Iranian Journal of Basic Medical Sciences最新文献

Objectives: Post-traumatic stress disorder (PTSD) is a crippling mental illness that commonly co-occurs with anxiety and depression. Recent studies have established a link between neuroinflammation and the development of PTSD. Studies have revealed that tert-butylhydroquinone (tBHQ) exhibits anti-inflammatory effects. This research investigated the impact of tBHQ on the amelioration of PTSD-induced depression- and anxiety-like behaviors with respect to amygdala and hippocampal MAO-A, MAO-B, IL-6, IL-10, and glucocorticoid receptor in rats.

Materials and methods: PTSD was triggered through the use of Single Prolonged Stress (SPS). The Elevated Plus Maze (EPM) and Forced Swim Test (FST) were employed to evaluate anxiety and depression, respectively. Protein assessment utilized Western blot assay for IL-6, IL-10, and the glucocorticoid receptor, in addition to enzyme-linked immunosorbent assay (ELISA) for MAO-A and MAO-B.

Results: The data demonstrated that treatment with tBHQ ameliorates the depression- and anxiety-like behaviors in rats with PTSD. The ELISA findings indicated a rise in both MAO-A and B proteins in the hippocampus and amygdala due to PTSD, which was counteracted by a subthreshold amount of tBHQ. Additionally, the Western blot assay techniques revealed that PTSD led to an elevation in IL-6 levels, a pro-inflammatory cytokine, and a reduction in IL-10 levels, along with a decrease in glucocorticoid receptor expression in both brain regions, which was also counteracted by a subthreshold amount of tBHQ.

Conclusion: These findings suggested that the beneficial effect of tBHQ on anxiety and depression induced by PTSD through hippocampal and amygdala MAO-A, MAO-B, IL-6, and IL-10, and glucocorticoid receptor.

Objectives: Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18β-glycyrrhetinic acid-loaded silver nanoparticles (18β-GA-AgNPs) on brain injury in diabetic rats.

Materials and methods: Fifty-six male Wistar rats were divided into eight groups: Sham, 18β-GA, AgNPs, 18β-GA-AgNPs, DM, DM+18β-GA, DM+AgNPs, and DM+18β-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-α, and IL-1β) were evaluated.

Results: The DM group exhibited significant increases in MDA, TNF-α, IL-1β, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18β-GA-AgNPs markedly reduced MDA, TNF-α, IL-1β, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18β-GA-AgNPs substantially attenuated these changes. Overall, 18β-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses.

Conclusion: These findings suggest that 18β-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.

Objectives: This study compared the effects of daidzein (DZD) and 17-β-estradiol (E2) on uterine histopathology, expression of endometrial cancer-related genes, and anti-oxidant status in ovariectomized (OVX) rats.

Materials and methods: Thirty rats were divided into five groups (n=6): Sham, OVX, OVX+E2 (10 μg/kg/day), OVX+DZD (20 mg/kg/day), and DZD-only. After 50 days of treatment, uterine tissues were analyzed for histopathological changes, mRNA expression of ERα, ERβ, PTEN, EZH2, and Ki67, and oxidative stress markers (TAC, SOD, CAT, and MDA).

Results: Ovariectomy induced endometrial atrophy, significantly downregulated the expression of all target genes (ERα, ERβ, PTEN, EZH2, and Ki67), decreased SOD and CAT activity and TAC level, and increased MDA. E2 treatment reversed these changes but induced hyperplastic effects. DZD administration significantly increased CAT and SOD activity and elevated ERβ and Ki67 expression compared with the OVX group. Crucially, DZD prevented uterine atrophy without inducing hyperplasia.

Conclusion: DZD demonstrated a potentially beneficial effect by improving uterine anti-oxidant capacity and preventing atrophy, but without the hyperplastic changes associated with estradiol. These findings suggest that DZD may be a safer alternative for managing hypoestrogenic conditions, warranting further investigation.

Objectives: We aimed to demonstrate that electroacupuncture (EA) alleviates vascular cognitive impairment (VCI) induced by cerebral ischemia in rats by modulating oxygen homeostasis and energy metabolism through the HIF-1α/p53/NGB signaling pathway.

Materials and methods: Male Sprague‒Dawley rats underwent bilateral common carotid artery occlusion (BCCAO) to establish a VCI model. EA was administered once daily for 30 min over two weeks. Thirty minutes prior to EA, the hypoxia-inducible factor-1α (HIF-1α) inhibitor 2-methoxyestradiol (2ME2) was injected intraperitoneally. Cognitive function following BCCAO and EA was assessed using the Morris water maze test. Western blotting was performed to analyze the protein expression of HIF-1α, heme oxygenase-1 (HO-1), and neuroglobin (NGB). In addition, p53 mRNA expression was quantified by real-time PCR, and energy metabolite levels were determined using ELISA.

Results: EA significantly improved learning and memory in VCI model rats. Histopathological analysis revealed that EA attenuated neuronal apoptosis and ultrastructural damage in the cortex and hippocampus. EA upregulated HIF-1α, NGB, and HO-1 expression but downregulated p53 mRNA expression in these regions. Moreover, EA treatment reversed the expression of glucose, lactic acid, and acetone aldehyde. Notably, the beneficial effects of EA on cerebral energy metabolism were abolished by 2ME2 in VCI model rats.

Conclusion: EA alleviated BCCAO-induced neurological impairment and cognitive dysfunction in rats, possibly by reducing hypoxic stress and enhancing energy metabolism in the cortex and hippocampus, potentially through modulation of the HIF-1α/p53/NGB signaling pathway.

Inflammation is a natural immune response triggered by multiple factors such as pathogens, damaged cells, and toxic substances. These triggers can lead to both acute and chronic inflammatory reactions in different tissues, contributing to the development of several inflammatory disorders, including cardiovascular diseases, neuroinflammation, arthritis, and cancer. Both infectious and non-infectious stimuli activate immune cells and initiate critical inflammatory signaling pathways. Raspberries (Rubus idaeus) are abundant in bioactive constituents, especially polyphenols like anthocyanins, flavanols, phenolic acids, urolithin A, and ellagic acid, all of which possess notable anti-inflammatory and anti-oxidant activities. These compounds have been shown to regulate various inflammatory signaling pathways, including MAPKs, NF-κB, PI3K/Akt, AP-1, IL-6, TNF-α, IL-1β, CD40, nitric oxide (NO), caspases, and the JAK-STAT pathway. Studies have emphasized their broad pharmacological effects, such as anti-inflammatory, anti-oxidant, hepatoprotective, cardioprotective, gastroprotective, anti-obesity, skin depigmenting, and bone-regenerative properties. This review emphasizes mechanistic insights into raspberries' protective roles in managing inflammatory-related disorders, particularly cardiovascular diseases, neurodegenerative conditions, and cancer, and highlights their therapeutic potential.

Objectives: Androgen and TGF-β1/Smad signaling pathways play important roles in epithelial-mesenchymal transition (EMT), fibrosis, and the development of benign prostatic hyperplasia (BPH). Cinnamophilin is extracted from Cinnamomum philippinense. The anti-proliferative and anti-fibrosis effects of cinnamophilin on the prostate remain unclear. This study aimed to investigate the therapeutic effects and molecular mechanism of action of cinnamophilin on prostate growth in testosterone propionate (TP)-treated mice.

Materials and methods: The study was conducted both in vivo and in vitro. TP was injected subcutaneously to induce prostate enlargement and growth. Cinnamophilin (40 mg/kg) was orally administered once a day in TP (7.5 mg/ kg)-treated mice for 28 days. The morphological characteristics and fibrosis of the prostate were examined by H&E (Hematoxylin and Eosin) and Masson's trichrome stain. Protein expression was determined by Western blot. BPH-1 and WPMY-1 cells were treated with different concentrations of cinnamophilin (1-100 μM).

Results: Cinnamophilin (40 mg/kg) significantly reduced prostate weight and prostate index in animal models. Cinnamophilin inhibited the protein expression of 5α-reductase type II and prostate-specific antigen (PSA) in TP-treated mice. Cinnamophilin reversed morphological changes, EMT, and fibrosis in TP-treated mice. Cinnamophilin increased E-cadherin but decreased N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, p-Smad2/3, collagen I, collagen III, and collagen IV protein expressions. The expression of Smad2/3 was not significantly different among these groups. Cinnamophilin (100 μM) inhibited proliferation at 48 hr in BPH-1 and WPMY-1 cells.

Conclusion: These findings suggest that cinnamophilin inhibits prostate growth and mitigates EMT and fibrosis by regulating TGFβ/Smad signaling pathways.

Objectives: To investigate the therapeutic effect and protective mechanism of resveratrol (Res) on mice with lupus nephritis (LN).

Materials and methods: We used Res to intervene in MRL/lpr mice and employed biochemical techniques to assess kidney function, inflammation levels, and oxidative stress. We also evaluated changes in immune function and used immunohistochemistry to assess Sirt1 protein and mRNA expression.

Results: Res improved the kidney function, alleviated proteinuria, and renal pathological damage in MRL/lpr mice. Res also ameliorated spleen weight and spleen index, and inhibited urinary protein/creatinine levels. Moreover, Res inhibited the expression of circulating inflammatory factors, oxidative stress levels, and kidney cell apoptosis in MRL/lpr mice. Res effectively promoted Sirt1 protein and mRNA expression in the kidneys of MRL/lpr mice.

Conclusion: Res has a protective effect on MRL/lpr mice, and its mechanism may involve activation of the Sirt1 signaling pathway.

Objectives: This study aimed to determine the effect of 8-week high-intensity interval training (HIIT) on oxidative stress and apoptosis in the hippocampus of male rats with type 2 diabetes (T2D). The study focused on examining the role of proliferator-activated receptor gamma co-activator 1α (PGC1α)/Kelch-like ECH-associated protein Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

Materials and methods: Twenty-eight 8-week-old Wistar rats were randomly assigned to one of four groups (n=7): control (Con), type 2 diabetes (T2D), exercise (Ex), and exercise + type 2 diabetes (Ex+T2D). The Ex and Ex+T2D groups completed an 8-week exercise program consisting of 80-100% Vmax and 4-10 intervals. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to assess insulin resistance. The levels of Bcl2, BAX, musculoaponeurotic fibrosarcoma (Maf), Nrf2, Keap1, and PGC1α in the hippocampus were assessed using the western blot method. Additionally, the levels of antioxidant enzymes in the hippocampus were measured using ELISA.

Results: The findings indicated that the T2D group had lower levels of antioxidant enzymes, Maf, Bcl2, PGC1α, and Nrf2, and higher levels of BAX and Keap1 in the hippocampus. Conversely, the HIIT group exhibited increased levels of antioxidant enzymes, Maf, Bcl2, Nrf2, and PGC1α, along with decreased levels of BAX and Keap1 in the hippocampus.

Conclusion: The study demonstrated that 8-week HIIT was effective in reducing hippocampal apoptosis and oxidative stress induced by T2D by activating the PGC1α-Keap1-Nrf2 signaling pathway. The metabolic changes induced by exercise may lead to an increase in PGC1 expression, which is the primary stimulator of the Keap1-Nrf2 signaling pathway.

Objectives: Brain ischemia remains a leading cause of death and neurological disability worldwide, with current treatments limited by narrow therapeutic windows and insufficient neuroprotection. Kojic acid (KA), a natural compound with demonstrated anti-oxidant and anti-inflammatory properties, has not been thoroughly evaluated in cerebral ischemia. Its limited brain bioavailability may have hindered the identification of its potential therapeutic effects. This study aimed to investigate the effects of both KA and its nanostructured lipid carriers (nKA) in a rat bilateral common carotid artery occlusion (BCCAO) model.

Materials and methods: Adult male rats were randomly allocated to seven groups: sham, BCCAO, KA (1 and 10 mg/kg), nKA (1 and 10 mg/kg), and vehicle. Following BCCAO surgery, animals received intraperitoneal treatments for seven days. Behavioral assessments included the modified neurological severity score and grid walk test. Brain and serum samples were collected to evaluate histopathology, gene expression, oxidative stress markers, inflammatory cytokines, and pharmacokinetic parameters.

Results: Histological analysis indicated reduced neuronal loss in both KA and nKA-treated groups. Notably, only nKA significantly improved behavioral outcomes. Both treatments reduced the pro-apoptotic gene BAX and the pro-inflammatory cytokine TNF-α, while nKA additionally increased Nrf2 and reduced IL-6 expression. Both formulations mitigated oxidative stress by decreasing reactive oxygen species, protein carbonylation, and malondialdehyde levels, while also increasing glutathione concentrations.

Conclusion: Nano-kojic acid showed better neurobehavioral improvements, while both forms reduced oxidative stress and inflammation, indicating neuroprotective potential. Further studies are needed to clarify mechanisms and long-term safety.

Objectives: This study aims to design and fabricate innovative polymer-ceramic-metal scaffolds for bone tissue engineering, utilizing 3D printing and freeze-drying techniques to enhance bone repair.

Materials and methods: Stainless steel scaffolds were produced via selective laser melting (SLM) and coated with varying weight percentages (0, 5, 10, 15) of polyvinylpyrrolidone (PVP), carboxymethyl chitosan (CMC), and forsterite using freeze-drying. The scaffolds were characterized through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to assess functional groups, phase purity, porosity, and pore size. Biological assessments included bioactivity, ion emission tests (ICP-AES), and wettability evaluations. Artificial neural networks (ANN) were employed to predict mechanical and biological properties.

Results: The analysis revealed that scaffolds with 15% forsterite exhibited optimal mechanical and biological performance, enhancing the scaffold's potential for clinical applications in bone repair.

Conclusion: This study introduces a novel scaffold design that significantly improves bone tissue regeneration processes. The integration of advanced materials and predictive modeling through ANN paves the way for future research in the field of bone tissue engineering.