Journal of Molecular Histology最新文献

Acrylamide (ACR) is a harmful compound that forms in food cooked at high temperatures, influenced by food type, preparation methods, temperature, and cooking time. Recent studies have indicated that ACR adversely affects male reproductive system and sperm health, primarily through oxidative stress. Wheat sprout (WS) is a unique medicinal plant that contains a high number of antioxidants. The main objective of this study was to investigate the possible effects of WS treatment on histological, biochemical and immunohistochemical changes in the testis and prostate as well as on the sperm parameters of rats exposed to ACR. Twenty adult male rats were split into four groups. One group received 1 mL normal saline, another group received 50 mg/kg ACR, third group received 200 mg/kg WS and fourth group received a combination of ACR (50 mg/kg) and WS (200 mg/kg). After 21 days, the epididymis was immediately examined for assessment of sperm. The prostate and left testis were placed in 10% formalin for histomorphometric and immunohistochemical analyses. The right testes were removed to measure testosterone, malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. ACR consumption significantly decreased sperm count, viability, motility, and DNA fragmentation, whereas WS intake significantly improved these sperm parameters (p < 0.05). Compared with ACR, WS enhanced spermatogenesis indices, including TDI- and SI-positive seminiferous tubules, Johnson score, testis weight, body weight, and relative weight (p < 0.05). Furthermore, WS significantly reduced p53 expression and increased Bcl-2 expression, thereby counteracting ACR-induced apoptosis. The findings suggest that WS may effectively enhance and restore the histomorphometric, cellular, and hormonal changes in the male reproductive system caused by ACR.

Pressure ulcers represent a significant healthcare burden worldwide. Numerous research has demonstrated the therapeutic potential of adipose-derived stem cell (ADSC)-derived exosomes in promoting wound healing. This study aims to investigate whether exosomes derived from miRNA-modified ADSCs play a role in pressure ulcers by affecting inflammation and macrophage polarization. ADSCs were identified by detecting the surface markers and multilineage differentiation potential. Lentiviruses carrying miR-21-5p were transduced in ADSCs for stable overexpression. Exosomes were extracted from ADSCs and identified. RT-qPCR was employed to detect RNA levels. A mouse model of pressure ulcers was established, followed by injection of exosomes. DiO staining was conducted to assess exosome biodistribution at wound sites. Hematoxylin-eosin and Masson staining were conducted for histological analysis. Immunofluorescence staining was used to evaluate TNF-α and IL-6 expression in mouse wound tissues. Western blotting was conducted to evaluate protein levels of macrophage polarization markers in vivo and in vitro. The results revealed that exosomes derived from miR-21-5p-overexpressing ADSCs promoted wound healing and reduced inflammatory cytokine expression in mouse wound tissues. Moreover, exosomal miR-21-5p induced macrophage M2 polarization in both mouse wound tissues and bone marrow-derived macrophages. Mechanistically, exosomal miR-21-5p inhibited NF-κB signal transduction in mouse wound tissues. In conclusion, ADSC-derived exosomes promote M2 macrophage polarization and inhibit inflammatory response in pressure ulcers via miR-21-5p delivery.

This study aimed to investigate the effects of ozone exposure on apoptotic mechanisms in primary (Colo-320) and metastatic (Colo-741) cell lines. Colo-320 and Colo-741 cells were grown in RPMI-1640 medium supplemented with 10% fetal bovine serum and treated with 20 µg/mL ozone for 72 h after MTT assay. Inverted microscopy was used for morphological assessment, and immunocytochemistry followed by H-SCORE analysis was performed to measure the expression of apoptotic markers. The statistical analysis was conducted using unpaired T-tests or Mann–Whitney U tests, with significance set at p < 0.05. Morphological analysis showed no significant changes in cell shape in Colo-320 or Colo-741 cells after ozone exposure. However, immunocytochemical analysis revealed significant increases in semi-quantitative histological scores (H-SCORES) for cleaved caspase-3, Bax, and cytochrome c in both cell lines, indicating enhanced apoptotic activity (p < 0.05). Conversely, Bcl-2 expression was significantly decreased in both Colo-320 and Colo-741 cell lines after ozone exposure (p < 0.05). Ozone exposure promoted apoptosis in both Colo-320 and Colo-741 cell lines, as evidenced by increased pro-apoptotic markers and decreased anti-apoptotic markers. These molecular changes were notable, yet they did not visibly alter cell morphology. The observed similarities between Colo-320 and Colo-741 cell responses suggest the need for further investigation. These findings indicate that ozone exposure may influence tumor cell apoptosis while preserving cell structure, highlighting the necessity of further research into its potential therapeutic implications.

Accelerating wound healing is a crucial objective in surgical and regenerative medicine. The wound healing process involves three key stages: inflammation, cell proliferation, and tissue repair. Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in promoting tissue regeneration, particularly by enhancing epidermal cell migration and proliferation. However, the precise molecular mechanisms underlying MSC-mediated wound healing remain unclear. This review highlights the pivotal role of MSCs and their exosomes in wound repair, with a specific focus on critical signaling pathways, including PI3K/Akt, WNT/β-catenin, Notch, and MAPK. These pathways regulate essential cellular processes such as proliferation, differentiation, and angiogenesis. Moreover, in vitro and in vivo studies reveal that MSCs accelerate wound closure, enhance collagen deposition, and modulate immune responses, contributing to improved tissue regeneration. Understanding these mechanisms provides valuable insights into MSC-based therapeutic strategies for enhancing wound healing.

Graphical abstract

Effects of mesenchymal stem cell and its derived-exosome treatment on skin regeneration and tissue repair via activation of different signaling pathways

This study investigates the effectiveness of quercetin (QUE) in preventing sarcopenia via the PI3K/AKT signaling pathway. Thirty SD rats were categorized into three groups: a young control group (Y), an old control group (O), and an old QUE-supplemented group (O + QUE). Body weight and grip strength were monitored weekly during the experiment. Soleus and gastrocnemius muscle weights, gastrocnemius tissue pathological examination, cell apoptosis, and mitochondrial damage were evaluated using HE, TUNEL staining, electron microscopy, and JC-1 staining. Biochemical assays and molecular biology techniques (qPCR and Western blot) were used to assess oxidative stress markers and the expression of sarcopenia-related genes and proteins. QUE supplementation increased muscle weight and improved grip strength in aged rats. Furthermore, QUE supplementation alleviated tissue damage, apoptosis, enhanced antioxidant capacity, and decreased damage to oxidative stress and mitochondria in the gastrocnemius of old rats. Molecular assessments revealed downregulation of muscle degradation markers (MuRF1, Atrogen-1, Bnip3) and upregulation of PI3K/AKT pathway proteins, suggesting a mechanistic pathway through which QUE mitigates sarcopenia. QUE maybe modulate the PI3K/AKT pathway to alleviate oxidative stress, mitochondrial damage, and muscle degradation due to aging, highlighting its potential as a therapeutic agent against sarcopenia.

Fatty liver disease is a build-up of fats in the liver that can damage the organ and lead to serious complications. This study aimed to investigate the effects of exercise training and supplementation (milk thistle, chicory and cumin) on liver metabolites related to its function and health in rats with non-alcoholic fatty liver disease (NAFLD). Forty adult male Wistar rats with an average weight of 215 ± 10 g were divided into a control group fed on the basal diet and four experimental groups fed with high-fat diet (HFD) for 6 weeks to induce non-alcoholic fatty liver disease (NAFLD). The 4 NAFLD groups were subdivided and treated with (a) plain HFD, (b) high-intensity interval training (HIIT), (c) supplement (milk thistle, chicory, and cumin), and (d) combined HIIT and supplementation for 4 weeks. The induction of NAFLD through HFD yielded dyslipidemia, liver tissue damage, increased malondialdehyde, uncoupling protein 2 (UCP2), and phosphatidylinositol-3 kinase (PI3K), as well as decreased superoxide dismutase (SOD) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) in liver tissue (p < 0.05). The 4 weeks intervention with either HIIT, supplement or especially the combined application of both, reversed these factors (p < 0.05) through changes in their concentrations in a direction indicative of enhanced liver health and function. HIIT beside supplementation (milk thistle, chicory, and cumin) improved indices related to oxidative stress, lipid profile, and the expression of PI3K, UCP2, PGC-1α genes expression and PGC-1α protein content, making it potentially promising in the treatment of liver damage caused by HFD.

Shammah, also known as smokeless tobacco, is a form of tobacco product consumed without combustion, commonly used in various cultures, particularly in the Middle East and parts of Africa. The experiment was conducted in four groups control male and female, also treated male and female. The administration of Shammah extract induced significant hematological, biochemical, and histopathological changes in both female and male rats. Treated females showed a decrease in total leukocyte count (TLC) to 9900, while treated males increased to 14,525. Lymphocyte percentage decreased by 9.5% in females and 6.02% in males, with neutrophil counts rising by 24.6% and 20.5%, respectively. Eosinophil levels surged by 240% in females and 50.3% in males. Hemoglobin levels decreased by 12.4–13.1% in females, while males showed a non-significant increase to 15.68. Malondialdehyde (MDA) levels increased to 1.57 in females (57% increase) and 1.93 in males (70.8% increase). Antioxidant enzymes decreased, with superoxide dismutase (SOD) at 3.53 (116.2% decrease) in females and 3.90 (45.8% decrease) in males. Kidney function assessments revealed elevated urea levels of 36.35 (84.8% increase) in females and 43.17 (131.2% increase) in males, alongside creatinine levels of 1.28 (75.3% increase) in females and 1.56 (90.2% increase) in males. Histopathological examinations showed untreated livers with a typical structure, while treated livers exhibited infiltrative cell aggregations, venous congestion, hemorrhage, and edema. Treated kidneys showed severe glomerular atrophy and degeneration. Spleens from treated groups had blending of white and red pulp, while brains displayed hemorrhage and distorted neurons in males, and ghost neurons in females. Treated testes exhibited dilated blood vessels, edema, and reduced spermatogenesis, while treated ovaries showed cyst formation and vacuolar degeneration. These findings indicate significant oxidative stress and organ damage associated with Shammah extract exposure.

PIWI-interacting RNAs (piRNAs) play an important role in cancer development and progression. Although recent studies had advanced our understanding of the functions of various piRNAs in cancer, the specific role of piR-38736 in gastric cancer remained poorly understood. This study aimed to investigate the clinical significance and underlying mechanisms of piR-38736 in gastric cancer. This study found that piR-38736 was significantly upregulated in gastric cancer cells and tissues. Positive piR-38736 expression was closely correlated with larger tumor size and medium to poor differentiation. Survival analysis revealed that patients with positive piR-38736 expression had significantly shorter survival times compared to those with negative expression. Knockdown of piR-38736 markedly inhibited cell proliferation and tumor growth in gastric cancer. Furthermore, piR-38736 was found to directly bind to the 3′ untranslated region (UTR) of SMAD4 mRNA, resulting in significant downregulation of SMAD4 at both the mRNA and protein levels upon overexpression of piR-38,736. In conclusion, these findings indicate that piR-38,736 promotes cell proliferation and tumor growth in gastric cancer by downregulating SMAD4 expression. piR-38,736 may serve as a prognostic biomarker and a potential therapeutic target for gastric cancer. Further studies are required to fully elucidate the underlying mechanisms of piR-38,736 and explore its clinical implications in gastric cancer management.

Diagnostic and prognosis of hepatocellular carcinoma (HCC) remain major challenge in clinic. This study aimed to explore a gene signature for diagnosis and prognosis prediction of HCC followed by mechanism investigation. Differentially expressed genes (DEGs) in HCC were screened using TCGA. With specific formula, clinic features of prognosis associated DEGs were calculated to obtained a specific model followed by Kaplan–Meier analysis. Protein–protein interaction (PPI) were predicted using STRING and associations between hub gene and clinic features were analyzed using R software. The hub gene was silenced in HCC cell lines followed by cell behaviors analyses. A prognosis associated 14-gene model was identified in this study which could significantly distinguish samples into high-risk and low-risk groups. PBK, BUB1, NUF2, and CDCA8 were the key nodes involved in the 14 gene-coded PPI with high diagnostic values, and only PBK was an independent risk factor of disease specific survival (DSS) of HCC. Moreover, higher PBK was positively correlated with pathological and histological grades, higher AFP, and infiltrations of Th2, T helper cells and aDC of HCC, but negatively correlated with the killer immune cells. Dysregulated methylation might contribute to the higher expression of PBK and silencing PBK significantly suppressed the proliferation, growth, migration, and invasion of HCC cells. PBK, BUB1, NUF2, and CDCA8 played crucial role in prognosis associated 14-gene model with high diagnostic values. Methylation dysregulation-induced PBK accumulation might promote the development of HCC via modulating immune surveillance.