Publications by authors named "Qingyi Wang"

25 Publications

  • Page 1 of 1

Enhancing Host-Cell Protein Detection in Protein Therapeutics Using HILIC Enrichment and Proteomic Analysis.

Anal Chem 2020 08 17;92(15):10327-10335. Epub 2020 Jul 17.

Biophysical and Chemical Characterization Center of Excellence, Analytical Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08901, United States.

Liquid chromatography-mass spectrometry (LC-MS)-based proteomics approaches have been widely used to identify residual host-cell proteins (HCPs) in support of process and product characterization for protein therapeutics. Particularly, these methods can provide a general and unbiased approach for the detection of HCPs and may generate critical information on HCPs that are outside the coverage provided by a conventional immunoassay. A significant technical hurdle for HCP analysis is the overwhelmingly large background of biotherapeutic that obscures HCP detection and quantification. In this work, we developed a method that relies on hydrophilic interaction chromatography (HILIC) for HCP enrichment followed by concentration and digestion prior to LC-MS analysis. This approach has enabled detection of HCPs in a drug substance that were not observed in other conventional flow rate LC-MS strategies. For example, 28% of HCPs identified in NISTmAb (20 out of 71) were not previously published or identified by established methods such as the native digestion technique. For an IgG1 protein spiked with 1000 ppm HCP standards, we detected 83 HCPs, 61 out of which were not identified by the native digestion method. Similar improvement in performance was demonstrated for an Fc-fusion protein therapeutic. Our method can be readily implemented in most protein mass spectrometry laboratories to support process development for protein therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c00360DOI Listing
August 2020

[Research Progress of Immunotherapy and Prognostic Markers in Small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2020 Mar 27;23(3):182-188. Epub 2020 Feb 27.

Second Department of Thoracic Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410006, China.

The efficacy of non-small cell lung cancer (NSCLC) has been obviously improved recent years, while the survival of small cell lung cancer (SCLC) patients remains inferior for limit treatment options. The incidence of SCLC accounts for 15% of the overall incidence of lung cancer, and it is characterized with high malignancy, rapid growth, early widespread metastasis, making it very difficult to treat. With the approval of immunotherapy for a variety of solid tumors including NSCLC, as a relatively immunogenic cancer species, relevant clinical researchs on SCLC are also underway and have made certain progress. More importantly, due to the existence of tumor heterogeneity, exploring relevant markers that can predict the efficacy of SCLC is essential for accurate therapy. This review describes the latest advances in SCLC immunotherapy and biomarkers related to the efficacy of immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3779/j.issn.1009-3419.2020.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118334PMC
March 2020

Monolithic mtesla-level magnetic induction by self-rolled-up membrane technology.

Sci Adv 2020 01 17;6(3):eaay4508. Epub 2020 Jan 17.

Department of Electrical and Computer Engineering and Micro and Nanotechnology Laboratory, University of Illinois, Urbana, IL 61801, USA.

Monolithic strong magnetic induction at the mtesla to tesla level provides essential functionalities to physical, chemical, and medical systems. Current design options are constrained by existing capabilities in three-dimensional (3D) structure construction, current handling, and magnetic material integration. We report here geometric transformation of large-area and relatively thick (~100 to 250 nm) 2D nanomembranes into multiturn 3D air-core microtubes by a vapor-phase self-rolled-up membrane (S-RuM) nanotechnology, combined with postrolling integration of ferrofluid magnetic materials by capillary force. Hundreds of S-RuM power inductors on sapphire are designed and tested, with maximum operating frequency exceeding 500 MHz. An inductance of 1.24 μH at 10 kHz has been achieved for a single microtube inductor, with corresponding areal and volumetric inductance densities of 3 μH/mm and 23 μH/mm, respectively. The simulated intensity of the magnetic induction reaches tens of mtesla in fabricated devices at 10 MHz.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aay4508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968933PMC
January 2020

Identifying microRNAs and Their Editing Sites in .

Cells 2019 07 5;8(7). Epub 2019 Jul 5.

Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming 650500, Yunnan, China.

MicroRNAs (miRNAs) are small non-coding RNAs that are critical in post-transcriptional regulation. is an important nonhuman primate that is often used in basic and translational researches. However, the annotation of miRNAs in is far from complete, and there are no reports of miRNA editing events in , although editing may affect the biogenesis or functions of the miRNAs. To improve miRNA annotation and to reveal editing events of miRNAs in , we generated 12 small RNA profiles from eight tissues and performed comprehensive analysis of these profiles. We identified 479 conserved pre-miRNAs that have not been reported in and 17 species specific miRNAs. Furthermore, we identified 3386 editing sites with significant editing levels from 471 pre-miRNAs after analyzing the 12 self-generated and 58 additional published sRNA-seq profiles from 17 different types of organs or tissues. In addition to 16 conserved A-to-I editing sites, we identified five conserved C-to-U editing sites in miRNAs of and . We also identified 11 SNPs in the miRNAs of . The analysis of the potential targets of 69 miRNAs with editing or mutation events in their seed regions suggest that these editing or mutation events severely changed their targets and their potential functions. These results significantly increase our understanding of miRNAs and their mutation/editing events in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells8070682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678584PMC
July 2019

Analysis of microRNAs, phased small interfering RNAs and their potential targets in Rosarugosa Thunb.

BMC Genomics 2019 Apr 18;19(Suppl 9):983. Epub 2019 Apr 18.

Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming, 650500, China.

Background: MicroRNAs (miRNAs) are small non-coding RNAs that play important roles by regulating other genes. Rosa rugosa Thunb. is an important ornamental and edible plant, yet there are only a few studies on the miRNAs and their functions in R. rugosa.

Results: We sequenced 10 samll RNA profiles from the roots, petals, pollens, stamens, and leaves and 4 RNA-seq profiles in leaves and petals to analysis miRNA, phasiRNAs and mRNAs in R. rugosa. In addition, we acquired a degradome sequencing profile from leaf of R. rugosa to identify miRNA and phasiRNA targets using the SeqTar algorithm. We have identified 321 conserved miRNA homologs including primary transcripts for 25 conserved miRNAs, and 22 novel miRNAs. We identified 592 putative targets of the conserved miRNAs or tasiRNAs that showed significant accumulations of degradome reads. We found differential expression patterns of conserved miRNAs in five different tissues of R. rugosa. We identified three hundred and thirty nine 21 nucleotide (nt) PHAS loci, and forty nine 24 nt PHAS loci, respectively. Our results suggest that miR482 triggers generations of phasiRNAs by targeting nucleotide-binding, leucine-rich repeat (NB-LRR) disease resistance genes in R. rugosa. Our results also suggest that the deregulated genes in leaves and petals are significantly enriched in GO terms and KEGG pathways related to metabolic processes and photosynthesis.

Conclusions: These results significantly enhanced our knowledge of the miRNAs and phasiRNAs, as well as their potential functions, in R. rugosa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-5325-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394236PMC
April 2019

Gas-Phase Hydrogen/Deuterium Scrambling in Negative-Ion Mode Tandem Mass Spectrometry.

J Am Soc Mass Spectrom 2019 May 25;30(5):855-863. Epub 2019 Feb 25.

Department of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, MI, 48109-1055, USA.

Hydrogen/deuterium exchange coupled with mass spectrometry (HDX MS) has become a powerful method to characterize protein conformational dynamics. Workflows typically utilize pepsin digestion prior to MS analysis to yield peptide level structural resolution. Tandem mass spectrometry (MS/MS) can potentially facilitate determination of site-specific deuteration to single-residue resolution. However, to be effective, MS/MS activation must minimize the occurrence of gas-phase intramolecular randomization of solution-generated deuterium labels. While significant work has focused on understanding this process in positive-ion mode, little is known about hydrogen/deuterium (H/D) scrambling processes in negative-ion mode. Here, we utilize selectively deuterated model peptides to investigate the extent of intramolecular H/D scrambling upon several negative-ion mode MS/MS techniques, including negative-ion collision-induced dissociation (nCID), electron detachment dissociation (EDD), negative-ion free radical-initiated peptide sequencing (nFRIPS), and negative-ion electron capture dissociation (niECD). H/D scrambling was extensive in deprotonated peptides upon nCID and nFRIPS. In fact, the energetics required to induce dissociation in nCID are sufficient to allow histidine C-2 and C hydrogen atoms to participate in the scrambling process. EDD and niECD demonstrated moderate H/D scrambling with niECD being superior in terms of minimizing hydrogen migration, achieving ~ 30% scrambling levels for small c-type fragment ions. We believe the observed scrambling is likely due to activation during ionization and ion transport rather than during the niECD event itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13361-019-02143-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680243PMC
May 2019

Genotype- and tissue-specific miRNA profiles and their targets in three alfalfa (Medicago sativa L) genotypes.

BMC Genomics 2018 Dec 31;19(Suppl 10):913. Epub 2018 Dec 31.

Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK, 74078, USA.

Background: Alfalfa (Medicago sativa L.) is a forage legume with significant agricultural value worldwide. MicroRNAs (miRNAs) are key components of post-transcriptional gene regulation and essentially regulate many aspects of plant growth and development. Although miRNAs were reported in alfalfa, their expression profiles in different tissues and the discovery of novel miRNAs as well as their targets have not been described in this plant species.

Results: To identify tissue-specific miRNA profiles in whole plants, shoots and roots of three different alfalfa genotypes (Altet-4, NECS-141and NF08ALF06) were used. Small RNA libraries were generated and sequenced using a high-throughput sequencing platform. Analysis of these libraries enabled identification of100 miRNA families; 21 of them belong to the highly conserved families while the remaining 79 families are conserved at the minimum between M. sativa and the model legume and close relative, M. truncatula. The profiles of the six abundantly expressed miRNA families (miR156, miR159, miR166, miR319, miR396 and miR398) were relatively similar between the whole plants, roots and shoots of these three alfalfa genotypes. In contrast, robust differences between shoots and roots for miR160 and miR408 levels were evident, and their expression was more abundant in the shoots. Additionally, 17 novel miRNAs were identified and the relative abundance of some of these differed between tissue types. Further, the generation and analysis of degradome libraries from the three alfalfa genotypes enabled confirmation of 69 genes as targets for 31 miRNA families in alfalfa.

Conclusions: The miRNA profiles revealed both similarities and differences in the expression profiles between tissues within a genotype as well as between the genotypes. Among the highly conserved miRNA families, miR166 was the most abundantly expressed in almost all tissues from the three genotypes. The identification of conserved and novel miRNAs as well as their targets in different tissues of multiple genotypes increased our understanding of miRNA-mediated gene regulation in alfalfa and could provide valuable insights for practical research and plant improvement applications in alfalfa and related legume species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-5280-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311939PMC
December 2018

Colloidal Metal-Organic Framework Hexapods Prepared from Postsynthesis Etching with Enhanced Catalytic Activity and Rollable Packing.

ACS Appl Mater Interfaces 2018 Dec 16;10(48):40990-40995. Epub 2018 Nov 16.

Recent studies on the effect of particle shapes have led to extensive applications of anisotropic colloids as complex materials building blocks. Although much research has been devoted to colloids of convex polyhedral shapes, branched colloids remain largely underexplored because of limited synthesis strategies. Here we achieved the preparation of metal-organic framework (MOF) colloids in a hexapod shape, not directly from growth but from postsynthesis etching of truncated rhombic dodecahedron (TRD) parent particles. To understand the branch development, we used in situ optical microscopy to track the local surface curvature evolution of the colloids as well as facet-dependent etching rate. The hexapods show unique properties, such as improved catalytic activity in a model Knoevenagel reaction likely due to enhanced access to active sites, and the assembly into open structures which can be easily integrated with a self-rolled-up nanomembrane structure. Both the postsynthesis etching and the hexapod colloids demonstrated here show a new route of engineering micrometer-sized building blocks with exotic shapes and intrinsic functionalities originated from the molecular structure of materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b17477DOI Listing
December 2018

Genome-wide identification and comprehensive analysis of microRNAs and phased small interfering RNAs in watermelon.

BMC Genomics 2018 May 9;19(Suppl 2):111. Epub 2018 May 9.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.

Background: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs involved in the post-transcriptional gene regulation and play a critical role in plant growth, development and stress responses. Watermelon (Citrullus lanatus L.) is one of the important agricultural crops worldwide. However, the watermelon miRNAs and phasiRNAs and their functions are not well explored.

Results: Here we carried out computational and experimental analysis of miRNAs and phased small interfering RNAs (phasiRNAs) in watermelon by analyzing 14 small RNA profiles from roots, leaves, androecium, petals, and fruits, and one published small RNA profile of mixed tissues. To identify the targets of miRNAs and phasiRNAs, we generated a degradome profile for watermelon leaf which is analyzed using the SeqTar algorithm. We identified 97 conserved pre-miRNAs, of which 58 have not been reported previously and 348 conserved mature miRNAs without precursors. We also found 9 novel pre-miRNAs encoding 18 mature miRNAs. One hundred and one 21 nucleotide (nt) PHAS loci, and two hundred and forty one 24 nt PHAS loci were also identified. We identified 127 conserved targets of the conserved miRNAs and TAS3-derived tasiRNAs by analyzing a degradome profile of watermelon leaf.

Conclusions: The presented results provide a comprehensive view of small regulatory RNAs and their targets in watermelon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-018-4457-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954288PMC
May 2018

Pine needle oil induces G2/M arrest of HepG2 cells by activating the ATM pathway.

Exp Ther Med 2018 Feb 15;15(2):1975-1981. Epub 2017 Dec 15.

Department of Hygienic Microbiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

Over the last two decades, inducing DNA damage of cancer cells by natural medicines has become a research hotspot in the field of cancer treatment. Although various natural medicines have anticancer effects, very few studies have been conducted to explore the anti-cancer effect of pine needle oil. In the present study, the role of pine needle oil in inducing G2/M arrest in HepG2 cells was investigated. The data revealed that pine needle oil could induce DNA damage in a dose-dependent manner. In the pine needle oil-treated HepG2 cells, the protein levels of phosphorylated (p)-ataxia-telangiectasia mutated (ATM), γ-H2A histone family, member X, p-p53, p-checkpoint kinase 2 and p-cell division cycle 25C were evidently increased, indicating that pine needle oil facilitated G2/M arrest in HepG2 cells through the ATM pathway. In response to the treatment with pine needle oil, ATM was activated in HepG2 cells, which subsequently phosphorylated downstream targets and induced G2/M arrest. In summary, the data of the present study indicated that pine needle oil induces G2/M arrest in HepG2 cells by facilitating ATM activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2017.5648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776635PMC
February 2018

Phased secondary small interfering RNAs in Panaxnotoginseng.

BMC Genomics 2018 01 19;19(Suppl 1):41. Epub 2018 Jan 19.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China.

Background: Recent results demonstrated that either non-coding or coding genes generate phased secondary small interfering RNAs (phasiRNAs) guided by specific miRNAs. Till now, there is no studies for phasiRNAs in Panax notoginseng (Burk.) F.H. Chen (P. notoginseng), an important traditional Chinese herbal medicinal plant species.

Methods: Here we performed a genome-wide discovery of phasiRNAs and its host PHAS loci in P. notoginseng by analyzing small RNA sequencing profiles. Degradome sequencing profile was used to identify the trigger miRNAs of these phasiRNAs and potential targets of phasiRNAs. We also used RLM 5'-RACE to validate some of the identified phasiRNA targets.

Results: After analyzing 24 small RNA sequencing profiles of P. notoginseng, 204 and 90 PHAS loci that encoded 21 and 24 nucleotide (nt) phasiRNAs, respectively, were identified. Furthermore, we found that phasiRNAs produced from some pentatricopeptide repeat-contain (PPR) genes target another layer of PPR genes as validated by both the degradome sequencing profile and RLM 5'-RACE analysis. We also found that miR171 with 21 nt triggers the generations of 21 nt phasiRNAs from its conserved targets.

Conclusions: We validated that some phasiRNAs generated from PPRs and TASL genes are functional by targeting other PPRs in trans. These results provide the first set of PHAS loci and phasiRNAs in P. notoginseng, and enhance our understanding of PHAS in plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-017-4331-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780745PMC
January 2018

Similar outcomes after haploidentical transplantation with post-transplant cyclophosphamide versus HLA-matched transplantation: a meta-analysis of case-control studies.

Oncotarget 2017 Sep 29;8(38):63574-63586. Epub 2017 Jun 29.

Department of Hematology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Background: Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT.

Methods: A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases. Using a random model, the risk ratios (RRs) and 95% confidence intervals (95% CI) were pooled for the final analysis.

Results: Nine case-control studies including 2258 patients (827 patients in the haplo-HCT with PT-Cy group, 748 controls from HLA-matched related donors (MRD), and 683 controls from HLA-matched unrelated donors (MUD)) met the inclusion criteria. No differences were found between haplo-HCT with PT-Cy and HLA-matched HCT with regard to acute graft-versus-host-disease (GVHD), non-relapse mortality, relapse, progression free survival and overall survival. However, haplo-HCT with PT-Cy was found to be associated with a lower incidence of moderate to severe chronic GVHD (Haplo vs MRD: RR=0.54; 95% CI=0.39-0.75; Haplo vs MUD: RR=0.70; 95% CI=0.56-0.88).

Conclusions: The results of this meta-analysis suggest that haplo-HCT with PT-Cy can achieve comparable outcomes with those of HLA-matched HCT. Haploidentical donors can be a feasible and valid alternative when conventional HLA-matched donors are unavailable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.18862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609944PMC
September 2017

Long-term clinical results following Charite III lumbar total disc replacement.

Spine J 2018 06 21;18(6):917-925. Epub 2017 Sep 21.

Department of Orthopaedic Surgery, Capital Medical University Affiliated Beijing Chaoyang Hospital, No. 8 Workers' Stadium South Rd, Chaoyang District, Beijing 100020, China.

Background Context: Lumbar total disc replacement (TDR) operation represents an alternative to lumbar fusion for the treatment of symptomatic lumbar intervertebral disc degeneration and has gained increasing attention in recent years.

Purpose: This study aimed to assess clinical outcomes in a cohort of patients with TDR and the long-term survival rate of the prostheses.

Study Design: This is a retrospective, single-center clinical study.

Patient Sample: The sample comprised 30 patients, giving a total of 35 prostheses after an average follow-up (FU) of 15.2 years following TDR, which was performed for the treatment of lumbar degenerative disc disease.

Outcome Measures: Clinical evaluation included visual analog scale (VAS) and the Oswestry Disability Index (ODI). Radiological parameters of intervertebral disc height (IDH), range of motion (ROM), lumbar lordosis, lumbar scoliosis, and prosthesis position were evaluated in surgical and adjacent levels. Complications and re-operation rates were also assessed.

Methods: Clinical evaluation and radiological parameters were evaluated preoperatively and at final FU. All data were collected by members of our department, including research assistants and nurses who were not involved in the decision making of this study.

Results: Thirty of the 35 patients participated in the final FU. The cumulative survival rate of the prosthesis at a mean FU of 15.4 years was 100%. The clinical success rate was 93.3%. The VAS and ODI scores at final FU were significantly lower than preoperatively (p<.001). The average ROM of the operated and superior adjacent segment decreased significantly at the final FU, whereas the inferior adjacent segment was not affected. The IDH of all surgical and adjacent levels were well maintained at the final FU. Ten patients had a lumbar scoliosis >3° and the mean angle was 8.5°, of which 7 had left convex curvature. Three prostheses were offset more than 5 mm from the midline on the coronal plane. Four prostheses showed subsidence. Twenty-six operative segments and five adjacent segments showed heterotopic ossification. Two patients of the total 35-patient cohort underwent a secondary operation.

Conclusions: Satisfactory clinical results and good prosthesis survival can be achieved in the long term. Lumbar TDR surgeries also have the potential to reduce the incidence of adjacent segment disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.spinee.2017.08.252DOI Listing
June 2018

Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes.

J Diabetes Investig 2018 Jan 18;9(1):83-90. Epub 2017 May 18.

Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Aims/introduction: In previous studies, hydrogen gas (H administration has clearly shown effectiveness in inhibiting diabetes. Here, we evaluated whether subcutaneous injection of H shows enhanced efficacy against type 2 diabetes mellitus induced in mice by a high-fat diet and low-dose streptozotocin treatment.

Material And Methods: H was injected subcutaneously at a dose of 1 mL/mouse/week for 4 weeks. Type 2 diabetes mellitus-associated parameters were then evaluated to determine the effectiveness of subcutaneous H administration.

Results: The bodyweight of H -treated mice did not change over the course of the experiment. Compared with the untreated control animals, glucose, insulin, low-density lipoprotein and triglyceride levels in the serum were significantly lower in treated mice, whereas high-density lipoprotein cholesterol in the serum was significantly higher. Glucose tolerance and insulin sensitivity were both improved in H -treated mice. Diabetic nephropathy analysis showed significant reductions in urine volume, urinary total protein and β2-microglobulin, kidney/bodyweight ratio, and kidney fibrosis associated with subcutaneous injection of H .

Conclusions: Subcutaneous injection of H significantly improves type 2 diabetes mellitus and diabetic nephropathy-related outcomes in a mouse model, supporting further consideration of subcutaneous injection as a novel and effective route of clinical H administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.12674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754517PMC
January 2018

5-HTR3 and 5-HTR4 located on the mitochondrial membrane and functionally regulated mitochondrial functions.

Sci Rep 2016 11 22;6:37336. Epub 2016 Nov 22.

Laboratory of Molecular Pharmacology, Institute of Molecular Medicine, Peking University, Beijing, China.

5-HT has been reported to possess significant effects on cardiac activities, but activation of 5-HTR on the cell membrane failed to illustrate the controversial cardiac reaction. Because 5-HT constantly comes across the cell membrane via 5-HT transporter (5-HTT) into the cytoplasm, whether 5-HTR is functional present on the cellular organelles is unknown. Here we show 5-HTR3 and 5-HTR4 were located in cardiac mitochondria, and regulated mitochondrial activities and cellular functions. Knock down 5-HTR3 and 5-HTR4 in neonatal cardiomyocytes resulted in significant increase of cell damage in response to hypoxia, and also led to alternation in heart beating. Activation of 5-HTR4 attenuated mitochondrial Ca uptake under the both normoxic and hypoxic conditions, whereas 5-HTR3 augmented Ca uptake only under hypoxia. 5-HTR3 and 5-HTR4 exerted the opposite effects on the mitochondrial respiration: 5-HTR3 increased RCR (respiration control ratio), but 5-HTR4 reduced RCR. Moreover, activation of 5-HTR3 and 5-HTR4 both significantly inhibited the opening of mPTP. Our results provided the first evidence that 5-HTR as a GPCR and an ion channel, functionally expressed in mitochondria and participated in the mitochondria function and regulation to maintain homeostasis of mitochondrial [Ca], ROS, and ATP generation efficiency in cardiomyocytes in response to stress and O tension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep37336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118798PMC
November 2016

Gα12 is required for renal cystogenesis induced by Pkd1 inactivation.

J Cell Sci 2016 10 5;129(19):3675-3684. Epub 2016 Aug 5.

Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

Mutation of PKD1, encoding the protein polycystin-1 (PC1), is the main cause of autosomal dominant polycystic kidney disease (ADPKD). The signaling pathways downstream of PC1 in ADPKD are still not fully understood. Here, we provide genetic evidence for the necessity of Gα12 (encoded by Gna12, hereafter Gα12) for renal cystogenesis induced by Pkd1 knockout. There was no phenotype in mice with deletion of Gα12 (Gα12). Polyinosine-polycytosine (pI:pC)-induced deletion of Pkd1 (Mx1CrePkd1Gα12) in 1-week-old mice resulted in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1 and Gα12 (Mx1CrePkd1Gα12) had no structural and functional abnormalities in the kidneys. These mice could survive more than one year without kidney abnormalities except multiple hepatic cysts in some mice, which indicates that the effect of Gα12 on cystogenesis is kidney specific. Furthermore, Pkd1 knockout promoted Gα12 activation, which subsequently decreased cell-matrix and cell-cell adhesion by affecting the function of focal adhesion and E-cadherin, respectively. Our results demonstrate that Gα12 is required for the development of kidney cysts induced by Pkd1 mutation in mouse ADPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jcs.190496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087651PMC
October 2016

miR-34a and its novel target, NLRC5, are associated with HPV16 persistence.

Infect Genet Evol 2016 10 14;44:293-299. Epub 2016 Jul 14.

Department of Microbiology, Harbin Medical University, Immunity and Infection, Pathogenic Biology Key Laboratory in Heilongjiang Province, Harbin 150081, Heilongjiang, PR China. Electronic address:

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2016.07.013DOI Listing
October 2016

[An imaging study on effect of total artificial disc replacement on lumbar sagittal alignment].

Zhonghua Wai Ke Za Zhi 2016 Feb;54(2):104-7

Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Objective: To investigate effect of Activ L total lumbar disc replacement on lumbar sagittal alignment.

Methods: The imaging data of patients with degenerative disc disease received Activ L total lumbar disc replacement at Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University from March 2009 to March 2013 were retrospectively analyzed. The average age was 45.6 years(range, 35-60 years)and the surgery levels were as follows: L3-4 2 cases, L4-5 15 cases, L5/S1 5 cases, L3-4+ L4-5 3 cases, L4-5+ L5/S1 7 cases. All patients were followed up for 15 to 63 months(average, 32 months). Radiographic parameters such as lumbar lordosis angle(LL), segment lordosis angle(SL) and sacral slope angle(SS) were recorded. All the radiographic parameters were compared using one-way ANOVA at different stage. Lumbar lordosis angle of the two-level was compared with the one of one-level by using independent sample t-test before and after the operation. A partial correction test was carried out to determine the corrections between the parameters preoperatively, one month after the operation and at final follow-up.

Results: One month after the operation, the lumbar lordosis angle decreased by an average of 1.8°, but there was no statistically significant(P>0.05). Compared with one month postoperation, the lumbar lordosis angle increased by an average of 6.8°(P<0.05), which also increased a lot compared with preoperation(P<0.05). The value of segment lordosis angle was rising up from preoperation to the final follow-up(P<0.05), so was the value of sacral slope angle, but there was no statistically significant between different stage(P>0.05). The lumbar lordosis angle showed no significant difference between double-level ones and single-level ones at different stage(P<0.05). The lumbar lordosis angle showed positive correlation with the sacral slope(P<0.001), however, the lumbar lordosis angle showed no corrected with the segment angle all the time(P>0.05).

Conclusions: The total lumbar disc replacement with Activ L prosthesis had contributed to maintain and improve the lumbar alignment in the short and medium term. Double- or single-level total lumbar disc replacement had no significant effect on the value of lumbar lordosis angle. The lumbar lordosis angle showed positive correlation with the sacral slope all the time with no correlation between lumbar lordosis angle and sacral slope.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.0529-5815.2016.02.006DOI Listing
February 2016

Head-Up Tilt.

Int Heart J 2015 11;56(5):500-4. Epub 2015 Sep 11.

Department of Heart Function, Henan Province People's Hospital & The People's Hospital of Zhengzhou University.

Autonomic dysfunction has been associated with paroxysmal atrial fibrillation (PAF). The head-up tilt test (HUTT) is an important diagnostic tool for autonomic dysfunction. The aim of this study was to examine atrial fibrillation recurrence after RFCA by performing HUTT. A total of 488 consecutive patients with PAF who underwent RFCA were prospectively enrolled. HUTT was positive in 154 (31.6%) patients after a mean follow-up of 22.7 ± 3.5 months, and 163 (33.4%) had a recurrence. HUTT positive was significantly higher in PAF patients with recurrence compared to those without (68 (41.7%) versus 86 (26.5%), P < 0.001). Multivariate Cox regression analysis revealed that HUTT positive (HR: 1.96; 95% CI: 1.49-2.48, P < 0.001), left atrial diameter (HR: 1.77; 95%CI: 1.15-2.11, P = 0.004), AF duration (HR: 1.27; 95%CI: 0.98-1.83, P = 0.014), and sleep apnea (HR: 1.02; 95%CI: 0.81-1.53, P = 0.032) were independent predictors of clinical recurrence after RFCA. The success rate of ablation was 70.4% in patients in the HUTT negative group compared with 58.4% in patients in the HUTT positive group (log-rank P = 0.006). Patients with a positive headup tilt test were at an increased risk of AF recurrence after catheter ablation. Our results suggest that HUTT was a significant predictor for AF recurrence after catheter ablation for PAF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1536/ihj.15-039DOI Listing
January 2016

Metagenomic insights into the effects of volatile fatty acids on microbial community structures and functional genes in organotrophic anammox process.

Bioresour Technol 2015 Nov 12;196:621-33. Epub 2015 Aug 12.

School of Chemical Engineering & Technology, Xi'an Jiaotong University, Shaanxi 710049, China.

To explore the metabolic versatility of "Candidatus Brocadia sinica" in the presence of VFAs, the impacts of VFAs on anammox activity and nitrogen removal were investigated in this study. Results found that low VFAs concentrations has no affect on anammox activity and the removal efficiencies of NH4(+)-N and NO2(-)-N. However, "Ca. Brocadia sinica" showed higher adaptability to some VFAs stresses. Furthermore, Illumina MiSeq pyrosequencing results indicated that the microbial community structures varied significantly and the phyla Chloroflexi, Proteobacteria, Bacteroidetes and Chlorobi were dominated. Finally, qPCR was performed to validate the growth of anammox bacteria and gain the quantitative insights into the correlation between nitrogen transformation rates and the key functional genes in the organotrophic anammox system. Combined analysis clearly demonstrated that the coupling of the anammox, denitrification and DNRA were the noteworthy pathway for the simultaneous removal of nitrogen and organic carbon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2015.07.107DOI Listing
November 2015

Microbial structures and community functions of anaerobic sludge in six full-scale wastewater treatment plants as revealed by 454 high-throughput pyrosequencing.

Bioresour Technol 2015 Jun 19;186:163-172. Epub 2015 Mar 19.

School of Chemical Engineering & Technology, Xi'an Jiaotong University, 710049 Shaanxi, China.

The microbial communities and abundance in anaerobic sludge from 4 industrial and 2 municipal wastewater treatment plants were investigated using 454 pyrosequencing technology in this study. A total of 5482-8692 high-quality reads of 16S rRNA V3-V5 regions were obtained. Taxonomic analysis using QIIME and RDP classifier found that Proteobacteria, Bacteroidetes, Chloroflexi and Firmicutes were the most abundant phyla in these samples. Furthermore, real-time PCR was used to validate the absolute abundance of these 16S rRNAs and some functional genes, including total bacteria, anammox bacteria, NOB (Nitrobacter, Nitrospira), AOA amoA, AOB amoA, nosZ, nirS, nirK, narG, napA, nrfA, mcrA and dsrA. Multivariate linear regression analysis indicated that AOA might be mixotrophic. Finally, redundancy analysis was used to reveal the relationships between operation parameters and microbial communities. Results showed that the coexistence of anammox, denitrification and DNRA could be useful for the simultaneous removal of nitrogen and organic matter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2015.03.072DOI Listing
June 2015

Retrospective study on effectiveness of activ L total disc replacement: clinical and radiographical results of 1- to 3-year follow-up.

Spine (Phila Pa 1976) 2015 Apr;40(7):E411-7

From the Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Study Design: Retrospective case series study.

Objective: To assess the effectiveness of activ L total disc replacement (TDR) on degenerative disc diseases with the clinical and radiographical results.

Summary Of Background Data: There are few reports on activ L TDR. This is the first one from China.

Methods: From March 2009 to March 2012, 32 patients with degenerative disc diseases underwent mono- or bisegmental lumbar TDR. Mean age was 45.1 years (32-58 yr). Clinical outcomes were measured by Oswestry Disability Index and Visual analogue scale pre- and postoperatively (1, 2, and 3 yr). Radiographical parameters as range of motion and intervertebral disc height of the index- and adjacent segments were also measured. Prosthesis subsidence and heterotopic ossification were observed during the follow-up period. Work status was also tracked.

Results: Thirty patients were available for a mean follow-up of 28.8 months and had complete radiographical data. At the final follow-up, the success rate was 86.7%. Visual analogue scale score for low back pain and leg pain, and Oswestry Disability Index scores significantly improved after surgery. Average intervertebral disc heights of patients with more than 3 years' follow-up at the index segment and upper and lower adjacent segments were 12.87 mm, 12.61 mm, and 11.62 mm, respectively, showing no significant difference compared with preoperative scores. The range of motion of the index and upper adjacent segments showed a significant increase for patients with more than 3 years' follow-up. Changes of range of motion at lower adjacent segment were not significant. We observed tears of the iliac vein in 2 patients, prosthesis subsidence in 3 patients, and heterotopic ossification in 1 patient. At the final follow-up, 18 patients went back to their original work, 8 patients changed jobs, and 4 patients stopped working.

Conclusion: The 1- to 3-year follow-up of this cohort of patients showed satisfactory clinical outcomes. The long-term results of activ L TDR need more investigation.

Level Of Evidence: 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0000000000000773DOI Listing
April 2015

Acylated ghrelin protects hippocampal neurons in pilocarpine-induced seizures of immature rats by inhibiting cell apoptosis.

Mol Biol Rep 2013 Jan 6;40(1):51-8. Epub 2012 Nov 6.

Department of Pediatrics, Shengjing Hospital, China Medical University, Shenyang 110004, China.

Ghrelin has two major molecular forms, acylated ghrelin (AG) and unacylated ghrelin (UAG). Only AG to bind growth hormone secretagogue receptor 1a (GHSR-1a) has central endocrine activities. An antiapoptotic effect of AG in cortical neuronal cells has recently been reported. However, whether there is a neuroprotective effect of AG in hippocampal neurons of pilocarpine-induced seizures in rats, is still unknown. Therefore, in the present study, the underlying mechanism of AG on lithium-pilocarpine-induced excitotoxicity was examined in the hippocampus of rat. The results showed that AG inhibited pilocarpine-induced apoptosis. Exposure of rats to the receptor-specific antagonist D-Lys-3-GHRH-6 abolished the protective effects of AG against epilepsy. Administration of AG resulted in increased expression of phosphor-Akt in status epilepticus model in rats, which was accompanied with the attenuation of hippocampal cell death. Furthermore, administration of AG resulted in decreased expression of phosphor-JNK in pyramidal neurons of hippocampus after status epilepsy, which was also accompanied with the attenuation of hippocampal cell death, too. In addition, AG increased the Bcl-2/Bax ratio and inhibited caspase-3 activation. The data indicate that AG can function as a neuroprotective agent that inhibits apoptotic pathways. These effects may be mediated via activation of the PI3K/Akt pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-012-1993-1DOI Listing
January 2013

Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents.

Invest New Drugs 2010 Aug 17;28(4):472-81. Epub 2009 Jun 17.

Division of Nephrology, Nephrology institute of PLA, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.

Numerous studies have documented that various naturally derived ligands or synthetic non-thiazolidinediones (TZD) as peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have shown moderate or potent antitumor activities, which is PPARgamma independent or partially dependent. However, the PPARgamma agonistic or glucose-lowering activity is ranked first more often than antitumor activity to determine promising novel PPARgamma agonists for potential clinical use. In this study, we hypothesized that there might exist some compounds with less PPARgamma agonistic activity but potent antitumor activity. Thereafter, we evaluated the PPARgamma agonistic and antitumor activity of a novel series of alpha-aryloxy-alpha-methylhydrocinnamic acid derivatives synthesized with the initial aim of developing novel PPARgamma agonists as hypoglycemic agents. MTT assay results revealed that several compounds were able to inhibit cell proliferation in a dose-dependent manner with IC(50) 12.7-29.7 microM, better than that of rosiglitazone (45.9-141 microM), although the PPARgamma agonistic activity of most compounds is much lower than rosiglitazone. Some compounds induced cell cycle arrest and apoptosis tested by Flow Cytometry. Oral administration of DH9 (100 mg/kg/d) for 21 days to BALB/c nude mice bearing xenografts including MGC-803, NCI-H460, HT-29 and OS-RC-2 cells significantly retarded tumor growth. DG8 and DJ5 showed benefits in some of the above four xenografts. Our findings demonstrate that these compounds have potent antitumor activity in vitro and in vivo and pyrimidinyl-arylpropionic acid derivatives might be viable resources in the development of new antineoplastic agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-009-9278-9DOI Listing
August 2010

[The Predictive Role of Vascular Endothelial Growth Factor and Estradiol in Infertile Patients with Ovarian Hyperstimulation Syndrome].

Sichuan Da Xue Xue Bao Yi Xue Ban 2003 Jul;34(3):565-7

Department of Gynecology, Maternity and Child Health Hospital, Zhuhai 519000, China.

Objective: To determine the predictive values of vascular endothelial growth factor (VEGF) and estradiol (E2) in patients with ovarian hyperstimulation syndrome (OHSS) and to go further into the relevant pathogenisis.

Methods: Blood samples were collected from 51 high risk patients and 30 control patients undergoing superovulation on the day of hCG administration and follicular fluid at the time of egg retrieval. The high risk patients were divided into two groups[OHSS group (n=11) and non-OHSS group (n=40)] VEGF and E2 were detected and then differences between the high risk groups and control group were analyzed.

Results: There wa no significant difference in VEGF between high risk groups and control group on the day of hCG injection (P>0.05). After hCG administration, serum VEGF concentrations rose significantly in OHSS group (P<0.01). The serum and follicular fluid VEGF levels were obviously higher than those of the control group. The follicular fluid concentrations of VEGF were significantly higher than that of serum in every group (P<0.001). E2 concentrations of OHSS group rose obviously after hCG injection (P<0.01) and were significantly higher than those of the control group (P<0.01), but there no statistically significant change in E2 concentrations in non-OHSS groups (P>0.05).

Conclusion: The results from this study show that the serum and follicular fluid VEGF concentrations are significantly higher than those of control group on the day of ovum retrieval, indicating that VEGF may play an important role in the pathogenesis of OHSS. It cannot predict the risk of OHSS on the day hCG administration, but it may be considered as a predictive marker for the development of OHSS after hCG administration. Serum VEGF concentrations in combination with consective E2 measurements can assist in predicting OHSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2003