Journal of Molecular Histology最新文献

The effects of Marein on atherosclerosis progression, particularly its impact on macrophage ferroptosis and the NRF2 pathway, were investigated. RAW264.7 macrophage cells were cultured and treated with oxidized low-density lipoprotein (ox-LDL) to model dysfunction. The effects of Marein were evaluated by treating cells with different concentrations. Ferroptosis inducers and inhibitors were also used to examine the involvement of ferroptosis. Additionally, an NRF2 pathway inhibitor was applied to investigate the underlying mechanisms of action. ApoE^−/− mice fed a high-fat diet were used to induce atherosclerosis. Mice were treated with Marein, and the effects on atherosclerotic plaques, oxidative stress, ferroptosis markers, and the NRF2 pathway were assessed using histological analyses, biochemical assays, and Western blotting. The alleviation of ox-LDL-induced macrophage ferroptosis by Marein was achieved through restoration of GPX4 and xCT expression, reduction of ROS and MDA levels, and restoration of GSH levels. Additionally, Marein activated the NRF2 vias by upregulating nuclear NRF2, NQO1, and HO-1 expression. In ApoE^−/− mice, Marein reduced atherosclerotic plaque formation and lipid deposition, improved lipid metabolism, and attenuated ferroptosis in arterial tissues by activating the NRF2 pathway. Significant therapeutic potential against atherosclerosis was exhibited by Marein through the inhibition of macrophage ferroptosis and activation of the NRF2 pathway.

Graphical abstract

Cisplatin-induced acute kidney injury (AKI) represents a severe complication of anticancer therapy with no effective clinical interventions, frequently necessitating chemotherapy dose reduction or discontinuation. Natural products have emerged as promising therapeutic candidates against cisplatin nephrotoxicity due to their multi-target mechanisms, pleiotropic effects, and low resistance potential. This study explored the therapeutic potential of hesperetin (Hes) in ameliorating mitochondrial dysfunction during AKI through coordinated induction of autophagy and suppression of the cGAS-STING pathway. We established an HK-2 cell injury model through cisplatin exposure. Following Hes intervention, cell viability was quantified via CCK-8 assays, apoptosis assessed by Annexin V-FITC/PI staining, and mitochondrial function evaluated through ATP production measurement, mitochondrial reactive oxygen species (ROS) detection and mitochondrial membrane potential analysis employing JC-1 staining. For in vivo validation, C57BL/6 mice developed AKI following single intraperitoneal cisplatin administration. Renal function parameters were determined through serum biochemistry, while renal histopathology was examined using periodic acid-Schiff (PAS) staining. Protein expression changes in mitochondrial autophagy markers and cGAS-STING pathway components were subsequently analyzed through immunofluorescence and Western blotting techniques. Autophagy modulators were employed to elucidate the precise mechanisms through which autophagy mediates Hes’s protective effects against cisplatin-induced AKI. In vitro, Hes intervention effectively reversed cisplatin-induced HK-2 cell injury and mitochondrial dysfunction while enhancing mitochondrial autophagy. Notably, the autophagy activator rapamycin alone, or co-administered with Hes produced comparable cytoprotective effects to Hes. Conversely, the autophagy inhibitor 3-methyladenine exacerbated cellular damage and partially attenuated Hes-mediated protection. In vivo studies confirmed Hes significantly ameliorated AKI through improved renal function and histopathology, concurrently reducing mitochondrial ROS levels while promoting autophagic clearance. Furthermore, Hes treatment potently suppressed activation of the cGAS-STING pathway in both experimental models. Hes ameliorates mitochondrial dysfunction in AKI by enhancing mitochondrial autophagy and inhibiting the cGAS-STING pathway.

The research was planned to assess the ameliorative effects of fenugreek (FG) against DBP-induced functional and structural changes in the kidney and adrenal glands of male rats. The forty pubertal male rats were distributed (n = 10) into four groups: (i) Control: normal feed and drinking water; (ii) DBP: 250 mg/kg/BW of DBP dissolved in corn oil; (iii) FG: 200 mg/kg /BW of fenugreek aqueous extract; and (iv) DBP + FG: 250 mg/kg/BW of DBP dissolved in corn oil + 200 mg/kg /BW of fenugreek aqueous extract. All doses were administered through oral gavage. Following a 28-day experiment, we used the cervical dislocation technique to euthanize the animals and collect blood samples and organs. The results indicated that DBP causes adverse effects on serum urea, creatinine, and uric acid; malondialdehyde level and catalase activity; average cross-sectional area (ACSA) of glomeruli, Bowman’s capsule, proximal & distal tubules of the kidney, and the mean number of glomerulosa (G), fasciculata (F), reticularis (R), and adrenal medulla (M); average width of adrenal medulla; and ACSA of the adrenal medulla of the adrenal gland. Conversely, concurrent treatment with FG substantially attenuated the kidney and adrenal glands’ toxic effects of DBP. In conclusion, FG, using its antioxidant potential, would be an important phytonutrient against the DBP-intoxicated kidney and adrenal gland.

Edible bird’s nest (EBN) has a variety of pharmacological effects, such as improving immunity, antioxidant, promoting brain development, nerve prevention, degenerative diseases, and whitening and moisturizing skin, but its role in wound healing is still unknown. In this study, full-thickness excisional wounds were made on the back of mice to establish the wound model. The mice were treated with EBN, a positive drug, and 0.9% NaCl for 14 days. At days 3, 7, and 14 post-injury, the traumatic skin and intestinal contents of mice were collected. ELISA, western blot and quantitative PCR assay were used to evaluate the expression of inflammatory factor, protein, and mRNA. The damaged skin of the mice was analyzed by histopathology. Biochemical experiment was used to evaluate the content of hydroxyproline. Gas chromatograph was used to detect mouse intestinal contents. Results showed that EBN can narrow the wound area, reduce the expression of inflammatory factors, upregulate the expression of collagen and α-SMA, improve the damaged skin structure, increase the content of SCFAs and promote wound recovery rapidly. Current findings may suggest that EBN might serve as a potential effective substance for wound healing therapy either orally or externally.

Podocyte injury from oxidative stress and pyroptosis is closely linked with diabetic kidney disease (DKD). Here, Tetrandrine (TET), derived from tetrandrine root, with anti-inflammatory and antioxidant traits, was studied for its role in podocyte oxidative stress and pyroptosis in DKD. A rat model of DKD was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ). Renal function was assessed using urinary albumin to creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN) levels. Renal pathological morphology was evaluated by hematoxylin-eosin (HE) staining and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected with commercially available kits. DCFH-DA probe was used to detect intracellular ROS levels. Western blot detected pyroptosis-related proteins (TXNIP, NLRP3, GSDMD-N, pro-caspase-1). Inflammatory factors (IL-1β and IL-18) levels were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining observed the expression and localization of GSDMD. Administration of TET alleviated renal damage in rats with DKD. In DKD rats, TET suppressed the TXNIP/NLRP3/GSDMD pathway, leading to a decrease in oxidative stress and pyroptosis within the renal tissue. In vitro, by inhibiting the TXNIP/NLRP3/GSDMD signaling pathway, TET mitigated podocyte oxidative stress and pyroptosis triggered by high glucose. Following TXNIP overexpressing, podocyte oxidative stress and pyroptosis that TET initially suppressed were subsequently reversed. Our results reveal that TET represses podocyte oxidative stress and pyroptosis through TXNIP/NLRP3/GSDMD pathway, which provides new therapeutic targets for DKD treatment.

Aspartame is a widely used non-nutritive sweetener suspected of having immunotoxic effects. This study evaluated the protective role of sesame oil against aspartame-induced toxicity in Swiss albino mice. Male Swiss albino mice were divided into four groups (n = 40): control, aspartame-treated (40 mg/kg/day), aspartame + sesame oil, and sesame oil alone. Over 60 days, aspartame (ASP) administration resulted in increased body weight, feed, and water intake, alongside a reduction in relative organ weights. Hematological analysis showed a significant decline in WBCs, eosinophils, and monocytes in the ASP group. Antioxidant activity (GSH, GPx) was significantly impaired in ASP-treated mice. Histopathological analysis revealed structural anomalies in both thymus and spleen, including capsular thickening, trabecular enlargement, white pulp degeneration, and increased apoptotic macrophages in the thymic cortex. Co-administration of sesame oil ameliorated these toxic effects, with notable improvements in organ morphology, hematological parameters, and histological integrity. Mice treated with sesame oil alone showed no significant deviations from control values. These findings suggest that sesame oil may offer protective effects against aspartame-induced immunotoxicity, possibly via its antioxidant properties.

Graphical abstract

Methodology of the experiment

Sodium valproate (VPA, valproic acid) is one of the most frequently prescribed antiepileptic drugs. However, this drug is known to cause significant oxidative damage and toxicity in various tissues and organs, including pancreatic tissue. Moringa oleifera (M) is a plant with antioxidant, anti-inflammatory, and anticancer effects, whose consumption and properties have gained prominence in recent years. This study investigates the protective effects of ethanolic extract of Moringa oleifera leaves against VPA-induced pancreatic oxidative damage in a rat model. Four experimental groups (Control, M, VPA, and VPA + M) comprising female Sprague Dawley rats were evaluated through biochemical, histological, and immunohistochemical analyses. The Moringa extract (0.3 g/kg/day) and VPA (0.5 g/kg/day) were given for 15 days. Bioactive compounds such as quercetin, kaempferol, ascorbic acid in Moringa oleifera leaf were predicted via Dr. Duke’s Phytochemical and Ethnobotanical Database. According to our results, Moringa administration increased antioxidant enzyme activities after VPA-induced damage, while significantly decreasing lipid peroxidation, advanced oxidation protein products, and other oxidant species. Histological analysis revealed the cytoprotective effect of Moringa on pancreas tissue by reducing pancreatic histological damage and decreasing PCNA-positive cells in the VPA + M group. These findings indicate the protective potential of Moringa oleifera against VPA-induced oxidative stress and pancreatic toxicity.

Graphical abstract

The aim of this study is to evaluate the therapeutic effects of Scutellaria baicalensis total flavonoids (STF) in a rat model of metabolic syndrome (MS), with particular focus on the core regulatory mechanisms contributing to metabolic homeostasis. Additionally, the modulation of peroxisome proliferator-activated receptors (PPARs) by STF was investigated to elucidate its molecular targets and associated features within the pathophysiology of MS. Metabolic syndrome was induced in Sprague Dawley rats through the administration of a high-fat/high-glucose diet combined with streptozotocin (STZ). STF was administered orally during the induction period. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and fasting insulin (FINS) were quantified. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hepatic concentrations of TC and TG were also measured. Histopathological alterations were evaluated using hematoxylin and eosin (HE) staining, while hepatic lipid accumulation was assessed through Oil Red O staining. Hepatic expression levels of PPARα and PPARγ proteins were determined via Western blot analysis. Treatment with STF at doses of 50 and 100 mg·kg⁻¹ significantly reduced serum levels of TC, TG, LDL-C, FBG, FINS, and HOMA-IR, while preventing the decline in HDL-C levels among rats with MS. STF administration also alleviated abnormal liver weight and suppressed hepatic accumulation of TC and TG, accompanied by improvements in histological features. Western blot analysis revealed upregulation of hepatic PPARα and PPARγ protein expression following STF treatment. STF demonstrated the capacity to reduce body weight and improve lipid profiles and insulin resistance in rats with MS. These effects may be associated with the regulation of PPARα and PPARγ protein expression.

Dementia, a syndrome characterized by cognitive impairment, significantly impacts the global elderly population. Given their paracrine properties, mesenchymal stem cells (MSCs) represent a promising avenue for developing novel treatments for neurodegenerative disorders. Chronic hypoxia models Alzheimer’s disease-like pathology by triggering neuroinflammation and altering key biomarkers. This study evaluated the therapeutic potential of MSCs, insulin-induced MSCs, and insulin in a rat model of Alzheimer’s disease (AD). Forty-eight rats were allocated into eight experimental groups: normoxic control, sham-surgery control, and six hypoxic intervention groups (exposed to 8% O₂). Intraventricular administration of MSCs or insulin-induced MSCs, intranasal administration of insulin, or both insulin and MSCs were used in the intervention groups. Hypoxic exposure significantly elevated pro-inflammatory cytokines (IL-1β, TNF-α) and increased expression of glial fibrillary acidic protein (GFAP) and amyloid precursor protein (APP), while decreasing levels of the neuroprotective factor Seladin-1. Administration of MSCs or Ins-MSCs effectively mitigated these hypoxia-induced alterations. Specifically, treatment with MSCs or Insulin induced-MSCs restored Seladin-1, GFAP, and APP expression levels to those observed in normoxic controls. Furthermore, these treatments attenuated the hypoxia-associated increase in Nissl body pathology within the hippocampal pyramidal cell layer. The most pronounced therapeutic benefits were observed following combined intranasal insulin and intraventricular MSC administration. Consequently, the combinatorial approach of MSCs and insulin warrants further investigation as a potential therapeutic strategy for Alzheimer’s disease. Combining intranasal insulin with insulin-induced MSCs may offer a strategy to target multiple AD pathology pathways.

Acute lung injury (ALI) is a severe inflammatory condition marked by alveolar damage and cytokine dysregulation. Exosomes, as carriers of bioactive molecules, regulate immune responses through intercellular communication. However, the cytokine profile of serum-derived exosomes during ALI remains unclear, and their functional role in modulating inflammation is poorly defined. A murine model of ALI was established via intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg), and samples were collected at 2 h and 8 h post-injection. Lung injury severity was assessed using hematoxylin and eosin staining and lung W/D weight ratio. Serum-derived exosomes were isolated using the ExoQuick precipitation method and characterized by transmission electron microscopy and western blotting. Cytokine and chemokine profiles were quantified using a 32-plex Luminex xMAP assay. Exosome-mediated immune modulation was evaluated through a scratch migration assay in RAW264.7 macrophages. LPS treatment led to increased pulmonary edema and histopathological damage, which were more pronounced at 8 h. A total of 14 cytokines in the serum, including IL-6, TNF-α, and MCP-1, were significantly elevated at either 2–8 h compared to the control group. However, chemokines such as IP-10, G-CSF, and MIP-1β were markedly upregulated in serum-derived exosomes from ALI mice. Functional assays demonstrated that exosomes from ALI mice significantly enhanced the migratory capacity of RAW264.7 macrophages. This study demonstrates that serum-derived exosomes from ALI mice are enriched in specific chemokines and promote macrophage migration in vitro. These findings suggest that exosomes may participate in inflammatory cell recruitment during ALI and hold potential as biomarkers or modulators in the inflammatory response.