Glycolysis is reduced in dengue virus 2 infected liver cells.

Infections with dengue virus (DENV) remain a worldwide public health problem. A number of bona fide cellular targets of DENV have been identified including liver cells. Despite the many lines of evidence confirming the involvement of hepatocytes during DENV infection, only a few studies have used proteomic analysis to understand the modulation of the cellular proteome occurring upon DENV infection.

A 2D-proteomic analysis identifies proteins differentially regulated by two different dengue virus serotypes.

The mosquito transmitted dengue virus (DENV) is a major public health problem in many tropical and sub-tropical countries around the world. Both vaccine development and drug development are complex as the species Dengue virus consist of four distinct viruses (DENV 1 to DENV 4) each of which is composed of multiple lineages and strains. To understand the interaction of DENV with the host cell machinery, several studies have undertaken in vitro proteomic analysis of different cell lines infected with DENV.

In-vitro antimalarial activity of methanolic leaf- and stem-derived extracts from four Annonaceae plants.

Objective: Plants in the Annonaceae family are known for having abundant biologically active secondary metabolites. They have been used in alternative drugs for various diseases in several countries, for instance, the bark of Cananga odorata (Lam.) Hook and Thomson is used for Ophthalmic inflammation and wound healing in Malaysia.

The anti-leukemic activity of a luteolin-apigenin enriched fraction from an edible and ethnomedicinal plant, Elsholtzia stachyodes, is exerted through an ER stress/autophagy/cell cycle arrest/ apoptotic cell death signaling axis.

Background: Elsholtzia is a genus in the family Lamiaceae, and some species in this genus are commonly used for food and in ethnomedicinal formulations by some ethnic groups of China and Thailand. Despite their apparent utility, few studies have been conducted to evaluate their potential as sources of medicinally active agents.

Purpose: We aimed to investigate the cytotoxicity of ethanolic extracts from three selected edible plant species of the genus Elsholtzia and the most promising extract was further characterized for the bioactive constituents and signaling mechanisms associated with the anti-leukemic activity.

An IgM monoclonal antibody against domain 1 of CD147 induces non-canonical RIPK-independent necroptosis in a cell type specific manner in hepatocellular carcinoma cells.

CD147/Basigin/EMMPRIN is overexpressed in several cancerous tissues and it has been shown to induce matrix metalloproteinases (MMPs) whose expression is associated with cancer metastasis. Thus, targeting CD147 with monoclonal antibodies (mAbs) potentially has therapeutic applications in cancer immunotherapy. Here, we report the use of anti-CD147 mAbs targeting domain 1 of CD147, namely M6-1D4 (IgM), M6-1F3 (IgM), M6-2F9 (IgM) and M6-1E9 (IgG2a), against several human cancer cell lines.

Cytotoxic and cytostatic effects of four Annonaceae plants on human cancer cell lines.

Several species of the Annonaceae plants have been used as complementary medicine for cancer-associated illnesses in some ethnic groups of northern Thailand. This study investigated the cytotoxic and cytostatic activity of methanolic extracts derived from the stems of these plants, including Uvaria longipes (Craib) L.L.

Functional characterization of lysosomal interaction of Akt with VRK2.

Serine-threonine kinase Akt (also known as PKB, protein kinase B), a core intracellular mediator of cell survival, is involved in various human cancers and has been suggested to play an important role in the regulation of autophagy in mammalian cells. Nonetheless, the physiological function of Akt in the lysosomes is currently unknown. We have reported previously that PtdIns(3)P-dependent lysosomal accumulation of the Akt-Phafin2 complex is a critical step for autophagy induction.

A First Phylogeny of the Genus Dimocarpus and Suggestions for Revision of Some Taxa Based on Molecular and Morphological Evidence.

Dimocarpus longan, commonly known as the longan, belongs to the family Sapindaceae, and is one of the most economically important fruits commonly cultivated in several regions in Asia. There are various cultivars of longan throughout the Thai-Malay peninsula region, but until now no phylogenetic analysis has been undertaken to determine the genetic relatedness of these cultivars. To address this issue, 6 loci, namely ITS2, matK, rbcL, trnH-psbA, trnL-I and trnL-trnF were amplified and sequenced from 40 individuals consisting of 26 longan cultivars 2 types of lychee and 8 herbarium samples.

A comprehensive ethnic-based analysis of alpha thalassaemia allelle frequency in northern Thailand.

Alpha (α)-thalassaemia is one of the most prevalent hereditary blood disorders, commonly affecting Southeast Asian people, with the highest incidence (30-40%) being seen in northern Thailand. However, this high incidence was estimated without consideration of the variations between ethnic populations and the geographical location of the populations. To address this issue, a total of 688 samples from 13 different northern Thai ethnic groups (30 villages) categorized into three linguistic groups were genotyped for deletional alpha-thalassaemia (-α, -α, -- and --) and/or non-deletional alpha-thalassaemia (α and α) via multiplex gap-PCR and dot-blot hybridization, respectively.

Cell cycle arrest and apoptosis induction by methanolic leaves extracts of four Annonaceae plants.

Background: Uvaria longipes (Craib) L.L.Zhou, Y.

Endogamous marriage and the prevalence of hemoglobin E in ethnic groups of northern Thailand.

Objective: To investigate the impact of the endogamous marriage culture on the prevalence of the hemoglobin E (HbE) recessive variant.

Methods: The prevalence of the hemoglobin E (HbE) recessive variant was determined by dot-blot hybridization in 4 endogamous villages (1 Mlabri and 3 Htin ethnic groups) in comparison with 9 other nearby non-endogamous populations.

Results: Although the overall HbE prevalence in the population studied (8.

Iron dysregulation in beta-thalassemia.

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis.

Hypermethylation of 28S ribosomal RNA in β-thalassemia trait carriers.

Ribosome biogenesis is the process of synthesis of the cellular ribosomes which mediate protein translation. Integral with the ribosomes are four cytoplasmic ribosomal RNAs (rRNAs) which show extensive post-transcriptional modifications including 2'-O-methylation and pseudouridylation. Several hereditary hematologic diseases including Diamond-Blackfan anemia have been shown to be associated with defects in ribosome biogenesis.

Correction: Hemoglobin E Prevalence among Ethnic Groups Residing in Malaria-Endemic Areas of Northern Thailand and Its Lack of Association with Plasmodium falciparum Invasion In Vitro.

[This corrects the article DOI: 10.1371/journal.pone.

Analysis of protein profiling studies of β-thalassemia/Hb E disease.

A number of studies have used global protein profiling technologies on a range of patient samples to detect proteins that are differentially expressed in β-thalassemia/Hb E as an aid for understanding the physiopathology of this disease. Seven studies have identified a total of 111 unique, differentially expressed proteins. Seven proteins (prothrombin, alpha-1-antichymotrypsin, fibrinogen beta chain, hemoglobin beta, selenium-binding protein, microtubule-actin cross-linking factor and adenomatous polyposis coli protein 2) have been identified in two independent studies, whereas two proteins (carbonic anhydrase 1 and peroxiredoxin-2) have been identified in three independent studies.

Mitochondrial Changes in β0-Thalassemia/Hb E Disease.

The compound β°-thalassemia/Hb E hemoglobinopathy is characterized by an unusually large range of presentation from essentially asymptomatic to a severe transfusion dependent state. While a number of factors are known that moderate presentation, these factors do not account for the full spectrum of presentation. Mitochondria are subcellular organelles that are pivotal in a number of cellular processes including oxidative phosphorylation and apoptosis.

The prevalence of alpha-thalassemia amongst Tai and Mon-Khmer ethnic groups residing in northern Thailand: A population-based study.

Background: Northern Thailand is one of the highest α-thalassemia incidence areas where 30-40% of inhabitants have been reported to carry aberrant α-globin genes. However, all previous α-thalassemia prevalence surveys in northern Thailand have been undertaken without consideration of ethnicity. Here we report the prevalence of α-thalassemia genes in 4 Tai (Yong, Yuan, Khuen, Lue) and 4 Mon-Khmer speaking populations (Blang, Mon, Paluang, Lawa).

Hemoglobin E Prevalence among Ethnic Groups Residing in Malaria-Endemic Areas of Northern Thailand and Its Lack of Association with Plasmodium falciparum Invasion In Vitro.

Hemoglobin E (HbE) is one of the most common hemoglobin variants caused by a mutation in the β-globin gene, and found at high frequencies in various Southeast Asian groups. We surveyed HbE prevalence among 8 ethnic groups residing in 5 villages selected for their high period malaria endemicity, and 5 for low endemicity in northern Thailand, in order to uncover factors which may affect genetic persistence of HbE in these groups. We found the overall HbE prevalence 6.

Dysregulation of ferroportin gene expression in β(0)-thalassemia/Hb E disease.

During erythropoiesis, iron levels need to be carefully regulated to ensure there is sufficient iron available for hemoglobin synthesis, but that there is no excess to cause damage to the developing erythroblast. Iron influx to the developing erythroblast is controlled by the expression of the transferrin receptor, while iron efflux is regulated by ferroportin (FPN), the sole iron-exporting protein. FPN is encoded through multiple messenger RNAs (mRNAs) some of which contain an iron-responsive element (variant I mRNAs) and some of which do not (variant II mRNAs).

Proteomic analysis of hemoglobin H-constant spring (Hb H-CS) erythroblasts.

Hemoglobin H disease (Hb H) arises through the loss or dysfunction of three of the four alpha globin genes through the co-inheritance of either gross gene deletions or an abnormal hemoglobin which causes a non-deletional loss of α-globin expression. This study sought to investigate erythropoiesis in Hb H-Constant Spring (Hb H-CS) disease, a common form of Hb H disease in Southeast Asia, caused by the inheritance of the Constant Spring variant hemoglobin together with deletion of two of the alpha globin genes. In comparison to normal erythroblasts, Hb H-CS erythroblasts showed reduced cell expansion although no difference in differentiation was observed.

Increased oxidative metabolism is associated with erythroid precursor expansion in β0-thalassaemia/Hb E disease.

Erythropoiesis in β0-thalassaemia/Hb E patients, the most common variant form of β-thalassaemia in Southeast Asia, is characterized by accelerated differentiation and over-expansion of erythroid precursor cells. The mechanism driving this accelerated expansion and differentiation remain unknown. To address this issue a proteomic analysis was undertaken to firstly identify proteins differentially expressed during erythroblast differentiation and a second analysis was undertaken to identify proteins differentially expressed between β0-thalassaemia/Hb E erythroblasts and control erythroblasts.

Enhanced activation of autophagy in β-thalassemia/Hb E erythroblasts during erythropoiesis.

Erythropoiesis in β-thalassemia patients is ineffective, primarily because of death of the erythroid progenitor cells at the polychromatic normoblast stage. While it is known that autophagy plays a critical role during erythropoiesis by removing organelles from erythroid cells during terminal differentiation, its role in erythroid cells whose function is impaired remains to be explored. To investigate this, CD34+ erythroid progenitor cells from normal controls and β-thalassemia/Hb E patients were isolated from peripheral blood and cultured under conditions driving differentiation into an erythroid lineage, and levels of autophagy and apoptosis were analyzed both directly and after biochemical manipulation with L: -asparagine.

A mechanism of ineffective erythropoiesis in β-thalassemia/Hb E disease.

Background: Cells respond to stress stimuli through a number of response pathways, of which one of the most important and well characterized is the unfolded protein response. Despite a large body of work which suggests that stress in erythroblasts may play a pivotal role in the pathogenesis of beta-thalassemia/Hb E disease, this pathway remains uninvestigated.

Design And Methods: Day 10 erythroblasts from normal controls and beta-thalassemia/Hb E patients were subjected to internal (treatment with tunicamycin) and external (serum and growth factor withdrawal) stress stimuli and the activation of the unfolded protein response pathway was investigated.

Increased erythropoiesis of beta-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation.

Beta-thalassaemia is one of the most common inherited anaemias, arising from a partial or complete loss of beta-globin chain synthesis. In severe cases, marked bone marrow erythroid hyperplasia, believed to result from erythropoietin (EPO)-mediated feedback from the anaemic condition is common, however, as yet, no study has investigated EPO-mediated signal transduction in thalassaemic erythroid cells. Using proerythroblasts generated from peripheral blood circulating CD34+ haematopoietic progenitor cells, the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERKs) pathway was examined under conditions of steady state growth, cytokine deprivation and post-EPO stimulation.