Journal of Molecular Histology最新文献

Cyclophosphamide (CP) is widely used in chemotherapy to treat various types of cancer. However, it is toxic to the liver and other organs. Rosmarinic acid (RA) possesses anti-inflammatory, antioxidant, and cytoprotective properties. This study investigated the protective effects of RA against CP-induced liver injury in mice. Mice were treated with RA (25, 50, and 100 mg/kg) for 15 days and followed by a single injection of CP on day 16th. CP injection resulted in an elevation in serum AST, ALT, and ALP, along with multiple histopathological alterations in the liver. CP also induced increased levels of MDA and NO, associated with declined GSH, SOD and CAT. RA pretreatment prevented liver injury, alleviated the enhanced levels of MDA and NO, and restored antioxidants defenses, hence avoiding the oxidative injury in the liver. Moreover, RA pretreatment attenuated NF-κB p65 and proinflammatory cytokines levels. Liver of CP-injected mice also showed a decrease in Bcl2, accompanied with elevated BAX and caspase-3 expression, an effect that RA pretreatment alleviated. In addition, pretreatment of CP-administrated mice with RA restored the Nrf2 expression in the liver. Taken together, this study suggests a potential application value of RA in preventing CP hepatotoxicity and sheds light on the possible mechanism.

Graphical abstract

Schematic diagram summarizing the hepatoprotective role of RA in a mouse model of CP hepatotoxicity. RA restored cellular redox status, suppressed inflammatory response, mitigated apoptosis, and upregulated Nrf2 pathway in the liver of CP-injected mice. CP cyclophosphamide, RA rosmarinic acid

Traditional antidiabetic treatments often carry the risk of beta-cell exhaustion, highlighting the need for therapies that promote beta-cell regeneration. This study investigates the comparative effects of Liraglutide, naltrexone/bupropion (NTX + BUP), and caloric restriction on metabolic control and beta-cell regeneration in a rat model of obese type 2 diabetes. Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + caloric restriction (50%), diabetic + NTX + BUP (4 mg/45 mg /kg/day orally), and diabetic + liraglutide (0.3 mg/kg/day, S.C). Body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 were assessed. All interventions significantly improved body weight, BMI, glycemic control, lipid profiles (except HDL), and atherogenic indices compared to the diabetic control group. NTX + BUP and caloric restriction resulted in greater weight loss compared to liraglutide. Of note, liraglutide significantly decreased β-arrestin-1 levels compared to both NTX + BUP and caloric restriction. Furthermore, liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 indicating beta-cell regeneration, while NTX + BUP showed insignificant effects. Thus we can conclude that, while NTX + BUP demonstrates efficacy in improving metabolic parameters in obese type 2 diabetic rats, it shows limitations in promoting beta-cell regeneration compared to liraglutide and caloric restriction.

Fish may have different sensitivity to pollutants present in the water. We analyzed the liver histology, and P-gp expression in six species of fish from the Doce River basin. Fish were caught at six different points in the Doce River, and liver samples were taken for histological analysis. P-gp expression was analyzed using an immunohistochemical technique. In Astyanax lacustris, Hoplias intermedius, Hypostomus affinis, Trachelyopterus striatulus and Oligosarcus acutirostris, a double arrangement of hepatocyte plates was generally observed (tubular-form), while in Deutorodon taeniatus, a single arrangement of hepatocyte plates was frequently observed (cord-like). Histological changes, such as cytoplasmic vacuolation and nuclear alteration, were observed in the livers of all species analyzed, however, the species A. lacustris (34.1%) and H. affinis (33.3%) were those with the fewest individuals with histological changes. The H. intermedius, T. striatulus, and O. acutirostris were the species that presented more than 80% of their individuals with histological changes. The A. lacustris and H. affinis were the species that showed the highest P-pg immunolabeling in the liver, while the T. striatulus and O. acutirostris had the lowest levels. These results support the hypothesis that levels of P-gp expression could respond to the resistance or sensitivity of each species to environmental pollutants.

When a lower limb is injured, the most delicate organs that are at risk of harm are the lungs. Among the flavonoids, quercetin is a significant component that is found in apples and onions in the highest proportions. Numerous biological actions, including as anti-inflammatory, antioxidant, and anti-cancer properties, have been linked to quercetin. To investigate the impact of quercetin on lung injury induced by skeletal muscle ischemia reperfusion (IR) injury. Three equal groups of twenty-four adult rats were used: control, Ischemia-reperfusion (IR) group and IR group treated with quercetin. Rats in (IR) group were exposed to ischemia by ligation of femoral artery for 2h then after removal of the clamp, reperfusion was estabilished for another 24h. IR group treated with quercetin, rats were underwent hind limb IR as described in group II then were given quercetin that was administered at a dose of 20mg/kg intraperitoneally. Measurement of cytokines in serum, MDA in tissue homogenate and VEGF in serum and tissue homogrnate in addition to mRNA expression level and detection of protein level of both sirtuin-1(SIRT1) and NF-κB were assessed at the end of experiment. Histological and immunohistochemical assessment of the lungs were also carried. IR group showed notable rise of inflammatory cytokines such as IL-1β, IL-6 and TNF-α in addition to high level of VEGF and MDA in IR group when compared to the IR group treated with quercetin. Also, gene expression and protein level of SIRT1 were reduced while NF-κB mRNA expression and protein level were significantly upregulated in IR group compared to IR group treated with quercetin. Histologically, IR group indicated marked histological alterations of lung tissue. Also, IR showed strong brownish cytoplasmic immunostaining for iNOS and abundance of Ki67-positive cells. These alterations were significantly reversed in IR group treated with quercetin. Biochemical and immunohistochemical findings of this study demonstrate that quercetin administration have protective effects against lung injury induced by lower limb IR.

Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60 min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman’s space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-β1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN.

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Pancreatic development is a complex process vital for maintaining metabolic balance, requiring intricate interactions among different cell types and signaling pathways. Fibroblast growth factor receptors 2b (FGFR2b)-ligands signaling from adjacent mesenchymal cells is crucial in initiating pancreatic development and differentiating exocrine and endocrine cells through a paracrine mechanism. However, the precise critical time window that affects pancreatic development remains unclear. To explore the roles of FGFR2b-ligands and identify the narrow window of time during which FGFR2b-ligand signaling affects pancreatic development, we used an inducible mouse model to control the expression of soluble dominant-negative FGFR2b (sFGFR2b) at various stages of pancreatic development. Our findings revealed a significant effect of FGFR2b-ligand signaling on epithelial morphology, lumen formation, and pancreatic branching during primary and secondary transition stages. Additionally, sFGFR2b expression reduced the number of Pdx1+ progenitor cells and altered the pancreatic islet structure. Furthermore, we examined the effect of mutation in FGF10, an FGFR2b ligand, on embryonic pancreatic β-cell function. FGF10 null mutant embryos exhibited reduced pancreatic size and a decrease number of islet-like structure. Although neonatal mice with haploinsufficiency for FGF10 exhibited abnormal glucose tolerance test results, indicating a potential diabetes predisposition, these abnormalities normalized with age, aligning with observations in wild type mice. Our study underscores the critical role of FGFR2b-ligand signaling in pancreatic development and postnatal islet function, offering insights into potential therapeutic targets for pancreatic disorders.

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.

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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.