Iranian Biomedical Journal最新文献

Background: Melanoma differentiation-associated gene-7 (Mda-7) selectively suppresses growth and induces apoptosis in various tumor cells without harming normal cells. Inhibition of autophagy has been shown to enhance the efficacy of many cancer therapies. However, its effect on the anticancer activity of Ad/Mda-7 in GBM has remained unclear. This study investigated the combined effect of an autophagy inhibitor (CQ) and Mda-7 in U87 cancer cells.

Methods: Cell proliferation was assessed using the MTT assay. Apoptosis rates, autophagy induction, and ROS levels were measured using flow cytometry. Caspase-9 and β-actin protein levels were analyzed by Western blotting. ELISA was employed to quantify HSP70 and TRAIL level in the culture medium. Real-time PCR evaluated the expression levels of cell death-related genes (P38 MAPK, Bax, and TRAIL) and specific miRNAs (miR-7, miR-122, and miR-21) in treated cells.

Results: Combined treatment with Ad/Mda-7 and the autophagy inhibitor CQ significantly reduced cell viability and proliferation. Ad/Mda-7 induced LC3-II protein expression in U87 cancer cells, which was further increased by autophagy inhibition through CQ. The combination treatment also increased apoptosis rates, elevated ROS levels, and decreased HSP70 protein expression, highlighting its synergistic anticancer effects. Increasing the expression of miR-7 and miR-122 indicated that the elevated levels of these endogenous miRNAs may help improve the treatment process.

Conclusion: Our findings indicate that the combination of Ad/Mda-7 and CQ synergistically could inhibit U87 cancer cell growth and could serve as a promising approach for treating human GBM.

Background: Prolactin is a neurohypophyseal hormone that plays a major role in behavior, growth, and angiogenesis. CAB suppresses the effects of PRL by targeting the D2R. In this study, we used in silico and in vivo approaches to examine the side effects of CAB using chicken as a model.

Methods: Thirty fertilized eggs were equally divided into three groups: one control and two experimental groups treated with CAB at doses of 0.5 mg/kg and 1 mg/kg, respectively. After 18 days of experiment, embryo weight, average body length, chorioallantoic vessels length, and relative PRL gene expression were analyzed. Also, prolactin-protein interaction and functional pathways regulated by PRL and associated proteins were investigated using the STRING database.

Results: Macroscopic analysis showed a significant increase (17.54 ± 0.28) and decrease (12.92 ± 0.38) in weight in the 0.5 mg/kg and 1 mg/kg groups, respectively, as compared to the control. A significant reduction in body size and an increase in chorionic vessel development were observed only in the 0.5 mg/kg group. PRL expression levels significantly decreased in both CAB-treated groups. In silico analysis revealed PRL interactions with INS and POMC proteins, which are conserved between H. sapiens and G. gallus.

Conclusion: Our findings indicate that CAB not only reduces prolactin levels but also affects fetal weight and body size.

Neurodegenerative diseases are major global health concerns due to progressive neuronal deterioration. Natural compounds, particularly plant polyphenols, are being explored for their neuroprotective potential. O. sanctum (Holy Basil or Tulsi) polyphenols, which possess pharmacological activities, were emphasized in this review. O. sanctum contains flavonoids, phenolic acids, and tannins, which exhibit strong antioxidant activity through scavenging free radicals and boosting endogenous antioxidants. These compounds also demonstrate anti-inflammatory activities, modulate cytokine production, and increase synaptic plasticity. Their anti-apoptotic effects inhibit the degeneration of neuronal cells. Preclinical studies demonstrated potential neuroprotective effects of O. sanctum polyphenols in different NDD models, with a few clinical studies suggesting their safety and efficacy over conventional neuroprotective medicines. Elucidating these mechanisms could help the development of O. sanctum polyphenols as drugs to combat NDDs and improve patient outcomes.

Background: Colon cancer remains a leading cause of cancer-related mortality, with the efficacy of standard chemotherapy agents such as 5-FU limited by resistance and toxicity. This study aimed to identify metabolites that enhance 5-FU efficacy in CRC using GEM.

Methods: GEM was applied using the FVSEOF algorithm to identify metabolites that enhance the therapeutic efficacy of 5-FU in CRC. Context-specific metabolic models were constructed from TCGA data using the ftINIT algorithm. By simulating TS inhibition, we identified aspartate, lysine, and valine as candidate metabolites with altered uptake under constrained biomass production. Among them, lysine and valine are essential amino acids and were chosen for experimental validation using MTT assays and flow cytometry in HT-29 CRC cells and HU02 normal fibroblasts.

Results: Our approach identified aspartate, lysine, and valine as candidate synergistic metabolites. Experimental validation confirmed the strong synergy of lysine and valine with 5-FU in HT-29 cells, while showing significantly reduced effects in normal fibroblasts. Mechanistic analysis suggested that these amino acids enhance nucleotide demand and metabolic activity, amplifying 5-FU-induced stress.

Conclusion: This study demonstrates synergistic interventions and introduces amino acid co-supplementation as a potential strategy to improve CRC therapy with reduced toxicity. To our knowledge, this is the first study to employ GEM for the systematic prediction of metabolites that synergize with 5-FU, aiming to improve therapeutic outcomes in CRC.

Background: Gentamicin, a powerful aminoglycoside antibiotic, is limited in clinical use due to dose-related kidney toxicity, mainly caused by oxidative stress. A. pinnata, an antioxidant-rich aquatic fern, has not been extensively studied for renoprotection against GM-induced kidney damage. This research assessed the protective effects of a hydroalcoholic extract of A. pinnata on GM nephrotoxicity.

Methods: Forty male Wistar rats were divided into five groups (n = 8): control, sham, GM (100 mg/kg/day, i.p.), and GM plus A. pinnata extract (10 or 20 mg/kg/day, orally). After seven days, renal function markers (serum creatinine and urea), oxidative stress parameters (MDA, FRAP, CAT, and GPX), TNF-α, and renal histopathology were assessed.

Results: GM significantly damaged kidney function and induced oxidative stress, as shown by increased levels of creatinine, urea, and MDA, along with reduced FRAP and CAT activity (p < 0.05). Co-treatment with A. pinnata extract, especially at 20 mg/kg, significantly lessened these effects by restoring kidney function markers, boosting antioxidant defenses, and lowering lipid peroxidation. The extract did not have a significant impact on either GPX activity or TNF-α levels. Histopathological analysis revealed that GM-induced tubular necrosis and glomerular damage were significantly ameliorated by A. pinnata in a dose-dependent manner.

Conclusion: A. pinnata extract offers notable protection against kidney damage caused by gentamicin, mainly by enhancing the body's natural antioxidant defenses, decreasing lipid peroxidation, and maintaining the normal structure of kidney tissue. These findings suggest that A. pinnata could serve as a valuable complementary treatment to improve the safety of GM use.

Background: Sulfur mustard exposure causes chronic cutaneous injuries characterized by inflammation, fibrosis, and delayed wound healing. MiRNAs, such as miR-148a-5p, have been implicated in regulating the TGF-β signaling pathways involved in these processes. This study aimed to evaluate whether alterations in the expression of miR-148a-5p, TGF-β1, and TGF-βR2 are associated with long-term SM-induced skin damage.

Methods: Skin biopsy samples were collected from 20 SM-exposed veterans and 20 healthy controls. Total RNA was extracted, and quantitative real-time PCR was performed to assess the expression levels of miR-148a-5p, TGF-β1, and TGF-βR2. Group differences were analyzed using a t-test, and ROC curves were generated to evaluate diagnostic performance.

Results: Expression levels of miR-148a-5p, TGF-β1, and TGF-βR2 were significantly lower in SM-exposed skin compared with controls (miR-148a-5p: p = 0.0010; TGF-β1: p < 0.0001; TGF-βR2: p < 0.0001). Based on ROC analysis, miR-148a-5p and TGF-βR2 indicated promising discriminative potential, whereas TGF-β1 did not reach statistical significance (AUC = 0.65; p = 0.0877).

Conclusion: Our findings suggest that reduced expression of miR-148a-5p and TGF-βR2 may contribute to SM-related skin injury. Both markers demonstrated potential diagnostic utility and could aid in risk stratification and monitoring in SM-induced skin disease, pending further validation in larger cohorts.

Insulin therapy is essential for regulating glucose levels in diabetic patients. However, subcutaneous insulin injection, despite being a standard procedure, is invasive and often painful and can lead to complications such as skin damage and infections. These issues often result in poor patient compliance and inadequate glycemic control. Recently, transdermal insulin administration has been explored as an alternative to subcutaneous methods; however, no universally accepted protocol has been developed for its use. This systematic review aimed to evaluate the effect of iontophoresis on transdermal insulin administration in laboratory animals. Using the PICO search strategy and in accordance with PRISMA guidelines, relevant articles published from January 1980 to May 2025 were retrieved from Scopus, PubMed, ISI Web of Science, PEDro, Science Direct, and Google Scholar databases. The findings from these studies suggest that combining iontophoresis with physical enhancers of skin penetration can effectively regulate blood glucose levels while minimizing the risk of hypoglycemia.

Background: DNA vaccines offer dual humoral and cellular immunity, showing potential effectiveness against intracellular parasites, including Leishmania. However, challenges in delivering large DNA constructs has been already existed, which influence protein expression and immune efficacy. This study evaluated the expression of P. sergenti salivary protein PsSP42 in COS-7 cells. Confirming the expression of PsSP42 is crucial before its use as a DNA vaccine in preclinical experiments.

Methods: The expression of the PsSP42 protein was achieved using two plasmids: the small, antibiotic-free plasmid NTC9385R and the conventional plasmid VR1020. Both recombinant vectors were transfected into COS-7 cells using electroporation and PEI-mediated transfection methods. Ni-NTA beads were utilized to enrich proteins from the supernatants collected from transfected cells, and expression was confirmed by Western blotting.

Results: Successful expression of the PsSP42 protein was affirmed from both VR1020-PsSP42 and NTC-PsSP42 constructs in the transfected COS-7 cells, regardless of the transfection method employed (PEI or electroporation). A 39.6 kDa band corresponding to the PsSP42 protein was detected, indicating its secretion into the supernatants of COS-7 cells transfected with both plasmids.

Conclusion: Plasmids VR1020-PsSP42 and NTC-PsSP42 demonstrated similar protein expression levels in vitro, regardless of the transfection method used. Performing these evaluations is recommended to thoroughly assess construct expression levels before conducting in vivo studies.

Background: The selective delivery of drugs to their targets prevents their possible side effects; hence, the development of selective transport systems is considered extremely promising. In the present study, we aimed to develop a drug delivery system for targeting bacteria.

Methods: Functionalization of apoferritin with wheat germ agglutinin (WGA), as a bacteria-recognizing lectin, was conducted. Afterwards, the complex was loaded with ampicillin. The affinity of the conjugate to Gram-positive bacteria, Bacillus subtilis, was evaluated by anisotropic silver nanoparticles conjugated with this complex, and its interaction with the bacteria was also assessed.

Results: The drug-delivery capabilities of the composite were evaluated. Results from the disk diffusion assay revealed that its bactericidal activity is 10-fold greater compared to free antibiotics. The effectiveness of the bactericidal effects of ampicillin-loaded ferritin was also confirmed in whole blood.

Conclusion: Lectin-conjugated and ampicillin-loaded apoferritin can be considered as effective drug delivery systems for targeting bacteria.

Background: From the perspective of drug delivery systems, oral films (OFs) have received increased attention, mainly for pediatric and geriatric applications. Beeswax, a naturally derived and FDA-approved material, is often mixed with other polymers to enhance its mechanical properties. This study presented the first use of precisely controlled, solvent-free pressure-assisted micro-syringe printing to produce OFs.

Methods: Solvent casting and pressure-assisted micro-syringe printing were employed to produce hybrid film structures composed of beeswax, polyvinyl alcohol, borax, and hydroxypropyl methylcellulose, loaded with betamethasone as a model drug. The films were characterized by scanning electron microscopy for their physical appearance, mechanical properties, surface structure, and ultrastructural morphology, as well as their drug content and in vitro drug release.

Results: Films without the drug showed greater irregularities and roughness compared to the drug-loaded films. The physical properties of the formulations improved through three-dimensional (3D) printing.

Conclusion: By using 3D printing methods in pharmaceuticals, the treatment procedure would be highly acceptable to patients, increasing their treatment adherence. It is also useful for personal drug delivery.