Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes-associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM-stimulated mice, DADS significantly ameliorated histopathological changes and interleukin-1ß levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF-1α, inflammatory cytokines, and epithelial-mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial-mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.

Total Syntheses of Kopsaporine, Kopsinol and Kopsiloscine†A.

Kopsia alkaloids represent a complex class of natural products bearing a polycyclic ring system with two or three consecutive quaternary carbon centers. In this article, we report the first total synthesis of Kopsaporine related alkaloids. Features of our structure-unit-based strategy are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza-Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an olefin migration vinylogous alkylation to establish the C20 all-carbon quaternary center, an iridium complex mediated radical addition to fuse the aspidofractine framework, an unprecedented IBX oxidation to introduce the α-hydroxyketone moiety, and a bioinspired retro-Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A.

A Novel Mechanism for SIRT1 Activators That Does Not Rely on the Chemical Moiety Immediately C-Terminal to the Acetyl-Lysine of the Substrate.

SIRT1, an NAD+-dependent deacetylase, catalyzes the deacetylation of proteins coupled with the breakdown of NAD+ into nicotinamide and 2'-O-acetyl-ADP-ribose (OAADPr). Selective SIRT1 activators have potential clinical applications in atherosclerosis, acute renal injury, and Alzheimer's disease. Here, we found that the activity of the potent SIRT1 activator CWR is independent of the acetylated substrate. It adopts a novel mechanism to promote SIRT1 activity by covalently bonding to the anomeric C1' carbon of the ribose ring in OAADPr. In addition, CWR is highly selective for SIRT1, with no effect on SIRT2, SIRT3, SIRT5, or SIRT6. The longer distance between the anomeric C1' carbon of the ribose ring in OAADPr and Arg274 of SIRT1 (a conserved residue among sirtuins) than that between the anomeric C1' carbon in OAADPr and the Arg of SIRT2, SIRT3, SIRT5, and SIRT6, should be responsible for the high selectivity of CWR for SIRT1. This was confirmed by site-directed mutagenesis of SIRT3. Consistent with the in vitro assays, the activator also reduced the acetylation levels of p53 in a concentration-dependent manner via SIRT1 in cells. Our study provides a new perspective for designing SIRT1 activators that does not rely on the chemical moiety immediately C-terminal to the acetyl-lysine of the substrate.

Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway.

CONTEXT: Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke. OBJECTIVE: To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro. RESULTS: PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3ß (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively). CONCLUSIONS: PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

Continuous-wave pumped frequency upconversions in an InSe-integrated microfiber.

We report the achievement of continuous-wave (CW)-pumped second-harmonic generation (SHG) and sum frequency generation (SFG) in a layered indium selenide (InSe)-integrated microfiber. As a result of the strong interaction between the InSe nanosheets and the evanescent field, the second-order nonlinear processes are greatly enhanced in the InSe-integrated microfiber pumped by a few milliwatt CW lasers. The experimental results reveal that the intensities of SHG and SFG are quadratic and linear dependencies with the incident pump power, respectively, which is consistent with theoretical predictions. Additionally, the SHG intensity is strongly polarization-dependent on the nonaxisymmetrical distribution of the InSe nanosheets around the microfiber, providing the possibility of the SHG-polarized manipulation. The proposed device has the potential to be integrable into all-fiber systems for nonlinear applications.

Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia.

Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation and the ratio of Bax to Bcl-2 in the ischemic brain. CAG also inhibited NF-κB p65 nuclear translocation. As a result, CAG suppressed the mRNA expression of pro-inflammatory cytokines, including TNF-α and IL-1ß, and inhibited the activation of microglia and astrocytes in the ischemic brain. Our findings suggest that CAG is neuroprotective against ischemic brain injury in mice and that its beneficial effect may involve SIRT1 upregulation and the inhibition of apoptosis and neuroinflammation in the ischemic brain.

Umbilical Cord Mesenchymal Stem Cell-Derived Nanovesicles Potentiate the Bone-Formation Efficacy of Bone Morphogenetic Protein 2.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.

Copper-Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza-[n.2.1] Skeletons.

Catalytic cycloisomerization-initiated cascade cyclizations of terminal alkynes have received tremendous interest, and been widely used in the facile synthesis of a diverse array of valuable complex heterocycles. However, these tandem reactions have been mostly limited to noble-metal catalysis, and are initiated by an exo-cyclization pathway. Reported herein is an unprecedented copper-catalyzed endo-cyclization-initiated tandem reaction of indolyl homopropargyl amides, where copper catalyzes both the hydroamination and Friedel-Crafts alkylation process. This method allows the practical and atom-economical synthesis of valuable bridged aza-[n.2.1] skeletons (n=3-6) with wide substrate scope, and excellent diastereoselectivity and enantioselectivity by a chirality-transfer strategy. Moreover, the mechanistic rationale for this novel cascade cyclization is also strongly supported by control experiments, and is distinctively different from the related gold catalysis.

Impact of gamma-ray radiation-induced photodarkening on mode instability degradation of an ytterbium-doped fiber amplifier.

The laser performance of a high-power ytterbium-doped fiber amplifier is mainly hindered by the onset of mode instability. In this work, the slope efficiency and mode instability threshold of the ytterbium-doped fiber under various gamma-ray radiation doses have been measured. Experimental results reveal that gamma-ray radiation-induced photodarkening degrades mode instability severely, and gamma-ray radiation-induced mode instability degradation can be partly bleached by hours of pump-light injection. It is shown that gamma-ray radiation-induced photodarkening results in a steep reduction of slope efficiency and mode instability threshold; moreover, the entire irradiated fiber can be partly bleached by hours of pump-light injection and exhibits both time and gamma-ray radiation-dose saturation properties. The experimental results indicate that mode instability mitigation can be partly realized by pump-light injection and implies photodarkening suppression is beneficial for TMI mitigation, which is very promising for the advancement of high-power fiber lasers.

Isolation of a peptide from Ph.D.-C7C phage display library for detection of Cry1Ab.

Traditional ELISA methods of using animal immunity yield antibodies for detection Cry toxin. Not only is this incredibly harmful to the animals, but is also time-intensive. Here we developed a simple method to yield the recognition element. Using a critical selection strategy and immunoassay we confirmed a clone from the Ph.D-C7C phage library, which has displayed the most interesting Cry1Ab-binding characteristics examined in this study (Fig. 1). The current study indicates that isolating peptide is an alternative method for the preparation of a recognition element, and that the developed assay is a potentially useful tool for detecting Cry1Ab.

Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells.

Genipin, an aglycon of geniposide, has been reported to have anti-inflammatory effect. However, the anti-inflammatory activity of genipin on LPS-stimulated BV2 microglial cells has not been reported. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory activity of genipin both in vivo and in vitro. The levels of TNF-α, IL-1ß, NO and PGE2 were detected by ELISA. The expression of Nrf2, HO-1, and NF-κB were detected by western blot analysis. In vivo, genipin significantly attenuated LPS-induced memory deficit in the Morris water maze and passive avoidance tasks. Genipin also inhibited LPS-induced TNF-α and IL-1ß expression in brain tissues. In vitro, our results showed that genipin inhibited LPS-induced TNF-α, IL-1ß, NO and PGE2 production in a concentration-dependent manner. Genipin also suppressed LPS-induced NF-κB activation. In addition, the expression of Nrf2 and HO-1 were up-regulated by treatment of genipin. Furthermore, the inhibition of genipin on inflammatory mediator production was attenuated by transfection with Nrf2 siRNA. In conclusion, genipin inhibited LPS-induced inflammatory response by activating Nrf2 signaling pathway in BV2 microglia.

Vaccination with toxofilin DNA in combination with an alum-monophosphoryl lipid A mixed adjuvant induces significant protective immunity against Toxoplasma gondii.

BACKGROUND: A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; therefore, development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The purpose of the present study is to assess the protective efficacy of a DNA vaccine encoding the T. gondii toxofilin gene (pEGFP-toxofilin). In addition, toxofilin DNA vaccine combined with the individual adjuvants, alum or monophosphoryl lipid A (MPLA), or a mixture of alum-MPLA adjuvant were screened for their ability to enhance antibody responses. METHODS: Using bioinformatics, we analyzed the gene and amino acid sequences of the toxofilin protein, recognizing and identifying several potential linear B and T helper (Th)-1 cell epitopes. BALB/c mice were immunized three times with either toxofilin DNA vaccine alone or in combination with the adjuvants such as alum, MPLA or an alum-MPLA mixture. The systemic immune response was evaluated by cytokine, the percentage of CD4 (+) and CD8 (+) T cells and specific antibody measurement. Two weeks after the last immunization, protective efficacy was evaluated by challenging intraperitoneally with 1 × 104 tachyzoites of T. gondii or intragastrically with 20 cysts of T. gondii PRU strain. RESULTS: All experimentally immunized mice developed strong humoral and cellular immune responses compared with the control groups. Moreover, by comparison with the non-adjuvant toxofilin DNA vaccine group, adding alum adjuvant to toxofilin DNA vaccine resulted in an increase in humoral response and a skewed Th2 response. However, the MPLA adjuvant with toxofilin DNA vaccine induced significantly enhanced humoral and Th1-biased immune responses. Importantly, the co-administration of alum-MPLA adjuvant in combination with the toxofilin DNA vaccine shifted the Th2 immune response to a Th1 response compared with the alum-toxofilin group, and elicited the strongest humoral and Th1 responses among all the groups. At the same time, a longer survival time and less cyst amounts against T. gondii infection were also observed in the alum-MPLA-toxofilin group in comparison with single or no adjuvant groups. CONCLUSIONS: Toxoplasma gondii toxofilin is a promising vaccine candidate that warrants further development. Co-administration of the alum-MPLA adjuvant mixture with DNA vaccine could effectively enhance immunogenicity and strongly skew the cellular immune response towards a Th1 phenotype.

Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis.

BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. METHODS: The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), peripheral intravenous injection (PV group) and intrahepatic injection (IH group). The living conditions and survival time were recorded. Blood samples before and after MSCs transplantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) were analyzed by Western blotting. RESULTS: The average survival time of each group was 10.7+/-1.6 days (InP), 6.0+/-0.9 days (AH), 4.7+/-1.4 days (PV), 4.3+/-0.8 days (IH), respectively, when compared with the average survival time of 3.8+/-0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference (P<0.01). Pathological and biochemical analysis showed that liver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group (3.17+/-1.04, P<0.01) and AH group (8.17+/-0.76, P<0.05) as compared with that in the D-Gal group (11.50+/-1.32). The apoptosis rate in the InP group (25.0%+/-3.4%, P<0.01) and AH group (40.5%+/-1.0%, P<0.05) was lower than that in the D-Gal group (70.6%+/-8.5%). The expression of active caspase-3 was inhibited, while the expression of survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) was elevated in the InP group. CONCLUSIONS: Intraportal injection was superior to other pathways for MSC transplantation. Intraportal MSC transplantation could improve liver function, inhibit apoptosis and prolong the survival time of swine with ALF. The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALF.

Muted protein is involved in the targeting of CD63 to large dense-core vesicles of chromaffin cells.

Large dense-core vesicles (LDCVs) are characterized as a class of lysosome-related organelles (LROs), which undergo regulated release and play important roles in development, metabolism and homeostasis. The Muted protein is a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), which functions in the biogenesis of lysosomes and LROs. CD63 is a membrane component of lysosomes and LROs. Whether and how CD63 is sorted into LDCVs is largely unknown. In this study, we aim to identify the localization of CD63 in chromaffin cells by colocalization, living cell imaging and cell fractionation. We found that a proportion of CD63-YFP colocalized with NPY-dsRed labeled LDCVs. By sucrose density gradient fractionation, a proportion of CD63 was found to be highly enriched in LDCVs fractions. The Muted mutant mouse is a model of Hermansky-Pudlak syndrome (HPS). We also found that the level of CD63 was significantly decreased in Muted-deficient adrenal glands, suggesting that the Muted protein is important for the steady-state level of CD63. Our results suggest that CD63 is a membrane component of LDCVs and the stability of CD63 is dependent on the Muted protein, which provides a clue to the pathogenesis of LRO defects in HPS.

Impact of Admission Glucose on Non-Diabetic Patients with ST-Segment Elevation Myocardial Infarction Treated with Percutaneous Coronary Intervention: A Meta-Analysis.

BACKGROUND: Impaired admission glucose (AG) is thought to significantly increase the risk of both early and late death with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients. However, several earlier studies contradict these relationships. Through our meta-analysis, we aimed to evaluate such a relation between impaired AG, the risk of death and STEMI. METHODS: We accessed PubMed, EMBASE, Web of Science, and the Cochrane Library and systematically searched their databases to identify all related prospective cohort studies. The relative risks (RRs) with their 95% confidence interval (CI) were pooled quantitatively. RESULTS: The pooled, unadjusted relative risks of early outcome events indicated that patients who had glucose concentrations ≥ the range of 6.1-11.1 mmol/L, had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. For late outcome events, the pooled unadjusted RR indicated patients who had glucose concentrations ≥ the range 7.8-11.1 mmol/L, and had a 2.69-fold (95% CI, 2.16-3.34) higher late mortality based on full participants, whereas patients had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on based on in-hospital or 30-day survivors. CONCLUSIONS: In conclusion, the present meta-analysis demonstrated that impaired admission glucose may be an effective prognostic marker for significantly increased risk of early death. Regarding the long-term outcomes based on full population or early survival, high admission glucose also has a distinct but poorer prognostic impact on long-term mortality than early mortality. KEY WORDS: Admission glucose • Meta-analysis • Myocardial infarction • Non-diabetic.

Molecular phylogenetics and evolutionary history of sect. Quinquefoliae (Pinus): implications for Northern Hemisphere biogeography.

Climatic changes and tectonic events in the Cenozoic have greatly influenced the evolution and geographic distribution of the temperate flora. Such consequences should be most evident in plant groups that are ancient, widespread, and diverse. As one of the most widespread genera of trees, Pinus provides a good model for investigating the history of species diversification and biogeographic disjunction in the Northern Hemisphere. In this study, we reconstructed the phylogeny and investigated the evolutionary and biogeographic history of sect. Quinquefoliae (Pinus), a species-rich lineage disjunctly distributed in Asia, Europe and North America, based on complete taxon sampling and by using nine DNA fragments from chloroplast (cp), mitochondrial (mt) and nuclear genomes. The monophyly of the three subsections, Krempfianae, Gerardianae, and Strobus, is well-supported by cpDNA and nuclear gene phylogenies. However, neither subsect. Gerardianae nor subsect. Strobus forms a monophyletic group in the mtDNA phylogeny, in which sect. Quinquefoliae was divided into two major clades, one consisting of the North American and northeastern Asian species as well as the European P. peuce of subsect. Strobus, and the other comprising the remaining Eurasian species belonging to three subsections. The significant topological incongruence among the gene trees, in conjunction with divergence time estimation and ancestral area reconstruction, indicates that both ancient and relatively recent introgressive hybridization events occurred in the evolution of sect. Quinquefoliae, particularly in northeastern Asia and northwestern North America. In addition, the phylogenetic analysis suggests that the species of subsect. Strobus from subtropical eastern Asia and neighboring areas may have a single origin, although species non-monophyly is very widespread in the nuclear gene trees. Moreover, our study seems to support a Tethyan origin of sect. Quinquefoliae given the distributions and phylogenetic positions of subsects. Krempfianae and Gerardianae, and also highlights the importance of active mountain buildings and climatic changes during the Late Neogene in shaping the species diversity and geographic distribution of Pinus.

Activating transcription factor 3 interferes with p21 activation in histone deacetylase inhibitor-induced growth inhibition of epidermoid carcinoma cells.

Inhibition of histone deacetylase (HDAC) activity by HDAC inhibitors (HDACis) results in cancer cell growth inhibition, and HDACis have been revealed as potential anti-skin cancer agents. p21 is a cyclin-dependent kinase inhibitor and an essential regulator of growth inhibition. Recently, we reported that activating transcription factor 3 (ATF3) could significantly promote skin cancer cell growth. This study explored the relationship between ATF3 and HDACi-induced growth inhibition of epidermoid carcinoma cells. We found that trichostatin A (TSA) treatment inhibited cell growth in A431 epidermoid carcinoma cells in a dose-dependent manner. Simultaneously, p21 and ATF3 expression levels were upregulated and downregulated upon TSA stimulation, respectively. ATF3 overexpression promoted cell growth and downregulated p21 expression. In contrast, ATF3 depletion resulted in cell growth reduction and p21 transcriptional upregulation. More importantly, ATF3 overexpression partially antagonized TSA-induced growth inhibition and p21 activation. Collectively, these data demonstrate that ATF3 acts as an essential negative regulator of TSA-induced cell growth inhibition through interfering with TSA-induced p21 activation.

Admission glucose and risk of early death in non-diabetic patients with ST-segment elevation myocardial infarction: a meta-analysis.

BACKGROUND: Impaired admission glucose (AG) is considered to significantly increase risk on both early and late death of the patients with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients; however, some reports contradict the relationship. We therefore conducted a meta-analysis to clarify this issue. MATERIAL/METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched to identify all related prospective cohort studies. The relative risks (RR) with their 95% confidence interval (CI) were pooled quantitatively. RESULTS: The pooled RR of early outcome events indicated patients with glucose concentrations ≥6.1-11.1 mmol/L had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. The pooled RR of late outcome events indicated that the patients with glucose concentrations ≥7.8-11.1 mmol/L had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on in-hospital or 30-day survivors. CONCLUSIONS: High AG may be a helpful prognostic marker of significantly increased risk on early death in non-diabetic patients with STEMI, and has an explicit but prognostic adverse impact on long-term mortality but not early mortality in these patients.

No transmission of porcine endogenous retrovirus in an acute liver failure model treated by a novel hybrid bioartificial liver containing porcine hepatocytes.

BACKGROUND: A novel hybrid bioartificial liver (HBAL) was constructed using an anionic resin adsorption column and a multi-layer flat-plate bioreactor containing porcine hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs). This study aimed to evaluate the microbiological safety of the HBAL by detecting the transmission of porcine endogenous retroviruses (PERVs) into canines with acute liver failure (ALF) undergoing HBAL. METHODS: Eight dogs with ALF received a 6-hour HBAL treatment on the first day after the modeling by D-galactosamine administration. The plasma in the HBAL and the whole blood in the dogs were collected for PERV detection at regular intervals until one year later when the dogs were sacrificed to retrieve the tissues of several organs for immunohistochemistry and Western blotting for the investigation of PERV capsid protein gag p30 in the tissue. Furthermore, HEK293 cells were incubated to determine the in vitro infectivity. RESULTS: PERV RNA and reverse transcriptase activity were observed in the plasma of circuit 3, suggesting that PERV particles released in circuit 3. No positive PERV RNA and reverse transcriptase activity were detected in other plasma. No HEK293 cells were infected by the plasma in vitro. In addition, all PERV-related analyses in peripheral blood mononuclear cells and tissues were negative. CONCLUSION: No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.

Comparison of primary coronary percutaneous coronary intervention between Diabetic Men and Women with acute myocardial infarction.

OBJECTIVE: This study aimed to explore the short-term efficacy and safety of primary percutaneous coronary intervention (PCI) in female diabetic patients complicated with acute myocardial infarction (AMI). METHODS: A total of 169 diabetic patients with AMI who underwent primary PCI were selected and divided into group A (52 females) and group B (117 males). The clinical data, characteristics of coronary artery lesions, lengths of hospital stay, and incidences of complications were then compared between two groups. RESULTS: The average age, history of hyperlipidemia, double branch lesions, triple branch lesions, and left main lesions were significantly higher in group A than in group B (P < 0.05). Smoking history, PCI history, and pre-infarction angina were distinctly lower in group A than in group B (P < 0.05). Thrombolysis in myocardial infarction 3 (TIMI3) flow and TIMI myocardial perfusion grade 3 (TMPG3) after PCI were markedly lower in group A than in group B (P < 0.001). Group A had a higher incidence of complications, such as severe arrhythmia, cardiac function Killip III/IV, cardiogenic shock, major, moderate and mild bleed event, as well as a 30-day mortality rate, compared with group B (P < 0.05). CONCLUSION: In summary, our study demonstrated that female diabetic patients with AMI had lower TIMI3 flow and TMPG3 following PCI than male patients, while there was higher incidence of complications and 30-day mortality rate. Therefore, more attention should be paid to the therapy of diabetic women with acute myocardial infarction as well as the control of risk factors.