Iranian Journal of Basic Medical Sciences最新文献

Objectives: The key ingredient in Nigella sativa, thymoquinone (TQ), has several beneficial (antioxidant and anti-inflammatory) properties. This study aimed to investigate the vitamin D metabolism in insulin resistance and the effects of TQ.

Materials and methods: Male Wistar albino rats were used. TQ was administered as a therapy, and prophylaxis and treatment with metformin were set up for the groups in which insulin resistance had been developed. The gene groups implicated in vitamin D metabolism underwent RT-PCR gene expression analysis and western blot protein analysis.

Results: The analysis shows that the application of TQ reduced HOMA-IR (a sign of insulin resistance). The expression of the VDR gene may be responsible for TQ's effect on treating insulin resistance.

Conclusion: It has been demonstrated that using TQ for therapeutic and preventive reasons is advantageous for improving insulin resistance metrics. Serum vitamin D level was also found to be impacted, which was found to be directly related to the expression of several genes involved in vitamin D metabolism in the liver. However, some of these genes were found to be relatively ineffective in the present study.

Objectives: Increased nuclear factor (NF-kβ) and carbonyl stress due to decreased glyoxalase-1 activity (Glo-I) contribute significantly to insulin resistance and vascular complications. Therefore, we aimed to study the impact of the combination of thiamine and niacin on hepatic NF-kβ signaling, metabolic profile, and Glo-I activity in male rats with type-2 diabetes (T2DM).

Materials and methods: Forty male rats were divided equally into five groups: control, diabetic, diabetic treated with thiamine (180 mg/l in drinking water), niacin (180 mg/l), and a combination of both. The treated groups received the treatments daily in drinking water for two months. T2DM was induced using a combination of nicotinamide and alloxan. Metabolic profile and renal dysfunction parameters were assessed. Additionally, various glycation, oxidative stress, and inflammatory markers were measured.

Results: The treated group with both vitamins showed the lowest blood sugar and insulin resistance indices, cardiovascular indices, renal dysfunction parameters, hepatic NF-kβ expression, oxidative stress, inflammatory and glycation markers, and the highest anti-oxidant and anti-glycation markers, β cell activity, and insulin sensitivity. Thiamine exhibited more anti-inflammatory activity than niacin in diabetic rats, while niacin demonstrated stronger anti-oxidant activity (P<0.001).

Conclusion: The combined use of vitamins had a more beneficial impact on macro and microvascular complications in diabetes than each alone, attributed to their higher anti-oxidant, anti-inflammatory, and anti-glycation characteristics. The vitamins also had a more corrective effect on glucose-lipid metabolism, insulin sensitivity, and renal function through a stronger lowering effect on hepatic NF-kβ expression.

Objectives: Thymoquinone (TQ) is the main bioactive component of Nigella sativa L. and has anti-oxidant, anti-hepatotoxic, anti-cancer, anti-hypertensive, hypoglycemic, anti-inflammatory, and lipid-lowering properties. In this study, we investigated the protective properties of TQ on the cytochrome P450 enzyme system, peroxisome proliferator-activated receptors, and gene expressions involved in apoptosis, which are disrupted by valproic acid (VPA).

Materials and methods: The rats were put into control, VPA, and VPA+TQ groups. The weight of the body and liver were recorded. Liver tissue samples were evaluated for gene expressions (Bcl-2, p53, CYP2B1, CYP2B2, PPARα, and PPARγ), histopatology, and immunohistochemistry (CAS-3 and NOX-4). Additionally, serum was used to measure liver function parameters (ALT, AST, LDH, LDL, and HDL).

Results: The VPA+TQ group had significantly lower expression of p53 (P<0.05), CYP2B1 (P<0.05), CYP2B2 (P<0.05), PPARα (P<0.05), and PPARγ (P<0.05) genes compared to the VPA groups, while Bcl-2 (P<0.05) gene expression increased. TQ decreased CAS-3 and NOX-4 levels. Also, TQ reduced ALT (P<0.05), AST (P<0.05), LDL (P<0.01), total bilirubin (P<0.05), and LDH (P<0.05) enzyme activity while increasing HDL (P<0.0001). TQ treatment improved fresh liver weight considerably (P<0.0001).

Conclusion: TQ substantially protects liver tissue by modifying gene expression, lowering oxidative stress, and increasing liver function. It significantly counteracts VPA's toxic effects, demonstrating its promise as a hepatoprotective agent in avoiding liver damage.

Objectives: The relationship between exercise and mitochondrial function is unclear. This study investigated the relationship between voluntary exercise and mitochondrial dynamics in ischemic stroke model mice.

Materials and methods: This experiment used 54 male C57BL/6 J mice to assess the therapeutic effect of voluntary exercise on ischemic stroke in a middle cerebral artery occlusion (MCAO) model. Body weight and the number of wheel turns were recorded to monitor the physiological condition of the mice. The degree of brain injury was evaluated via hematoxylin and eosin (H&E) staining and measurement of the cerebral infarction volume. Western blotting and immunofluorescence were used to measure dynein-1-like protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), and optic atrophy type 1 (OPA1) levels to assess mitochondrial dynamics and analyze the degree of mitochondrial apoptosis by measuring cytochrome c (CYT-C), cleaved caspase-3, and caspase-3 expression.

Results: Voluntary exercise positively affected the behavioral score and infarct volume. H&E staining revealed that voluntary exercise reversed MCAO-induced cortical damage. Furthermore, voluntary exercise improved mitochondrial dynamics by inhibiting DRP1 and FIS1 expression and inducing OPA1 expression. Additionally, the mitochondrial apoptosis pathway was inhibited by down-regulating the expression of CYT-C, cleaved caspase-3, and caspase-3.

Conclusion: Voluntary exercise exerts a significant neuroprotective effect against MCAO-induced brain injury by regulating mitochondrial dynamics and the mitochondrial apoptotic pathway.

Objectives: Stroke is an acute cerebrovascular disease with a high incidence, high disability rate, and high mortality. Stroke damages the integrity of the blood-brain barrier. Immune cells are concerned with multiple facets of ischemic stroke; peripheral immune cells, including neutrophils, T cells, B cells, and macrophages, infiltrate the ischemic brain tissue and are essential in regulating the progression of ischemic brain damage. The current study investigated the effects of estrogen and progesterone (PROG) hormones (E/P) on the expression of CD4⁺ and Gene expression of IL-1β (interleukin-1β) in MCAO rat models.

Materials and methods: Stroke was induced in male adult rats by transient middle cerebral artery occlusion (tMCAO). Rats were collected 24 hr after reperfusion, and then the doses of estrogen and progesterone were administered two hours after tMCAO. The expression of CD4⁺ using the immunohistochemistry (IHC) method and gene expression of IL-1β using the Real-time PCR in the ischemic penumbra of the male rat's brain cortex were determined, and infarct volume was determined 24 hr after ischemia using TTC staining.

Results: CD4⁺ and Gene expression of IL-1β were significantly increased in the Ischemia group compared to the control group. Also, E/P administration reduced infarct volume and CD4⁺ and gene expression of IL-1β compared to the Ischemia group.

Conclusion: The results of the present study showed that induction of tMCAO altered the expression of CD4⁺ and gene expression of IL-1β in the ischemic penumbra. Moreover, E/P treatment could reverse these effects of stroke.

Objectives: Hyperalgesia is a clinical condition related to chronic pain in which patients experience increased nociceptive sensitivity. Intrathecal oxytocin has been shown to induce significant anti-hyperalgesia in both rodents and humans. However, in our previous studies, we demonstrated a clear sex difference in oxytocin's effects at the spinal level in rodents. We suggested that this sex difference could be partially due to the higher expression of the oxytocin-degrading enzyme, insulin-regulated aminopeptidase (IRAP), in the spinal cord of females. Thus, we aimed to evaluate non-peptide oxytocin receptor (OTR) agonists, which we speculated could effectively reduce inflammatory hyperalgesia in both sexes due to their resistance to IRAP degradation.

Materials and methods: Plantar tests were conducted on adult S.D. rats of both sexes to examine intraplantar carrageenan-induced hyperalgesia. This was followed by an intrathecal (i.t.) injection of non-peptide OTR agonists, WAY 267,464 and TC OT 39, to assess their effects on hyperalgesia. Atosiban, an OTR antagonist, was also co-administered with these compounds to confirm their involvement in OTR activation.

Results: WAY 267,464 and TC OT 39 were both effective in ameliorating anti-hyperalgesia in male and female rats, suggesting no sex difference. Additionally, atosiban attenuated the anti-hyperalgesia effects of WAY 267,464 and TC OT 39, confirming these compounds' involvement in OTR activation.

Conclusion: These compounds induced significant anti-hyperalgesia without any sex differences, suggesting that the inhibition of IRAP degradation eliminated the variation in oxytocin's effects based on sex. Therefore, we propose these compounds as promising candidates for treating inflammatory hyperalgesia in clinical applications.

Objectives: This study aimed to characterize the progression of chronic mycetoma caused by Nocardia brasiliensis in a BALB/c murine model, focusing on the interplay between host cellular immune responses, bacterial burden, and histopathological evolution.

Materials and methods: BALB/c mice were inoculated with N. brasiliensis in the left hind footpad to establish the mycetoma model. The mice were divided into four experimental groups: 0, 70, 100, and 365 days post-infection (dpi). Lesion volume was assessed throughout the course of infection. At the defined time points, bacterial load (serial dilution method), percentages of immune cell populations (flow cytometry), serum cytokines (interleukins IL-6, IL-10, and IL-12p70, monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor (TNF)) via cytometric bead array (CBA), as well as histopathology and bacterial grain morphology (H&E staining), were evaluated.

Results: Chronic mycetoma progression revealed stable bacterial burden and lesion volume stabilization after 70 dpi through 365 dpi. Systemic expansion of CD4+ T cells in the spleen and sustained neutrophil dominance (>90% infiltration) characterized chronic lesions. Progressive tissue necrosis and panniculitis, undetectable by external lesion size, emerged histologically. Serum IL-6 levels surged during chronicity, suggesting a Th17 polarization, contrasting with declining MCP-1. Bacterial grains transitioned from club-shaped to circular over time, suggesting structural grain remodeling.

Conclusion: In chronic experimental mycetoma, the cell response is mainly characterized by neutrophil infiltration, an altered CD4+ T cell response, and dysregulated cytokine production. The shape of bacterial grains continues to change, and the bacterial load remains constant.

Objectives: Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB1 and CB2. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid agonists and antagonists on ovarian health and function in female mice.

Materials and methods: 80 NMRI mice were divided into 10 groups. Treatment groups received CB1 or CB2 agonists, antagonists, or their combinations for five days. The animals were then sacrificed, the ovaries were excised and weighed, and their volume was measured. Total RNA was extracted from the left ovary for qPCR analysis, while the right ovary was fixed in Bouin's solution for histological evaluation following H&E staining.

Results: Treatment with CB1/CB2 agonist+CB1 antagonist (W102+AM251) decreased the level of NAPE-PLD (a key factor in the production of endocannabinoids in cells) and increased the level of FAAH (responsible for cannabinoid degradation) genes compared to all groups. CB2 antagonist (AM630) increased the number of primary, preantral, and antral follicles, the volume and weight of ovaries, and estrogen levels. Meanwhile, the CB1 antagonist (AM251) significantly increased microvascular density in the ovaries.

Conclusion: Cannabinoids modulate ovarian physiology and folliculogenesis, with CB2 receptors playing a particularly significant role. Antagonism at CB2 appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and differentially affect their maturation. However, our preliminary novel findings in mice require human studies before clinical application.

Objectives: Toxin B and isotoxin B (TB, isoTB) are major constituents of the Taxus baccata tree. This study investigates the inhibitory effect of TB and isoTB on adult T-cell leukemia/lymphoma (ATLL), particularly on human T-lymphotropic virus type 1 protease (HTLV-1 PR). HTLV-1 protease (HTLV-1 PR) is an aspartic acid protease and a promising therapeutic target for human immunodeficiency virus (HIV) PR inhibitors.

Materials and methods: The anticancer properties of T. baccata plant components encapsulated in PLGA nanoparticles (NPs/ PLGA/TB) were evaluated by in vitro assays using different cell lines. Cancerous cell lines, including HTLV-1-infected-MT2, were treated with varying concentrations of TB and alcoholic extract, and a combined peptide was designed and expressed using recombined NPs/PLGA/TB in a human Fc gamma1 (HTLV-1 PR: hFc gamma1) against HTLV-1.

Results: Our results show that the viability of cancer cells after NPs/ PLGA/TB treatment significantly decreased in a time- and dose-dependent manner using the MTT assay. The inhibitory effect of NPs/ PLGA/TB on the HTLV-1-infected-MT2 cell line, in the absence of recombinant peptide, was (38.98 ± 0.23) and in the presence was (16.18 ± 2.03) in 72 hr (P<0.001). This indicates a double inhibitory effect in the presence of the peptide. The enzymatic effect of HTLV-1-protease on its fluorochrome substrate in the presence of TB and isoTB showed nearly complete enzyme inhibition.

Conclusion: These findings present a promising avenue for introducing therapeutic agents with anticancer properties to treat progressive cancers, such as viral ATLL, and inducing effective antiviral responses.

Objectives: This study aims to investigate the effects of fucoidan-alginate combined dressings on wound healing in rats with full-thickness skin defects and to explore the underlying mechanisms.

Materials and methods: Male SD rats were divided into three groups (n=15): Control, 2% fucoidan, and 5% fucoidan. Full-thickness skin wounds were created on each rat. Fucoidan-alginate dressings were prepared by applying 20 mg/ml and 50 mg/ml fucoidan solutions to alginate dressings (2×2 cm), resulting in 2% and 5% (w/v) fucoidan-alginate combined dressings, respectively. The control group utilized alginate dressings. Wound healing was assessed through various methods, including wound area measurement, histopathological analysis, white blood cell counts, ELISA for TNF-α and IL-1β, Masson's trichrome staining for collagen, immunohistochemistry for TGF-β1, and western blotting for TGF-β1 and Smad-related proteins.

Results: The results revealed that wound healing was significantly more effective in rats treated with 5% fucoidan-alginate combined dressings. Compared to the control group (P<0.01) and the 2% FUC group (P<0.05), the 5% FUC group exhibited reduced inflammatory cell infiltration and lower levels of TNF-α and IL-1β. Moreover, in comparison to the control group, the 5% FUC group demonstrated a significant up-regulation in the mean density of TGF-β1 (P<0.01) and significantly elevated protein expression levels of Col I, α-SMA, and p-Smad2/3 (P<0.01). Additionally, a notable amount of collagen production was observed.

Conclusion: The findings suggested that fucoidan-alginate dressings promote wound healing, reduce inflammation, and enhance collagen synthesis in rats, likely via the TGF-β1/Smad signaling pathway.