Journal of Molecular Histology最新文献

Nowadays, Manganese (Mn) become an unavoidable ingredient in agriculture, medical and manufacturing industries. Manganese deficiency is rare, and even though recurrent exposure to manganese is inevitable for humans, concerns have been voiced regarding public health hazards. This research was designed to evaluate the manganese toxicity and potential protective effects of turmeric in Swiss albino male mice. Eight-week albino mice (33 ± 01 g) were randomized equally into seven groups (n = 10), as control (untreated), VC-I (received 0.1 ml of saline water), Mn-I, Mn-II & Mn-III administrated manganese (5 mg/kg, 10 mg/kg & 20 mg/kg body-weight (B.W.) respectively), Mn + Tu (co-administrated with 20 mg/kg Mn &100 mg/kg B. W turmeric), VC-II (received 0.1 ml of olive oil), orally for four weeks consecutively. Before administrations, ferric reducing antioxidant power (FRAP), total phenolic content (TPC) and gass chromatography-mass spectroscopy (GC- MS) assays were performed to assess the antioxidant capacity of turmeric. After 28 days of dosing, mice were acclimatized for 10 days, then sacrificed and recovered samples (tissues & blood). Morphological observations showed changes in color, shape disruption, dilation and flattening of organs as compared to controls. Morphometric studies showed that the average body weight, organs weight and size of Mn intoxicated mice reduced remarkably (P ≤ 0.05) as compared to control groups. Sideways Mn + Tu group showed non-significant change in both parameters. Hematological (CBC) and biochemical markers, liver function test & renal function test (LFT & RFT) showed significant differences in manganese groups against controls. Histopathological findings of both tissues (liver & kidney) showed multiple anatomic alterations in Mn exposed as compared to other groups. While the aforementioned deviations were less obvious in Mn + Tu administrated group. Manganese also decreased glutathione-s-transferase, superoxide dismutase, reduced glutathione contents and increased lipid peroxidation as compared to control groups. It is concluded by the abovementioned findings that turmeric showed remedial efficacy against Mn-instigated histomorphometric, biochemical and enzymatic alterations in mice.

Placenta Accreta Spectrum (PAS) is a serious placental abnormality assosiated with significant maternal death during pregnancy. Due to its invasive characteristics resembling tumor growth, PAS is often associated with tumor-related proteins. While DNA methylation is known to regulate genes involved in development, its potential role in the development of PAS remains unclear. The aim of our study was to investigate the impact of PAS on DNA methylation and DNA methyltransferases (DNMTs). The groups were categorized into three groups: vaginal birth, cesarean delivery, and cesarean delivery with PAS. To measure DNMT protein levels in placental tissue, we employed immunohistochemistry (IHC) and Western blot (WB) techniques. Global DNA methylation levels were assessed using 5-methylcytosine staining. We found that DNMT1, DNMT3A and DNMT3L levels were significantly increased in the placentas of PAS group compared to control counterparts in both WB and IHC analysis. Compatible with DNMTs expressions, global DNA methylation levels were found to be significantly higher in placentas from women with PAS compared to controls. Our results suggest that significant alterations in DNMTs expressions and global DNA methylation within placentas may contribute to the development of Placenta Accreta Spectrum (PAS). To elucidate the precise molecular mechanisms underlying these changes and their role in PAS pathogenesis, further research required.

The aim of this study was to examine the relationship between the renin-angiotensin system (RAS) and histological and biochemical changes occurring in the kidney tissue of male rats exposed to a 0.9 GHz electromagnetic field (EMF). Twelve male rats aged 21 days were randomly assigned to control (C-Gr) and EMF (EMF-Gr) groups. No procedure was performed on C-Gr, while the EMF-Gr rats were exposed to a 0.9 GHz EMF on postnatal days 21–45 (one hour a day for 25 days). Tissues were removed at the end of the experiment and evaluated using biochemical, and histopathological methods. Increased kidney tissue volume and weight and total body weight were determined in the group exposed to EMF. Lipid peroxidation, glutathione, catalase, and superoxide dismutase also increased in the kidney tissue of the EMF-Gr rats. Histopathological evaluation revealed cortical/medullary bleeding/obstruction and widespread fibrosis, dilatation, vacuolization, and degeneration in distal and proximal tubules, decreased and atypical parietal cells, and degeneration in epithelial cells. Additionally, dilated and degenerated glomeruli in the Malpighian body, Bowman’s membrane degeneration and degeneration in the vascular pole, podocyte, pedicel and mesangial cells were also observed. As a result of exposure to EMF, oxidative stress, tissue volume and weight increased, and histopathological changes caused the formation of a pathway that triggers RAS in kidney tissues. In conclusion, long-term exposure to 0.9 GHz EMF can activate the renin-angiotensin system in the rat kidney, and we think that such activation may be associated with structural, histopathological, and biochemical changes occurring in renal tissue.

We aimed to investigate the protective effects of low dose cyclosporin A (CsA) on ischemia–reperfusion (IR) injury in rat the kidney and on the apoptotic and necroptotic mechanisms involved. 1. Control group (received a single intraperitoneal (i.p.) dose of 1 ml sterile saline 15 min before the surgical procedure), 2. IR group (was subjected to 30 min of bilateral kidney ischemia followed by 90 min of reperfusion; and received a single i.p. dose of 1 ml sterile saline 15 min before the IR procedure, 3. IR + CsA group (received a single i.p. dose of 3 mg/kg CsA 15 min before the IR procedure. Renal functions (renal perfusion pressures, and serum urea-creatinine levels), kidney histological scores, MDA levels, and TNF-α, caspase-3, RIP1, RIP3, MLKL, CaMKII and CypD protein expressions were also measured. Renal perfusion pressures (PP), serum urea and creatinine levels, renal tissue MDA levels, and the protein expression levels of TNF-α, caspase-3, RIP1, RIP3, MLKL, CAMKII and CypD were significantly increased in the IR group compared to the control group (p < 0.05), Additionally, there were significant decreases in all the parameters in the IR + CsA group compared to those in the IR group (p < 0.05). Furthermore, histopathological analyses revealed significantly higher kidney injury scores in the IR group compared to the control group, and low dose CsA treatment improved the injury. A single low dose of CsA injection 15 min before IR, demonstrated a protective effect on bilateral renal IR injury and a reduction in apoptotic and necroptopic markers which is resulted in improvement of renal functions.

Non-alcoholic fatty liver disease is a prevalent liver condition that can progress to fibrosis and cirrhosis. It also poses a risk for hepatocellular carcinoma, underscoring the importance of identifying effective treatments. N-acetylcysteine, an inhibitor of glutathione depletion, shows promise in modulating intracellular glutathione biosynthesis and combating oxidative stress, making it a potentially beneficial therapy for liver fibrosis in non-alcoholic fatty liver disease. This study assesses the impact of N-acetylcysteine on HepG2 cells which were induced into fatty liver cells was evaluated. HepG2 cells were cultured in DMEM and seeded onto six-well plates at a density of 5 × 10⁵ cells. Following a 24-h incubation period, the cells were exposed to a medium inducing fat accumulation. Subsequently, the cells were treated with varying concentrations of N-acetylcysteine for 48 h. Some plates were utilized for Real-Time-PCR tests, while others underwent Oil Red staining. The findings indicated a significant increase in the expression of fatty acid β-oxidation genes in the group treated with 10mM N-acetylcysteine (p < 0.05), along with reduced expression of lipogenesis-related genes (p < 0.05) in N-acetylcysteine-treated groups. Analysis of apoptotic gene expression revealed decreased BAX expression but increased BCL2 expression in the N-acetylcysteine-treated groups. Oil Red staining demonstrated a dose-dependent reduction in lipid droplets compared to the control group. This study's results suggest that N-acetylcysteine has the potential to decrease lipid droplets and modulate lipid metabolism effectively.

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We focused on investigation of E. coli infection influence on the turnover and apoptosis of intestinal mucosa. We have verified changes in proliferation and apoptosis in epithelial lining as well as in lamina propria of jejunum and colon of germ-free (GF) piglets as healthy control group and GF piglets in which at 5th day their gut was colonized with E. coli bacteria (ECK group). According to our results we detected significant increase in proliferation of the epithelial cells only in the jejunum of the ECK group, indicating a higher sensitivity to colonization with E. coli. Significant changes in the TUNEL assay and immunohistochemistry of other studied markers (TNF-α, Caspase-3 and HSP-70) were noted only in the lamina propria mucosae of both intestinal segments in the ECK group. In conclusion, we found that the commensal gut microbiota plays a role in regulation of the turnover rate in the epithelial lining, but also in the cells in the lamina propria mucosae in both intestinal segments, and that the host response is dependent on the colonising bacteria.

Caloric Restriction (CR) and cinnamon promote several benefits, including the modulation of lipid metabolism and body fat mass. We hypothesize that cinnamon may act as a mimetic of restriction or enhance the effects of caloric restriction on adipose tissue. Adult male Wistar rats were divided into Control (CT, n = 8) and Cinnamon (CIN, n = 7), with free access to standard chow; Calorie Restriction (CR, n = 8) and Calorie Restriction with Cinnamon (CIN-CR, n = 7), subjected to a 30% reduction in food intake compared to the average consumption of CT rats. Both CIN groups received 50 mg cinnamon powder (Cinnamomun verum) per kg body mass, by gavage, over 6 weeks. Cinnamon treatment did not alter food intake under either ad libitum or caloric restriction conditions. The CR and CIN-CR groups exhibit lower body mass. Basal glycemia, lipid profile, and triglyceride-glycemic index were similar between groups. The combination of both interventions induced lower visceral white adipose tissue (WAT) mass, and smaller adipocyte diameter in the visceral and subcutaneous WAT compartments, accompanied by reduced expression of genes related to lipid metabolism (Acaca, Fasn, Cd36, Srebf1c), suggesting decreased lipid synthesis. Histological analyses identified a browning phenotype in the CR, CIN, and CIN-CR groups, positive for UCP1 immunostaining. The CR and CIN-CR groups showed lower Atg7 expression, and CIN-CR animals expressed increased levels of Lamp2, suggesting modulation of autophagy. Brown adipose tissue mass and lipid content were not influenced by any intervention. These findings suggest that cinnamon may enhance the effects of caloric restriction in promoting adipocyte metabolic health.

Targeting ferroptosis pathway becomes a new solution for cisplatin (DDP) resistance in lung adenocarcinoma (LUAD), and further research is required to explore the molecular mechanisms underlying ferroptosis and DDP resistance, providing biotargets for LUAD treatment. In this study, DDP-sensitive A549 cells and DDP-resistant A549/DDP cells were treated with DDP, DDP sensitivity was detected through using CCK-8 method and colony formation assay, ferroptosis-related markers were determined through commercial kits, and the molecular regulatory mechanism was analyzed through methylated RNA immunoprecipitation, RNA pull-down, dual luciferase assay, quantitative real-time polymerase chain reaction and western blotting assay. Results showed that compared to A549 cells, FENDRR was downregulated in A549/DDP cells, and FENDRR increased iron content, labile iron pool, lipid peroxidation, LDH release and ROS levels, accelerating ferroptosis to promote DDP sensitivity. Interestingly, we found that METTL3-mediated N6-methyladenosine modification YTHDF2 dependently resulted in FENDRR degradation, and FENDRR overexpression elevated TFRC expression through sponging miR-761. Mechanistically, METTL3 inhibited the FENDRR/TFRC axis to alleviate DDP-induced ferroptosis, promoting DDP resistance in LUAD cells. Collectively, our findings identify a novel molecular regulatory mechanism in DDP resistance of LUAD, and suggest that FENDRR might be an attractive target for addressing DDP resistance.

Ischemic-anoxic injury plays an important role in the pathophysiology of diabetes retinopathy, optic neuropathy, even glaucoma and other ocular diseases. It may ultimately cause damage to neuronal death like retinal ganglion cells (RGCs) and subsequent visual loss. RGCs are essential elements of the retina and optic nerve that are crucial to visual formation. Ischemic-anoxic injury, inflammation, and oxidative stress are vital causes of RGC death. Thus, neuroprotection is essential for the treatment of these ocular diseases. Recent studies have shown the neuroprotective property of apelin-13 in many disease models. In this study, we isolated RGCs and found that apelin-13 promoted the viability of RGCs and increased the phosphorylation of Protein kinase B (PKB, Akt) in an in vitro oxygen-glucose deprivation model. Moreover, apelin-13 increased the expressions of glucose-6-phosphate dehydrogenase (G6PD) and nicotinamide adenine dinucleotide phosphate (NADPH) and reduced the level of reactive oxygen species (ROS). And, we also found that apelin-13 could promote the expressions of glucose transporter-1 (GLUT1) and adenosine triphosphate (ATP). These results indicated that apelin-13 could delay or stop RGC death, which might be as potential therapeutic targets for treatment of diseases mediated by ischemic-anoxic damage like diabetes retinopathy, optic neuropathy, even glaucoma.

Mercury is a highly toxic metal that causes a variety of neurological disorders through oxidative stress. Allium sativum, a cooking spice in diverse cultures around the world, has a long history of medicinal use due to its rich antioxidant constituents. This study was designed to evaluate the protective activity of aqueous Allium sativum bulb extract (ASBE) on mercuric chloride (HgCl₂)-induced neurotoxicity. Forty Wistar rats were randomly divided into five groups namely I (control), II (HgCl₂; 4 mg/kg), III (250 mg/kg of ASBE and 4 mg/kg of HgCl₂), IV (500 mg/kg of ASBE and 4 mg/kg of HgCl₂) and V (500 mg/kg of Vitamin E and 4 mg/kg of HgCl₂). At the end of the administration, neurobehavioural, antioxidant enzymes, lipid peroxidation and apoptotic activities as well as the histology of the cerebrum, cerebellum and hippocampus were assessed. Body and brain weights, locomotion, exploration, cognition, memory and antioxidant enzymes were significantly impaired (p < 0.05) in HgCl₂-exposed rats following comparison to control. Lipid peroxidation, mercury concentration and caspase-3 activity were significantly upregulated (p < 0.05) in HgCl₂-exposed rats following comparison to control. In addition, significant alterations to the histology of the cerebrum, cerebellum and hippocampus were observed in the HgCl₂-exposed rats. Conversely, the adverse effects induced by HgCl₂ were significantly attenuated (p < 0.05) following ASBE and Vitamin E pretreatment. Taken together, these results suggest that ABSE exerts its neuroprotective activity through its potent antioxidant and anti-apoptotic properties.