Iranian Journal of Basic Medical Sciences最新文献

Objectives: The invention of corneal tissue engineering is essential for vision due to the lack of effective treatments and donated corneas. Finding the right polymer is crucial for reducing inflammation, ensuring biocompatibility, and mimicking natural cornea properties.

Materials and methods: In this study, solvent casting and physical crosslinking (freeze-thaw cycles) were used to fabricate polymeric scaffolds of Polyvinyl alcohol, alginate, gelatin, carboxymethyl chitosan, carboxymethyl cellulose, polyacrylic acid, polyvinyl pyrrolidone, and their combinations. The mechanical evaluation of scaffolds for tension and suture ability was conducted. Biodegradability, swelling, water vapor, bacterial permeability, anti-inflammatory properties, blood compatibility, Blood Clotting Index (BCI), pH alterations, and cell compatibility with human Mesenchymal Stem cells (MSCs) were investigated with MTT. The hydrophilicity of the samples and the ability to adhere to surfaces were also compared with the contact angle and adhesive test, respectively. Finally, quantitative and qualitative analysis was used to check the transparency of the samples.

Results: The mechanical strength of polyvinyl alcohol and polyvinyl pyrrolidone samples was highest, showing good suture ability. All samples had blood compatibility below 5% and cell compatibility above 75%. Polyvinyl alcohol was the most transparent at around 93%. Carboxymethyl chitosan effectively inhibited bacterial permeability, while its anti-inflammatory potential showed no significant difference.

Conclusion: This study aims to choose the best polymer composition for corneal tissue engineering. The selection depends on the study's goals, like mechanical strength or transparency. Comparing polymers across different dimensions provides better insight for polymer selection.

Objectives: Colorectal cancer is one of the deadliest cancers worldwide, which can be prevented and even cured by early diagnosis and more efficient treatment modalities. Comprehensive transcriptional analysis has highlighted the importance of lncRNAs in CRC tumorigenesis. In this study, we identified co-expressed lncRNA networks based on public RNA sequencing data for biomarker prediction in CRC and then verified the best candidate experimentally.

Materials and methods: Publicly available RNA-sequencing data (BioProject PRJEB27536) of CRC samples and normal adjacent tissues were reanalyzed using the DESeq2 package in R to find differentially expressed lncRNAs. Pathway enrichment and gene network analysis were accomplished using GSEA and WGCNA to identify potential functions of lncRNAs with possible roles in tumorigenesis pathways. Subsequently, the expression of RP11-109D20.2 (lnc-Duox2-1:1) was assessed in fresh/frozen tissues obtained from 46 CRC patients by quantitative RT-PCR.

Results: A total of 17939 DElncRNAs were identified between CRC and normal tissues via bioinformatics analyses. A significant up-regulation of RP11-109D20.2 (48%) was observed in CRC samples. Functional enrichment analysis showed that RP11-109D20.2 was mainly related to pathways like phosphoric ester hydrolase, oxidoreductase, phosphoric diester hydrolase, and cyclic-nucleotide phosphodiester activities. Moreover, elevated expression of DUOX2 in tumors with high levels of RP11-109D20.2 suggests a link between these genes.

Conclusion: Our data revealed that RP11-109D20.2 may have a considerable role in CRC progression. However, further functional analyses are essential to evaluate the probable role of RP11-109D20.2 as a potential diagnostic marker and its potential role in the dysregulation of cyclic nucleotide phosphodiesterase genes in CRC.

Objectives: There is a considerable interest in combination therapy targeting the complex interlinked pathways in prostate cancer due to the development of drug resistance with monotherapies. A standardized fraction of Bacopa monnieri CDRI-08 was developed and patented by the Central Drug Research Institute (CDRI), Lucknow, for the treatment of neurodegenerative diseases. Recent studies with the plant and its phytocompounds have shown effective anticancer and antioxidant activity. Therefore, in the current research, the combined effect of Abiraterone acetate (AA) and CDRI-08 was studied in androgen-independent prostate cancer cells in vitro.

Materials and methods: Initially, the in vivo toxicity of CDRI-08 was studied in zebrafish embryos. In vitro individual cytotoxicity and the synergistic effect of AA and CDRI-08 were studied in PC3 cell lines with and without growth factors. Nuclear staining with AO/EB and western blotting were performed to analyse apoptotic cell death and changes in protein expression of p-AKT and Casp3 in individual and combination-treated cells.

Results: CDRI-08 has shown no toxicity and teratogenicity in zebrafish embryos. AA and CDRI-08 have shown dose-dependent cytotoxic effects in PC3 cell lines with and without growth factors. Synergism was observed with different concentration ratios of AA and CDRI-08 with and without growth factors, with a good combination index (CI). Apoptosis was observed in individual and combination treated cells with an increase in Casp3 and simultaneous decrease in p-AKT expression levels.

Conclusion: The study confirms the synergistic effect of CDRI-08 and AA at a lower dose, targeting the tyrosine kinase and androgen receptor pathways.

Cancer is considered a serious threat to human life and one of the major leading causes of death in the world. As a critical medical challenge in developing and developed countries globally, progress in the design of theranostic nanomedicine is associated with the control of temporal-spatial variability, enhancing the site-specific therapy, and reducing the toxicity to normal tissue. As the primary noninvasive cancer treatment technique, photothermal therapy through radiation absorption in the near-infrared region generates hyperthermia for the ablation of cancerous cells. Photothermal therapy combined with other therapeutic techniques, including chemodynamic, photodynamic, and sonodynamic, has synergistic and enhanced effects on cancer therapy. Nanozymes, as intrinsic multienzyme mimics, can be robust cancer nanotherapeutics owing to the dual effect of catalytic functions and physicochemical advantages of nanomaterials. Nanozymes possess remarkable stability, precise penetrability, exceptional specificity, outstanding recoverability, and minimal toxicity. These attributes make them immensely powerful for therapeutic applications. In light of the significance of multifunctional nanozymes and their increasing focus on catalytic therapy for cancer tumors through reactive oxygen species (ROS), we have compiled a comprehensive overview of recent advancements in various photothermal-based assays utilizing nanozymes. Notably, our analysis reveals that incorporating nanozymes in PTT enhances the generation of ROS, leading to improved therapeutic efficacy against the tumor. In summary, this comprehensive overview highlights the significance of multifunctional nanozymes in advancing photothermal-based assays for cancer treatment. The findings underscore the potential of these innovative approaches to improve treatment precision and effectiveness while reducing adverse effects on healthy tissues.

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: Recent studies have increasingly focused on applying nanotechnology to treat neurodegenerative diseases. In this study, we compared the effects of the monoterpene linalool and linalool-loaded chitosan nanoparticles on key pathological features of Alzheimer's disease (AD), including oxidative stress, neuroinflammation, neuronal death, amyloid plaque deposition, alterations in tryptophan metabolism, and memory deficit in a rat model of AD.

Materials and methods: An intracerebroventricular injection of Aβ₄₂ (10 µg) was used to induce the AD model. Linalool (25 mg/kg) and nano-linalool (25 mg/kg) were administered orally once daily for 30 consecutive days.

Results: Both linalool and nano-linalool significantly reduced malondialdehyde levels and enhanced superoxide dismutase activity in the hippocampus. They also decreased the mRNA levels of monocyte chemoattractant protein-1, inhibited the up-regulation of beta-secretase, reduced amyloid plaque deposition, and attenuated pyramidal neuron death in the CA1 region. Additionally, treatment with both compounds down-regulated indoleamine 2,3-dioxygenase, lowered kynurenine levels, and increased serotonin concentrations in the hippocampus. Although both treatments improved learning and spatial memory in Aβ-injected rats, nano-linalool's effectiveness was more significant than that of linalool in modulating the molecular, biochemical, and histological parameters.

Conclusion: Encapsulating linalool in chitosan nanoparticles enhances its effectiveness in improving molecular, biochemical, and histological changes in the hippocampus of rat models of AD.

Objectives: Psoriasis is an autoimmune disease that mainly affects the skin and joints, which is mediated via T-cells. Several factors contribute to its pathogenesis, including genetic and environmental triggers, as well as intrinsic immune processes that lead to an autoimmune response. Silymarin, a flavonoid complex extracted from Silybum marianum, exhibits anti-inflammatory, immunostimulatory, and anti-oxidant properties, rendering it a viable candidate for treating psoriasis. This study aimed to investigate the effect of silymarin on imiquimod (IMQ) induced psoriasis-like skin lesions in male mice applied as a cream for seven consecutive days (1 mg per mouse).

Materials and methods: Thirty-five male mice were assigned to seven groups (n=5 per group): (I) control group, (II) IMQ group, (III-V) oral silymarin groups (30, 60, and 120 mg/kg), (VI) topical betamethasone group, and (VII) topical silymarin 2% group.

Results: Silymarin, both orally and topically, significantly reduces erythema, thickness, and scaling induced by IMQ after seven days of treatment. The treatment also reversed the increase in spleen weight/body weight ratio. Immunofluorescence analysis revealed that silymarin reduced the expression of nuclear factor κB (NF-κB) (P<0.01) and toll-like receptor 4 (TLR4) (P<0.01) compared to the IMQ group.

Conclusion: These findings suggest that silymarin effectively alleviates psoriasis lesions by reducing inflammation and modulating the TLR4/ NF-κB signaling pathway.

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.