Iranian Biomedical Journal最新文献

Nanocarriers as powerful tools for delivering drugs to tumors provide new strategies for cancer treatment. These delivery systems encompass a diverse variety of structures, including polymeric nanoparticles (NPs), liposomes, dendrimers, micelles, and inorganic NPs such as gold and silica. Each type exhibits distinct physicochemical advantages that contribute to stability, drug-loading capacity, and targeting efficacy. Engineered nanocarriers can be utilized for the active targeting of tumor-specific receptors or for passive targeting of tumors via the enhanced permeability (EPR) and retention effect, a characteristic of abnormal tumor vasculature. This targeting approach enables the precise delivery of the therapeutic agents at tumor sites, increasing drug efficacy while minimizing exposure to healthy tissues. The benefits of these strategies include reduced systemic adverse effects, improved bioavailability, and an optimized therapeutic index. This review examines both active and passive drug delivery systems, with a special focus on the characteristics of the EPR effect.

Background: Hepatitis B virus (HBV) is responsible for more than one million deaths annually, mainly due to HBV-related diseases and hepatocellular carcinoma (HCC). HBV enters hepatocytes and interacts with the sodium taurocholate co-transporting polypeptide. While several single nucleotide polymorphisms (SNPs) have been linked to HBV infection and HCC, further research is needed to clarify the precise role of SNPs. The relationship of the rs4646287 SNP with the risk of HBV infection and the progression of cirrhosis and HCC has been investigated in different populations. This study aimed to evaluate the association of the rs4646287 SNP with HBV infection, cirrhosis, and HCC in an Iranian population.

Methods: The whole blood DNA was extracted from healthy individuals and patients with HBV, cirrhosis, and HCC. Primers for the C and T variants were designed using Primer1. The genotypes of the samples were identified using Tetra-ARMS PCR. The Tetra-ARMS PCR products were analyzed by electrophoresis on 2.5% agarose gels.

Results: Individuals with the rs4646287 TT genotype exhibited a significantly reduced risk of developing cirrhosis and HCC compared to healthy controls. The TT genotype also showed a decreased correlation between the HBV group and those with cirrhosis and HCC.

Conclusion: Our findings suggest that the rs4646287 TT genotype is associated with a lower risk of developing HBV-related diseases and HCC in an Iranian population.

Background: Hepatitis B virus is responsible for more than one million deaths annually, mainly due to HBV-related diseases and HCC. HBV enters hepatocytes and interacts with the NTCP. While several SNPs have been linked to HBV infection and HCC, further research is needed to clarify the precise role of SNPs. The relationship of the rs4646287 SNP with the risk of HBV infection and the progression of cirrhosis and HCC has been investigated in different populations. This study aimed to evaluate the association of the rs4646287 SNP with HBV infection, cirrhosis, and HCC in an Iranian population.

Methods: The whole blood DNA was extracted from healthy individuals and patients with HBV, cirrhosis, and HCC. Primers for the C and T variants were designed using Primer1. The genotypes of the samples were identified using Tetra-ARMS PCR. The Tetra-ARMS PCR products were analyzed by electrophoresis on 2.5% agarose gels.

Results: Individuals with the rs4646287 TT genotype exhibited a significantly reduced risk of developing cirrhosis and HCC compared to healthy controls. The TT genotype also showed a decreased correlation between the HBV group and those with cirrhosis and HCC.

Conclusion: Our findings suggest that the rs4646287 TT genotype is associated with a lower risk of developing HBV-related diseases and HCC in an Iranian population.

Background: Helicobacter pylori is an extracellular bacterium responsible for various gastrointestinal diseases, such as peptic ulcers and gastric cancer. It uses multiple mechanisms to colonize the harsh, acidic environment of the stomach and establish its pathogenic processes, mostly through CagA translocation. While cell surface integrin molecules were previously believed to be the main mediators anchoring H. pylori and facilitating this process, recent studies highlight the critical role of the interaction between the bacterial adhesin Helicobacter pylori outer membrane protein Q (HopQ) and host carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in CagA translocation and subsequent pathogenic signaling.

Methods: Recombinant proteins, including HopQ, HopQ-GFP (green fluorescent protein), HopQ-HRP (horseradish peroxidase), and recombinant N-terminal domain of human CEACAM1 (C1ND), were produced via gene cloning, expression, and purification techniques. Ligand-receptor interactions were evaluated using FACS analysis along with antigen- and cell-based ELISA assays.

Results: In this study, we have developed antigen and cell-based platforms using recombinant fusion proteins (HopQ-GFP and HopQ-HRP) that effectively interact with recombinant C1ND, as well as various CEACAM molecules expressed on gastric cell lines (MKN45 and AGS).

Conclusion: These assay platforms enable detailed investigation of the HopQ-CEACAM interaction and supports high-throughput screening of inhibitors, facilitating the identification of potential drugs or vaccine candidates targeting H. pylori infection.

Acute kidney injury (AKI) is the sudden loss of kidney function that occurs within hours or days, resulting in the accumulation of waste materials in the blood and disruption of fluid balance. AKI is prevalent among hospitalized patients, especially the elderly in the intensive care units. Inflammation, oxidative stress, and apoptosis are typical physiological responses following AKI. Peptides, especially bioactive peptides, exhibit various properties, including immunomodulatory and antihypertensive effects, and functions against diabetes, obesity, and cancer. In recent years, much attention has been drawn to the application of peptides and bioactive peptides in pharmaceuticals, particularly for their potential use, alone or in combination, in the treatment of AKI. Given the critical role of inflammation, oxidative stress, and apoptosis pathways in AKI, along with the anti-inflammatory, anti-apoptotic, and antioxidant effects of peptides, this study was designed to review the effects and underlying mechanisms of peptides in AKI.

Background: Identifying novel diagnostic biomarkers with stable structures, such as circulating circular RNAs (circRNAs) can improve the early detection and management of BC. Herein, we conducted this study to analyze the expression profile of four circRNAs, including circCSPP1 (hsa_circ_0001806), circNRIP1 (hsa_circ_0004771), circSMAD2 (hsa_circ_0000847), and circFOXP1 (hsa_circ_0008234) in BC.

Methods: Tumor tissues and adjacent normal tissues were obtained from patients with sporadic breast cancer (BC). Divergent primers were designed to amplify the target transcripts using quantitative real-time PCR. The expression profiles of circRNAs were analyzed in tumor and adjacent normal tissues. Sanger sequencing was performed to confirm the back-splicing junctions of circRNAs. ROC curves were generated to assess the potential of the mentioned RNAs as diagnostic biomarkers.

Results: We observed a significant upregulation of circCSPP1, circNRIP1, and circSMAD2 in tumor tissue compared to adjacent normal tissues. Among them, circCSPP1 was the most highly upregulated one in tumor samples from 39 patients. Expression of circCSPP1 was significantly higher in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, human epidermal growth factor receptor-2 (HER2)-negative, and triple-negatives compared to ER-positive, PR-positive, HER2-positive, and non-triple-negative ones. Expression of circNRIP1 was also significantly elevated in the ER-negative and the triple-negative subgroups. These three circRNAs also displayed a desirable potential as diagnostic biomarkers.

Conclusion: : This is the first paper that reports the upregulation of circCSPP1 and circSMAD2 in BC and upregulation of circCSPP1 and circNRIP1 in the triple-negative subgroup. Our findings suggest that circCSPP1, circNRIP1, and circSMAD2 may serve as promising diagnostic biomarkers for BC. Identifying the downstream pathways regulated by these circRNAs could lead to the discovery of new therapeutic targets.

Background: BAX and caspase-3 are essential genes in the apoptotic pathway of cells, promoting the apoptotic cascade through different mechanisms. Inhibition of these genes can increase the longevity of cells in cell culture. This study aimed to compare the effects of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9)-mediated knockdown of BAX and caspase-3 genes on apoptosis inhibition, cell lifespan, and erythropoietin (EPO) production in CHO cell lines.

Methods: The BAX and caspase-3 gene expression was evaluated in the recombinant Chinese hamster ovary (rCHO) cell lines producing EPO using the CRISPR-Cas9 method. Their anti-apoptotic effects and the level of EPO expression were also compared. In addition, oleuropein (OP) as an apoptosis inducer, was introduced to the manipulated cell line to assess the stability and viability of the manipulated cell lines.

Results: The rCHO cells with the manipulated BAX gene exhibited a higher cell density than those with the manipulated caspase-3 gene (152% vs. 142%). Despite the increased cell density in the cells with the BAX gene manipulation, EPO production was higher in the cells with the manipulated caspase-3 gene (1.58-fold increase in the BAX-manipulated cells compared to a 1.70-fold increase in the caspase-3-manipulated cells).

Conclusion: Our observations suggest that the downregulation of the BAX and caspase-3 genes using the CRISPR method, inhibits apoptosis and enhances the yield of recombinant EPO, even in the presence of an apoptosis inducer. Additionally, reduction of caspase-3 expression was proved to be more effective than BAX in extending the lifespan of cells and producing heterologous recombinant proteins.

Background: Oropharyngeal candidiasis, primarily caused by Candida albicans, is the most common opportunistic fungal infection in patients with head and neck cancer. The increasing emergence of fluconazole (FLZ) resistance has led to higher morbidity and mortality rates. Streptomyces, a genus of Actinomycetes, produces bioactive molecules with antimicrobial effects. This study investigated the antifungal potential of S. monomycini strain 615 against FLZ-resistant C. albicans clinical isolates in vitro.

Methods: S. monomycini strain 615 was cultured, and an aqueous crud extract containing its metabolites was prepared. The effects of extract were tested on five FLZ-resistant C. albicans isolates. Key pathogenic factors such as protease activity, biofilm formation, and gene expressions related to virulence (SAP1, SAP2, HWP1, and ERG11) and azole resistance (ERG11) were evaluated. Cytotoxicity of the extract (1.8-0.0008 µg/ml) was assessed on KYSE-30 esophageal epithelial cells using the MTT assay.

Results: Strain 615 showed strong antifungal activity with minimum inhibitory concentration (MIC) values of 0.0008-0.0035 µg/ml and minimum fungicidal concentration (MFC) values of 0.0017-0.0035 µg/ml after 48 hours. The extract significantly reduced ergosterol content by 31.81%, completely inhibited phospholipase and proteinase activities at 0.0035 µg/ml and suppressed biofilm formation at 0.0035-0.0140 µg/ml. Expression of all tested virulence genes decreased except for ERG11, indicating a possible mechanism to overcome azole resistance. The highest extract concentration caused 76.7% cytotoxicity in KYSE-30 cells after 72 hours.

Conclusion: S. monomycini strain 615 could serve as an alternative or adjunct therapy for FLZ-resistant oropharyngeal candidiasis in head and neck cancer patients, warranting further research to confirm safety and efficacy.

Background: Acute lymphoblastic leukemia (ALL) is the most prevalent form of acute leukemia in children, arising from the known and unknown factors. This complexity has limited advancements in patient recovery. Recently, long noncoding RNAs lncRNA (lncRNA) molecules have emerged as significant but not fully understood players in leukemia research. Studies have indicated that c-Myc can stimulate and enhance gene expression through multiple pathways, particularly by activating the PI3K and WNT pathways. The present study investigated the expression levels of lncRNAs involved in the upstream regulation of the PI3K/WNT pathways in patients diagnosed with ALL.

Methods: This case-control cross-sectional study was conducted using RNA from blood samples. The study examined 36 patients with ALL and 36 healthy controls. The expression levels of SNHG16 and TCF7 lncRNAs and their target genes were determined using qRT-PCR.

Results: The expression of Akt, β-catenin and c-Myc genes in the patient group showed a significant increase compared to the control group (p < 0.05). The expression levels of SNHG16 and TCF7 were significantly elevated in ALL patients compared to the control group (p < 0.05). Furthermore, a significant positive correlation was observed between the expression levels of these two lncRNAs in the patient group (p < 0.05).

Conclusion: Our findings demonstrate that SNHG16 and TCF7 lncRNA may act as crucial regulators of the Akt and β-catenin in ALL, which in turn influence c-Myc expression levels in affected individuals. Further research is needed to better understand the molecular mechanisms underlying ALL, potentially leading to improved treatment and monitoring strategies for patients.

Background: Skin tissue engineering is an innovative alternative to traditional methods for addressing skin injuries. This study aimed to synthesize a hydrogel consisting of carboxymethyl cellulose (CMC) and gelatin (Gel) containing atorvastatin (ATR) with the potential to accelerate tissue regeneration and wound healing in an animal model.

Methods: Five unique formulations of hydrogel with different concentrations of ATR (0.1%, 0.5%, 1%, and 2% w/v) were synthesized using CMC-Gel. The structural characteristics of the hydrogels were assessed using SEM and FTIR spectroscopy. Additional evaluations carried out included swelling behavior, degradability, ATR release, compatibility, hemolytic activity, and the viability of NIH/3T3 fibroblast cells. The therapeutic effectiveness of these hydrogels in enhancing wound healing was investigated in an animal model by making a full-thickness skin incision in Wistar rats.

Results: The synthesized CMC-Gel scaffolds had a porous structure with interconnected pores measuring 103 ± 8.74 μm and the ability to enhance cell migration. The MTT analysis showed a concentration-dependent relationship between ATR and cell proliferation, among which, the desirable concentration was 0.1% w/v. Furthermore, increased ATR concentrations were associated with decreased dressing capacity for hemostasis and coagulation. In vivo studies revealed that all the hydrogel-treated groups significantly outperformed the control group in promoting wound closure rates. Remarkably, the CMC-Gel-ATR 0.1% group exhibited the highest rates of wound closure, re-epithelialization, and angiogenesis.

Conclusion: Our results suggest the CMC-Gel-ATR as a desirable wound dressing for clinical application due to its unique physicochemical properties and comprehensive biocompatibility in in vitro and in vivo investigations.