Iranian Journal of Basic Medical Sciences最新文献

Objectives: This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on lactate-induced mitophagy in the hippocampus of rats with type 2 diabetes.

Materials and methods: 28 Wistar male rats were divided into four groups randomly: (i) control (Co), (ii) exercise (EX), (iii) type 2 diabetes (T2D), and (iv) type 2 diabetes + exercise (T2D + Ex). The rats in the T2D and T2D + Ex groups were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + Ex groups performed 4-10 intervals of treadmill running at 80-100% of Vmax. Serum and hippocampal levels of lactate, as well as hippocampal levels of monocarboxylate transporter2 (MCT2), sirtuin1 (SIRT1), forkhead box protein O (FOXO3), light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin, beta-amyloid (Aβ), hyperphosphorylated tau protein (TAU), Malondialdehyde (MDA), and antioxidant enzymes were measured. One-way ANOVA and Tukey post-hoc tests were used to analyze the data.

Results: Serum and hippocampal levels of lactate as well as hippocampal levels of MCT2, SIRT1, FOXO3, LC3, PINK1, Parkin, and antioxidant enzymes were higher while hippocampal levels of Aβ, TAU, and MDA were lower in T2D+EX compared to T2D group (P-value<0.05).

Conclusion: HIIT could improve mitophagy through Lactate-SIRT1-FOXO3-PINK1/Parkin signaling in the hippocampus of rats with T2D reducing the accumulation of Tau and Aβ, which may reduce the risk of memory impairments.

Objectives: Some species of Prunus L. are popularly used to treat gastric ulcers. However, the possible healing mechanisms of the anti-ulcer activity of P. spinosa, which has proven antioxidant, anti-inflammatory, and wound-healing properties, are unclear.

Materials and methods: Ethanol extracts of P. spinosa fruits were administered orally at 100 mg/kg and 200 mg/kg to Wistar albino rats, with an indomethacin-induced gastric ulcer model. The ulcerous areas on the stomach surface were examined macroscopically. Tissues were examined histopathologically and biochemically. LC-HRMS revealed the phytochemical content.

Results: TNF-α, IL-6, IL-1β, IL-8, and NF-kB levels were higher in the gastric ulcer group than in the extract groups. The VEGF values did not differ in each group. A significant difference was found between the lansoprazole group and the high-dose P. spinosa group regarding PGE2 levels. A histopathologically significant difference was observed between the healthy group and the indomethacin-applied groups in terms of neutrophilic infiltration of the gastric mucosa. Ascorbic acid (1547.521 µg/g), homoprotocatechuic acid (1268.217 µg/g), and genistein (1014.462 µg/g) were found as the main compounds in the P. spinosa extract by LC-HRMS.

Conclusion: Our results demonstrated that P. spinosa protected the gastric mucosa from inflammation and also modulated the PGE2 pathway. When considered in terms of TNF-α, IL-1β, IL-8, IL-6, PGE2, and NF-kB values, it can be concluded that it has a similar or even more positive effect than the reference substance. P. spinosa showed its effects in a dose-dependent manner.

Objectives: The current study aims to investigate the protective effect of iron oxide nanoparticles capped with curcumin (FeONPs-Cur) against motor impairment and neurochemical changes in a rat model of Parkinson's disease (PD) induced by reserpine.

Materials and methods: Rats were grouped into control, PD model induced by reserpine, and PD model treated with FeONPs-Cur (8 rats/group). The open field test was used to assess motor activity. The concentration of dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation (MDA), reduced glutathione (GSH), and nitric oxide (NO), and the activities of Na⁺,K⁺,ATPase, acetylcholinesterase (AchE), and monoamine oxidase (MAO) were determined in the midbrain and striatum. Data were analyzed by ANOVA at P-value<0.05.

Results: The PD model exhibited a decrease in motor activity. In the midbrain and striatum of the PD model, DA, NE, and 5-HT levels decreased significantly (P-value<0.05). However, an increase in MAO, NO, and MDA was observed. GSH, AchE and Na⁺,K⁺,ATPase decreased significantly in the two brain areas. FeONPs-Cur prevented the decline of dopamine and norepinephrine and reduced oxidative stress in both areas. It also prevented the increased MAO activity in the two areas and the inhibited activity of AchE and Na⁺,K⁺,ATPase in the midbrain. These changes were associated with improvements in motor activity.

Conclusion: The present data indicate that FeONPs-Cur could prevent the motor deficits induced in the PD rat model by restoring dopamine and norepinephrine in the midbrain and striatum. The antioxidant activity of FeONPs-Cur contributed to its protective effect. These effects nominate FeONPs-Cur as an antiparkinsonian candidate.

Objectives: Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells.

Materials and methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods.

Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity.

Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.

Objectives: In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds.

Materials and methods: PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds.

Results: SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing.

Conclusion: The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

Objectives: We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model.

Materials and methods: Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides TRPM gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation.

Results: It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that TRPM2,6,7,8 gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group.

Conclusion: We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing TRPM2,6,7,8 gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases.

Objectives: It is worthwhile to note that, some probiotics such as Lactobacilli and Bifidobacteria isolated from dairy products have significant therapeutic effects against cancer cells. Here, we evaluated anti-proliferation and the apoptotic effects of isolated Lactobacillus fermentum Ab.RS22 from traditional dairy products on the HeLa cervical cancer cells in vitro.

Materials and methods: The viability of treated HeLa cells with supernatant of Lactobacillus in 0.5, 0.75, 1, 1.5, and 2 ng/ml concentrations, and IC₅₀ values were detected by tetrazolium bromide. The L. fermentum Ab.RS22-induced cell death by flow cytometry was confirmed through evaluation of the expression of caspase-3, P53, PTEN, and AKT genes by quantitative reverse transcription-polymerase chain reactions (qRT-PCR).

Results: Most cytotoxicity effects of Lactobacillus on HeLa cells were detected in 2 ng/ml at 24 hr (P<0.01); also, the IC₅₀ value was measured as 1.5 ng/ml. The findings of the flow cytometry assay showed that L. fermentum Ab.RS22 in 1.5 ng/ml concentration at 24 hr increased the percentage of both apoptosis and necrosis cells. Lactobacillus-induced cell death was verified through results of Real-time PCR; where expression of caspase-3, P53, and PTEN genes was increased (P<0.01), and also expression of AKT gene (anti-apoptotic) was decreased (P<0.05).

Conclusion: Our findings showed that L. fermentum Ab.RS22 could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating PTEN/p53/Akt gene expression and activation of the caspase-3 mediated apoptosis pathway. Therefore, L. fermentum Ab.RS22 can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies.

Objectives: For safe and effective gene therapy, the ability to deliver the therapeutic nucleic acid to the target sites is crucial. In this study, lactosylated lipid phosphate calcium nanoparticles (lac-LCP) were developed for targeted delivery of pDNA to the hepatocyte cells. The lac-LCP formulation contained lactose-modified cholesterol (CHL), a ligand that binds to the asialoglycoprotein receptor (ASGR) expressed on hepatocytes, and polyethyleneimine (PEI) in the core.

Materials and methods: Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) were used to monitor the chemical modification, and the physicochemical properties of NPs were studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). To evaluate transfection efficiency, cellular uptake and GFP expression were assessed using fluorescence microscopy and flow cytometry.

Results: The results revealed that lactose-targeted particles (lac-LCP) had a significant increase in cellular uptake by hepatocytes. The inclusion of a low molecular weight PEI (1.8 KDa) with a low PEI/pDNA ratio of 1 in the core of LCP, elicited high degrees of GFP protein expression (by 5 and 6-fold), which exhibited significantly higher efficiency than PEI 1.8 KDa and Lipofectamine.

Conclusion: The successful functionalization and nuclear delivery of LCP NPs described here indicate its promise as an efficient delivery vector to hepatocyte nuclei.

Objectives: Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats.

Materials and methods: Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins.

Results: A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities.

Conclusion: Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.

Objectives: Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro.

Materials and methods: BM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively.

Results: Our findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7 µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group.

Conclusion: Our results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area.