Journal of Molecular Histology最新文献

An actin binding protein, gelsolin (GSN) has two isoforms, plasma (pGSN) and cytosolic (cGSN). Changes in pGSN and/or cGSN levels have been shown to be associated with the pathogenesis of several diseases. The aim of this study was to evaluate changes in intracellular and extracellular GSNlevels with HIF-1 in animals exposed to chronic sustained hypoxia (CSH), in addition to apoptosis and the cellular redox status. The rats in the Sham group were exposed to 21% O₂, and the rats in the hypoxia groups were exposed to 13 and 10% O₂, respectively. Plasma pGSN, HIF-1α, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS), and lung tissue pGSN, HIF-1α, TAS, TOS, GSN levels, and apoptotic cell numbers were measured. HIF-1α levels were found to increase significantly in the tissue, especially in the group with severe hypoxia, both in biochemical and histological examinations. pGSN levels were also significantly decreased in both plasma and tissue. Significant increases in tissue were observed in cGSN. It was observed that while the antioxidant activity was dominant in the tissue, the oxidant activity was dominant in the plasma. In particular, the response to hypoxia regulated by HIF-1 is very important for cellular survival. The results of this study showed that the increase in cGSN and TAS levels in the lung tissue together with HIF-1α can be considered as the activation of mechanisms for cellular protection.

We analyzed the toxic effect of the ethanolic extract of Passiflora incarnata (EEP) and its nanoformulation (N-EEP) in the in vitro and in vivo models (zebrafish embryos and Swiss albino mice). The EEP composition was verified by phytochemical and GC-MS analysis. The synthesized N-EEP was characterized using UV-visible spectroscopy and scanning electron microscopy. In vitro results showed both EEP and N-EEP have a dose-dependent effect in L132 cells (normal embryonic lung cells). In zebrafish embryos, no developmental changes were observed for both EEP and N-EEP at 200 µg/ml. The acute and sub-acute toxicity of EEP and N-EEP was identified by oral administration in Swiss albino mice. A single-day oral dose of EEP and N-EEP at different concentrations was administered for acute toxicity, and changes in body weight, food, water intake, temperature, respiration rate, skin color changes, and eye color till 72 h was observed. In a sub-acute toxicity study, 28 days oral administration of different concentrations of EEP and N-EEP was done. Hematological analysis, serum hepatic biochemical parameter analysis, and histopathological analysis for the liver, kidney, spleen, intestine, and heart were performed. The results indicated that lower than 600 mg/kg of EEP and N-EEP can safely be used for the remediation of a spectrum of diseases.

Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between HM13 expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. HM13 was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high HM13 expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. HM13 expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. HM13 was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.

Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway.

The aim of this study was to explore the mechanism of bone marrow stem cells (BMSCs) sheets constructed with different doses of Ascorbic acid 2-glucoside (AA-2G) in conjunction with N6-methyladenosine (m6A)-associated epigenetic genes analysing transcriptome sequencing data. Experimental groups of BMSCs induced by different AA-2G concentrations were set up, and the tissue structures were observed by histological staining of cell slices and scanning electron microscopy. Expression patterns of DEGs were analysed using short-time sequence expression mining software, and DEGs associated with m6A were selected for gene ontology analysis and pathway analysis. The protein-protein interaction (PPI) network of DEGs was analysed and gene functions were predicted using the search tool of the Retrieve Interacting Genes database. There were 464 up-regulated DEGs and 303 down-regulated DEGs between the control and high-dose AA-2G treatment groups, and 175 up-regulated DEGs and 37 down-regulated DEGs between the low and high-dose AA-2G treatment groups. The profile 7 exhibited a gradual increase in gene expression levels over AA-2G concentration. In contrast, profile 0 exhibited a gradual decrease in gene expression levels over AA-2G concentration. In the PPI network of m6A-related DEGs in profile 7, the cluster of metallopeptidase inhibitor 1 (Timp1), intercellular adhesion molecule 1 (Icam1), insulin-like growth factor 1 (Igf1), matrix metallopeptidase 2 (Mmp2), serpin family E member 1 (Serpine1), C-X-C motif chemokine ligand 2 (Cxcl2), galectin 3 (Lgals3) and angiopoietin-1 (Angpt1) was the top hub gene cluster. The expression of all hub genes was significantly increased after AA-2G intervention (P < 0.05), and the expression of Igf1 and Timp1 increased with increasing intervention concentration. The m6A epigenetic modifications were involved in the AA-2G-induced formation of BMSCs. Igf1, Serpine1 and Cxcl2 in DEGs were enriched for tissue repair, promotion of endothelial and epithelial proliferation and regulation of apoptosis.

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.

Background: In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing.

Methods: The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00 cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells.

Results: In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization.

Conclusion: The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.

Wounds are the common fates in various microbial infections and physical damages including accidents, surgery, and burns. In response, a healthy body with a potent immune system heals that particular site within optimal time by following the coagulation, inflammation, proliferation, and remodeling phenomenon. However, certain malfunctions in the body due to various diseases particularly diabetes and other physiological factors like age, stress, etc., prolong the process of wound healing through various mechanisms including the Akt, Polyol, and Hexosamine pathways. The current review thoroughly explains the wound types, normal wound healing mechanisms, and the immune system's role. Moreover, the mechanistic role of diabetes is also elaborated comprehensively.

Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200 mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.The results demonstrated that 100 and 200 mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200 mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine's gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings.