Iraj Khodadadi

The low cost, and pro-apoptotic property of gold nanoparticles (AuNPs) make them an attractive candidate for the investigation in cancer therapy. Despite promising advances made in cancer research using AuNPs, the molecular mechanisms involved in AuNPs-induced cell death is still remaining largely unknown. This study was undertaken to elucidate the anticancer property of AuNPs by determining the involvement of AuNPs-induced reactive oxygen species (ROS) in the stimulation of autophagy in MCF-7 human breast cancer cells. In this experimental study MCF-7 cells were cultivated in 6-well plates in the presence or absence of AuNPs for 24 h. In addition, to confirm the pivotal role of AuNPs in ROS generation, AuNPs-treated cells were also cultured in the presence of N-acetylcysteine (NAC; as an antioxidant agent) and hydroxychloroquine (HCQ; as an inhibitor of autophagosome formation). Then, the ROS contents of the cells were determined and the effects of AuNPs in the formation of autophagosome and induction of apoptosis were investigated. Also, the relative expression levels of Bax, Bcl2, MAPK P38, JNK, Beclin-1, and LC3 mRNA were analyzed by RT-qPCR and the protein contents of LC3-I/II and Beclin-1 were measured. AuNPs-induced generation of ROS was prevented by the administration of NAC. AuNPs increased formation of autophagosomes and enhanced the expression of autophagy-related proteins such as LC3 and Beclin-1. Moreover, AuNPs triggered apoptosis, increased the ratio of Bax to Bcl-2 gene expression level, and resulted in the loss of mitochondrial membrane potential. In AuNPs-treated cells, the involvement of ROS in boosting autophagy process and increasing apoptosis was confirmed by the ROS-scavenging effects of NAC which successfully suppressed ROS level and prevented autophagy and apoptosis. Our finding suggest that AuNPs-induced ROS can promote autophagy and apoptosis via mitochondrial dysfunction and regulation of the ROS/JNK signaling pathway in MCF-7 cancer cells. Thereby highlighting the potential therapeutic value of AuNPs as anticancer agents.

Golestannejad E, et al. Chonnam Med J. 2026 May;62(2):64-78. https://doi.org/10.4068/cmj.2026.62.2.64

Objective: Multiple sclerosis ( MS ) is characterized by chronic neuroinflammation and oxidative stress. Vitamin D is believed to exert immunomodulatory and antioxidant effects, yet its impact on specific inflammatory proteins such as CHI3L1 ( YKL ‐40) in MS remains unclear. This study evaluated whether 8‐week vitamin D3 supplementation affects serum CHI3L1 levels, oxidative stress markers, and antioxidant enzyme activities in patients with MS . Methods: In this single‐arm pre‐post clinical trial, 35 patients with MS (aged 30–56 years) received oral vitamin D3 supplementation (50 000 IU /week) for 8 weeks. Serum 25( OH )D and CHI3L1 levels were determined using commercial enzyme‐linked immunosorbent assay ( ELISA ) kits. oxidative stress markers were measured pre‐ and post‐intervention using commercial colorimetric kits. Statistical analysis was performed using paired t ‐tests or Wilcoxon signed‐rank tests. Results: Vitamin D3 supplementation significantly increased serum 25( OH )D levels (20.80 ± 8.6 to 39.11 ± 12.26 ng/ mL ; p < 0.001). CHI3L1 concentration decreased by 21.7% (33.28 ± 8.9 to 26.05 ± 9.1 ng/ mL ; p < 0.001). oxidative stress was reduced, evidenced by lower TOS (1.55 ± 0.50 to 0.59 ± 0.23 mmol H ₂ O ₂ equiv./L; p < 0.001) and MDA (0.08 ± 0.03 to 0.05 ± 0.026 nmol/ mL ; p < 0.001). Antioxidant capacity improved, as demonstrated by elevated TAC (0.622 ± 0.138 to 0.797 ± 0.15 mmol Fe ²⁺ /L; p < 0.001) and increased activities of SOD (10.5%; p < 0.001), CAT (19.5%; p < 0.001), and GPx (35.6%; p < 0.05). Significant inverse correlations were observed between serum 25( OH )D and CHI3L1 ( r = −0.999, p < 0.001), TOS ( r = −0.456, p = 0.0058), and MDA ( r = −0.577, p < 0.001). Conclusion: Vitamin D3 supplementation was associated with reductions in CHI3L1 and oxidative stress markers, while suggesting enhancement of antioxidant capacity. This observed biomarker changes support vitamin D3 as a potential adjunct therapy targeting interconnected pathological pathways in MS.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Metabolic and mitochondrial dysregulation are critical causal factors in the pathogenesis and progression of RA. Mitochondrial dysfunction include abnormal energy metabolism, and excessive production of reactive oxygen species (ROS). This study aimed to investigate the adenosine triphosphate (ATP), mitochondrial membrane potential (ΔΨm), ROS, and mRNA expression level of ROMO1 (as ROS modulator) and OMA1 (as regulator mitochondrial dynamics) of peripheral blood mononuclear cells (PBMC) in RA patients. The study participants were 50 patients with RA and 50 sex‐ and age‐matched healthy volunteers. PBMC of all participant were isolated by Ficoll‐Paque. Alteration in ΔΨm and cellular ROS were measured using flow cytometry, ATP level was also assessed via luminometry, and ROMO1 and OMA1 mRNA expression via qRT‐PCR assay. A significant decrease in ATP (p = .005) and ΔΨm (p < .001) was observed in the PBMC of RA compared to control. The ROS levels were significantly higher in the PBMC of RA compared to the control (p < .001). ROMO1 and OMA1 mRNA expression was also significantly increased in RA patients compared to control (p < .001). The decrease in ATP is strongly associated with ROS increasing in PBMC of RA patients, denoting an inverse and negative relationship between ATP and ROS production. Also, a decrease in ΔΨm was observed. It seems that in line with mitochondrial dysfunction in PBMC, increased expression of ROMO1 and OMA1 genes could also be involved in the development of RA.

Background: Among the serum biomarkers of infectious diseases, calprotectin and heparin-binding protein (HBP) seem to be of clinical and diagnostic value in patients with COVID-19. Objectives: This study aimed to investigate the serum levels of calprotectin, HBP, and some other inflammatory markers in COVID-19 patients. Methods: In this case-control study, serum samples of 35 outpatients with COVID-19 and 35 healthy individuals were collected, and the levels of calprotectin, HBP, C-reactive protein (CRP), ferritin (FERR), as well as platelet (PLT) and neutrophil (NEU) counts and LDH activity, were determined. Results: At first, SARS-CoV2 viral RNA was detected in the pharyngeal swab specimens of COVID-19 patients. Calprotectin, FERR, and CRP levels, LDH activity, and PLT and NEU counts were found to be significantly higher in COVID-19 patients compared with controls (P < 0.05), whereas no statistically significant difference was observed in HBP level (P > 0.05). Serum calprotectin showed a significant correlation with CRP and FERR levels, LDH activity, and NEU count (P < 0.001). Conclusions: Our findings showed that an increment in serum calprotectin level, together with increased CRP levels, might be a promising indicator of SARS-CoV2 infection.

Purpose We hypothesized that immature oocytes are associated with impaired energy production in surrounding granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Thus, this study investigated mitochondrial function, determined expression of glycolytic regulatory enzymes, and measured ATP levels in GCs of PCOS patients. Methods GCs were isolated from forty-five PCOS patients and 45 control women. Intracellular concentration of reactive oxygen species (ROS), mitochondrial membrane potential (Δψ_m), the rate of glycolysis, total antioxidant capacity (TAC), activities of catalase (CAT) and superoxide dismutase (SOD), and ATP level were measured in GCs. The gene expression and protein levels of glycolytic enzymes (hexokinase, muscular phosphofructokinase, platelet derived phosphofructokinase, and muscular pyruvate kinase) were determined. Association of GC energy level with oocyte maturation was further validated by measuring glycolysis rate and ATP level in GCs isolated from mature and immature follicles from new set of fifteen PCOS patients and 15 controls. Results PCOS patients showed higher ROS level, decreased TAC, reduced CAT and SOD activities, and lower Δψ_m together with reduced expression of key glycolytic enzymes. ATP concentration and biochemical pregnancy were lower in PCOS compared with control group. ATP levels were found to be significantly correlated with ROS and Δψ_m (r = − 0.624 and r = 0.487, respectively). GCs isolated from immature follicles had significantly lower ATP levels and rate of glycolysis compared with the GCs separated from mature follicles in both PCOS patients and control. Conclusion Declined energy due to the mitochondrial dysfunction and restrained glycolysis in GCs is associated with the immature oocytes and lower biochemical pregnancy in PCOS. Graphical Abstract