in treating this condition. First, we found that GPR4 was expressed in placental tissues. Mice were divided into three groups: wild-type, db/+ pair-fed, and db/+ pair-fed + NE 52-QQ57. GPR4 expression was significantly higher in the db/+ pair-fed mice compared with wild-type mice. Markedly increased blood glucose and serum insulin levels were observed in GDM mice on gestational days (GD), accompanied by disrupted lipid profiles, all of which were significantly alleviated by NE 52-QQ57. Moreover, undesirable fetal outcomes, including increased fetal mortality, decreased fetal weight, reduced crown-rump length, and decreased placental weight, were observed in GDM mice, however, all were notably improved by NE 52-QQ57. Increased oxidative stress (OS) and the release of inflammatory cytokines were observed in GDM mice, but these were significantly reversed by NE 52-QQ57. Additionally, activated nuclear factor κ-B (NF-κB) signaling in placental tissues of GDM mice was significantly suppressed by NE 52-QQ57. Collectively, antagonism of GPR4 protected against GDM-induced placental damage in mice, confirming the critical role of GPR4 in the development of GDM.

Background: Lung cancer (LC) is a leading cause of malignancy-related morbidity and mortality worldwide. The activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1), one of the chaperones of heat shock protein 90 kDa (heat shock protein 90, HSP90), is involved in the maturation, stabilization, degradation, and function of oncogenic proteins. The aim of this study was to investigate the specific mechanism and role of AHSA1 in LC development.

Methods: Expression of AHSA1 in LC was analyzed using The Cancer Genome Atlas (TCGA) database. AHSA1 expression in LC cells and tissues was assessed by qRT-PCR and western blotting. In addition, Kaplan-Meier plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between AHSA1 and clinicopathological variables and prognosis. The effects of AHSA1 on LC cell proliferation and migration were observed using cell counting kit-8, flow cytometry, wound healing, and Transwell assays. Target genes were predicted by bioinformatics and subsequently validated using a qRT-PCR assay.

Results: AHSA1 exhibited significant upregulation in LC tissues and cell lines, with its elevated expression correlating with adverse prognostic outcomes in LC patients. Functional assays revealed that downregulation of AHSA1 markedly impedes the proliferation, migration, and invasion of LC cells. Conversely, overexpression of AHSA1 enhanced these malignant behaviors. Furthermore, bioinformatics analysis suggested a potential interaction between AHSA1 and HSP90α, which was also found to be highly expressed in LC cells, exhibiting a notable increase in expression levels following AHSA1 upregulation.

Conclusions: AHSA1 is implicated in promoting the progression of LC by enhancing the malignant phenotype of cancer cells through the upregulation of HSP90α expression, which may underlie the association of AHSA1 expression with adverse clinicopathologic features in LC patients. These findings indicate that AHSA1 serves as a potential prognostic biomarker and represents a viable therapeutic target for LC.

Different types of bioartificial corneas have been generated by tissue engineering through combining cells, biomaterials, and bioactive molecules. Orthotypical corneal cells can be obtained from corneal biopsies, and include epithelial, stromal, and endothelial cells, whereas heterotypical cells are obtained from alternative cell sources with corneal differentiation potential, such as mesenchymal stem cells. In turn, two main types of biomaterials have been applied to corneal tissue engineering: those generated by the decellularization of natural tissues and biomaterials generated de novo using synthetic or natural biomaterials, especially collagen, fibrin, and agarose. Cells and biomaterials are combined with bioactive factors, inducing cell proliferation and differentiation. A review of previous studies revealed that most bioartificial corneas were not able to fulfill the complex requirements required for clinical translation, which include a thorough preclinical characterization, generation of the tissue as an advanced therapy medicinal product, a clinical research phase, and a final authorization by the European Medicines Agency or another competent regulatory agency. Most authorized products correspond to partial corneal substitutes consisting of one cell type associated or not with a scaffold, and only one product consisting of a human bioartificial cornea containing a fibrin-agarose scaffold and two corneal cell lineages (epithelial and stromal cells) called NANOULCOR was evaluated in patients in the context of an advanced therapy medicinal product. These findings confirm the existence of a bottleneck between basic and clinical research and suggest the need to implement novel clinical studies to develop new therapies that can improve the results of current corneal therapies.