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On page 4 showing 61 ~ 80 papers out of 1,607 papers

Stem-Cell Therapy for Esophageal Anastomotic Leakage by Autografting Stromal Cells in Fibrin Scaffold.

  • Xiang Xue‎ et al.
  • Stem cells translational medicine‎
  • 2019‎

Esophageal anastomotic leakage (EAL) is a devastating complication for esophagectomy but the available therapies are unsatisfactory. Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffold (FS), we evaluated the efficacy of a stem-cell therapy for EAL by engrafting adult and autologous MSCs (AAMSCs) in FS and investigated the potential mechanism. Twenty-one rabbits were assigned to AAMSC/FS group (n = 12) and control group (n = 9). After harvested, AAMSCs were identified and then labeled with lenti.GFP. To construct EAL model, a polyethylene tube was indwelled through the anastomosis for 1 week. A total of 2 × 106 AAMSCs in 0.2 ml FS were engrafted onto the EAL for the AAMSC/FS group, whereas FS was injected for control. Magnetic Resonance Imaging (MRI) examination was performed after 5 weeks. Esophageal tissues were harvested for macroscopic, histological analyses, Western blot, and immunohistochemistry at 8 weeks. The animal model of EAL was established successfully. MRI scanning revealed a decreased inflammation reaction in AAMSC/FS group. Accordingly, AAMSC/FS group presented a higher closure rate (83.3% vs. 11.1%, p = .02) and lower infection rate (33.3% vs. 88.9%, p = .02). Histological analyses showed the autografted MSCs resided in the injection site. Furthermore, milder inflammation responses and less collagen deposition were observed in AAMSC/FS group. Western blot and immunohistochemistry studies suggested that the therapeutic effect might be related to the secretions of IL-10 and MMP-9. Engrafting AAMSCs in FS could be a promising therapeutic strategy for the treatment of EAL by suppressing inflammation response and alleviating fibrosis progression. Stem Cells Translational Medicine 2019;8:548-556.


Synergistic cytotoxicity of homoharringtonine and etoposide in acute myeloid leukemia cells involves disrupted antioxidant defense.

  • Jingjing Zhang‎ et al.
  • Cancer management and research‎
  • 2019‎

Cytotoxicity induced by reactive oxygen species (ROS) is critical for the effectiveness of chemotherapeutic drugs used in the treatment of acute myeloid leukemia (AML). This study aimed to investigate whether ROS contributes to cytotoxicity in AML cells when treated with homoharringtonine (HHT) and etoposide (ETP) in combination.


Unraveling the molecular mechanism of the response to changing ambient phosphorus in the dinoflagellate Alexandrium catenella with quantitative proteomics.

  • Shu-Feng Zhang‎ et al.
  • Journal of proteomics‎
  • 2019‎

Phosphorus (P) is a key macronutrient limiting cell growth and bloom formation of marine dinoflagellates. Physiological responses to changing ambient P have been investigated in dinoflagellates; however, the molecular mechanisms behind these responses remain limited. Here, we compared the protein expression profiles of a marine dinoflagellate Alexandrium catenella grown in inorganic P-replete, P-deficient, and inorganic- and organic-P resupplied conditions using an iTRAQ-based quantitative proteomic approach. P deficiency inhibited cell growth and enhanced alkaline phosphatase activity (APA) but had no effect on photosynthetic efficiency. After P resupply, the P-deficient cells recovered growth rapidly and APA decreased. Proteins involved in sphingolipid metabolism, organic P utilization, starch and sucrose metabolism, and photosynthesis were up-regulated in the P-deficient cells, while proteins associated with protein synthesis, nutrient assimilation and energy metabolism were down-regulated. The responses of the P-deficient A. catenella to the resupply of organic and inorganic P presented significant differences: more biological processes were enhanced in the organic P-resupplied cells than those in the inorganic P-resupplied cells; A. catenella might directly utilize G-6-P for nucleic acid synthesis through the pentose phosphate pathway. Our results indicate that A. catenella has evolved diverse adaptive strategies to ambient P deficiency and specific mechanisms to utilize dissolved organic P, which might be an important reason resulting in A. catenella bloom in the low inorganic P environment. BIOLOGICAL SIGNIFICANCE: The ability of marine dinoflagellates to utilize different phosphorus (P) species and adapt to ambient P deficiency determines their success in the ocean. In this study, we investigated the response mechanisms of a dinoflagellate Alexandrium catenella to ambient P deficiency, and resupply of inorganic- and organic-P at the proteome level. Our results indicated that A. catenella initiated multiple adaptive strategies to ambient P deficiency, e.g. utilizing nonphospholipids and glycosphingolipids instead of phospholipids, enhancing expression of acid phosphatase to utilize organic P, and reallocating intracellular energy. Proteome responses of the P-deficient A. catenella to resupply of inorganic- and organic-P differed significantly, indicating different utilization pathways of inorganic and organic P, A. catenella might directly utilize low molecular weight organic P, such as G-6-P as both P and carbon sources.


Reducing the occurrence rate of catheter dysfunction in peritoneal dialysis: a single-center experience about CQI.

  • Jing Hu‎ et al.
  • Renal failure‎
  • 2018‎

To reduce the occurrence rate of peritoneal dialysis (PD) catheter dysfunction caused by catheter displacement or plugging, this study screened all patients with peritoneal dialysis catheterization from 2002 to 2015 from the Third Xiangya Hospital of Central South University. There were 256 patients before continuous quality improvement (CQI) (from 2002 to 2007) and 813 patients after CQI (from 2008 to 2015). The occurrence rate of catheter dysfunction was 5.9% in the preCQI group: seven cases were associated with peritonitis, six cases were involved in omentum wrapping, one case was blocked by oviduct, and one case was blocked by blood clot. Through PDCA (plan-do-check-act) four-step of CQI, the following measures were adopted: (1) Preoperative: treat complications, enema and urine catheterization (2) Intraoperative: strengthen analgesia, Lower the insert position of catheter to 7.5 ∼ 8.5 cm above the pubic symphysis, extending the straight distance of catheter in rectus abdominis and decrease the times of peritoneal dialysis catheter implantation. (3) Postoperative: strengthen the training of nurses, patients and their families. (4) strengthen anticoagulation therapy during peritonitis treatment. (5) use laparoscopic technology for refractory patients, and so on. The occurrence of catheter dysfunction was 1.5% in the postCQI group (p < 0.05): two cases were associated with peritonitis, ten cases were involved in omentum wrapping. The measures we adopted in CQI reduce the occurrence rate of catheter displacement or plugging in peritoneal dialysis.


Targeting the DNA Repair Endonuclease ERCC1-XPF with Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) and Its Prodrug to Enhance Cisplatin Efficacy in Human Cancer Cells.

  • Joshua R Heyza‎ et al.
  • Nutrients‎
  • 2018‎

The 5'-3' structure-specific endonuclease ERCC1/XPF (Excision Repair Cross-Complementation Group 1/Xeroderma Pigmentosum group F) plays critical roles in the repair of cisplatin-induced DNA damage. As such, it has been identified as a potential pharmacological target for enhancing clinical response to platinum-based chemotherapy. The goal of this study was to follow up on our previous identification of the compound NSC143099 as a potent inhibitor of ERCC1/XPF activity by performing an in silico screen to identify structural analogues that could inhibit ERCC1/XPF activity in vitro and in vivo. Using a fluorescence-based DNA-endonuclease incision assay, we identified the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) as a potent inhibitor of ERCC1/XPF activity with an IC50 (half maximal inhibitory concentration) in the nanomolar range in biochemical assays. Using DNA repair assays and clonogenic survival assays, we show that EGCG can inhibit DNA repair and enhance cisplatin sensitivity in human cancer cells. Finally, we show that a prodrug of EGCG, Pro-EGCG (EGCG octaacetate), can enhance response to platinum-based chemotherapy in vivo. Together these data support a novel target of EGCG in cancer cells, namely ERCC1/XPF. Our studies also corroborate previous observations that EGCG enhances sensitivity to cisplatin in multiple cancer types. Thus, EGCG or its prodrug makes an ideal candidate for further pharmacological development with the goal of enhancing cisplatin response in human tumors.


Selective effects of non-thermal atmospheric plasma on triple-negative breast normal and carcinoma cells through different cell signaling pathways.

  • Yuan Liu‎ et al.
  • Scientific reports‎
  • 2017‎

Non-thermal atmospheric plasma (NTP) has shown its selective anticancer effects in many types of tumors in vitro and one of the main mechanisms is that the different increase of intracellular ROS in cancer and homologous normal cells. In this study, we report that NTP treatment reduces the proliferation in triple negative breast cancer (TNBC) and normal cell lines. Simultaneously, STAT3 pathway is inhibited by NTP effects. However, it is observed that normal cells MCF10A are more sensitive to ROS toxicity induced by NTP than cancer cells MDA-MB-231. When 5 mM of ROS inhibitor N-acetyl cysteine (NAC) is employed in NTP treatments, the proliferation of normal breast cells MCF10A recovers. Meanwhile, NTP effects remain significant inhibition of MDA-MB-231 cells. Our results further reveal that NTP can induce apoptosis in MDA-MB-231 cells through inhibiting interleukin-6 receptor (IL-6R) pathway. Moreover, the mechanism of NTP anti-cancer selectivity relates to constantly HER2/Akt activation induced by NTP especially in MCF10A cells but not in MDA-MB-231 cells. Therefore, these two different cell signaling pathways induced by NTP treatments in TNBC and homologous normal cells make NTP becoming a potential tool in future therapy.


Loop-Mediated Isothermal Amplification Method for the Rapid Detection of Ralstonia solanacearum Phylotype I Mulberry Strains in China.

  • Wen Huang‎ et al.
  • Frontiers in plant science‎
  • 2017‎

Ralstonia solanacearum phylotype I mulberry strains are causative agent of bacterial wilt of mulberry. Current diagnostic methods are not adopted to the mulberry wilt disease. In this study, we developed a rapid method, loop-mediated isothermal amplification (LAMP), to detect R. solanacearum phylotype I mulberry strains. A set of six primers was designed to target the clone MG67 sequence in this LAMP detection which can be completed in 20 min at 64°C. The results of the LAMP reaction could be observed with the naked eye due to magnesium pyrophosphate precipitate produced during the reaction or the color change after adding SYBR Green I. The specificity of the LAMP was confirmed using DNA from 46 representative strains of R. solanacearum and 7 other soil-borne bacteria strains. This method was also of high sensitivity and could be used to detect the presence of less than 160 fg genomic DNA or 2.2 × 102 CFU/ml of bacterial cells per 25 μl reaction volume, moreover, the presence of plant tissue fluid did not affect the sensitivity. Since it does not require expensive equipment or specialized techniques, this LAMP-based diagnostic method has the potential to be used under field conditions to make disease forecasting more accurate and efficient.


Biochemical characterization of an enantioselective esterase from Brevundimonas sp. LY-2.

  • Jing Zhang‎ et al.
  • Microbial cell factories‎
  • 2017‎

Lactofen, a member of the diphenylether herbicides, has high activity and is commonly used to control broadleaf weeds. As a post-emergent herbicide, it is directly released to the environment, and easily caused the pollution. This herbicide is degraded in soil mainly by microbial activity, but the functional enzyme involved in the biodegradation of lactofen is still not clear now.


Exploration of binding and inhibition mechanism of a small molecule inhibitor of influenza virus H1N1 hemagglutinin by molecular dynamics simulation.

  • Shanshan Guan‎ et al.
  • Scientific reports‎
  • 2017‎

Influenza viruses are a major public health threat worldwide. The influenza hemagglutinin (HA) plays an essential role in the virus life cycle. Due to the high conservation of the HA stem region, it has become an especially attractive target for inhibitors for therapeutics. In this study, molecular simulation was applied to study the mechanism of a small molecule inhibitor (MBX2329) of influenza HA. Behaviors of the small molecule under neutral and acidic conditions were investigated, and an interesting dynamic binding mechanism was found. The results suggested that the binding of the inhibitor with HA under neutral conditions facilitates only its intake, while it interacts with HA under acidic conditions using a different mechanism at a new binding site. After a series of experiments, we believe that binding of the inhibitor can prevent the release of HA1 from HA2, further maintaining the rigidity of the HA2 loop and stabilizing the distance between the long helix and short helices. The investigated residues in the new binding site show high conservation, implying that the new binding pocket has the potential to be an effective drug target. The results of this study will provide a theoretical basis for the mechanism of new influenza virus inhibitors.


Dissecting structures and functions of SecA-only protein-conducting channels: ATPase, pore structure, ion channel activity, protein translocation, and interaction with SecYEG/SecDF•YajC.

  • Ying-Hsin Hsieh‎ et al.
  • PloS one‎
  • 2017‎

SecA is an essential protein in the major bacterial Sec-dependent translocation pathways. E. coli SecA has 901 aminoacyl residues which form multi-functional domains that interact with various ligands to impart function. In this study, we constructed and purified tethered C-terminal deletion fragments of SecA to determine the requirements for N-terminal domains interacting with lipids to provide ATPase activity, pore structure, ion channel activity, protein translocation and interactions with SecYEG-SecDF•YajC. We found that the N-terminal fragment SecAN493 (SecA1-493) has low, intrinsic ATPase activity. Larger fragments have greater activity, becoming highest around N619-N632. Lipids greatly stimulated the ATPase activities of the fragments N608-N798, reaching maximal activities around N619. Three helices in amino-acyl residues SecA619-831, which includes the "Helical Scaffold" Domain (SecA619-668) are critical for pore formation, ion channel activity, and for function with SecYEG-SecDF•YajC. In the presence of liposomes, N-terminal domain fragments of SecA form pore-ring structures at fragment-size N640, ion channel activity around N798, and protein translocation capability around N831. SecA domain fragments ranging in size between N643-N669 are critical for functional interactions with SecYEG-SecDF•YajC. In the presence of liposomes, inactive C-terminal fragments complement smaller non-functional N-terminal fragments to form SecA-only pore structures with ion channel activity and protein translocation ability. Thus, SecA domain fragment interactions with liposomes defined critical structures and functional aspects of SecA-only channels. These data provide the mechanistic basis for SecA to form primitive, low-efficiency, SecA-only protein-conducting channels, as well as the minimal parameters for SecA to interact functionally with SecYEG-SecDF•YajC to form high-efficiency channels.


The Fusarium graminearum Histone Acetyltransferases Are Important for Morphogenesis, DON Biosynthesis, and Pathogenicity.

  • Xiangjiu Kong‎ et al.
  • Frontiers in microbiology‎
  • 2018‎

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a central role in the regulation of gene expression and various biological processes in eukaryotes. Although HAT genes have been studied in many fungi, few of them have been functionally characterized. In this study, we identified and characterized four putative HATs (FgGCN5, FgRTT109, FgSAS2, FgSAS3) in the plant pathogenic ascomycete Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. We replaced the genes and all mutant strains showed reduced growth of F. graminearum. The ΔFgSAS3 and ΔFgGCN5 mutant increased sensitivity to oxidative and osmotic stresses. Additionally, ΔFgSAS3 showed reduced conidia sporulation and perithecium formation. Mutant ΔFgGCN5 was unable to generate any conidia and lost its ability to form perithecia. Our data showed also that FgSAS3 and FgGCN5 are pathogenicity factors required for infecting wheat heads as well as tomato fruits. Importantly, almost no Deoxynivalenol (DON) was produced either in ΔFgSAS3 or ΔFgGCN5 mutants, which was consistent with a significant downregulation of TRI genes expression. Furthermore, we discovered for the first time that FgSAS3 is indispensable for the acetylation of histone site H3K4, while FgGCN5 is essential for the acetylation of H3K9, H3K18, and H3K27. H3K14 can be completely acetylated when FgSAS3 and FgGCN5 were both present. The RNA-seq analyses of the two mutant strains provide insight into their functions in development and metabolism. Results from this study clarify the functional divergence of HATs in F. graminearum, and may provide novel targeted strategies to control secondary metabolite expression and infections of F. graminearum.


Modulation of functional activity and connectivity by acupuncture in patients with Alzheimer disease as measured by resting-state fMRI.

  • Weimin Zheng‎ et al.
  • PloS one‎
  • 2018‎

Acupuncture has been used in the therapy of Alzheimer disease (AD); however, its neural mechanisms are still unclear. The aim of this study is to examine the effect of acupuncture on the functional connectivity in AD by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-eight subjects (14 AD and 14 normal controls) participated in this study. The rs-fMRI data were acquired before and after acupuncture stimulation at the acupoints of Tai chong (Liv3) and Hegu (LI4). During the baseline resting state, by using the amplitude of low-frequency fluctuations (ALFF), we found a significantly decreased or increased ALFF in the AD patients relative to the controls. These regions were located in the right superior frontal gyrus (SFG), left postcentral gyrus, subgenual cingulate cortex (SCC), right middle cingulate cortex (MCC), right inferior frontal gyrus (IFG), right hippocampus and the right inferior temporal gyrus (ITG). Then, we selected these brain regions as seeds to investigate whether regional activity and functional connectivity could be modulated by acupuncture in the AD patients. When compared to the pre-acupuncture stage, several of the above regions showed an increased or decreased ALFF after acupuncture in the AD patients. In addition, the functional connectivity between the hippocampus and the precentral gyrus showed enhancement after acupuncture in the AD patients. Finally, there were close correlations between the functional activity, connectivity and clinical performance in the AD patients. The current study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can modulate functional activity and connectivity of specific cognition-related regions in AD patients.


Effect of medium-chain triglycerides on growth performance, nutrient digestibility, plasma metabolites and antioxidant capacity in weanling pigs.

  • Yue Li‎ et al.
  • Animal nutrition (Zhongguo xu mu shou yi xue hui)‎
  • 2015‎

The aim of this study was to investigate the effect of medium-chain triglycerides (MCTs) on growth performance, nutrient digestibility, plasma metabolites and antioxidant capacity in weanling pigs. A total of 160 weanling (Duroc × Landrace × Yorkshire) pigs (age: 21 ± 1 d; body weight: 7.50 ± 0.28 kg) were randomly allotted to 4 treatments, receiving the following diets for 28 d: control diet [containing 3.5% soybean oil (SO)], MCT1 diet (containing 0.7% MCTs and 2.8% SO), MCT2 diet (containing 1.4% MCTs and 2.1% SO) and MCT3 diet (containing 2.1% MCTs and 1.4% SO). Dietary inclusion of MCTs improved the average daily gain and feed efficiency (FE) of pigs compared with the control during the first 2 weeks post-weaning (P < 0.05). A similar positive effect was also observed for the overall FE in MCT2 group (P < 0.05). Compared with the control, apparent total tract digestibility (ATTD) of ether extract was improved by MCT2 and MCT3 treatment from day 12-14 post-weaning (P < 0.05). In addition, MCT2 treatment also exerted a beneficial effect on the ATTD of dry matter (P < 0.05). The increased total protein concentration and decreased urea nitrogen and malondialdehyde levels of plasma were observed in both MCT2 and MCT3 groups on day 14 post-weaning (P < 0.05). In conclusion, MCTs could improve growth performance, nutrients utilization, and antioxidant ability of weanling piglets.


Differential microRNA Expression in Porcine Endometrium Involved in Remodeling and Angiogenesis That Contributes to Embryonic Implantation.

  • Linjun Hong‎ et al.
  • Frontiers in genetics‎
  • 2019‎

Background: In western swine breeds, up to 30% of embryonic losses occur during early pregnancy, and the majority of embryonic losses happens during implantation. In this period, maternal recognition of pregnancy begins to occur and blastocysts undergo dramatic morphologic changes. As with other species, changes in the uterine environment plays an important role in the process of embryo implantation in pigs. Erhualian (ER) pigs, one of the Chinese Taihu swine breeds, are known to have the highest litter size in the world. Experiments demonstrated that the greater embryonic survival on gestation day (GD) 12 in Chinese Taihu pigs is one important factor that contributes to enhanced litter size. This is largely controlled by maternal genes. In this study, endometrial samples were collected from pregnant Landrace×Large Yorkshire (LL) sows (parity 3) and ER sows (parity 3) on GD12 and the expression profiles of microRNAs (miRNAs) in the endometrium were compared between ER and LL using miRNA-seq technology. Results: A total of 288 miRNAs were identified in the pig endometrium, including 202 previously known and 86 novel miRNAs. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that highly abundant miRNAs might affect endometrial remodeling. Comparison between LL and ER sows revealed that 96 known miRNAs were differentially expressed between the two groups (including 78 up-regulated and 18 down-regulated miRNAs in ER compared to LL). Bioinformatics analysis showed that the target genes of some differentially expressed miRNAs were involved in pathways related to angiogenesis, proliferation, apoptosis, and tissue remodeling, which play critical roles in implantation by regulating endometrial structural changes and secretions of hormones, growth factors, and nutrients. Furthermore, the results demonstrated that insulin-like growth factor-1 protein expression was directly inhibited by miR-206. The lower expression of miR-206 in ER compared to LL might facilitate the angiogenesis of the endometrium during embryo implantation. Conclusions: The identified miRNAs that are differentially expressed in the endometrium of ER and LL pigs will contribute to the understanding of the role of miRNAs in embryonic implantation and the molecular mechanisms of the highest embryonic survival in Chinese ER pigs.


Proteomics analysis of asthenozoospermia and identification of glucose-6-phosphate isomerase as an important enzyme for sperm motility.

  • Yueshuai Guo‎ et al.
  • Journal of proteomics‎
  • 2019‎

Asthenozoospermia, in which sperm motility is affected, is one of the primary causes of male infertility. However, the exact mechanism responsible for the defective motility remains unknown. It is important to identify the precise proteins or pathways involved in sperm motility. The present study analyzed five asthenozoospermic sperm samples and five healthy controls using TMT-based quantitative method and identified 152 differentially expressed proteins, with 84 upregulated and 68 downregulated in asthenozoospermia. Four proteins (GPI, MDH1, PGAM1 and PGAM2) were found in several over-represented energy metabolism pathways using bioinformatics analysis. Glucose-6-phosphate isomerase (GPI), a rate-limiting enzyme converting glucose-6-phosphate to fructose-6-phosphate, was found to be significantly decreased in asthenozoospermia by Western blotting and ELISA on an extended sample size. Furthermore, substitution of glucose with fructose-6-phosphate significantly promoted asthenozoospermic sperm motility in vitro. Taken together, our results suggest that the poor motility of sperm in asthenozoospermia may partly result from defects in GPI-associated energy metabolism. SIGNIFICANCE: To identify the key proteins or pathways involved in sperm motility, the accurate TMT-based quantitative method was applied to characterize protein profiles of asthenozoospermic sperm. GPI, an enzyme involved in energy metabolism, was found to be differentially abundant, and validated by extended sample analysis. The supplement of the product of GPI, fructose-6-phosphate, could significantly improve sperm motility. Our study could provide new insights into the molecular basis of sperm motility and the improvement of motility in asthenozoospermia.


Adhesive Bifidobacterium Induced Changes in Cecal Microbiome Alleviated Constipation in Mice.

  • Linlin Wang‎ et al.
  • Frontiers in microbiology‎
  • 2019‎

Constipation, which seriously affects living quality of people, is a common gastrointestinal disease. The engagement of the intestinal flora in the development of symptoms of constipation has been frequently hypothesized. In this study, constipated mice induced by loperamide were used to investige the alleviation of constipation by Bifidobacteria. Bifidobacteria was sorted out according to their adhesive properties into two groups. One group combined multiple strains of Bifidobacterium with adhesion property (CMB1), the other combined multiple strains of Bifidobacterium without adhesion property (CMB2). It was found that CMB1 can alleviate constipation more efficiently by improving the water, propionate and butyrate content in feces, and overall gastrointestinal transit time. Meanwhile, from the perspective of fecal microbiota, CMB1 alleviated constipation mainly by increasing the relative abundances of genera (Bifidobacterium, Lactobacillus, and Prevotella) associated with rapid bowel movement. From the perspective of cecal microbiota, CMB1 alleviated constipation mainly by increasing the relative abundances of genera Lactobacillus, Bacteroides, unclassified S24-7, Dorea, Ruminococcus, Coprococcus, and Rikenella, and decreasing the relative abundances of genera Oscillospira, Odoribacter and Unclassified F16, which are associated with methane production and colonic transit. Overall, changes of microbiota in caecum by CMB1 reflect the stage of constipation in mice more comprehensively than that in feces.


Analysis of outcome and factors correlated with maintenance peritoneal dialysis.

  • Min Li‎ et al.
  • The Journal of international medical research‎
  • 2019‎

This study aimed to analyze the outcome and factors correlated with maintenance peritoneal dialysis (PD) to provide guidance for improving prognosis, and prolonging the catheterization and survival times of patients on PD with end-stage renal disease.


Detection of Exosomal PD-L1 RNA in Saliva of Patients With Periodontitis.

  • Jialiang Yu‎ et al.
  • Frontiers in genetics‎
  • 2019‎

Periodontitis is the most prevalent inflammatory disease of the periodontium, and is related to oral and systemic health. Exosomes are emerging as non-invasive biomarker for liquid biopsy. We here evaluated the levels of programmed death-ligand 1 (PD-L1) mRNA in salivary exosomes from patients with periodontitis and non-periodontitis controls. The purposes of this study were to establish a procedure for isolation and detection of mRNA in exosomes from saliva of periodontitis patients, to characterize the level of salivary exosomal PD-L1, and to illustrate its clinical relevance. Bioinformatics analysis suggested that periodontitis was associated with an inflammation gene expression signature, that PD-L1 expression positively correlated with inflammation in periodontitis based on gene set enrichment analysis (GSEA) and that PD-L1 expression was remarkably elevated in periodontitis patients versus control subjects. Exosomal RNAs were successfully isolated from saliva of 61 patients and 30 controls and were subjected to qRT-PCR. Levels of PD-L1 mRNA in salivary exosomes were higher in periodontitis patients than controls (P < 0.01). Salivary exosomal PD-L1 mRNA showed significant difference between the stages of periodontitis. In summary, the protocols for isolating and detecting exosomal RNA from saliva of periodontitis patients were, for the first time, characterized. The current study suggests that assay of exosomes-based PD-L1 mRNA in saliva has potential to distinguish periodontitis from the healthy, and the levels correlate with the severity/stage of periodontitis.


A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

  • Rizwan Ahmed‎ et al.
  • Cell‎
  • 2019‎

T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. In concordance, a synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Moreover, mAbs bearing this clonotype are autoreactive against CD4 T cells and inhibit insulin tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute, and violators of this paradigm are likely key drivers of autoimmune diseases.


Phycobilisomes Harbor FNRL in Cyanobacteria.

  • Haijun Liu‎ et al.
  • mBio‎
  • 2019‎

Cyanobacterial phycobilisomes (PBSs) are photosynthetic antenna complexes that harvest light energy and supply it to two reaction centers (RCs) where photochemistry starts. PBSs can be classified into two types, depending on the presence of allophycocyanin (APC): CpcG-PBS and CpcL-PBS. Because the accurate protein composition of CpcL-PBS remains unclear, we describe here its isolation and characterization from the cyanobacterium Synechocystis sp. strain 6803. We found that ferredoxin-NADP+ oxidoreductase (or FNRL), an enzyme involved in both cyclic electron transport and the terminal step of the electron transport chain in oxygenic photosynthesis, is tightly associated with CpcL-PBS as well as with CpcG-PBS. Room temperature and low-temperature fluorescence analyses show a red-shifted emission at 669 nm in CpcL-PBS as a terminal energy emitter without APC. SDS-PAGE and quantitative mass spectrometry reveal an increased content of FNRL and CpcC2, a rod linker protein, in CpcL-PBS compared to that of CpcG-PBS rods, indicative of an elongated CpcL-PBS rod length and its potential functional differences from CpcG-PBS. Furthermore, we combined isotope-encoded cross-linking mass spectrometry with computational protein structure predictions and structural modeling to produce an FNRL-PBS binding model that is supported by two cross-links between K69 of FNRL and the N terminus of CpcB, one component in PBS, in both CpcG-PBS and CpcL-PBS (cross-link 1), and between the N termini of FNRL and CpcB (cross-link 2). Our data provide a novel functional assembly form of phycobiliproteins and a molecular-level description of the close association of FNRL with phycocyanin in both CpcG-PBS and CpcL-PBS.IMPORTANCE Cyanobacterial light-harvesting complex PBSs are essential for photochemistry in light reactions and for balancing energy flow to carbon fixation in the form of ATP and NADPH. We isolated a new type of PBS without an allophycocyanin core (i.e., CpcL-PBS). CpcL-PBS contains both a spectral red-shifted chromophore, enabling efficient energy transfer to chlorophyll molecules in the reaction centers, and an increased FNRL content with various rod lengths. Identification of a close association of FNRL with both CpcG-PBS and CpcL-PBS brings new insight to its regulatory role for fine-tuning light energy transfer and carbon fixation through both noncyclic and cyclic electron transport.


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    From here we'll present any options for the literature, such as exporting your current results.

  10. Further Questions

    If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.

Publications Per Year

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Year:

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