Is Cataract in Patients under 60 Years Associated with Oxidative Stress?

Oxidative stress is considered as a possible factor in the genesis of cataract. The study aimed to determine the systemic antioxidant status in cataract patients under 60 years. We studied 28 consecutive cataract patients, mean of 53 years (SD = 9.2), a range of 22-60 and 37 controls. In erythrocytes, activity of antioxidant enzymes was determined: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), in contrast with plasma concentrations of vitamin A and E. Conjugated dienes (CD) level and protein carbonyls (PC) concentration were also determined in plasma. Malondialdehyde (MDA) concentrations in erythrocytes and plasma were also measured. SOD and GPx activity and vitamin A and E concentrations were lower in cataract patients (p = 0.000511, 0.02, 0.022, and 0.000006, respectively). MDA plasma and erythrocytes concentrations were higher in cataract patients (p = 0.000001 and 0.0000001, respectively). PC concentration was higher in cataract patients than in controls (p = 0.00000013). There were statistically significant correlations between oxidative stress markers both in the cataract patients group as well as in the control group. Cataract incidence in patients under 60 years seems to be accompanied by enhanced lipid peroxidation and protein oxidation, as well as antioxidant defense depletion. Thus, supplementation with antioxidants could be beneficial in this group of patients.

Inhibition of lymphangiogenesis impairs antitumour effects of photodynamic therapy and checkpoint inhibitors in mice.

Photodynamic therapy (PDT) has been shown to destroy tumour-associated lymphatic vessels. Therefore, we sought to investigate the functional outcomes of PDT-mediated damage to the lymphatic vessels. We observed that PDT with verteporfin, completely but transiently, blocks the functional lymphatic drainage in the orthotopic mammary tumour models. Sustained inhibition of lymphatic vessels regeneration induced by lenalidomide or the soluble form of vascular endothelial growth factor receptor 3 (sVEGFR3) that neutralises lymphangiogenic vascular endothelial growth factor C (VEGF-C), significantly impaired antitumour efficacy of PDT. Antilymphangiogenic compounds also significantly inhibited the ability of intratumourally inoculated dendritic cells (DCs) to translocate to local lymph nodes and diminished the number of tumour-infiltrating interferon-γ-secreting or tumour antigen-specific CD8+ T cells. Lenalidomide also abrogated antitumour effects of the combination immunotherapy with PDT and anti-programmed death-ligand 1 (PD-L1) antibodies. Altogether, these findings indicate that PDT-mediated damage to the lymphatic vessels negatively affects development of antitumour immunity, and that drugs that impair lymphatic vessel regeneration might not be suitable for the use in combination with PDT.

Efficacy and safety of radioiodine therapy for mild Graves ophthalmopathy depending on cigarette consumption: a 6­month follow­up.

INTRODUCTION    Graves ophthalmopathy (GO) is an autoimmune disease associated with Graves disease. Its treatment is largely dependent on the severity and activity of ocular lesions. Particular attention should be given to radioiodine (RAI) therapy. Although its use is a valuable therapeutic option for hyperthyroidism, it may be followed by worsening of GO.  OBJECTIVES    The aim of the present study was to analyze how the severity of nicotine addiction affects the response to RAI treatment in patients with GO. PATIENTS AND METHODS    A total of 106 patients (58 smokers and 48 nonsmokers) with mild GO treated with 800 MBq of RAI were included to the study. We assessed the serum levels of thyroid­stimulating hormone (TSH), thyroid hormones, autoantibodies against thyroperoxidase, thyroglobulin, and TSH receptor (TSHR­Abs), as well as urinary cotinine levels and severity of ophthalmopathy. Analyses were conducted at baseline (before RAI treatment) and 2 and 6 months after the therapy. RESULTS    Significant differences in serum levels of TSHR­Abs were found between nonsmokers and smokers at 2 and 6 months after RAI therapy, whereas there were no differences at baseline. In smokers, there were significant differences in the severity of ophthalmopathy and the concentration of serum TSHR­Abs assessed at baseline and at 6 months of follow­up. Six months after RAI therapy, 46.2% of smokers and 4.3% of nonsmokers (P <0.001) progressed from mild to moderate GO.  CONCLUSIONS    High urinary cotinine levels in smokers were associated with the deterioration of ocular lesions after RAI treatment. A high dose of RAI did not induce an exacerbation of GO in nonsmokers who were administered oral steroid prophylaxis.

Adenanthin targets proteins involved in the regulation of disulphide bonds.

Adenanthin has been recently shown to inhibit the enzymatic activities of peroxiredoxins (Prdx) I and II through its functional α,ß-unsaturated ketone group serving as a Michael acceptor. A similar group is found in SK053, a compound recently developed by our group to target the thioredoxin-thioredoxin reductase (Trx-TrxR) system. This work provides evidence that next to Prdx I and II adenanthin targets additional proteins including thioredoxin-thioredoxin reductase system as well as protein disulfide isomerase (PDI) that contain a characteristic structural motif, referred to as a thioredoxin fold. Adenanthin inhibits the activity of Trx-TR system and PDI in vitro in the insulin reduction assay and decreases the activity of Trx in cultured cells. Moreover, we identified Trx-1 as an adenanthin binding protein in cells incubated with biotinylated adenanthin as an affinity probe. The results of our studies indicate that adenanthin is a mechanism-selective, rather than an enzyme-specific inhibitor of enzymes containing readily accessible, nucleophilic cysteines. This observation might be of importance in considering potential therapeutic applications of adenanthin to include a range of diseases, where aberrant activity of Prdx, Trx-TrxR and PDI is involved in their pathogenesis.