Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value

Selection and evaluation of Bradyrhizobium inoculum for peanut, Arachis hypogea production in the Lao People’s Democratic Republic

The interaction between leguminous plants and Bradyrhizobium is limited, known as host specificity. Therefore, the selection of an appropriate Bradyrhizobia for use as biofertilizer inoculum for legumes is necessary. The Arachis hypogea L. is the most popular legume produced in the Lao People's Democratic Republic (PDR). Therefore, this research aimed to obtain the appropriate Bradyrhizobia that provides high efficiency in A. hypogea production in the Lao PDR. The 14 isolates were obtained from root nodules of A. hypogea L. trapped with Lao PDR soil samples. Three were the top isolates PMVTL-01, SMVTL-02, and BLXBL-03 showing high efficiency for peanut growth promotion. Strains PMVTL-01 and SMVTL-02 were closely related to the Bradyrhizobium geno sp. SA-3 Rp7b and B. zhanjiangense, respectively, whilst strain BLXBL-03 was closely related to Bradyrhizobium sp. CCBAU51745 and B. manausense BR3351. The competitiveness of these strains with Bradyrhizobium sp. SUTN9-2::GFP was analyzed, and only Bradyrhizobium sp. SMVTL-02 performed a number of occupied nodules higher than SUTN9-2::GFP. In addition, the competitiveness of the selected strain Bradyrhizobium sp. SMVTL-02 in a soil sample from the Lao PDR in the pot level was employed by tagging the SMVTL-02 with the DsRed gene. The results demonstrated that the DsRed-expressing tagged strain showed higher nodule occupancy than indigenous strains. Moreover, the results of the acetylene reduction assay (ARA), nodule number, nodule dry weight, and total plant dry weight from the pot experiment that inoculated with the SMVTL-02::DsRed were presented as having high potential to promote peanut growth as compared to non-inoculation. Thus, Bradyrhizobium sp. SMVTL-02 could be considered a potential biofertilizer inoculum for A. hypogea production in the Lao PDR

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

Osteoporosis, a global age-related health problem in both male and female elderly, insidiously deteriorates the microstructure of bone, particularly at trabecular sites, such as vertebrae, ribs and hips, culminating in fragility fractures, pain and disability. Although osteoporosis is normally associated with senescence and estrogen deficiency, diabetes mellitus (DM), especially type 1 DM, also contributes to and/or aggravates bone loss in osteoporotic patients. This topic highlight article focuses on DM-induced osteoporosis and DM/osteoporosis comorbidity, covering alterations in bone metabolism as well as factors regulating bone growth under diabetic conditions including, insulin, insulin-like growth factor-1 and angiogenesis. Cellular and molecular mechanisms of DM-related bone loss are also discussed. This information provides a foundation for the better understanding of diabetic complications and for development of early screening and prevention of osteoporosis in diabetic patients