Astragalus-mediated stimulation on antigen-presenting cells could result in higher IL-21 production from CXCR5+ Tfh-like cells and better IL-21-mediated effector functions.

T cells in renal cell carcinoma (RCC) patients display multiple features of impairment and exhaustion. Here, we hypothesize that Astragalus membranaceus, a herbal medicine commonly used to accompany chemotherapy, might have adjuvating effects on T cells from RCC patients. To investigate this, circulating T cells from healthy individuals and RCC patients were cocultured ex vivo with aqueous extract from Astragalus. Functional characteristics of T cells in the absence and presence of Astragalus extract were then compared. We first identified a downregulation of IL-21 expression in RCC patients in association with a functional dysregulation of CXCR5+ Tfh-like cells. Astragalus extract could significantly increase IL-21 expression in a dose-dependent manner. This Astragalus-mediated effect depended on the presence of antigen-presenting cells (APCs), as purified CXCR5+ Tfh-like cells presented little IL-21 upregulation following Astragalus stimulation. APCs primed by Astragalus extract also promoted IL-21 expression from Tfh-like cells. Interestingly, Astragalus-stimulated Tfh-like cells presented enhanced helper function and resulted in higher humoral responses and better CD8 T cell survival. This effect was dependent on the presence of IL-21. Overall, these data indicated that Astragalus could enhance IL-21 production and effector function from CXCR5+ Tfh-like cells in a manner that depended on the presence of APCs.

Exosomal miR-34b inhibits proliferation and the epithelial-mesenchymal transition by targeting Notch2 in ovarian cancer.

Exosomal microRNA (miR) can affect signaling pathways in various physiological and pathological conditions, including ovarian cancer (OC). miR-34b, the first microRNA targeted in a human clinical trial for cancer treatment, exhibited decreased expression in several cancer types. However, the biological function of exosomal miR-34b in OC has not been elucidated. In the present study, using reverse transcription-quantitative PCR, it was reported that exosomal miR-34b is downregulated in OC cells. Exosomal miR-34b reduced cell proliferation and epithelial-mesenchymal transition (EMT) in the OC cell line SKOV3. In addition, it was confirmed that Notch2, which is upregulated in SKOV3 cells, is a target of miR-34b. Moreover, exosomal miR-34b and Notch2 levels were found to be negatively correlated. The present data highlights the importance of exosomal miR-34b-mediated inhibition of cell proliferation and EMT, suggesting that exosomal miR-34b has value as a diagnostic biomarker and a potential molecular target for the treatment of OC.

miR-502-5p inhibits the proliferation, migration and invasion of gastric cancer cells by targeting SP1.

Gastric cancer (GC) is the third most common cause of cancer-associated mortality in China. Aberrant microRNA (miR) expression can occur through multiple biological processes and has been implicated in cancer development. However, to the best of our knowledge, the function of miR-502-5p in GC is currently unclear. In the present study, the expression and function of miR-502-5p in GC was evaluated. Reverse transcription-quantitative (RT-q) PCR was used to measure the expression levels of miR-502-5p in GC tissues, normal adjacent tissues, a normal human gastric epithelial cell line (GES-1) and two GC cell lines. miR-502-5p expression levels were significantly lower in GC tissues and GC cell lines compared with those in adjacent normal tissues and GES-1 cells, respectively. Subsequently, the target genes of miR-502-5p were predicted, and it was demonstrated that the transcription factor SP1 was a direct target. SP1 expression, cell viability, migration and invasion, and SP1 protein levels were examined using RT-qPCR, an MTT assay, Transwell assay and western blotting, respectively. Human GC cells were then transfected with an miR-502-5p mimic to emulate miR-502-5p overexpression, resulting in inhibition of the proliferation, migration and invasion capacities of human GC cells. Compared with the negative control, cells overexpressing miR-502-5p had decreased levels of SP1 mRNA and protein. These data suggest that miR-502-5p serves as a tumor suppressor gene by targeting SP1 to regulate the proliferation, migration and invasion of GC cells.

BRI1 and BAK1 interact with G proteins and regulate sugar-responsive growth and development in Arabidopsis.

Sugars function as signal molecules to regulate growth, development, and gene expression in plants, yeasts, and animals. A coordination of sugar availability with phytohormone signals is crucial for plant growth and development. The molecular link between sugar availability and hormone-dependent plant growth are largely unknown. Here we report that BRI1 and BAK1 are involved in sugar-responsive growth and development. Glucose influences the physical interactions and phosphorylations of BRI1 and BAK1 in a concentration-dependent manner. BRI1 and BAK1 physically interact with G proteins that are essential for mediating sugar signaling. Biochemical data show that BRI1 can phosphorylate G protein ß subunit and γ subunits, and BAK1 can phosphorylate G protein γ subunits. Genetic analyses suggest that BRI1 and BAK1 function in a common pathway with G-protein subunits to regulate sugar responses. Thus, our findings reveal an important genetic and molecular mechanism by which BR receptors associate with G proteins to regulate sugar-responsive growth and development.

Roles of the Arabidopsis G protein γ subunit AGG3 and its rice homologs GS3 and DEP1 in seed and organ size control.

The size of seeds and organs is coordinately determined by cell proliferation and cell expansion, but the mechanisms that set final seed and organ size are largely unknown in plants. In a recent study, we have demonstrated that the plant specific G protein γ subunit (AGG3) promotes seed and organ growth by increasing the period of proliferative growth in Arabidopsis. AGG3 is localized in plasma membrane and interacts with the G protein ß subunit (AGB1). Homologs of AGG3 in rice (GS3 and DEP1/qPE9-1) have been identified as important quantitative trait loci for seed size and yield. However, rice GS3 and DEP1 influence seed and organ growth by restricting cell proliferation. Here, we discuss the possible molecular mechanisms by which Arabidopsis AGG3 and its rice homologs GS3 and DEP1 control seed and organ size.

(4-Chloro-benzoato)bis(5-methyl-2-pyridylamine)silver(I).

The title compound, [Ag(C(7)H(4)ClO(2))(C(6)H(8)N(2))(2)], is a mononuclear silver(I) complex. The Ag(I) atom is three-coordinated by two pyridine N atoms from two 5-methyl-pyridin-2-ylamine ligands and by one O atom of a 4-chloro-benzoate ligand, forming a distorted T-shaped coordination. In the crystal structure, the mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds, forming chains running along the b axis.