Extraction, Structural Characterization, and Biological Functions of Lycium Barbarum Polysaccharides: A Review.

Lycium barbarum polysaccharides (LBPs), as bioactive compounds extracted from L. barbarum L. fruit, have been widely explored for their potential health properties. The extraction and structural characterization methods of LBPs were reviewed to accurately understand the extraction method and structural and biological functions of LBPs. An overview of the biological functions of LBPs, such as antioxidant function, antitumor activity, neuroprotective effects, immune regulating function, and other functions, were summarized. This review provides an overview of LBPs and a theoretical basis for further studying and extending the applications of LBPs in the fields of medicine and food.

Hypoxia-induced Downregulation of SRC-3 Suppresses Trophoblastic Invasion and Migration Through Inhibition of the AKT/mTOR Pathway: Implications for the Pathogenesis of Preeclampsia.

Preeclampsia (PE) is characterized by poor placentation, consequent on aberrant extravillous trophoblast (EVT) cell function during placental development. The SRC family of proteins is important during pregnancy, especially SRC-3, which regulates placental morphogenesis and embryo survival. Although SRC-3 expression in mouse trophoblast giant cells has been documented, its role in the functional regulation of extravillous trophoblasts and the development of PE remains unknown. This study found that SRC-3 expression was significantly lower in placentas from PE pregnancies as compared to uncomplicated pregnancies. Additionally, both CoCl2-mimicked hypoxia and suppression of endogenous SRC-3 expression by lentivirus short hairpin RNA attenuated the migration and invasion abilities of HTR-8/SVneo cells. Moreover, we demonstrated that SRC-3 physically interacts with AKT to regulate the migration and invasion of HTR-8 cells, via the AKT/mTOR pathway. We also found that the inhibition of HTR-8 cell migration and invasion by CoCl2-mimicked hypoxia was through the SRC-3/AKT/mTOR axis. Our findings indicate that, in early gestation, accumulation of HIF-1α inhibits the expression of SRC-3, which impairs extravillous trophoblastic invasion and migration by directly interacting with AKT. This potentially leads to insufficient uterine spiral artery remodeling and placental hypoperfusion, and thus the development of PE.

High-mobility group protein N2 induces autophagy by activating AMPK/ULK1 pathway and thereby boosts UPEC proliferation within bladder epithelial cells.

Urinary tract infection is one of the most common bacterial infections which is mainly caused by Escherichia coli (UPEC). Autophagy plays a key role in immune response to eliminate invading pathogens. Exploring the effect of autophagy on UPEC infection and the molecular mechanisms will be benefit for the treatment of urinary tract infection. High-mobility group protein N2 (HMGN2), a highly conserved nuclear protein and an antibacterial peptide, has been associated with bacterial infection induced immune response; however, whether this function is due to the regulation of autophagy remains unclear. In this study, we demonstrate for the first time that HMGN2 is upregulated in UPEC infection of bladder epithelial cell line 5637 (BEC 5637). Furthermore, HMGN2 enhances autophagy in BEC 5637 via activation of AMPK and ULK1, whereas UPEC suppresses autophagy. In addition, the enhanced autophagy activity by HMGN2 overexpression or rapamycin boosts the proliferation of UPEC J96 in BEC 5637. In summary, our data indicate that HMGN2 activates autophagy via AMPK/ULK1 pathway which can be utilized by UPEC J96 for their proliferation within bladder epithelial cells.

The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia.

OBJECTIVE: Special AT-rich sequence binding protein 1 (SATB1) play potential roles in invasion and metastasis of tumor cells, and involves in human placental and fetal development. The objective of this study is to explore the role of SATB1 in migration and invasion of trophoblast and the potential mechanism. METHODS: Human placental tissues from first trimester, second trimester, term, and preeclampsia (PE) pregnancies were used to detect the expression and subcellular location of SATB1 and ß-catenin. The human trophoblast cell line HTR8/SVneo, which was treated with hypoxia/re-oxygenation (H/R), lithium chloride (LiCl) or SATB1-siRNA to investigate the role of SATB1 and ß-catenin signaling in human trophoblast function. RESULTS: We observed that SATB1 specifically localized within trophoblast cells of placenta tissues. Gradually reduced expression of SATB1 was observed during gestation, and lower expression were detected in placenta of PE compared with normal pregnancy. Moreover, the expression of SATB1 was decreased in H/R-treated HTR8/Svneo cells and villous explants. The Wnt/ß-catenin signaling pathway interacted with SATB1 expression and H/R treatment resulted in Wnt pathway inhibition in trophoblast, while lithium chloride (LiCl) treatment enhanced H/R-exposed HTR8/SVneo migration and invasion. Knockdown of SATB1 significantly reduced the level of ß-catenin and the migratory and invasive abilities of trophoblast. CONCLUSIONS: Our data suggested that oxidative stress reduced SATB1 leading to inhibition of Wnt/ß-catenin, and participate in the subdued migration and invasion of trophoblast, which indicated a potential pathological mechanism of PE.

Non-histone nuclear protein HMGN2 differently regulates the urothelium barrier function by altering expression of antimicrobial peptides and tight junction protein genes in UPEC J96-infected bladder epithelial cell monolayer.

The urinary tract is vulnerable to frequent challenges from environmental microflora. Uropathogenic Escherichia coli (UPEC) makes a major contribution to urinary tract infection (UTI). Previous studies have characterized positive roles of non-histone nuclear protein HMGN2 in lung epithelial innate immune response. In the study presented here, we found HMGN2 expression was up-regulated in UPEC J96-infected urothelium. Surprisingly, over-expression of HMGN2 promoted disruption of BECs 5637 cells' intercellular junctions by down-regulating tight junction (TJs) components' expression and physical structure under J96 infection. Further investigation showed that BECs 5637 monolayer, in which HMGN2 was over-expressed, had significantly increased permeability to J96. Our study systemically explored the regulatory roles of HMGN2 in BECs barrier function during UPEC infection and suggested different modulations of intracellular and paracellular routes through which UPEC invades the bladder epithelium.

MiR-204 inhibits the proliferation and invasion of renal cell carcinoma by inhibiting RAB22A expression.

While miR-204 expression may be linked to renal cell carcinoma (RCC) progression, the detailed mechanisms remain unclear. In the present study, we demonstrated that miR-204 was differentially expressed in RCC tissues when compared with surrounding normal kidney tissues. Ectopic overexpression of miR-204 in human RCC cells suppressed cell proliferation and invasion in vitro and in vivo. Mechanism dissection revealed that miR-204 may function through RAB22A signals to inhibit RCC proliferation and invasion. Overexpression of RAB22A by oe-RAB22A was able to partially reverse the miR-204-mediated suppression of RCC tumor progression. Together, these results revealed that miR-204 suppressed RCC proliferation and invasion by directly targeting the RAB22A gene. Targeting newly identified RAB22A with miR-204 may aid in the suppression of RCC proliferation and invasion.