Iranian Journal of Basic Medical Sciences最新文献

Objectives: Acetaminophen (APAP)-mediated liver injury poses a significant public health concern. Curcuma xanthorrhiza extract (CXE) has been traditionally used for its hepatoprotective properties. This research aimed to assess the hepatoprotective effects of CXE in APAP-mediated hepatotoxicity by investigating the modulatory effects of CXE on key biomarkers, including Interleukin (IL), namely, (IL-6), IL-10, IL-1β, Nitric Oxide (NO), Lactate Dehydrogenase (LDH), and the genes expression related to apoptosis-like Caspase-3 (Casp-3), Casp-9, and genes related to liver metabolic c-Jun N-terminal Kinase (JNK), in APAP-mediated HepG2 cells.

Materials and methods: APAP-induced HepG2 cells were treated with different concentrations of CXE. IL-6, IL-10, IL were measured using an Enzyme-linked Immunosorbent Assay (ELISA) and NO, LDH were measured using colorimetric assay. Gene expression was analyzed using quantitative Real-Time Reverse Transcription (qRT-PCR).

Results: CXE significantly reduced IL-1β and IL-6 levels, enhanced IL-10 production, and attenuated NO levels in APAP-mediated hepatotoxicity. CXE also suppressed the expression of Casp-9, Casp-3, JNK, and LDH levels. The study presented a concentration-dependent response, with 125 μg/ml CXE exhibiting the most pronounced effects. CXE effectively modulated immune responses, decreased oxidative stress, and inhibited apoptotic and inflammatory pathways in APAP-mediated hepatotoxic cells.

Conclusion: These studies highlight the CXE potential as a therapeutic candidate for liver disorders, particularly in drug-mediated liver injury.

Objectives: One of the leading causes of endometriosis is the return of menstrual blood flow into the pelvic cavity and the establishment of menstrual blood mesenchymal stem cells (MenSCs) outside the uterus. MenSCs from endometriosis patients (E-MenSCs) and healthy women have been shown to vary in terms of surface markers and gene expression, which may suggest the involvement of these cells in the development and expansion of ectopic lesions. This study aimed to investigate the effects of beta-catenin signaling inhibitor C-82 and naringenin as PI3K signaling pathway inhibitors on E-MenSCs to modulate their gene expression and functional pattern.

Materials and methods: Briefly, E-MenSCs isolated by density-gradient centrifugation were treated with C-82 and naringenin, and the genes and pathways related to inflammation, proliferation, and survival were evaluated. E-MenSCs showed increased early apoptosis and decreased levels of ROS, IL-6 and IL-8, ER, α-SMA, and Ki-67 protein expression.

Results: Our results shed light on the function of C-82 and naringenin in modulating E-MenSCs.

Conclusion: However, more research is needed to analyze the precise effects of small molecule C-82 and naringenin on endometriosis.

Objectives: Isoflavone Daidzein (DDZ) has emerged as a promising alternative to hormone replacement therapy (HRT) for ameliorating estrogen deficiency (ED). However, the stereological and molecular mechanism of its effects in the OVX-hippocampus are unclear. We studied the impact of DDZ on stereological changes, estrogen receptor (ERs) expression, BDNF, GSK-3β, and inflammatory and apoptosis-related genes in the hippocampus of ovariectomized rats, compared to 17β-estradiol (E2).

Materials and methods: OVX rats were treated with DDZ or E2. The stereological analysis assessed the total volume and number of pyramidal and granular neurons in the hippocampus CA1 and DG subregions. Expression of proinflammatory cytokines, apoptotic-related genes, ERs, and BDNF genes was evaluated using Real-Time PCR, and the GSK-3β phosphorylation level was measured by western blot analysis.

Results: DDZ has effectively increased the volume and total number of pyramidal neurons in the CA1 region, the expression of ERα, ERβ, BDNF, and Bcl-2 genes, and the phosphorylation rate of GSK-3β protein. However, the effect of DDZ on the DG region, ERα, and BDNF genes was not significant in comparison with E2; DDZ significantly suppressed the expression of TNF-α, IL-6, and the Bax/Bcl2 ratio compared with OVX rats.

Conclusion: DDZ effectively reversed the stereological changes in the CA1 region by stimulating BDNF gene expression, increasing the phosphorylation ratio of the GSK-3β protein, and modulating inflammatory and apoptotic pathways. Although its effects on the DG region, BDNF, and ERα molecules were less significant than E2, DDZ could still be a promising candidate for ameliorating ED.

Objectives: Substrate engineering is one of the attractive fields of changing cell behavior and fate, especially for stem cell (SC) therapies. The SC pool is an essential factor in transplantation outcomes. Here, the objective was to preserve the stemness of the cornea's limbal epithelial stem cell (LESC) using naturally biomimicking corneal cell topography.

Materials and methods: A cell-imprinted substrate was prepared using the natural topography of rabbit cornea's LESC. The LESC cells were characterized by immunostaining (ABCG2 and Cytokeratin-12), then re-cultivated on a topography mold (imprinted PDMS), on FLAT PDMS (without any pattern), and the control group (tissue culture plate). Ultimately, an alkaline burn model was created on a rabbit's cornea, and the effectiveness of cell-imprinted molds as implants for healing corneal wounds was examined in vivo.

Results: The in vitro results showed that imprinted PDMS kept LESC cells in a state of stemness with high expression of ∆NP63 and ABCG2 genes (stemness-associated genes) compared to the other two groups and low Cytokeratin-3 and -12 expression (as differentiation-related genes). In vivo studies showed a more significant number of cells and the expression of the ABCG2 gene in the imprinted PDMS group. In contrast, higher expressions of the ∆Np63 gene and more stratification were observed in the control group (no treatment). Histological studies showed that the imprinted PDMS group had normal morphology with fully organized collagens.

Conclusion: The results of LESC cultured on imprinted PDMS suggested that LESC cell imprinting could be an excellent substrate for LESC expansion and preserve their stemness for cell therapy.

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.

Despite advancements in antimicrobial and anti-inflammatory treatments, inflammation and its repercussions continue to pose a considerable challenge in medicine. Acute inflammation may cause life-threatening conditions like septic shock, while chronic inflammation leads to tissue degeneration and impaired function. Lipopolysaccharides (LPS), a well-known pathogenic trigger contributing to several dysfunctions, is a crucial part of the outer membrane of gr-negative bacteria. LPS are well-known for eliciting acute inflammatory responses by activating a pathogen-associated molecular pattern (PAMP), which stimulates the innate immune system and triggers local or systemic inflammatory responses. LPS also activate numerous intracellular molecules that modulate the expression of a wide range of inflammatory mediators. These mediators subsequently initiate or exacerbate various inflammatory processes. Beyond immune cells, LPS can also activate non-immune cells, leading to inflammatory reactions. These excessive inflammatory responses are often detrimental and typically result in chronic and progressive inflammatory diseases, including neurodegenerative, cardiovascular diseases, and cancer. This review delves into the mechanisms by which the bacterial endotoxin LPS contribute to multiple inflammatory diseases. These insights into LPS signaling pathways could inform the design of new treatment strategies such as TLR4, NLRP3, HMGA1, MAPK, and NF-kB inhibitors. This enables precise targeting of inflammation-related processes in disease management.

Objectives: Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.

Materials and methods: Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.

Results: Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell infiltration (P<0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (P<0.01 and P<0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (P<0.01 and P<0.001), and inflammatory cytokines in brain tissue (P<0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (P<0.01), cerebral infarction volume (P<0.01), inflammatory cell number (P<0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (P<0.05 and P<0.01), ASC mRNA level and IL-1β protein level (P<0.01), and IL-1β and IL-18 level in brain tissue (P<0.01) compared to positive control.

Conclusion: EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.