Background: Abnormal expression of inflammatory cytokines in major depressive disorder (MDD) suggests the activation of an inflammatory process. The pattern of alterations in cytokine levels is still ambiguous. The present study aimed to evaluate interleukin-7 (IL-7) and interleukin-10 (IL-10) for their involvement in the pathophysiology of MDD and determine their relationships with depression risk. Methods: The study included 166 medication-free subjects: 84 MDD patients and 82 sex- and age-matched healthy controls (HCs). A qualified psychiatrist diagnosed patients and evaluated controls based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Hamilton depression rating scale (Ham-D) was used to measure the severity of depression in MDD patients. Serum IL-7 and IL-10 levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results: Compared with HCs, the serum levels of IL-7 were significantly decreased, whereas that of IL-10 increased in MDD patients. Moreover, the severity of depression is correlated with the altered levels of IL-7 and IL-10 in MDD patients. We found a negative correlation between IL-7 and Hamilton depression rating (Ham-D) scores ( r = –0.580, p < 0.05), whereas there was a positive correlation between IL-10 and Ham-D scores ( r = 0.555, p < 0.05). Conclusions: The altered levels of serum IL-7 and IL-10 in MDD patients may represent a homeostatic mechanism that enhances the inflammatory process during depression. The alterations of these cytokine levels in MDD and their association with the severity of depression support them as promising, but there may still be controversial factors for understanding the pathophysiology of depression.
The main objective of this study was to determine the possible effects of thymoquinone (TQ) and curcumin (Cur) on immune-response and pathogenesis of H9N2 avian influenza virus (AIV) in turkeys. The experiment was performed on 75 non-vaccinated mixed-sex turkey poults, divided into 5 experimental groups (A, B, C, D, and E) of 15 birds each. Group A was kept as non-infected and a non-treated negative control (ctrl group) while group B was kept as infected and non-treated positive control (H9N2 group). Turkeys in groups A and B received normal commercial feed while turkeys in groups C and D received TQ, and Cur respectively, and group E concurrently received TQ and Cur from d one through the entire experiment period. All groups were challenged intra-nasally with H9N2 AIV (A/chicken/Pakistan/10RS3039-284-48/2010) at the fourth wk of age except group A. Infected turkeys showed clinical signs of different severity, showing the most prominent disease signs in turkeys in group B. All infected turkeys showed positive results for virus shedding; however, the pattern of virus shedding was different, and with turkeys in group B showing more pronounced virus secretion than the turkeys in the other groups receiving different levels of TQ and Cur. Moreover, significantly higher antibody titer against H9N2 AIV in turkeys shows the immunomodulatory nature of TQ and Cur. Similarly, increased cytokine gene expression suggests antiviral behavior of TQ and Cur especially in combination, leading to suppressed pathogenesis of H9N2 viruses. However, reduced virus shedding and enhanced immune responses were more pronounced in those turkeys receiving TQ and Cur concurrently. This study showed that supplements of TQ and Cur in combination would significantly enhance immune responsiveness and suppress pathogenicity of influenza viruses in turkeys.
Hepatocellular carcinoma (HCC) is the world’s third most widespread cancer. Currently available circulating biomarkers for this silently progressing malignancy are not sufficiently specific and sensitive to meet all clinical needs. There is an imminent and pressing need for the identification of novel circulating biomarkers to increase disease-free survival rate. In order to facilitate the selection of the most promising circulating protein biomarkers, we attempted to define an objective method likely to have a significant impact on the analysis of vast data generated from cutting-edge technologies. Current study exploits data available in seven publicly accessible gene and protein databases, unveiling 731 liver-specific proteins through initial enrichment analysis. Verification of expression profiles followed by integration of proteomic datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 previously characterized circulating HCC biomarkers. Finally, interactome analysis of these proteins with midkine (MDK), dickkopf-1 (DKK-1), current standard HCC biomarker alpha-fetoprotein (AFP), its interacting partners in conjunction with HCC-specific circulating and liver deregulated miRNAs target filtration highlighted seven novel statistically significant putative biomarkers including complement component 8, alpha (C8A), mannose binding lectin (MBL2), antithrombin III (SERPINC1), 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), alcohol dehydrogenase 6 (ADH6), beta-ureidopropionase (UPB1) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6). Our proposed methodology provides a swift assortment process for biomarker prioritization that eventually reduces the economic burden of experimental evaluation. Further dedicated validation studies of potential putative biomarkers on HCC patient blood samples are warranted. We hope that the use of such integrative secretome, interactome and miRNAs target filtration approach will accelerate the selection of high-priority biomarkers for other diseases as well, that are more amenable to downstream clinical validation experiments.
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