Histology and histopathology最新文献

Diabetes mellitus (DM) causes numerous systemic diseases in animals and humans. This may also lead to reproductive problems among individuals of reproductive age. Detrimental effects such as apoptosis in ovarian granulosa cells, degradation of communication proteins, decreased oocyte quality, delayed meiotic maturation, and atrophy are among the increasing evidence that chronic hyperglycemia causes reproductive problems. Numerous studies have reported that the antidiabetic properties of the antioxidant curcumin may be due to its inhibition of oxidative stress, inflammation, and insulin resistance. There are also data indicating that curcumin reduces the risk of DM and its associated symptoms. This review discusses the protective or curative properties of curcumin in the treatment of DM-related problems in the ovary and seeks to elucidate potential underlying mechanisms. While the use of curcumin as a supportive/therapeutic agent has been introduced for the reduction of reproductive problems that may be caused by uncontrolled DM, more studies on this subject are needed.

Sex hormones regulate gut function and mucosal immunity; however, their specific effects on the mucosa-associated lymphoid tissue (MALT) in the rectum of mammals remain unclear. Here, we aimed to investigate the influence of sex on MALT in the rectum of mammals by focusing on the rectal mucosa-associated lymphoid tissues (RMALTs) of C57BL/6NCrSIc mice. Histological analysis revealed that RMALTs were predominantly located in the lamina propria and submucosa of the rectal mucosa, with a significant sex-related difference in the distance from the anorectal junction to the first appearance of the RMALT. Despite similar RMALT numbers, females exhibited significantly larger RMALTs than males. Immunostaining revealed the presence of various immune cells, including T cells, B cells, macrophages, proliferative immune cells, lymphatic vessels, and high endothelial venules (HEVs), in RMALTs. Compared with males, females showed elevated T cell, helper T cell, and cytotoxic T-cell gene expression levels, along with high percentages of specific T-cell subsets. The factors influencing RMALT development, such as the presence of HEVs, C-X-C motif chemokine ligand 13 expression, and RMALT-containing cell proliferation, were also explored. Overall, this study revealed the detailed attributes of RMALTs, their immune cell composition, and their determinants in male and female mice, providing insights into the sex-specific characteristics of the rectal mucosal immune system.

Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively. High heterogeneity of the intraepithelial TIL density was found to be an independent prognostic factor, with a hazard ratio of 1.970 (1.207-3.215) in the multivariate analysis of recurrence-free survival. High heterogeneity was closely associated with a high T category, venous invasion, perineural invasion, and KRAS mutation. The combination of both intraepithelial TIL density and density heterogeneity was significantly associated with the prognosis of patients: low TIL density/high TIL heterogeneity showed hazard ratios of 3.284 (1.639-6.578) and 4.176 (1.713-10.178) in the discovery and validation cohorts, respectively. Our findings suggest that the heterogeneity status of intraepithelial TIL density might help delineate patients with better vs. worse survival when combined with intraepithelial TIL density.

Iron, a vital element for numerous peripheral and central nervous system functions, is a key player in DNA synthesis, gene expression, myelination, neurotransmission, and mitochondrial electron transport. Iron has utmost importance in various neurological functions, including neurotransmitter synthesis and brain cell metabolism. Migraine is a neurogliovascular disorder in which neuroinflammation plays a crucial role. Iron deficiency has been associated with various neurological issues and could potentially influence migraine frequency or severity. However, the relationship between iron levels and migraine is not fully clear and necessitates further research. On the other hand, iron overload could also have negative effects, as excessive iron might contribute to oxidative stress and inflammation, which may impact migraine-related pathways. The interplay between iron levels and neuroinflammation might affect migraines. While iron deficiency could exacerbate inflammation or disrupt neurotransmitter balance, iron overload might increase oxidative stress and neuroinflammation. Comprehending this balance is fundamental, as both iron deficiency and overload can have detrimental effects on brain health and migraine symptoms. In this review, we will summarize the current interconnection between migraine, iron levels, and neuroinflammation that are currently under active investigation.

Recent advancements in single-cell spatial proteomics have revolutionized our ability to elucidate cellular signaling networks and their implications in health and disease. This review examines these cutting-edge technologies, focusing on mass spectrometry (MS) imaging and multiplexed immunofluorescence (mIF). Such approaches allow high-resolution protein profiling at the single-cell level, revealing intricate cellular heterogeneity, spatial organization, and protein functions within their native cellular contexts. MS imaging techniques offer unprecedented high-dimensional resolution and provide detailed insights into their subcellular protein localization and abundance. mIF enables rapid and high-throughput protein profiling, enhancing its accessibility for diverse research and clinical applications. This review assesses the current challenges associated with these methodologies and also discusses the potential solutions to overcome these obstacles. The integration of spatial proteomics with other systems biology approaches holds great promise for enhancing our understanding of complex biological systems. It could also lead to significant advancements in molecular diagnostics and personalized treatment strategies.

Research towards regenerative dentistry focused on developing scaffold materials whose high performance induces cell adhesion support and guides tissue growth. An early study investigated the proliferation abilities and attachment of human periodontal ligament fibroblasts (HPLFs) on two bovine pericardium membranes with different thicknesses, 0.2 mm and 0.4 mm. Following those published results, we examined the ultrastructure of HPLFs in contact with these membranes. The HPLFs were cultured in standard conditions, exposed to the tested materials, and, after 24 hours, subjected to transmission electron microscopy preparation. The examined parameters included the quality and distribution of mitochondria, Golgi apparatus, and the nucleus. HPLFs exposed to membranes showed ultrastructural changes. The cellular compartments aimed at protein synthesis and metabolism increased compared with the control. Unpaired t-test and one-way ANOVA showed that HPLFs exposed to membranes displayed an increase in the number of mitochondria (89.23±7.44 vs. 66.90±9.58; T1 and control; p<0.05 and 84.05±14.01 vs. 66.90±9.58; T2 and control; p<0.05). The reported ultrastructural evidence suggests an active synthesis state of HPLFs, probably triggered by the bovine collagen membrane, showing an active role of this material in the biology of the regeneration process.

Extracellular adenine nucleotides serve as crucial signaling molecules and influence a broad spectrum of physiological and pathological processes. CD73, the rate-limiting enzyme in the metabolism of extracellular adenine nucleotides, is ubiquitously expressed on various cell types, particularly stem cells. CD73⁺ mesenchymal stem cells (MSCs) have emerged as promising candidates for therapeutic applications due to their immunomodulatory and pro-regenerative properties. Numerous studies have highlighted the crucial role of CD73 in mediating tissue protection in myocardial infarction (MI). In this review, a brief overview of the cell type-specific expression, regulatory effects of CD73 on MSCs, and proangiogenic and immunomodulatory mechanisms is provided, with a focus on current findings concerning the protective functions of CD73 in the context of MI within the framework of stem cell therapy.

Due to the late-stage diagnosis of head and neck squamous cell carcinoma (HNSCC), treatment remains a significant clinical challenge. The metalloproteinases MMP-9 and MT1-MMP play a pivotal role in extracellular matrix remodeling, thereby facilitating tumor growth and metastasis. Tumor progression requires the degradation of the basement membrane. The principal components of this structure, namely collagen IV and laminin, are the main targets of both MMP-9 and MT1-MMP. However, they can also exert influence over the expression of these enzymes. Oxidative stress plays an instrumental role in tumor development, functioning as a key inducer of metalloproteinase expression. The present study investigates the distribution of MMP-9 and MT1-MMP within tumor nests and along the basement membrane, comparing these with the distributions of collagen IV, laminin-332, and the antioxidant MnSOD. Biopsies from 12 patients with HNSCC and poor prognostic factors were subjected to immunofluorescence analysis. MMP-9 and MT1-MMP were found to be predominantly present in tumor cells, with a significant decrease in expression from the periphery to the center of tumor nests. Co-localization studies with laminin-332 and collagen IV, revealed substantial overlap, in accordance with the role of MMPs in basal membrane degradation. The cellular expression of laminin-332 associated with MMP-9 expression suggests an intricate relationship between metalloproteinases and their targets. While the previously observed pattern of glutathione-producing enzyme was similar to the metalloproteinases pattern, MnSOD expression was homogeneously distributed within tumor nests. Our findings reveal various distribution patterns of oxidative stress regulators, suggesting a complicated interplay in the development of HNSCC.

Background: High levels of histocompatibility minor 13 (HM13) have been related to the progression of several cancers. Here, we investigated the function of HM13 in colorectal cancer (CRC).

Methods: HM13 expression, clinicopathology analysis, and its influence on survival were analyzed in multiple public databases (TCGA, TIMER2.0, and GEPIA). HM13 mRNA and protein levels in CRC cells were examined by qRT-PCR and western blot, respectively. CCK-8, Transwell, wound-healing, and adhesion assays were used to measure cell proliferation, migration, invasion, and adhesion in HM13-overexpressed and -silenced cells. The relationship between HM13 expression and neutrophil infiltration was also analyzed. CRC xenograft mouse models were used for in vivo verification of HM13 function.

Results: In this study, TCGA dataset analysis revealed that elevated HM13 levels correlated with malignant progression and worse survival outcomes in CRC. Cell migration, proliferation, invasion, and adhesion were suppressed through the knockdown of sh-HM13 and enhanced through HM13 overexpression. Additionally, HM13 expression significantly correlated with the infiltration level of neutrophils in CRC in TCGA and TIMER analyses. HM13 levels were also positively correlated with myeloperoxidase (MPO) levels. In addition, in vivo studies further confirmed that MPO overexpression partially abolished the inhibition of tumor growth by sh-HM13 in CRC.

Conclusion: The results suggested that high HM13 expression in CRC could promote tumor growth and metastasis by reducing neutrophil infiltration and may serve as a useful target in the treatment of metastatic CRC.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor. Among the S100 protein family members, the imbalance of S100 calcium-binding protein A2 (S100A2) was related to the pathogenesis of several types of cancer, and S100A2 has been reported to be upregulated in the plasma of NPC patients; however, its specific role in NPC pathogenesis remains unclear. Thus, this study aims to determine the potential role of S100A2 in NPC to provide novel insights into NPC management. C666-1 and NPC/HK-1 cells were transfected with S100A2 silencing/overexpression (si/oe) constructs. For in vivo investigations, NPC/HK-1 cells were transfected with si/oe-S100A2 to induce tumor formation in nude mice. Cellular viability and apoptosis were assessed using the CCK8 assay, colony-forming assay, and flow cytometry. Glucose uptake and lactate production levels were quantified using biochemical assays. S100A2 expression was measured via RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence were performed to determine the levels of S100A2, PI3K, AKT, p-PI3K, p-AKT, GLUT1, HK-2, LDHA, and ki-67 proteins. S100A2 expression levels were significantly higher in NPC cancer tissues than in adjacent tissues. Similarly, C666-1 and NPC/HK-1 cells exhibited increased S100A2 expression, and silencing S100A2 significantly inhibited NPC cell viability, proliferation, glucose uptake, and lactate production, and induced apoptosis and decreased the protein levels of GLUT1, LDHA, and HK2 in NPC cells. Conversely, S100A2 overexpression enhanced these characteristics in NPC cells but could be mitigated by the PI3K/AKT inhibitor (LY294002). Silencing S100A2 suppressed the tumor formation of NPC/HK-1 cells, while S100A2 overexpression promoted tumor formation and could be hindered by a GLUT1 inhibitor (WZB117). S100A2 is upregulated in cancer tissues of NPC patients and was found to promote proliferation, glycolysis, and tumor formation in NPC cells through its interaction with GLUT1.