The effect of hydraulic retention time on the performance and fouling characteristics of membrane sequencing batch reactors used for the treatment of synthetic petroleum refinery wastewater

The use of membrane sequencing batch reactors, operated at HRT of 8, 16 and 24 h, was considered for the treatment of a synthetic petroleum wastewater. Increase in HRT resulted in statistically significant decrease in MLSS. Removal efficiencies higher than 97% were found for the three model hydrocarbon pollutants at all HRTs, with air stripping making a small contribution to overall removal. Particle size distribution (PSD) and microscopic analysis showed reduction in the protozoan populations in the activated sludge with decreasing HRT. PSD analysis also showed a higher proportion of larger and smaller sized particles at the lowest HRT. The rate of membrane fouling was found to increase with decreasing HRT; SMP, especially carbohydrate SMP, and mixed liquor apparent viscosity also showed a pronounced increase with decreasing HRT, whereas the concentration of EPS and its components decreased. FTIR analysis identified organic compounds as the main component of membrane pore fouling.     

Autoantibody-mediated IL-6-dependent endothelin-1 elevation underlies pathogenesis in a mouse model of preeclampsia

Preeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy. Elevated circulating endothelin-1 (ET-1) is associated with the disease. However the molecular basis of increased ET-1 production and its role in PE are unknown. This study aimed to investigate the causative factors, pathological role of elevated ET-1 production in PE, and the underlying mechanisms. In this study, we found that IgG from women with PE, in contrast to IgG from normotensive pregnant women, induced preproET-1 mRNA expression via angiotensin II type 1 receptor activation in kidneys and placentas in pregnant mice. The ET-A receptor-specific antagonist BQ123 significantly attenuated autoantibody-induced hypertension, proteinuria, and renal damage in pregnant mice, demonstrating that autoantibody-induced ET-1 production contributes to pathophysiology. Mechanistically, we discovered that IL-6 functioned downstream of TNF-α signaling, contributing to increased ET-1 production in pregnant mice. IL-6 blockade inhibited preeclamptic features in autoantibody-injected pregnant mice. Extending the data to human studies, we found that IL-6 was a key cytokine underlying ET-1 induction mediated by IgG from women with PE in human placental villous explants and that endothelial cells are a key source of ET-1. Overall, we provide human and mouse studies showing that angiotensin II type I receptor-agonistic autoantibody is a novel causative factor responsible for elevated ET-1 production and that increased TNF-α/IL-6 signaling is a key mechanism underlying increased ET-1 production and subsequent maternal features. Significantly, our findings revealed novel factors and signaling cascades involved in ET-1 production, subsequent disease symptom development, and possible therapeutic intervention in the management of PE.     

Angiotensin receptors, autoimmunity, and preeclampsia

Preeclampsia is a pregnancy-induced hypertensive disorder that causes substantial maternal and fetal morbidity and mortality. Despite being a leading cause of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Recent studies indicate that women with preeclampsia have autoantibodies that activate the angiotensin receptor, AT1, and that autoantibody-mediated receptor activation contributes to pathophysiology associated with preeclampsia. The research reviewed here raises the intriguing possibility that preeclampsia may be a pregnancy-induced autoimmune disease.     

Activation of BRCA1/BRCA2-associated helicase BACH1 is required for timely progression through S phase

BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G(1) phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability.     

High-density lipoprotein functionality and breast cancer: A potential therapeutic target

Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high-density lipoprotein (HDL)-cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.     

Involvement of TNF-α in differential gene expression pattern of CXCR4 on human marrow-derived mesenchymal stem cells

Cell therapy and tissue repair are used in a variety of diseases including tissue and organ transplantation, autoimmune diseases and cancers. Now mesenchymal stem cells (MSCs) are an attractive and promising source for cell-based therapy according to their individual characteristics. Soluble factors which are able to induce MSCs migration have a vital role in cell engraftment and tissue regeneration. Tumor necrosis factor α (TNF-α) is a major cytokine present in damaged tissues. We have investigated the pattern of gene expression of chemokine receptor CXCR4 in nine groups of human bone marrow-derived MSCs stimulated with TNF-α in different dose and time manner. Comparison of TNF-α treated with untreated MSCs revealed the highest expression level of CXCR4 after treatment with 1, and 10 ng/ml of TNF-α in 24 h, and the production of CXCR4 mRNA was regulated up to 216 and 512 fold, respectively. Our results demonstrated the differential gene expression pattern of chemokine receptor CXCR4 in human marrow-derived MSCs stimulated with inflammatory cytokine TNF-α. These findings suggest that in vitro control of both dose and time factors may be important in stem cell migration capacity, and perhaps in future-stem cell transplantation therapies.     

Evaluation of Lovastatin Effects on Expression of Anti-apoptotic Nrf2 and PGC-1α Genes in Neural Stem Cells Treated with Hydrogen Peroxide

Reactive oxygen species and oxidative stress are associated with various cell processes, including cell survival and apoptosis. Oxidative stress has been implicated in the pathogenesis of several neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). In the present study, we evaluated the effects of lovastatin chemoprotection against hydrogen peroxide-induced oxidative stress in bone marrow stromal cell-derived neural stem cells (BMSC-derived NSCs) and whether it has protective effects. BMSC-derived NSCs were pretreated with different doses of lovastatin for 48 h and then exposed to 125 μM H₂O₂ for 30 min. Using MTT, TUNEL assay, and real-time RT-PCR, we evaluated the effects of lovastatin on cell survival, apoptosis, and PGC-1α and Nrf2 expression rates in pretreated BMSC-derived NSCs compared to control groups. Results showed that apoptosis rate in the lovastatin-pretreated BMSC-derived NSCs was significantly decreased compared to the control group. Our findings suggest that lovastatin protects NSCs against oxidative stress-induced cell death, and therefore, it may be used to promote the survival rate of NSCs and can be a candidate for treatment of oxidative stress-mediated neurological diseases.