Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron’s axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8+ T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.
Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed.
Background: Natalizumab is a humanized monoclonal antibody directed against very late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple sclerosis. Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance. Methods: Longitudinal ex vivo and in vitro study to determine the effect of natalizumab on the frequency of distinct immune cells and on the frequency and suppressive function of natural CD4+CD25+ regulatory T cells (Tregs). Results: Natalizumab binding to VLA-4 was more marked for B cells than for T cells (49% reduction in VLA-4-expressing B cells compared to 24.5% reduction of T cells). There was an increase in circulating B cells over T cells (2.6 vs. 1.5 fold, p < 0.001). Natural killer cells increased 1.5-fold (p = 0.01). Natalizumab led to a relative decrease in CD4+CD25+ Tregs from 18.9 to 14.1% (p = 0.04). The impaired suppressive capacity of Tregs was not restored. Conclusion: Natalizumab reduces VLA-4 expression on all investigated immune cells, but changes were most marked for B cells. Further differential effects on immune cells may be relevant to opportunistic central nervous system infections during treatment with natalizumab.
Ebola virus (EBOV), member of genus Ebolavirus, family Filoviridae, have a non-segmented, single-stranded RNA that contains seven genes: (a) nucleoprotein (NP), (b) viral protein 35 (VP35), (c) VP40, (d) glycoprotein (GP), (e) VP30, (f) VP24, and (g) RNA polymerase (L). All genes encode for one protein each except GP, producing three pre-proteins due to the transcriptional editing. These pre-proteins are translated into four products, namely: (a) soluble secreted glycoprotein (sGP), (b) Δ-peptide, (c) full-length transmembrane spike glycoprotein (GP), and (d) soluble small secreted glycoprotein (ssGP). Further, shed GP is released from infected cells due to cleavage of GP by tumor necrosis factor α-converting enzyme (TACE). This review presents a detailed discussion on various functional aspects of all EBOV proteins and their residues. An introduction to ebolaviruses and their life cycle is also provided for clarity of the available analysis. We believe that this review will help understand the roles played by different EBOV proteins in the pathogenesis of the disease. It will help in targeting significant protein residues for therapeutic and multi-protein/peptide vaccine development.
Altered expression of many genes and proteins is essential for cancer development and progression. Recently, the affected expression of metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric, has been implicated in various aspects of cancer progression and metastasis. Elevated expression of MTDH/AEG-1 has been reported in many cancers including breast, prostate, liver, and esophageal cancers, whereas its expression is low or absent in non-malignant tissues. These expression studies suggest that MTDH may represent a potential tumor associated antigen. MTDH also regulates multiple signaling pathways including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK which cooperate to promote the tumorigenic and metastatic potential of transformed cells. Several microRNA have also been found to be associated with the increased MTDH expression in different cancers. Increased MTDH levels were linked to the tumor chemoresistance making it an attractive novel therapeutic target. In this review, we summarize data on MTDH function in various cancers.
Context Dunaliella salina Teodoresco (Dunaliellaceae) is one of the promising microalgae consumed as food and medicine for many years. Objective Dunaliella salina was grown under different stress conditions for enhancing carotene production. The carotene enriched extract was evaluated for antioxidant and cytotoxic activity. Materials and methods Carotene content was calculated under salinity, nitrogen and temperature stress conditions. Antioxidant activity was determined through DPPH assay by incubating the samples for 45 min with 250 μg/mL of extract and reducing power assay was performed with 50, 100, 150 and 200 μg/mL of extract. Cytotoxicity was determined by incubating ∼2 × 104 MCF-7 (breast cancer) cells with 250 μg of extract in each well for 72 h by MTT assay. Result Carotene content was significantly increased to 9.8 (3.5 M NaCl), 13.9 (37 °C), 8.2 (250 mM KNO3) and 10.6 μg/mL (nitrogen-depleted medium) as compared with 3.2 μg/mL in normal conditions (1.7 M NaCl, 0.75 mM KNO3 and 28 °C). Free radical scavenging activity increased at 3.0 and 3.5 M NaCl (27.8 and 57.5%, respectively), 37 °C (31.4%) and in nitrogen-depleted medium (41.9%) compared with normal (15%) conditions. Carotene content and scavenging activity were positively correlated under salinity (r = 0.97), temperature (r = 0.85) and nitrogen (r = 0.7) stress conditions. Cytotoxicity against MCF-7 cell lines increased due to increase in carotene content suggesting that cytotoxicity may be associated with carotene accumulation. Discussion and conclusions Carotene content enhanced by D. salina under stress conditions increased the antioxidant and cytotoxic activity.