Iranian Journal of Basic Medical Sciences最新文献

Metabolic syndrome is a clustering of metabolic abnormalities and anthropometric factors that increase the risk of cardiovascular disease and type 2 diabetes mellitus. As the search for effective treatments intensifies, attention has turned towards natural substances with potential medicinal benefits. Among them, vanillic acid, a phenolic acid present in many plants, has attracted some attention due to its wide range of biological activities. This review aimed to provide an in-depth summary of the potential therapeutic use of vanillic acid in metabolic syndrome. The potential mechanisms of action of vanillic acid, including its anti-oxidant, anti-inflammatory, and hypolipidemic properties, are discussed. The effect of vanillic acid on glucose homeostasis, insulin sensitivity, and adipocyte activity is also addressed. The effect of vanillic acid on lipid metabolism, including the control of lipid synthesis, breakdown, and transport, is also reviewed. The emerging evidence for the beneficial effects of vanillic acid in animal models, in vitro studies, and preliminary clinical studies is also highlighted. The data suggests that vanillic acid has the potential to ameliorate metabolic syndrome. However, further preclinical and clinical research is needed to determine the specific mechanisms of action, appropriate dose, and subsequent advantages of vanillic acid. A more comprehensive understanding of the therapeutic potential of vanillic acid could pave the way for developing innovative techniques for preventing and treating metabolic syndrome and its implications.

Objectives: To investigate the physicochemical properties, in vitro efficacy, and in vivo therapeutic potential of novel tree turmeric root and nano-hydroxyapatite (TRE@NHA) composites in mitigating chemotherapy-induced peripheral neuropathy (CIPN).

Materials and methods: TRE@NHA composites were synthesized and characterized using FTIR, XRD, TGA, and HRTEM. In vitro studies using PC12 cells assessed cytotoxicity, anti-inflammatory effects, and neuroprotective properties. An in vivo rat model of CIPN was established using paclitaxel (PTX). Behavioral assessments, histopathological analysis, and oxidative stress markers were evaluated in sciatic nerve tissues.

Results: TRE@NHA composites demonstrated successful integration of TRE into the NHA matrix. In vitro studies revealed significant anti-inflammatory and neuroprotective effects of TRE@NHA-2, particularly in suppressing cytokine production, enhancing cell viability, and mitigating oxidative stress. In vivo, TRE@NHA-2 effectively alleviated PTX-induced neuropathic pain, reduced neuronal damage, and exhibited potent antioxidant properties.

Conclusion: This study demonstrates the successful development and characterization of novel TRE@NHA composites. The findings strongly suggest that TRE@NHA-2 possesses promising therapeutic potential for mitigating CIPN due to its anti-inflammatory, antioxidant, and neuroprotective properties.

Objectives: This study aimed to engineer miR-216-overexpressing umbilical cord mesenchymal stem cells (UCMSCs) to generate miR-216-enriched UCMSC-derived exosomes (UCMSC-Exos) and evaluate their therapeutic potential in Spinal cord injury (SCI).

Materials and methods: miR-216 overexpression was achieved in UCMSCs, and exosomes were subsequently isolated. The biological effects of miR-216-overexpressing UCMSC-Exos (UCMSC-miR-216^OE-Exos) were assessed using in vitro migration, and tube formation assays with vascular endothelial cells. For in vivo evaluation, SCI mouse models were treated with either UCMSC-Exos or UCMSC-miR-216^OE-Exos. Functional recovery was measured using the BMS scores, while angiogenesis, neuronal apoptosis, and proinflammatory cytokine expression were analyzed through immunohistochemistry and molecular assays.

Results: qPCR analysis confirmed successful miR-216 overexpression in UCMSCs and their derived exosomes. In vitro, UCMSC-miR-216^OE-Exos significantly enhanced endothelial cell migration and tube formation compared to control UCMSC-Exos. In vivo, both UCMSC-Exos and UCMSC-miR-216^OE-Exos improved BMS scores, promoted angiogenesis, and reduced neuronal apoptosis and proinflammatory cytokine expression in SCI mice. Notably, UCMSC-miR-216^OE-Exos demonstrated superior therapeutic effects, including greater improvements in functional recovery, enhanced angiogenic responses, and more pronounced reductions in neuronal apoptosis and inflammation compared to control UCMSC-Exos. Additionally, in vitro experiments revealed that PTEN expression was down-regulated, and the AKT pathway was activated following treatment with UCMSC-miR-216^OE-Exos.

Conclusion: These findings demonstrate that miR-216-overexpressing UCMSC-Exos exhibits enhanced therapeutic efficacy in promoting angiogenesis, reducing inflammation and neuronal apoptosis, and improving functional recovery after SCI. This study demonstrates the promise of miR-216-enriched exosomes as a novel cell-free therapeutic approach for SCI, paving the way for clinical translation through their biologically translatable mechanisms.

Objectives: This research aimed to investigate the effect of 2 types of exercise on apoptosis, neurogenesis, and angiogenesis factors in the penumbra area of stroke during the rehabilitation period after stroke.

Materials and methods: A transient distal middle cerebral artery occlusion (td-MCAO) model was used to induce stroke and after that, the animals were randomly divided into three groups: stroke, stroke + continuous exercise with increasing duration (CTID), and stroke + exercise with increasing intensity (CTII). At 24 hr spost-stroke , MRA, neurological deficit, and behavioral tests were conducted, and also continuous exercises were conducted for five consecutive days, Finally, MRI and behavioral tests were performed, and 24 hr after that, tissue separation and blood sampling were performed to evaluate plasma irisin, Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) / cAMP Response Element-Binding Protein (CREB) / 90 kDa Ribosomal S6 Kinase (P90RSK) pathway, Vascular Endothelial Growth Factor (VEGF) / Vascular Endothelial Growth Factor Receptor 2 (VEGF-R2), and Brain-Derived Neurotrophic Factor (BDNF) / Tropomyosin Receptor Kinase B (TrKB) levels. for statistical analysis, one-way and two-way ANOVA tests were used at the significance level of P<0.05.

Results: Both training models reduced the volume of stroke and neurological defects compared to the stroke group (P<0.05), while the amounts of irisin and CREB in the CTID group increased significantly compared to the CTII and stroke groups (P<0.01). VEGFR2 values in training groups increased significantly compared to the stroke group (P<0.05) but in the CTII group, VEGFR2 values increased significantly compared to the CTID group (P<0.05).

Conclusion: The findings of the present study showed it seems that doing exercises with moderate intensities and gradually increasing the duration of exercise in the acute phase after stroke can be considered a suitable treatment in future research.

Objectives: Diabetes increases the risk of heart disease and stroke, primarily through endothelial cell dysfunction and vascular damage. These vascular complications are partly due to defects in endothelial progenitor cells (EPCs). This study explores the efficacy of pharmacological priming of bone marrow EPCs (BMEPCs) with Deferoxamine (DFO), a hypoxia mimetic agent, in restoring dysregulated angiogenic pathways in streptozotocin (STZ)-induced mice with type-1 diabetes (T1D).

Materials and methods: BMEPCs were isolated from both normal and STZ-induced mice with T1D. The effects of an optimal concentration of DFO (80 µM) on the viability, proliferation, and tubulogenesis of EPCs were assessed. Furthermore, the probable beneficial effects of the conditioned medium from EPCs treated in the presence and absence of DFO were examined in mice (T1D) wound healing models.

Results: DFO (80 µM) increased cell viability, proliferation, and tubulogenesis. EPCs isolated from diabetic mice showed significant impairments in the expression of HIF-1α, VEGF, and SDF-1 proteins compared to controls. DFO-preconditioning significantly enhanced protein expression of these genes. The conditioned medium from diabetic EPCs treated with DFO had a substantially greater favorable effect on wound healing in diabetic mice, connected with elevated levels of HIF-1α, VEGF, phosphorylated Tie2/Tie2, and Ang1.

Conclusion: DFO reactivates proliferation and restores the impaired angiogenic properties of EPCs from diabetic mice by stabilizing HIF-1α and VEGF. Additionally, DFO enhanced the pro-angiogenic activity in the EPC-secretome, leading to improved wound healing. This improvement is attributed to the dual activation of HIF-1α /VEGF and Ang-1/Tie2 pathways, which are crucial for initiating and maturing new blood vessels.

Objectives: Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model.

Materials and methods: Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 μg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method.

Results: The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups.

Conclusion: The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants.

Objectives: Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative stress, neuroinflammation, and apoptosis, which are believed to be mediated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Two NMDA receptor antagonists, ketamine and memantine, have shown potential in mitigating the pathophysiological effects of TBI.

Materials and methods: To conduct the study, a controlled cortical impact model was used to induce TBI in rats. The rats with TBI were then divided into three groups: a group receiving only TBI, a group receiving TBI along with memantine, and a group receiving TBI along with ketamine. After 24 hr, the levels of oxidative stress markers (such as SOD, MDA, and total thiol) in the brain tissue were measured. Immunohistochemical staining was also performed seven days after TBI to assess the activation of glial cells and the TLR-4/NF-κB neuroinflammatory pathway.

Results: The results indicated that treatment with memantine led to a reduction in MDA levels and an increase in SOD and total thiol levels. Memantine also decreased astrogliosis and down-regulated the TLR-4/NF-κB pathway. On the other hand, ketamine increased the levels of anti-oxidant markers but did not significantly affect the MDA level. Additionally, ketamine decreased the expression of NF-κB seven days after TBI.

Conclusion: The findings suggest that NMDA receptor antagonists, such as ketamine and memantine, may have therapeutic effects on TBI by inhibiting oxidative stress and inflammatory responses.

Objectives: To formulate and evaluate ethosomes for the transdermal delivery of loxoprofen, a potent non-steroidal anti-inflammatory drug (NSAID).

Materials and methods: Fifteen ethosomal formulations were created via thin-film hydration and probe sonication techniques, with variations in the amounts of egg yolk lecithin, ethanol, cholesterol (CHOL), Tween 80 (TW80), and propylene glycol (PG). The formulations were assessed for their particle size (PS), zeta potential (ZP), polydispersity index (PDI), pH, and entrapment efficiency (EE). Field scanning electron microscopy (FSEM) was utilized to evaluate their morphology. The in vitro drug release and ex vivo permeability of the ethosomal formulations were evaluated against those in a hydroethanolic drug solution.

Results: The formulation labeled F14, comprising 1% loxoprofen, 1% egg yolk lecithin, 30% ethanol, 5% propylene glycol, and phosphate-buffered saline (PBS) up to 25 ml, was recognized as an optimized ethosomal formulation. These ethosomes demonstrated an average size of 164.2±19 nm, a PDI of 0.280±0.028, a ZP of +45.1±4.5 mV, and an EE of 96.8±0.43%. In vitro and ex vivo tests demonstrated that the ethosomal formulation (F14) showed superior drug release and penetration rates compared to a conventional hydroalcoholic solution. The differential scanning calorimetry (DSC) study showed that loxoprofen was completely trapped within ethosomes. On the other hand, the Fourier transform infrared (FTIR) study confirmed that the drug and the additives did not interact.

Conclusion: The current study revealed that loxoprofen can be effectively delivered transdermally via the ethosomal system.

Adipogenesis, the process of proliferation of adipocyte progenitor cells and their differentiation into mature adipocytes, plays a critical role in the development of obesity. In this context, exploring the effects of phytochemicals on adipogenesis is very promising, as nowadays, they are widely used as food, drink, or supplement and can significantly impact general health and obesity control. This systematic review attempts to evaluate new findings regarding the molecular mechanisms of different phytochemicals on adipogenesis in in vitro models. Between 2010 and July 2023, a comprehensive systematic search of PubMed and Scopus databases was conducted. The following keywords were used: ("adipogenic") AND ("inhibit" OR "suppress" OR "reduce" OR "anti" OR "decrease") AND ("cell" OR "cell line" OR "adipocyte") AND ("phytochemical" OR "plant" OR "herb"). In this review, 109 studies were comprehensively analyzed, which provided important insights into the process of adipogenesis. Among the numerous transcription factors studied, PPARγ, C/EBPα, and SREBP1c were found to be the most important regulators actively involved in adipocyte differentiation. These results highlight the critical role of these factors in the control of adipogenesis and suggest that they represent promising targets for therapeutic interventions aimed at reducing the excessive lipid accumulation associated with obesity. This study provides a compelling rationale for further exploring phytochemicals as potential therapeutics for treating obesity. The potential benefits of using natural products to influence adipogenesis are evident, and future studies should focus on translating these findings into clinical applications.

Objectives: In our study, the neuroprotective efficacy of pre- and post-traumatic applications of boric acid (BA) in rats with experimentally induced spinal cord injury (SCI) was investigated.

Materials and methods: The experimental animals were divided into four groups: control group (C), SCI group (SCI), BA-treated group before SCI (BA+SCI), and BA-treated group after SCI (SCI+BA). Forty-eight hours after SCI, biochemical levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and cytochrome c (Cytc) and caspase-3 (Casp3) expressions were measured in the spinal cord tissues and were examined histologically.

Results: After SCI, oxidative stress markers, such as MDA, TOS, and OSI, and apoptosis markers Cytc and Casp3 showed an increase in levels compared to Group C. The oxidative stress markers that increased after SCI decreased with BA+SCI application, while Cytc level, one of the apoptosis markers that increased after SCI, decreased in both groups with BA application. Cell, myelin, ependymal damage, and hemorrhage levels increased after SCI compared to Group C. These histological markers increased after SCI and decreased after BA+SCI. BA was found to reduce SCI-induced oxidative stress and oxidative stress-induced apoptosis.

Conclusion: BA administered before SCI was shown to be more effective in protecting neural damage.