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Samaneh Abolbashari,1,* Susan Darroudi,1,* Maryam Tayefi,2,3 Zahra Khashyarmaneh,4 Parvin Zamani,5 Hamideh Moalemzadeh Haghighi,4 Amir Hooshang Mohammadpour,6,7 Shima Tavalaei,8 Mahsa Ahmadnezhad,9 Habibollah Esmaily,10 Gordon A Ferns,11 Zahra Meshkat,12 Majid Ghayour-Mobarhan8 1Student Research Committee, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 2Cardiovascular Research Center, Mashhad University of Medical Science, Mashhad, Iran; 3University International Accreditation, International Office, Clinical Research Unit, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 5Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 6Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 7Clinical Pharmacy Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; 8Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 9Nutrition Research Center, Department of Community Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran; 10Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran; 11Brighton and Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK; 12Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran *These authors contributed equally to this work Introduction: Copper (Cu) and zinc (Zn) are important trace elements that are also structural ions of superoxide dismutase (SOD), which reduce oxidative stress. Zinc deficiency and excess copper have been reported to be associated with inflammation. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus, which is believed to cause systemic inflammation. The aim of this study is to measure levels of Zn, Cu, SOD, and prooxidant–antioxidant balance (PAB) in HTLV-1-positive patients and investigate the association between serum Zn and Cu concentrations and levels of oxidative stress in them.Methods: The serum samples of 1,116 subjects who had participated in the “Mashhad Stroke and Heart Atherosclerotic Disorder” study, including 279 HTLV-1-positive and 837 HTLV-1-negative patients, were used. Levels of Zn, Cu, SOD, and PAB were measured.Results: Zinc and SOD levels were lower in the HTLV-1-positive group; however, the difference was statistically significant only for the level of SOD (P=0.003). On the other hand, levels of copper and PAB were significantly higher in HTLV-1 positive subjects; P=0.004 and P=0.002, respectively.Conclusion: In HTLV-infected patients, serum Zn concentration is lower and Cu concentration is higher than healthy controls. This altered situation might be either primary or secondary to HTLV-1 infection, which should be investigated in larger studies. We showed that SOD is significantly lower in HTLV-1-infected subjects. As in some other viruses that evolve different mechanisms to potentiate virus replication by changing the physiologic condition of host cells, HTLV-1 too probably decreases the activity of copper–zinc SOD1 by suppressing its gene.Keywords: HTLV-1, trace elements, superoxide dismutase, prooxidant-oxidant balance

Background: Clozapine is an atypical antipsychotic drug used to treat treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude its more common use as a first-line therapy for schizophrenia. Toxicoproteomic approaches have been demonstrated to effectively guide the identification of toxicological mechanisms. Methods: To further our understanding of the molecular effects of clozapine, we performed a data-independent acquisition (DIA)-based quantitative proteomics investigation of clozapine-treated human liver spheroid cultures. Results: In total, we quantified 4479 proteins across the five treatment groups (vehicle; 15 µM, 30 µM, and 60 µM clozapine; and 10 ng/mL TNFα + IL-1β). Clozapine (60 µM) treatment yielded 36 differentially expressed proteins (FDR < 0.05). Gene-set enrichment analysis indicated perturbation of several gene sets, including interferon gamma signaling (e.g. interferon gamma receptor 1) and prominent autophagy-related processes (e.g. upregulation of sequestosome-1 (SQSTM1), MAP1LC3B/LC3B2, GABARAPL2, and nuclear receptor coactivator 4). The effects of clozapine on autophagy were confirmed by targeted mass spectrometry and western blotting using conventional SQSTM1 and LC3B markers. Conclusions: Combined with prior literature, our work suggests a broad contribution of autophagy to both the therapeutic and side effects of clozapine. Overall, this study demonstrates how proteomics can contribute to the elucidation of physiological and toxicological mechanisms of drugs.

Temperature has a major impact on plant development and growth. In temperate climates, the seasonal temperature displays large variations that can affect the early stages of plant growth and development. Sessile organisms need to be capable of responding to these conditions, so that growth temperature induces morphological and physiological changes in the plant. Besides development, there are also important molecular and ultrastructural modifications allowing to cope with different temperatures. The chloroplast plays a crucial role in plant energetic metabolism and harbors the photosynthetic apparatus. The photosynthetic light reactions are at the interface between external physical conditions (light, temperature) and the cell biochemistry. Therefore, photosynthesis requires structural flexibility to be able to optimize its efficiency according to the changes of the external conditions. To investigate the effect of growth temperature on the photosynthetic apparatus, we followed the photosynthetic performances and analyzed the protein and lipid profiles of Lepidium sativum (cress) grown at three different temperatures. This revealed that plants developing at temperatures above the optimum have a lower photosynthetic efficiency. Moreover, plants grown under elevated and low temperatures showed a different galactolipid profile, especially the amount of saturated galactolipids decreased at low temperature and increased at high temperature. From the analysis of the chlorophyll a fluorescence induction, we assessed the impact of growth temperature on the re-oxidation of plastoquinone, which is the lipidic electron carrier of the photosynthetic electron transport chain. We show that, at low temperature, along with an increase of unsaturated structural lipids and plastochromanol, there is an increase of the plastoquinone oxidation rate in the dark. These results emphasize the importance of the thylakoid membrane composition in preserving the photosynthetic apparatus under non-optimal temperatures., (Copyright © 2020 Sattari Vayghan, Tavalaei, Grillon, Meyer, Ballabani, Glauser and Longoni.)

Depression and Anxiety are two important public health problems that are known to be associated with viral infections. The association between the intake of nutrients such as zinc and copper with symptoms of depression has been studied previously. The aim of the current study was to investigate the association between depression with human T cell lymphotropic virus type 1 (HTLV-1) infection and serum content of zinc and copper in a large Iranian population cohort. The study population consisted of 279 HTLV-1-positive patients who were identified after recruitment as part of a large cohort study: the Mashhad Stroke and Heart Association Disorder (MASHAD) study. They were divided into two groups of diagnosed with or without depression based on their symptoms. Serum zinc and copper levels of all subjects were measured using the flame atomic absorption spectrometry. The population sample comprised of 279 individuals infected with HTLV-1 of whom 192 (68.8%) were women. The mean serum zinc in the group with and without depression was 78.69 ± 13.79 μg/dl and 86.87 ± 19.44 μg/dl, respectively (p < 0.001). Also, the serum copper level was higher in the depressive group (116.75 ± 39.56) than in the non-depressive group (104.76 ± 30.77) (p 0.004). The association between serum zinc and copper with depression in HTLV-1-infected patients which was shown in this study could be considered in the treatment strategies in these patients.

Objective: Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl ester from HDL-C to LDL-C and VLDL-C. The aim of the present trial was to evaluate the effect of curcumin and its modified formulation on serum CETP concentrations in patients with metabolic syndrome., Materials and Methods: Participants were randomly allocated to one of three groups of 40 subjects receiving either unmodified curcumin or its phospholipid complex or placebo. Lipid profile and plasma CETP were measured at the start and six weeks after initiation of the treatment. The normality of data distribution was assessed by Kolmogorov-Smirnov test. Wilcoxon test was used for comparing the data before and after the intervention. The percent changes of CETP and biochemical factors among the three groups were compared using Kruskal-Wallis test., Results: Serum CETP levels were not significantly altered among patients receiving curcumin., Conclusion: Curcumin and its complex had no significant effect on serum CETP concentrations., Competing Interests: None.