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In the present study, a polysaccharide fraction (PTP) was isolated and purified from the tubers of Pinellia ternata. We researched its structure and anti-tumor activity, and further studied its molecular mechanism of inducing apoptosis of Hep G2 cells. The results indicated that PTP was an acid heteropolysaccharide and the average molecular weight of PTP identified by HPGPC was 3.06 × 106 Da. Ion chromatography (IC) determined that PTP was mainly composed of Ara:Gal:Glu:Man:GlcA:GalA in a molar ratio of 6.98:16.56:7.25:2.04:1:4.16. Combined with the results of FT-IR and NMR spectroscopy, it was found that PTP is a pyranose containing α-configuration and β-configuration, mainly consist of β-D-Gal, α-D-Glu, α-D-Ara and β-D-Man. By analyzing the results of MTT, cell cycle, Annexin V-FITC/PI double staining and cell morphology observation, we concluded that PTP induced dose-dependent apoptosis of Hep G2 cells via S phase arrest. In addition, mitochondrial membrane potential detection and Western blot further indicated that PTP was capable of inducing apoptosis in Hep G2 cells through an endogenous mitochondria-mediated apoptotic pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • A pair of undescribed enantiomers (1a / 1b) was isolated from the roots of Ficus hirta. • Compound 4 showed enhanced cytotoxicity on HeLa, MCF-7 and H460 cells. • Compound 4 induced HeLa cells apoptosis and increased the PARP cleavage. • Compound 4 increased the expression of p-JNK and p-p38. • Compound 4 reduced the protein levels of p-AKT and p-ERK. A pair of undescribed enantiomers, (±) ficusflavonid A (1a / 1b), along with five known analogues, were isolated from the roots of Ficus hirta. Their structures were determined by the analysis of extensive spectroscopic data (including UV, IR, HRESIMS and NMR). Two enantiomers (1a and 1b) were successfully separated by chiral chromatographic column and their absolute configurations were assigned by the comparison of experimental and calculated ECD data. The cytotoxicity of all the isolates against HeLa, MCF-7, HepG2 and H460 cell lines were evaluated by MTT assay. Among them, 4 suppressed the proliferation of HeLa cells with the IC 50 value of 28.88 μM. Furthermore, the apoptotic effect of 4 on HeLa cells and the level of several crucial proteins in AKT/MAPKs signaling pathways were analyzed by flow cytometer and western blot assay. As a result, 4 induced HeLa cell apoptosis in a dose dependent manner and significantly increased the protein levels of p-JNK and p-p38, whereas distinctly reduced the expression of p-AKT, and p-ERK. Thus, compound 4 might induce HeLa cells apoptosis via MAPK and AKT signaling pathways, which could be considered as a potential leading compound for the development of anticancer drugs. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a β-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential. [ABSTRACT FROM AUTHOR]

Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin-related photosensitizer for photodynamic therapy (PDT). The aim of this study was to investigate HMME-induced apoptosis in CHMm cells, a canine breast cancer cell line. CHMm cells were treated with HMME and a He-Ne laser at a wavelength of 632.8 nm. Cell viability was determined using the trypan blue exclusion assay. Apoptosis was analyzed using Hoechst 33258, AO/EB, Annexin V/PI staining and single-cell gel electrophoresis (comet assay). Apoptotic morphology was further confirmed by Giemsa staining and transmission electron microscopy. Rates of apoptosis increased following PDT-HMME treatment in a time-dependent manner. Taken together, these results demonstrated that apoptosis plays a major role in PDT-HMME induced reduction in the viability of CHMm cells. [ABSTRACT FROM AUTHOR]

Abstract: B cell antigen receptor (BCR) density plays a role in the differentiation of immature B cells to their mature compartments; however, the exact strategy of its influence on the development of natural autoreactive B cells is still unclear. In the present study, we explored the role of BCR surface density in autoreactive B cell development by studying two lines of mice containing distinct copy numbers of an IgH transgene with VH derived from a poly-reactive natural antibody 3B4. Surface BCR levels were found to be related to the transgene copy number in these mice. In mice with higher copy numbers of the transgene, the BCRs were found to promote the remaining of autoreactive B cells into marginal zone (MZ) and B-1a subsets; meanwhile, elevated surface BCR levels were correlated with a significant decrease of follicular (Fo) B cell numbers and a reduction in the number of multiple stages of immature B cells both in spleen and bone marrow (BM). Interestingly, no difference in the ratio of cell apoptosis and proliferation was found in all stages of B cell development between two lines, except that more severely aberrant proliferation of pro/pre-B cells in BM was found in mice with higher transgene copies. This data supports the idea that natural poly-reactive B cells can be positively selected into MZ and B-1 cells, and high BCR surface density favors this selection. More importantly, our data suggests that the influence by receptor expression on the differentiation of natural poly-reactive B cells begins at an early stage of B cell development. [Copyright &y& Elsevier]

The expression of genes related to the Toll-like receptors (TLRs) signaling pathway were determined. Group A, B and C fed with basal diet and group D, E and F induced TD by feeding a basal diet containing 100 mg·kg−1 thiram. rGSTA3 protein was injected at 20 μg·kg−1 in group B, E and at 50 μg·kg−1 in C, F. Results suggested that lameness and death of chondrocytes were significant on day 14. TLRs signaling pathway related genes were screened based on the transcriptome enrichment, and validated on qPCR. IL-7, TLR2, 3, 4, 5, 7, 15, MyD88, MHC-II, MDA5 and TRAF6 were significantly (p < 0.05) expressed in group E and F as compared to group D on day 14 and 23. IL-7, MHCII, TRAF6, TLR3, TLR5, TLR7, and TLR15 determined insignificant in group D compared to group A on day 23. TD occur in an early phase and alleviated in the later period. rGSTA3 protein can prevent apoptosis and repair degraded chondrocytes. Image 1 • TD is an important undetected avian growth plate disease. • Immune genes regulate apoptosis, ultimately death of chondrocytes occured. • Toll-like receptor (TLRs) mediates cellular immune responses to cause apoptosis. • rGSTA3 protein treatment prevents the apoptosis by downregulating TLRs on day 14 and day 23. [ABSTRACT FROM AUTHOR]

Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds β-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38. Unlabelled Image • Two new compounds were obtained from the mangrove-derived fungus Acremonium citrinum. • Compound 1 showed obvious cytotoxicity against Hela cell line. • Compound 1 distinctly induced the apoptosis of Hela cell line. • Compound 1 significantly increased the expression of p-JNK and p-p38 in MAPK signaling pathway. [ABSTRACT FROM AUTHOR]