Journal of Molecular Histology最新文献

The study aimed to investigate the long-term effects of IUGR and consequent catch-up growth on metabolic health by using a comprehensive approach that included histopathological, immunohistochemical, biochemical, and metabolomics analyses. Sprague–Dawley pregnant rats either undergo bilateral uterine artery ligation or a sham surgery on the 19th day of gestation. The offspring reached catch-up growth, kidney samples were collected at postnatal weeks 2, 4, and 8 for analysis. IUGR rats exhibited a spectrum of changes including reduced glomeruli number, proliferating cell number, altered oxidative stress markers, various enzymes involved in Krebs cycle, mitochondrial dynamics, and energy metabolism. Examination of the 8-week-old cohort identified a broader spectrum of metabolic alterations, notably in the biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine, tyrosine, glyoxylate, dicarboxylate, pyruvate, alanine, aspartate, and glutamate metabolism, glycolysis/gluconeogenesis and citrate (TCA) cycle. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, hypertriglyceridemia, cardiovascular diseases, and mental retardation. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies to mitigate the risk of metabolic diseases in individuals with a history of IUGR.

Transferrin receptor (TFRC) is essential for iron uptake and may regulate ferroptosis, a form of iron-dependent cell death implicated in cervical cancer (CC). Bioinformatic analyses (GEPIA, UALCAN, SRAMP, starBase) were combined with in vitro and in vivo experiments. CC cell lines were transfected with shRNAs or overexpression plasmids targeting TFRC and LOXL1-AS1. Proliferation was assessed by colony formation, EdU staining, and Ki-67 immunostaining. Ferroptosis was evaluated by measuring malondialdehyde (MDA), lipid ROS, Fe²⁺, and ferroptosis-related proteins. RNA pull-down, RIP, and MeRIP assays were used to explore m6A-dependent regulation, and actinomycin D assays assessed mRNA stability. TFRC and LOXL1-AS1 were upregulated in CC and associated with poor prognosis. TFRC promoted CC cell proliferation and inhibited ferroptosis. LOXL1-AS1 positively regulated TFRC by stabilizing its mRNA via an m6A-IGF2BP2-dependent mechanism. Rescue experiments confirmed that TFRC overexpression reversed the effects of LOXL1-AS1 knockdown. In vivo, LOXL1-AS1 depletion suppressed tumor growth and enhanced ferroptosis. LOXL1-AS1 promoted CC progression by stabilizing TFRC mRNA through m6A-IGF2BP2 interaction, suppressing ferroptosis. Targeting the LOXL1-AS1/IGF2BP2/TFRC axis may offer a potential therapeutic strategy for CC.

This study aimed to study architecture of pancreatic islets by histological, ultrastructural, histochemical, and immunohistochemical investigations in male and female goats. The tissues were collected from different lobes of pancreas from local slaughterhouses and processed for paraffin sectioning. The sections were stained with different histomorphological, histochemical and immunohistochemical staining. For electron microscopy standard protocols were used. The study revealed no morphological differences in islets of male and female pancreas, however significantly larger (p < 0.05) islets were observed in male animals. Among the different lobes larger islets were observed in left lobe in both the sexes. Immunohistochemically, number of insulin positive cells were more in female than male and number of glucagon cells were more in male than female but the difference was non significant (p > 0.05). Low to moderate PCNA expression in both the sexes indicative of cellular proliferation within islets, while strong VEGF reactivity suggested its role in islet vascularization. This study has provided a baseline anatomical and immunohistochemical data for comparative endocrinology and disease models studies across species, especially in ruminants or domestic animals. Future study can help in early identification of sex-specific susceptibility to metabolic or endocrine disorders in goats (e.g., diabetes-like conditions).

The reproductive effects related to sodium benzoate (SB) are increasingly recognized as concerns for public health. To elucidate the underlying mechanistic pathway in SB-induced reproductive impairment, we evaluated its dose-dependent effects by assessing the key elements of HPG- axis, encompassing wide range of doses from dietary to presumably harmful levels. Thirty-five adult male rats (Sprague-Dawley) split into seven groups (n = 5/group); control, SB10, SB50, SB100, SB500, SB1000mg/kg and the co-treated group (SB + EB). SB and distilled water were gavage for 90 consecutive days. The co-treated group received SB500 from day one, while estradiol benzoate (EB; 40 µg/kg) was given at mid-study onward till completion of experiment. Biochemical parameters, sperm parameters, reproductive hormones, gonadal histopathology, hypothalamic kisspeptin and RFRP-3 expression were assessed. SB produced a concentration-dependent reduction in the testis, accessary sex organs weight, antioxidant activities (SOD, POD, CAT and GSH), testosterone and FSH levels. Testicular ROS, TBARs and plasma LH levels were significantly raised compared to control. Fertility parameters underwent a significant decline in SB rats. Notably, kisspeptin showed dose-related decline, while RFRP-3 upregulated in SB rats. Morphometric indices of seminiferous tubules highlighted apparent alterations and marked traces of histopathology were noticed in test groups. EB treatment restored kisspeptin hence stabilized hormones and improved fertility parameters were seen in co-treated rats. SB exposure significantly disrupts HPG-axis via neuroendocrine dysregulation and inducing testicular cytotoxicity, with oxidative stress serve as the key mediator of these effects. It underscores the dire need for careful usage and future studies of its long-term reproductive safety.

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Chinese ginger (Boesenbergia rotunda) is a culinary and traditional medicinal plant in Southeast Asia and Indo-China regions with several medicinal benefits. This study aims to assess the effectiveness of Chinese ginger extract against diabetic nephropathy and cardiomyopathy and the associated signaling pathways. Animals were randomly assigned to groups; control rats, diabetic rats, diabetic rats treated with 100 and 400 mg/kg of the B. rotunda EtOAc fraction (BRE). Treatment was administered for 5 successive weeks via oral gavage. Thereafter, the rats were evaluated for fasting blood glucose, tumour necrosis factor alpha, interleukin-6, interleukin-1 beta, reduced glutathione, superoxide dismutase, catalase, lipid peroxidation activities. Gene expression levels of nuclear factor erythroid 2-related factor 2, and Kelch-like ECH-associated protein 1 were examined. Cardiorenal histopathological and immunohistochemical were performed to assess tissue damage. BRE administration to diabetic rats notably ameliorated changes in body weight, kidney and heart weight and fasting blood glucose level. Furthermore, in diabetic rats, BRE significantly reduced malonaldehyde, tumour necrosis factor alpha, interleukin-6, interleukin-1 beta levels considerably with increasing activity of antioxidant enzymes in the kidney and cardiac tissues of rats treated with BRE. Diabetic rats treated with BRE showed upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2, while Kelch-like ECH-associated protein 1 mRNA expression in the kidney and cardiac tissues were downregulated. In addition, BRE treatment significantly reduced the cardiorenal protein expression of Bcl2 and collagen IV in the immunohistochemical analyses. From the results of this study, it can be concluded that B. rotunda exerts cardiorenal protective effect on diabetic rats due to its antidiabetic and antioxidant and may be considered a treatment for T2DM.

Cyclophosphamide (CP) is an effective chemotherapeutic agent whose clinical efficacy is often limited by toxicity, including intestinal injury. Oxidative stress and inflammation are central to CP-induced tissue damage and represent a valuable target to attenuate intestinal injury. Ambroxol (ABX), a clinically approved mucolytic agent, has demonstrated antioxidant, anti-inflammatory, and mucoregulatory properties that may confer multi-organ protection. This study investigated the protective effects of ABX against CP-induced intestinal injury in rats, exploring the involvement of oxidative stress, inflammation and Keap-1/Nrf2/HO-1 signaling. Adult male rats received ABX (20 mg/kg/day) orally for seven consecutive days, with CP (100 mg/kg, i.p.) administered on the fifth day. CP induced significant intestinal injury manifested by intestinal mucosal atrophy, decreased length of villi and goblet cell depletion. CP triggered oxidative stress characterized by increased MDA and decreased GSH, SOD, and catalase, upregulated NF-κB, IL-6, and TNF-α, and increased caspase-3 expression in the intestine. ABX attenuated histopathological alterations, mitigated oxidative stress, suppressed NF-κB and cytokines, and downregulated caspase-3. In addition, ABX preserved intestinal goblet cells while modulating the Keap-1/Nrf2/HO-1 pathway in intestinal tissue. These findings demonstrate the protective role of ABX against CP-induced intestinal injury via antioxidant, anti-inflammatory, and mucoprotective mechanisms, supporting its potential repurposing as an adjuvant during CP chemotherapy. The protective mechanism of ABX involves its ability to modulate the Keap-1/Nrf2/HO-1 signaling pathway.

Colon cancer remains a major cause of global cancer mortality, characterized by complex interactions between genetic, epigenetic, and immune factors. This study investigates the prognostic value of efferocytosis-related genes and their role in colon cancer progression and immune modulation. A prognostic signature relied on efferocytosis-related genes was developed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Immune infiltration, immune checkpoint expression, and tumor microenvironment characteristics were analyzed using single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and tumor immunophenotype (TIP) frameworks. S1PR5 was knocked down in SW1116 and SW620 cells. The effect of S1PR5 on colon cancer growth and macrophage regulation in vivo and in vitro. Colon cancer patients were stratified into high- and low-risk groups, with high-risk patients demonstrating significantly worse survival outcomes. S1PR5, a key gene in the model, was markedly overexpressed in colon cancer tumors and correlated with advanced clinical stages, poor survival outcomes, and diminished responses to immunotherapy. Furthermore, S1PR5 knockdown could inhibit colon cancer cell activity and increase macrophage polarization from M0 to M1. Our research developed an efferocytosis-related gene prognostic model and identified S1PR5 as a key biomarker. S1PR5 showed significant associations with advanced clinical stages, immunosuppressive microenvironments, and unfavorable survival outcomes, underscoring its potential as both a prognostic marker and a therapeutic target in colon cancer.

Extensive research has highlighted the involvement of excessive oxidative stress and pyroptosis in sepsis-caused acute lung injury (ALI). The present investigation delves into the potential role of Monoamine oxidase A (MAO-A) in this pathological process. Analyzing Gene Expression Omnibus (GEO) datasets alongside clinical samples revealed a significant upregulation of MAO-A in sepsis patients. To further elucidate this, cecal ligation puncture (CLP)-induced ALI were established in C57BL/6 mice. Additionally, human alveolar epithelial cells (HPAEpiC) treated with MAO-A inhibitor RO11-11639 were subjected to lipopolysaccharide (LPS) stimulation in vitro. The in-vivo experiments demonstrated that RO11-11639 mitigated CLP-induced ALI, significantly reducing pulmonary oxidative stress, inflammation and pyroptosis in lung tissue. Biochemical quantification revealed significant suppression of both oxidative stress biomarkers reactive oxygen species (ROS), malondialdehyde (MDA) and key inflammatory markers interleukin (IL)-1β, IL-16. Consistent with these findings, the in-vitro model confirmed that RO11-11639 reduced ROS and MDA accumulation, and inflammation in HPAEpiC, in response to LPS stimulation. Moreover, functional rescue analysis delineated the nuclear factor erythropoietin-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) pathway as the critical mediator of RO11-11639’s dual antioxidant and anti-pyroptosis activities in HPAEpiC. Mechanistically, MAO-A inhibition promoted the nuclear translocation of Nrf2, thereby activating the downstream regulatory proteins HO-1, quinone oxidoreductase 1 (NQO-1) and glutathione s-transferase (CST). These data cumulatively indicate that pharmacological targeting of MAO-A may offer therapeutic benefits in septic ALI by attenuating pathophysiological processes involving oxidative damage and inflammasome-mediated pyroptosis.

Gastric cancer (GC) development is influenced by crosstalk between tumor cells and host immune elements. Circ_0000372 has potential as an oncogene. This research aimed to investigate the circ_0000372 mechanism in GC. Circ_0000372 expressions were evaluated via the GSE194384 database. The overall survival of GC patients was determined via the Kaplan-Meier Survival Curve. Gene relationships were assessed using the Chi-square test. Circ_0000372 functions in GC were evaluated with qRT-PCR, Cell Counting Kit-8 analysis, 5-ethynyl-2’-deoxyuridine analysis, Transwell, Western blot, co-culture of peripheral blood mononuclear cells (PBMCs) and GC cells, flow cytometry, and ELISA. Meanwhile, the circ_0000372 mechanism was examined by RNA pull-down, dual-luciferase reporter assay, and Spearman Correlation Analysis. Finally, the circ_0000372 impact on tumor-bearing mice was analyzed by immunohistochemistry and western blot assays. Elevated circ_0000372 levels were detected in GC. Patients with raised circ_0000372 levels had a poor prognosis. Besides, circ_0000372 expressions were interrelated to TNM stage and lymph node metastasis. Silencing circ_0000372 repressed GC cell proliferation and invasion. Silencing circ_0000372 reduced immune escape with reduced PD-L1 protein levels and increased CD8 + T cell percentage. Moreover, circ_0000372 positively regulated PD-L1 expression via miR-488-3p, and circ_0000372 knockdown restrained GC cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p. The interference of circ_0000372 also reduced GC tumor formation, tumor weight, and PD-L1 level with elevated IFN-γ level in vivo. A high circ_0000372 level indicated a GC poor prognosis. Silencing circ_0000372 suppressed cell proliferation, invasion, and immune escape by derepressing PD-L1 via sponging miR-488-3p.

Graphical abstract

Mode pattern of circ_0000372/miR-488-3p/PD-L1 in mediating GC cell proliferation, invasion, immune escape