Journal of Molecular Histology最新文献

A peptic ulcer is a stomach lesion. It is generally caused by malnutrition, the use of anti-inflammatory medications, and an imbalance between mucosal defense systems. In fishes, the lubricous substance that called mucus secreted from the skin, prevents the entry of microorganisms that can enter the body through the skin. That mucus contains immune components such as antimicrobial peptides, lysozymes, lectins, proteases, and mucin. This study investigated the antiulcer activity of Rainbow Trout skin Mucus (RTM) in indomethacin induced ulcer model of rats and compared with famotidine as standard antiulcer drug. We administered 50, 100 and 200 mg/kg RTM dose on indomethacin-induced gastric ulcer model in rats and evaluated the numerical density of ulcer areas, histopathologic parameters and oxidative stress parameters (SOD, GSH, MDA) in the rat stomach. RTM was able to inhibit indomethacin-induced ulcer formation and exhibited a similar effect to 40 mg/kg dose of standard drug famotidine. 200 mg/kg dose of RTM had positive effects on oxidative stress biomarkers and histopathological results in the stomach tissue of rats. This is the first time we have fully demonstrated the gastroprotective effects of RTM as a waste product in rats. Analyses have shown that mucin, which has a positive regulatory effect on oxidative stress parameters, may be responsible for the gastroprotective effect.

Graphical Abstract

Olive Leaves Extract (OLE) holds therapeutic potential, traditionally used to treat hepatic ailments, though its molecular mechanisms remain unclear. This study evaluated the efficacy of ethanolic OLE against Carbon Tetrachloride (CCl₄)-induced oxidative stress in a rat model. Phytochemical analysis was performed using High Performance Liquid Chromatography (HPLC). For this porous, thirty rats were divided into six groups (n = 5): Group 1 (negative control) received a standard diet, while Groups 2–6 were subjected to CCl₄-induced toxicity. Group 2 served as the disease control, and Group 3 was treated with silymarin (100 mg/kg). Groups 4, 5, and 6 received OLE at 100 mg/kg, 200 mg/kg, and 300 mg/kg, respectively, for 21 days. OLE significantly modulated hepatic biomarkers (ALT, AST, ALP), increased Total Antioxidant Capacity (TAC), decreased Total Oxidation Capacity (TOC), and restored levels of SOD, GSH, and CAT compared to the CCl₄ group. Malondialdehyde (MDA) levels, elevated in the disease group, however downregulated by OLE, particularly at 300 mg/kg. Histological examination revealed normal liver integrity in the OLE-treated groups. Additionally, OLE modulated the mRNA expression of IL-1β, IL-6, TNF-α, NF-kB, Bcl2, and p-53. Apoptotic markers such as Nrf2, HO-1, Cytochrome c, caspase 3, caspase 7, and Bax were normalized with OLE treatment. The inhibition of KEAP1-NRF2 protein-protein interaction showed OLE’s superior efficacy compared to silymarin, with a better docking score. These findings suggest that OLE exerts significant hepatoprotective effects against CCl₄-induced oxidative stress and inflammation via the Nrf2-NFκB pathway.

Ghrelin, which is widely expressed in central and peripheral tissues, has several metabolic effects. It has been suggested that these effects may include anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Therefore, we aimed to investigate the effects of ghrelin administered to diabetic rats on DNA repair and apoptosis mechanisms, and differences in oxidative stress (OS) and pancreatic hormone levels in the pancreas. Twenty-one rats were randomly divided into three groups: control, type 2 diabetes mellitus (T2DM), and T2DM treated with ghrelin (T2DM + ghrelin). We examined PCNA and PARP-1 to evaluate the effect of ghrelin on DNA repair, caspase-3 and caspase-9 to evaluate its effect on apoptosis, and insulin and glucagon to evaluate its role in regulating glucose homeostasis by immunohistochemistry in diabetic rats. Malondialdehyde, glutathione, and protein carbonyl levels, as well as catalase, glutathione-S-transferase, and superoxide dismutase (SOD) activities, were measured spectrophotometrically to detect the ghrelin effect on OS. Homeostasis model assessment for insulin resistance (HOMA-IR) and pancreatic insulin levels were assessed by ELISA method. Ghrelin may be a potential regulator of apoptosis as it significantly reduced the number of caspase-3 and caspase-9 immunopositive cells (p < 0.0001). In addition, ghrelin treatment reduced OS by decreasing glutathione (p < 0.001), malondialdehyde, and protein carbonyl, as well as the activity of SOD (p < 0.05) in diabetic rats. The results suggest that ghrelin is a potential apoptotic regulator and may be considered as a therapeutic agent due to its significant ability to suppress OS in T2DM.

This study aims to elucidate the role of Kinesin Family Member 22 (KIF22) as a critical regulator of aggressive behavior in endometrial cancer (uterine corpus endometrial carcinoma, UCEC) and to uncover its underlying mechanisms, thereby providing a molecular rationale for future targeted treatment. Bioinformatics analyses were employed to assess KIF22 and TFDP1 expression in UCEC, examining their prognostic value and associations with disease progression. Expression levels were validated in UCEC tissues using qRT-PCR and western blotting. Potential TFDP1 binding sites on the KIF22 promoter were predicted using the JASPAR database and confirmed via dual-luciferase reporter assays. Functional assays, including CCK-8, transwell, and spheroid formation assays, were conducted to evaluate the effects of KIF22 knockdown on UCEC cell behavior. A mouse xenograft model was utilized to investigate the in vivo impact of KIF22 suppression on tumor growth and stemness. KIF22 expression was significantly elevated in UCEC tissues, correlating with reduced overall survival in patients with high KIF22 levels. Overexpression of KIF22 enhanced the proliferation, migration, and sphere formation of UCEC cells. Similarly, high TFDP1 expression was associated with poorer patient outcomes. KIF22 was found to be positively regulated by the TFDP1 transcription factor, which bound to the KIF22 promoter and activated its expression in UCEC cells. In vivo, KIF22 knockdown markedly impeded the tumor formation of cells and reduced stemness marker expression. KIF22, upregulated by TFDP1, enhances UCEC cell aggressiveness and is linked to poor prognosis, highlighting its potential as a target for therapeutic intervention in endometrial cancer.

Sevoflurane is extensively employed as an inhalation anesthetic in medical practices, due to its promising pharmacokinetics. Conversely, the data regarding effects of prolonged exposure to trace amounts of sevoflurane on the female reproductive system is obscure. Therefore, this study aimed to investigate the reproductive toxicity and underlying mechanism of long-term sevoflurane inhalation in female rats. A total 60 SPF grade SD female rats were randomly alienated into four equal groups as control group (A), 50 ppm sevoflurane group (B), 150 ppm sevoflurane group (C), and 300 ppm sevoflurane groups (D). Ovaries and uterine organs were collected for gross as well as histopathological analysis, western blotting, and immuno-histochemistry evaluation. Results revealed that pregnancy rate, number of fetuses (fetal mice) and general body weight of group B, C, and D were substantially lower (P < 0.05), while were compared with control. On the contrary, estrous period in groups B, C, D was shortened noticeably (P < 0.05), and estrus interval and cycle were significantly longer (P < 0.05). In fact, the ovarian and uterine coefficients of group B, C and D were significantly reduced as compared with control. However, ovarian and uterine histomorphology remained normal in control group, while obvious pathological alterations were detected in groups B, C, and D. Although, the expression of SOD protein in the ovarian and uterine tissues of groups B, C, and D was significantly reduced (P < 0.05), in contrast to group A. However, the MDA protein expression increased significantly (P < 0.05) as compared with group A. While expression of apoptosis-related genes (Bcl2 and Bax) and humoral immunity related genes (IL-6, IL-10 and TNF-α) showed highest elevation in groups exposure with sevoflurane (p < 0.001) in comparison to control. Conclusively, long-term inhalation of trace amounts of sevoflurane is toxic to female reproductive system and can severely affect reproductive organs and fertility by induction of oxidative stress and apoptosis.

Graphical abstract

Moringa oleifera (M. oleifera) is a popular medicinal plant that has become a wide research area in recent years due to its detected biological effects and its bioactive compounds. Valproic acid (VPA) is a medication used in the treatment of epilepsy and bipolar disorder and high doses or prolonged use of VPA can result in oxidative stress in cells. Since M. oleifera has high biological activities and contains many bioactive compounds, it is necessary to understand whether it plays a role in reducing oxidative damage, especially that caused VPA. The relationship between VPA and tongue tissue needs to be investigated, since VPA has negative effects on oral health and it is known that tongue tissue plays an important role in the continuity of oral health. In the present study, 3.0–3.5 month-old female Sprague Dawley rats (160–250 g) were divided into four groups (Control, Moringa, VPA, VPA + M), and VPA was administered via gavage. The aim was to understand the protective/preventive effects of ethanolic M. oleifera leaves extract against oxidative stress through biochemical parameters. Additionally, molecular docking studies were conducted on niazicin-A, niazimin-A, and niazimin-B found in M. oleifera leaves based on in vivo results. The results indicate that M. oleifera extract treats oxidative damage to the tongue tissue, and niazimin-A and niazimin-B particularly show high binding affinities to myeloperoxidase (MPO) and lactate dehydrogenase (LDH) enzymes. Further studies may suggest that the use of M. oleifera leaves extract with VPA could prevent potential negative effects on tongue tissue.

Arthritis is characterized by the progressive degeneration of articular cartilage, and the avascular nature of cartilage limits its capacity for self-repair. Stem cells are considered a promising treatment option due to their multipotent differentiation potential. The aim of this work was to investigate the structural changes in the hyaline articular cartilage of the knee joint in a model of arthritis induced by complete Freund’s adjuvant, and to assess intra-articular injection of bone marrow mesenchymal stem cells (BM-MSCs) through both histological and immunohistochemical study. Adult male albino rats were divided into four groups: group 0 (donor group), group I (control group), group II (arthritis group) and group III (BM-MSCs treated arthritis group). Samples were collected 2, 6 and 10 weeks after the onset of the experiment. Sections were stained with; hematoxylin and eosin, Safranin O fast green stain, Masson’s trichrome stain and anti-MMP9 antibody. In Group II (arthritis group), the articular cartilage showed signs of degeneration, including chondrocyte extensive proliferation, fibrillations, fissuring, and denudation, with fibrous tissue covering the exposed surface. There was a significant decrease in cartilage thickness, collagen content, and proteoglycan levels. The integrated density of MMP9 in the cartilage was significantly increased compared to Group I (control group). In contrast, Group III (BM-MSCs-treated arthritis group) exhibited a continuous cartilage surface with no cracks or fissures. There was a significant increase in cartilage thickness, collagen content, and proteoglycan levels, while the integrated density of MMP9 was significantly decreased compared to Group II (arthritis group).

Increasing incidences of fatty liver in humans and animals worldwide is the leading cause of liver related morbidities. Currently, in the face of the growing global increase in fatty liver, and the necessity to explore new factors significantly affecting it, aquaporins (AQPs) have become the focus of interest for many researchers. AQPs are membrane integral proteins involved in the transport of water, glycerol and other small solutes. These are expressed in all tissues and play multiple roles under normal and pathophysiological conditions. Despite ongoing advancements in understanding the involvement of aquaporins in metabolic processes, there remains a notable lack of knowledge concerning cellular and subcellular localization of the AQPs in bovine tissues and organs. Understanding this could provide a new therapeutic target for metabolic syndromes such as fatty liver disease in bovine. In this study, AQPs in bovine liver, adipose tissue and gall bladder are examined using immunohistochemistry. AQP9 immunoreactivity is predominantly detected at the sinusoidal surfaces of hepatocytes. AQP8 is mostly intracellular and localized to the central vein and sinusoid, whereas AQP7 is found around the portal vein. Notably, AQP3 is observed in the bovine gall bladder and adipose tissue but not in the liver. In adipose tissue, AQP7 is also detected in the cytoplasmic membranes of adipocytes. AQPs in liver and adipose tissue were also studied using the western blotting technique. Higher AQP9 and AQP3 expression is observed in the liver and adipose tissue, respectively, indicating they are the dominant aquaporins in these tissues. This suggests they could be potential therapeutic targets for treating fatty liver disease and other metabolic disorders in bovine.

Preeclampsia (PE) is a form of hypertension that manifests in the later stages of pregnancy. Since Kaempferol (Ka) has remedial potential hence this research was conducted to examine its therapeutic effect on Preeclampsia rats by regulating Wingless-related integration site/β-catenin (Wnt/B-catenin) pathway. To achieve this, thirty-two SD female rats were randomly allocated into four groups: control, preeclampsia (PE, LPS, 1 mg/kg), preeclampsia with kaempferol (PE + Ka), and preeclampsia with Dickkopf − 1 (DKK-1) and kaempferol (PE + DKK-1 + Ka). Rats in the PE + Ka and PE + DKK-1 + Ka groups received intraperitoneal injections at 50 mg/kg/d of kaempferol, whereas the PE + DKK-1 + Ka group was administered with 60 µg/kg/d of recombinant rat DKK-1 protein, an inhibitor of the Wnt/β-catenin signaling pathway. Our findings revealed that systolic blood pressure (SBP) in the PE + Ka group was significantly reduced in comparison to PE group (P < 0.05). The urine albumin levels in the PE + Ka group decreased noticeably (P < 0.05), whereas serum concentrations of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) in the PE + Ka group were reduced (P < 0.05) in comparison to PE group. Although PE + Ka group exhibited elevated levels of superoxide dismutases (SOD), glutathione (GSH), and catalase (CAT) in placental tissue relative to the PE group, whilst levels of malondialdehyde (MDA), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and serum glutamic-oxaloacetic transaminase (SGOT) considerably decreased (P < 0.05). Comparatively mRNA levels of Wnt1 and β-catenin in the PE + Ka group were elevated, whereas mRNA level of DKK-1 was diminished (P < 0.05). Administration of DKK-1 counteracted kaempferol effects on these parameters in Preeclampsia rats (P < 0.05). Devastatingly, ovarian and kidney histomorphology in the PE group exhibited significant degenerative alterations, whereas kaempferol groups demonstrated normal histomorphology in comparison to the PE group. Conclusively, Kaempferol can significantly lower systolic blood pressure and urine albumin in PE female rats while mitigating excessive oxidative stress. The therapeutic efficacy of kaempferol on Preeclampsia may be mediatated via Wnt/β-catenin signaling pathway.

Background

Breast cancer (BC) poses a significant global health challenge, with chemotherapy resistance, especially to docetaxel, remaining a major obstacle in effective treatment. The molecular mechanisms underlying this resistance are critical for developing targeted therapeutic strategies.

Objective

This study aims to explore the role of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), a member of the DYRK family, in docetaxel resistance in breast cancer cells and investigate its impact on cellular responses, including drug sensitivity and migration. Additionally, potential interactions between DYRK2 and Twist1, associated with epithelial-mesenchymal transition (EMT) and drug resistance, are explored. Methods: Docetaxel-resistant breast cancer cells were induced, and the expression levels of DYRK2, Twist1, and related genes were evaluated using real-time PCR and Western blotting. Lentivirus-mediated DYRK2 overexpression was employed to assess its effect on drug sensitivity, migratory ability, and Twist1 expression. The relationship between DYRK2 and Twist1 was examined, focusing on Twist1 ubiquitination. The impact of Twist1 on chemotherapy resistance and its binding to the Glutathione S-transferase Pi 1 (GSTP1) promoter were also investigated.

Results

Docetaxel-resistant cells exhibited down-regulated DYRK2 and up-regulated Twist1 expression. DYRK2 overexpression reversed drug resistance, decreased migration, and attenuated Twist1 and GST-π expression. DYRK2 was found to suppress Twist1 expression through ubiquitination, supported by decreased Twist1 phosphorylation and increased ubiquitination after DYRK2 overexpression. Twist1 overexpression counteracted DYRK2-induced drug sensitivity enhancement, promoting GST-π expression, EMT, migration, and proliferation. Twist1 was shown to bind to the GSTP1 promoter, enhancing its transcription. In vivo experiments confirmed DYRK2’s ability to suppress chemoresistance in breast cancer cells.

Conclusion

DYRK2 plays a pivotal role in overcoming docetaxel resistance in breast cancer cells by suppressing Twist1 expression through ubiquitination, impacting downstream signaling and cellular responses. This study provides valuable insights for developing targeted therapies to improve breast cancer treatment outcomes.