Deregulation of miR-93 and miR-143 in human esophageal cancer

Tumor Biology - Esophageal squamous cell carcinoma (ESCC) is the second and third most common malignancy in Iranian males and females, respectively. Treatment of ESCC is largely ineffective due to...     

Upregulation of neutrophil gelatinase-associated lipocalin, NGAL/Lcn2, in beta-thalassemia patients

BACKGROUND: One of the major consequences in beta- thalassemia is iron overload. Oxidative statuses have been reported in beta-thalassemia patients by several studies. It has been proven that iron plays a critical role in the formation of reactive oxygen species (ROS). More recently, we have found the induction of Lcn2/NGAL expression under oxidative stress condition. In this study, it was assumed that NGAL should be upregulated in beta-thalassemia patients because of oxidative stress condition. METHODS: Assessment of NGAL expressions in 25 adult beta-thalassemia and 9 pediatric patients was performed by semiquantitative RT-PCR, real-time RT-PCR and ELISA. RESULTS: Adult beta-thalassemia patients upregulated NGAL expression compared with the normal samples but no upregulation was observed in pediatric patients. CONCLUSIONS: Upregulation may play an important role in decreasing ROS or iron in beta-thalassemia patients.     

Immune responses to hepatitis B immunization 10–18 years after primary vaccination: a population‐based cohort study

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10–18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti‐HB surface antibody (HBsAb). Those with an HBsAb level of <10 IU/mL received a booster dose of the vaccine with subsequent doses to those without protective titres. HBsAb concentrations were determined 4 weeks after each dose of the booster vaccine. The data were analysed separately for three age groups: 10–11, 12–14 and 15–18 years old. A total of 541 healthy individuals were studied. The highest seroprotection rate of 48% was observed in the youngest vaccinees (10–11 years old). This declined to 26.5% in the oldest (15–18 years old) group (P = 0.008). The youngest vaccinees showed the highest rate of anamnestic immune responses (96%). However, 25% of oldest individuals failed to mount an anamnestic immune response in challenge with a booster dose of the vaccine (P = 0.005), suggesting waning immunity with increasing age. Age (OR: 0.80; P = 0.01) and prebooster HBsAb levels (OR: 0.37; P = 0.01) identified responders to first booster doses of the vaccine by logistic regression analysis. The majority of high‐risk vaccinees showed anamnestic immune response 10–11 years after primary immunization. However, we found a significant proportion (25%) of older individuals with no anamnetic response, which suggests a waning of immune memory. Detailed long‐term follow‐up studies are necessary to determine the risk of natural infection among these individuals before a booster schedule can be recommended.     

Mesenchymal Stem Cells on Horizon: A New Arsenal of Therapeutic Agents

Over 10 years, mesenchymal stem cells (MSCs) have been considered as valuable and suitable cells for cell-based therapy applications, particularly in clinical trials. In any case, they are as yet not utilized routinely in clinics. At first, it was believed that MSCs play their roles, especially in regenerative medicine due to their differentiation and cell replacement properties. Interestingly, it is well-known that MSCs mainly exert their therapeutic effects through their vast bioactive factors. These findings turned scientists’ consideration toward cell-free therapy concepts. From this point of view, MSCs can be considered as an arsenal of natural bioreactors in variety of therapeutic agents. MSCs inherently express various important therapeutic agents such as growth factors and cytokines that can be manufactured, handled and stored as a prepared-to-go biologic product. In this review, we provide a vision, highlight as well as discuss in order to introduce competitive natural robust bioreactor MSCs on the horizon.     

Neutrophil gelatinase-associated lipocalin acts as a protective factor against H(2)O(2) toxicity

BACKGROUND: Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily for which a variety of functions have been reported. However, the precise biological roles of NGAL are not fully known. We have investigated the ability of NGAL to prevent H(2)O(2) toxicity, which is considered to be the classical inducer of oxidative stress caused by ROS generation in an in vitro model. METHODS: NGAL cDNA was isolated from HepG2 cell line and cloned to pcDNA3.1(+) vector. The construct was transfected to CHO cell line. Stable clones were generated, and the expression of NGAL was determined by RT-PCR, Western blot analysis and ELISA. NGAL gene in A549 cell line was downregulated with the siRNA. CHO and A549 cells were intoxicated with H(2)O(2) and cell proliferation was performed by MTT assay. Apoptotic cells were detected by flow cytometry. RESULTS: Cell proliferation was higher in CHO expressing NGAL in doses of 5 and 10 mM H(2)O(2) after 2h compared with the control. H(2)O(2) was also more toxic in the presence of NGAL siRNA compared with the control in A549 cell. Our results also revealed that NGAL protect cells from apoptosis. CONCLUSIONS: Overall, our results revealed for the first time a new function for NGAL/Lcn2: acting as a protective factor against H(2)O(2) toxicity. In the future, NGAL may have the potential application to ameliorate the toxicity induced by oxidative stress conditions.     

Oxidative stress induced lipocalin 2 gene expression: addressing its expression under the harmful conditions

Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily with diverse functions such as the transport of fatty acids and the induction of apoptosis. Previous reports indicated that expression of Lcn2 is induced under harmful conditions. However, the mechanisms of the induction of Lcn2 expression remain to be elucidated. In this report, we intended to identify the factor or factors that induce Lcn2 expression. Up-regulation of Lcn2 expression after X-ray exposure was detected in the heart, the kidney and especially in the liver. Primary culture of liver component cells revealed that this up-regulation in the liver was induced in hepatocytes. Up-regulation of Lcn2 expression was also detected in HepG2 cells after the administration of X-rays or H(2)O(2). Interestingly, up-regulation of Lcn2 expression after H(2)O(2) treatment was canceled by the addition of the anti-oxidants, dimethylsulfoxide or cysteamine. These results strongly suggest that Lcn2 expression is induced by reactive oxygen species. Therefore, Lcn2 could be a useful biomarker to identify oxidative stress both in vitro and in vivo.     

Chitosan‐Coated Superparamagnetic Iron Oxide Nanoparticles for Doxorubicin Delivery: Synthesis and Anticancer Effect Against Human Ovarian Cancer Cells

Doxorubicin‐loaded chitosan‐coated superparamagnetic iron oxide nanoparticles (Fe₃O₄; SPIO‐NPs) were prepared by coprecipitation and emulsification cross‐linking method and uniform NPs with an average particle size of 82 nm, with high encapsulation efficiencies, were obtained. The drug‐loading efficiency of doxorubicin (3.2 mg/mg NPs) showed better results for the chitosan‐loaded SPIO‐NPs as compared to the bare ones (0.5 mg/mg; p < 0.05). The incubation of A2780 and OVCAR‐3 human ovarian cancer cells with doxorubicin‐loaded and doxorubicin‐loaded chitosan‐coated SPIO‐NPs, for 24, 48, 72, 96, and 120 h, showed significant IC₅₀ (2.0 ± 0.6 and 7.1 ± 2.7 mm doxorubicin) and IC₉₀ (4.0 ± 9.2 and 10 ± 0.5 mm doxorubicin), respectively, after 96 h of incubation. While, 95% and 98% growth inhibition was seen in A2780 and OVCAR‐3 cells after the 96‐h exposure to the doxorubicin‐chitosan‐SPIO‐NPs (p < 0.05). A 5‐day (120 h) incubation with doxorubicin‐chitosan‐SPIO‐NPs showed that A2780 and OVCAR‐3 cells were able to uptake 120 and 110 pg iron/cell, respectively, when treated with doxorubicin‐chitosan‐SPIO‐NPs for 72 h (p < 0.05).