Peripheral blood mononuclear cells show markers of mitochondrial dysfunction in rheumatoid arthritis.

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.

Association of proprotein convertase subtilisin/kexin type 9 protein and oxidative stress indicators in women with preeclampsia: A case-control study.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein is one of the factors associated with oxidative stress and dyslipidemia disorders. Objective: This study aimed to evaluate the lipid profile, PCSK9 levels, and oxidative stress in preeclampsia. Materials and Methods: This case-control study was conducted at Sina hospital in Hamadan University of Medical Sciences, Hamadan, Iran from August 2020-May 2021. The average maternal age of included participants was 30 yr with 30 preeclampsia and 30 healthy pregnant women. After clinical examination, the fasting blood samples were collected, and the serum PCSK9 protein concentration, superoxide dismutase, glutathione peroxidase activities, and glutathione levels were determined by enzyme-linked immunosorbent assay. Total antioxidant capacity, total oxidant status, and malondialdehyde levels were determined manually. Results: The average maternal age of participants were 29.97 ± 4.75 and 31.23 ± 5.85 yr, respectively. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), PCSK9, total antioxidant capacity, and malondialdehyde levels were higher in the preeclampsia group compared with control (p < 0.02). Total oxidant status, glutathione levels, superoxide dismutase, glutathione peroxidase activities were lower in the cases group compared with the control group (p < 0.01). The PCSK9 variable had a significant negative association with antioxidant parameters; however, a significant positive association was observed between PCSK9 level and parameters of LDL-C. Conclusion: PCSK9 is associated with increased serum levels of LDL-C and oxidative factors in pregnant women that increase the risk of endothelial damage and hypertension in preeclampsia.

Is nanoparaquat safer than bulk paraquat? An in vitro and in vivo evaluation.

Paraquat (PQ) is an herbicide which has brought some health problems through the production of reactive oxygen species. The increasing interest in the novel formulation of agrochemicals has been aiming to provide safety for non-target organisms. Chitosan is a well-known non-toxic polymer, commonly used in preparing particles via ionotropic gelation. In this study, we prepared PQ nanoparticles (PQNPs) and evaluated their toxicity in vivo and in vitro. PQNPs were prepared and characterized in two forms, with and without the utilization of chitosan. Relative cell survival of PQNPs were studied against bulk PQ in HEK-293. Also, the acute lung injury of PQNP was assessed against treatment with acetylcysteine. Total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), and hydroxyproline, along with histological changes were assessed in the lungs. The size, zeta potential, and polydispersity index of the optimum particles were about 157.7 ± 7.03, 22.25 ± 4.52, and 0.701, respectively. The encapsulation efficiency was 65.11 ± 10.45, and the loading percent of PQ was 58.57 ± 2.37. PQNPs showed an initial burst of PQ release followed by a zero-degree pattern. PQNPs displayed lower cell cytotoxicity compared to bulk PQ. LPO, TAC, TTG, and hydroxyproline levels in lungs generally showed more satisfying status in PQNPQs as well. The levels of oxidative status markers indicate lower oxidative damage in lungs and a more desirable response to acetylcysteine treatment, in line with histological changes. PQ loaded in chitosan-alginate particles offers safer characteristics compared with bulk PQ.