Wild Rheum tanguticum (Dahuang in Chinese) has becoming endangered in China. This study aims to examine the genetic structure and genetic diversity of R. tanguticum within species, and the genetic differentiation within and among populations in China.

Alzheimer's disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.

Endometriosis is a benign chronic gynecological disease that affects women of reproductive age, characterized by the presence of functional endometrial tissues outside the uterine cavity. GnRH agonists exhibit anti-proliferative and apoptosis-enhancing activities and have long been used for the treatment of endometriosis. There is a critical need to identify the signaling modules involving GnRH agonist therapy for the treatment of endometriosis. In this study, we compared the proteomic profiles of endometriosis in patients before and after GnRH agonist therapy to identify proteins that might provide further information concerning the mechanisms underlying the functions of GnRH agonists.

The molecules and mechanisms pertinent to the low immunogenicity of undifferentiated embryonic stem cells (ESCs) remain poorly understood. Here, we provide evidence that milk fat globule epidermal growth factor 8 (MFG-E8) is a vital mediator in this phenomenon and directly suppresses T cell immune responses. MFG-E8 is enriched in undifferentiated ESCs but diminished in differentiated ESCs. Upregulation of MFG-E8 in ESCs increases the successful engraftment of both undifferentiated and differentiated ESCs across major histocompatibility complex barriers. MFG-E8 suppresses T cell activation/proliferation and inhibits Th1, Th2, and Th17 subpopulations while increasing regulatory T cell subsets. Neutralizing MFG-E8 substantially abrogates these effects, whereas addition of recombinant MFG-E8 to differentiated ESCs restores immunosuppression. Furthermore, we provide the evidence that MFG-E8 suppresses T cell activation and regulates T cell polarization by inhibiting PKCθ phosphorylation through the α3/5βV integrin receptor. Our findings offer an approach to facilitate transplantation acceptance.

The metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is a highly conserved long non-coding RNA (lncRNA) gene. However, little is known about the pathological role of lncRNA MALAT1 in glioma. In the present study, we explored the expression level of lncRNA MALAT1 in primary glioma tissues as well as in U87 and U251 glioma cell lines. Using qRT-PCR, we found that the expression of lncRNA MALAT1 was significantly increased in glioma tissues compared with that of paracancerous tissues. Meanwhile, the expression of MALAT1 was highly expressed in U98 and U251 cells. In order to explore the function of MALAT1, the expression of MALAT1 was greatly reduced in U87 and U251 cells transfected with siRNA specifically targeting MALAT1. Consequently, cell viability of U87 and U251 cells were drastically decreased after the knockdown of MALAT1. Concomitantly, the apoptosis rate of the two cell lines was dramatically increased. Furthermore, the expression levels of some tumor markers were reduced after the knockdown of MALAT1, such as CCND1 and MYC. In summary, the current study indicated a promoting role of MALAT1 in the development of glioma cell.

Cardiomyocytes are understood to possess a limited regenerative capacity. Any myocardial insult leads to an irreversible injury. Mesenchymal stem cell differentiation into cardiomyocyte-like cells stands as one of the leading experimental therapies. However, a candidate cell source has yet to be defined. Here, we examined the in vitro and in vivo cardiac differentiation potential of human placenta derived stem cells (hPDSCs); a unique, abundant, and non-immunogenic cell source.

Decellularized xenogeneic whole-liver matrices are plausible biomedical materials for the bioengineering of liver transplantation. A common method to reduce the inflammatory potential of xenogeneic matrices is crosslinking. Nevertheless, a comprehensive analysis of the immunogenic features of cross-linked decellularized tissue is still lacking. We aimed to reduce the immunogenicity of decellularized porcine whole-liver matrix through crosslinking with glutaraldehyde or genipin, a new natural agent, and investigated the mechanism of the immune-mediated responses. The histologic assessment of the host's immune reaction activated in response to these scaffolds, as well as the M1/M2 phenotypic polarization profile of macrophages, was studied in vivo. The genipin-fixed scaffold elicited a predominantly M2 phenotype response, while the glutaraldehyde-fixed scaffold resulted in disrupted host tissue remodeling and a mixed macrophage polarization profile. The specific subsets of immune cells involved in the responses to the scaffolds were identified in vitro. Crosslinking alleviated the host response by reducing the proliferation of lymphocytes and their subsets, accompanied by a decreased release of both Th1 and Th2 cytokines. Therefore, we conclude that the natural genipin crosslinking could lower the immunogenic potential of xenogeneic decellularized whole-liver scaffolds.

Exosomes are nanovesicles released by different cell types, such as dendritic cells (DCs), mast cells (MCs), and tumor cells. Exosomes of different origin play a role in antigen presentation and modulation of immune response to infectious disease. In this study, we demonstrate that mast cells and CD4(+) T cells colocated in peritoneal lymph nodes from BALB/c mouse. Further, bone marrow-derived mast cells (BMMCs) constitutively release exosomes, which express CD63 and OX40L. BMMC-exosomes partially promoted the proliferation of CD4(+) T cells. BMMC-exosomes significantly enhanced the differentiation of naive CD4(+) T cells to Th2 cells in a surface contact method, and this ability was partly inhibited by the addition of anti-OX40L Ab. In conclusion, BMMC-exosomes promoted the proliferation and differentiation of Th2 cells via ligation of OX40L and OX40 between exosomes and T cells. This method represents a novel mechanism, in addition to direct cell surface contacts, soluble mediators, and synapses, to regulate T cell actions by BMMC-exosomes.

The number of percutaneous coronary interventions (PCI) in China has increased more than 20-fold over the last decade. Consequently, there is a need for national-level information to characterize PCI indications and long-term patient outcomes, including health status, to understand and improve evolving practice patterns.

Acute lung injury (ALI), characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema, and associated with a proteinaceous alveolar exudate, is a leading cause of morbidity and mortality. Currently, inflammation-oxidative stress interaction between TNF-α and NF-κB was identified as a key pathway of ALI. We hypothesized that a TNFR-Fc fusion protein would have beneficial effects in experimental ALI, and sought to test this idea in mice by blocking TNF-α.

This study examines the effect of passive hyperthermia on interhemispheric resting state functional connectivity and the correlation between interhemispheric resting state functional connectivity and efficiency of a succedent working memory task.

RNA interference (RNAi) is useful for selective gene silencing. Cytochrome P450 3A4 (CYP3A4), which metabolizes approximately 50% of drugs in clinical use, plays an important role in drug metabolism. In this study, we aimed to develop a short hairpin RNA (shRNA) to modulate CYP3A4 expression. Three new shRNAs (S1, S2 and S3) were designed to target the coding sequence (CDS) of CYP3A4, cloned into a shRNA expression vector, and tested in different cells. The mixture of three shRNAs produced optimal reduction (55%) in CYP3A4 CDS-luciferase activity in both CHL and HEK293 cells. Endogenous CYP3A4 expression in HepG2 cells was decreased about 50% at both mRNA and protein level after transfection of the mixture of three shRNAs. In contrast, CYP3A5 gene expression was not altered by the shRNAs, supporting the selectivity of CYP3A4 shRNAs. In addition, HepG2 cells transfected with CYP3A4 shRNAs were less sensitive to Ginkgolic acids, whose toxic metabolites are produced by CYP3A4. These results demonstrate that vector-based shRNAs could modulate CYP3A4 expression in cells through their actions on CYP3A4 CDS, and CYP3A4 shRNAs may be utilized to define the role of CYP3A4 in drug metabolism and toxicity.

Organ size determination is one of the most intriguing unsolved mysteries in biology. Aberrant activation of the major effector and transcription co-activator YAP in the Hippo pathway causes drastic organ enlargement in development and underlies tumorigenesis in many human cancers. However, how robust YAP activation is achieved during organ size control remains elusive. Here we report that the YAP signaling is sustained through a novel microRNA-dependent positive feedback loop. miR-130a, which is directly induced by YAP, could effectively repress VGLL4, an inhibitor of YAP activity, thereby amplifying the YAP signals. Inhibition of miR-130a reversed liver size enlargement induced by Hippo pathway inactivation and blocked YAP-induced tumorigenesis. Furthermore, the Drosophila Hippo pathway target bantam functionally mimics miR-130a by repressing the VGLL4 homolog SdBP/Tgi. These findings reveal an evolutionarily conserved positive feedback mechanism underlying robustness of the Hippo pathway in size control and tumorigenesis.

Melon fruit flesh color is primarily controlled by the "golden" single nucleotide polymorhism of the "Orange" gene, CmOr, which dominantly triggers the accumulation of the pro-vitamin A molecule, β-carotene, in the fruit mesocarp. The mechanism by which CmOr operates is not fully understood. To identify cellular and metabolic processes associated with CmOr allelic variation, we compared the transcriptome of bulks of developing fruit of homozygous orange and green fruited F3 families derived from a cross between orange and green fruited parental lines.

Many serum biochemical indices have been found to be associated with coronary heart disease (CHD); however, few studies have evaluated the value on screening CHD of the integrated serum biochemical indices.

The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84 (downregulated) genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates.

Interstitial lung disease (ILD) is a serious side-effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Therefore, it is necessary to study underlying mechanisms for the development of pulmonary fibrosis induced by EGFR-TKI and potential approaches to attenuate it. Metformin is a well-established and widely prescribed oral hypoglycemic drug, and has gained attention for its potential anticancer effects. Recent reports have also demonstrated its role in inhibiting epithelial-mesenchymal transition and fibrosis. However, it is unknown whether metformin attenuates EGFR-TKI-induced pulmonary fibrosis. The effect of metformin on EGFR-TKI-induced exacerbation of pulmonary fibrosis was examined in vitro and in vivo using MTT, Ki67 incorporation assay, flow cytometry, immunostaining, Western blot analysis, and a bleomycin-induced pulmonary fibrosis rat model. We found that in lung HFL-1 fibroblast cells, TGF-β or conditioned medium from TKI-treated lung cancer PC-9 cells or conditioned medium from TKI-resistant PC-9GR cells, induced significant fibrosis, as shown by increased expression of Collegen1a1 and α-actin, while metformin inhibited expression of fibrosis markers. Moreover, metformin decreased activation of TGF-β signaling as shown by decreased expression of pSMAD2 and pSMAD3. In vivo, oral administration of gefitinib exacerbated bleomycin-induced pulmonary fibrosis in rats, as demonstrated by HE staining and Masson staining. Significantly, oral co-administration of metformin suppressed exacerbation of bleomycin-induced pulmonary fibrosis by gefitinib. We have shown that metformin attenuates gefitinib-induced exacerbation of TGF-β or bleomycin-induced pulmonary fibrosis. These observations indicate metformin may be combined with EGFR-TKI to treat NSCLC patients.

To review the evidence from RCTs on clinical outcomes and benefit of acute tibial fracture and nonunion treated with and without BMPs.

Herein, a polyethylenimine derivative N-acetyl-L-leucine-polyethylenimine (N-Ac-L-Leu-PEI) was employed as a carrier to achieve the delivery of DNAzyme targeting aurora kinase A using PC-3 cell as a model. Flow cytometry and confocal laser scanning microscopy demonstrated that the derivative could realize the cellular uptake of nanoparticles in an energy-dependent and clathrin-mediated pathway and obtain a high DNAzyme concentration in the cytoplasm through further endosomal escape. After DNAzyme transfection, expression level of aurora kinase A would be downregulated at the protein level. Meanwhile, the inhibition of cell proliferation was observed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell colony formation assay, attributing to the activation of apoptosis and cell cycle arrest. Through flow cytometric analysis, an early apoptotic ratio of 25.93% and G2 phase of 22.58% has been detected after N-Ac-L-Leu-PEI-mediated DNAzyme transfection. Finally, wound healing and Transwell migration assay showed that DNAzyme transfection could efficiently inhibit the cell migration. These results demonstrated that N-Ac-L-Leu-PEI could successfully mediate the DNAzyme delivery and downregulate the expression level of aurora kinase A, triggering a significant inhibitory effect of excessive proliferation and migration of tumor cells.

Liver cancer is one of the most lethal cancers, but our knowledge of the molecular mechanism underlying this process remains insufficient. Through deep sequencing and expression regulation analysis in liver cancer cells, we identified two novel factors, AKR1C2 (positive factor) and NF1 (negative factor), as the AEG-1 downstream players in the process of metastasis in liver cancer. They were experimentally validated to have the capacities of regulating cell migration, cell invasion, cell proliferation, and EMT. Further clinic expression and animal model evidence confirmed their functions. Together, our findings provide a new insight into the pharmaceutical and therapeutic use of AEG-1 and downstream AKR1C2 and NF1.