ABSTRACT
Mass spectrometry imaging (MSI) has emerged as a revolutionary analytical strategy in biomedical research for molecular visualization. By linking the characterization of functional metabolites with tissue architecture, it is now possible to reveal unknown biological functions of tissues. However, due to the complexity and high dimensionality of MSI data, mining bioinformatics-related peaks from batch MSI data sets and achieving complete spatially resolved metabolomics analysis remain a great challenge. Here, we propose novel MSI data processing software, Multi-MSIProcessor (MMP), which integrates the data read-in, MSI visualization, processed data preservation, and biomarker discovery functions. The MMP focuses on the AFADESI-MSI data platform but also supports mzXML and imzmL data input formats for compatibility with data generated by other MSI platforms such as MALDI/SIMS-MSI. MMP enables deep mining of batch MSI data and has flexible adaptability with the source code opened that welcomes new functions and personalized analysis strategies. Using multiple clinical biosamples with complex heterogeneity, we demonstrated that MMP can rapidly establish complete MSI analysis workflows, assess batch sample data quality, screen and annotate differential MS peaks, and obtain abnormal metabolic pathways. MMP provides a novel platform for spatial metabolomics analysis of multiple samples that could meet the diverse analysis requirements of scholars.
Subject(s)
Metabolomics , Software , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Metabolomics/methods , Computational Biology , Image Processing, Computer-AssistedABSTRACT
BACKGROUND: A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. METHODS: Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. RESULTS: The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. CONCLUSIONS: Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.
Subject(s)
Arthroplasty, Replacement, Knee , Cefazolin , Animals , Rabbits , Cefazolin/therapeutic use , Anti-Bacterial Agents , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Antibiotic Prophylaxis/methods , Administration, IntravenousABSTRACT
The blend nanomorphology of electron-donor (D) and -acceptor (A) materials is of vital importance to achieving highly efficient organic solar cells. Exogenous additives especially aromatic additives are always needed to further optimize the nanomorphology of blend films, which is hardly compatible with industrial manufacture. Herein, we proposed a unique approach to meticulously modulate the aggregation behavior of NFAs in both crystal and thin film nanomorphology via self-regulation effect. Nonfullerene acceptor Z9 was designed and synthesized by tethering phenyl groups on the inner side chains of the Y6 backbone. Compared with Y6, the tethered phenyl groups participated in the molecular aggregation via the π-π stacking of phenyl-phenyl and phenyl-2-(5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (IC-2F) groups, which induced 3D charge transport with phenyl-mediated super-exchange electron coupling. Moreover, ordered molecular packing with suitable phase separation was observed in Z9-based blend films. High power conversion efficiencies (PCEs) of 19.0 % (certified PCE of 18.6 %) for Z9-based devices were achieved without additives, indicating the great potential of the self-regulation strategy in NFA design.
ABSTRACT
PURPOSE: Ankle impingement is generally characterised by limited range of motion and pain due to pathological contact between structures. Anterior ankle impingement is usually diagnosed by clinical examination and radiographic evidence of tibiotalar osteophytes. In addition to osteophytes, radiographs may show a correlation between the tibia and talus, which may further aid in the diagnosis of anterior ankle impingement. The purpose of this study is to investigate the relationship between the tibia and talus in anterior ankle impingement. METHODS: In this retrospective cohort study, the tibial coverage of 22 patients with anterior ankle impingement was compared with that of 67 healthy subjects. RESULTS: The percentage of tibial coverage was 0.674 ± 0.043 in the anterior ankle impingement group and 0.580 ± 0.032 in the control group. The difference between groups was statistically significant (P < 0.05). CONCLUSIONS: In addition to existing criteria, the percentage of tibial coverage may provide valuable information for the diagnosis of anterior ankle impingement.
Subject(s)
Osteophyte , Talus , Humans , Tibia/diagnostic imaging , Ankle , Retrospective Studies , Talus/diagnostic imagingABSTRACT
BACKGROUND: Prophylactic antibiotics reduce the risk of periprosthetic joint infection. However, conventional systemic administration may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Intraosseous regional administration is known to achieve significantly higher antibiotic tissue concentrations than systemic administration, but it is unclear how synovial fluid concentrations are affected. We aimed to compare synovial fluid cefazolin concentrations achieved by regional intraosseous versus systemic intravenous administration, and also to compare synovial fluid cefazolin concentrations with those in subcutaneous fat. METHODS: A total of 60 patients undergoing primary knee arthroplasty were randomized into 2 groups: group IO received 2 g interosseous cefazolin in 100 mL saline through a tibial cannula after tourniquet inflation and before skin incision; group IV received 2 g cefazolin in 100 mL saline via the median basilic or median cephalic vein 30 min before tourniquet inflation. Subcutaneous fat and synovial fluid samples were collected immediately after skin incision, and cefazolin concentrations were measured by high-performance liquid chromatography. RESULTS: The cefazolin concentration in synovial fluid was 391.3 ± 70.1 µg/ml in group IO and 17.6 ± 3.5 µg/ml in group IV. The cefazolin concentration in subcutaneous fat was 247.9 ± 64.9 µg/g in group IO and 11.4 ± 1.9 µg/g in group IV. CONCLUSION: Intraosseous regional administration results in several times higher tissue concentrations than systemic administration, especially in the synovial fluid.
ABSTRACT
Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital. Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies. Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. The virus-specific total antibody, IgG and IgM antibody of patients after one year of recovery were higher than those of healthy vaccinated participants (94.13 vs 4.65, 2.67 vs 0.44, 0.09 vs 0.06, respectively) (P < 0.001). Neutrophil count (OR = 1.73, 95% CI: 1.10-2.70, P = 0.016) and neutrophil-to-lymphocyte ratio (OR = 1.59, 95% CI: 1.05-2.41, P = 0.030) at discharge were the influencing factors for the positivity of virus-specific IgG antibody in patients after one year of recovery. The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge. Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.
Subject(s)
COVID-19 , Antibodies, Viral , COVID-19 Vaccines , Follow-Up Studies , Humans , Immunoglobulin G , Leukocytes , SARS-CoV-2ABSTRACT
Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.
Subject(s)
RNA, Long Noncoding , Receptor, PAR-1 , Stomach Neoplasms , Humans , Apoptosis/genetics , Cell Proliferation/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Phosphatidylinositol 3-Kinase/genetics , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Receptor, PAR-1/genetics , Receptor, PAR-1/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal Transduction/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. METHODS: PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. RESULTS: Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. CONCLUSION: We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.
Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Adrenal Cortex Hormones/administration & dosage , Age Distribution , Cardiovascular Diseases/epidemiology , Comorbidity , Databases, Factual , Dyspnea/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Inflammation/epidemiology , Kidney/physiopathology , Liver/physiopathology , Male , Observational Studies as Topic , Prognosis , Risk Factors , Sex Distribution , Smokers/statistics & numerical dataABSTRACT
The purpose of this paper is to prepare a stable apigenin nanosuspension with a drug concentration of 1.11 mg/mL through green and efficient antisolvent method. Compared with the traditional preparation process that may use toxic reagents, in this study, a green and effective strategy was applied for the preparation of stable apigenin nanosuspension by using an antisolvent method with PEG 400 as antisolvent to improve the solubility and bioavailability. It was found that the particle size of apigenin nanosuspension was about 280 nm, and the solubility and dissolution of the nanosuspension were 33 and 3 times higher than that of the apigenin, respectively. Pharmacokinetic study showed that the Cmax and AUC 0-8 h values of the nanosuspension in fasting rats achieved about 6- and 2.5-fold enhancement than that of the apigenin, respectively. Stability test showed that the apigenin nanosuspension could be stored stably for 12 months at 25â. Taken together, the antisolvent method with PEG 400 was proven to be a green and effective method to prepare the stable nanosuspension of poorly soluble drugs.
Subject(s)
Apigenin , Nanoparticles , Animals , Biological Availability , Particle Size , Polyethylene Glycols , Rats , Solubility , SuspensionsABSTRACT
Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.
Subject(s)
Axons/metabolism , Ganglia, Spinal/metabolism , Nerve Regeneration , Optic Nerve/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Telomerase/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Cells, Cultured , Female , Mice, Inbred C57BLABSTRACT
The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.
Subject(s)
Cerebral Cortex/growth & development , Neural Stem Cells/cytology , Proto-Oncogene Proteins c-myc/genetics , Stem Cells/cytology , Animals , Cell Differentiation/genetics , Cell Proliferation/genetics , Cerebral Cortex/metabolism , Embryonic Development/genetics , Female , Gene Expression Regulation, Developmental/genetics , Mice , Neural Stem Cells/metabolism , Neurogenesis/genetics , Neurons/cytology , Neurons/metabolism , Pregnancy , Stem Cells/metabolismABSTRACT
OBJECTIVES: Sepsis-induced inflammation injury and oxidative stress are well known causes of mortality. The anti-inflammatory effects of baicalin have been proposed in a mouse model of experimental sepsis. Here, we investigated its protective effects and associated mechanisms with respect to lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. METHODS: Worms were stimulated by LPS (100 µg/mL), with baicalin (1, 10, 100 µmol/L), for 24 h. Animal survival rates and behaviors (reversal and omega turn) were then determined. Further, levels of the inflammatory cytokines interleukin 6 (IL-6), IL-1, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. Western blotting was also performed to determine the protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), Bax, and Bcl-2. The activities of malondialdehyde (MDA) and superoxide dismutase (SOD) contents were determined using corresponding kits. RESULTS: Baicalin (10, 100 µmol/L) improved LPS-stimulated C. elegans survival and rescued behavioral phenotypes. It also suppressed the oxidative stress related to LPS injury by decreasing MDA levels and increasing SOD activity. Moreover, the inflammatory response was inhibited as evidenced by decreased levels of cytokines including IL-6, IL-1, and TNF-α. In addition, baicalin treatment significantly decreased cleaved Bax levels and increased Bcl-2 expression in C. elegans treated with LPS. Simultaneously, the expression of NF-κB and TLR4 was significantly decreased. CONCLUSION: Baicalin treatment protects against LPS-induced injury by decreasing oxidative stress, repressing the inflammatory cascade, and inhibiting apoptosis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Flavonoids/pharmacology , Lipopolysaccharides/toxicity , Protective Agents/pharmacology , Animals , Behavior, Animal/drug effects , Caenorhabditis elegans , Disease Models, Animal , NF-kappa B/metabolism , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Sepsis/metabolism , Toll-Like Receptor 4/metabolismABSTRACT
The matrix remodeling associated 7 (MXRA7) gene had been ill-studied and its biology remained to be discovered. Inspired by our previous findings and public datasets concerning MXRA7, we hypothesized that the MXRA7 gene might be involved in bone marrow mesenchymal stem cells (BMSCs) functions related to bone formation, which was checked by utilizing in vivo or in vitro methodologies. Micro-computed tomography of MXRA7-deficient mice demonstrated retarded osteogenesis, which was reflected by shorter femurs, lower bone mass in both trabecular and cortical bones compared with wild-type (WT) mice. Histology confirmed the osteopenia-like feature including thinner growth plates in MXRA7-deficient femurs. Immunofluorescence revealed less osteoblasts in MXRA7-deficient femurs. Polymerase chain reaction or western blot analysis showed that when WT BMSCs were induced to differentiate toward osteoblasts or adipocytes in culture, MXRA7 messenger RNA or protein levels were significantly increased alongside osteoblasts induction, but decreased upon adipocytes induction. Cultured MXRA7-deficient BMSCs showed decreased osteogenesis upon osteogenic differentiation induction as reflected by decreased calcium deposition or lower expression of genes responsible for osteogenesis. When recombinant MXRA7 proteins were supplemented in a culture of MXRA7-deficient BMSCs, osteogenesis or gene expression was fully restored. Upon osteoblast induction, the level of active ß-catenin or phospho-extracellular signal-regulated kinase in MXRA7-deficient BMSCs was decreased compared with that in WT BMSCs, and these impairments could be rescued by recombinant MXRA7 proteins. In adipogenesis induction settings, the potency of MXRA7-deficient BMSCs to differentiate into adipocytes was increased over the WT ones. In conclusion, this study demonstrated that MXRA7 influences bone formation via regulating the balance between osteogenesis and adipogenesis in BMSCs.
Subject(s)
Bone Diseases, Metabolic/metabolism , Cell Differentiation , Femur/metabolism , Membrane Proteins/metabolism , Mesenchymal Stem Cells/metabolism , Osteoblasts/metabolism , Osteogenesis , Adipocytes/metabolism , Adipocytes/pathology , Adipogenesis , Animals , Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/pathology , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases/metabolism , Femur/pathology , Membrane Proteins/deficiency , Membrane Proteins/genetics , Mesenchymal Stem Cells/pathology , Mice, Knockout , Osteoblasts/pathology , Phenotype , Signal Transduction , beta Catenin/metabolismABSTRACT
The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.
Subject(s)
Axons/physiology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Regeneration/physiology , STAT3 Transcription Factor/metabolism , Animals , Antibodies , Cells, Cultured , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Glyceraldehyde 3-Phosphate/pharmacology , Intracellular Signaling Peptides and Proteins/pharmacology , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , Optic Nerve , Proline/analogs & derivatives , Proline/pharmacology , Proto-Oncogene Proteins c-myc/genetics , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/genetics , Sciatic Nerve , Thiocarbamates/pharmacologyABSTRACT
While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.
Subject(s)
Actins/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics , Nerve Regeneration/genetics , Neuronal Outgrowth/genetics , Animals , Axons/metabolism , Axons/pathology , Calcium/metabolism , Central Nervous System/growth & development , Central Nervous System/metabolism , Ganglia, Spinal/growth & development , Ganglia, Spinal/metabolism , Growth Cones/metabolism , Humans , Mice , Peripheral Nerves/growth & development , Peripheral Nerves/pathology , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/pathologyABSTRACT
BACKGROUND: Steroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, anti-immune, and anti-shock properties. However, the long-term use in high doses has been found to cause necrosis of femoral head and other serious adverse reactions. Thus, it is of great importance to safely use these medications on patients without inducing bone necrosis. METHODS: In this preclinical study, we examined the effects of erythropoietin (EPO) to attenuate the induction of steroid-induced femoral bone necrosis using rats to build up the in-vivo models. Rats were randomly divided into three groups: negative control group (group A), disease group (group B), and EPO group (group C). 20 mg/kg methylprednisolone was administrated into group B and group C for 6 weeks with two intramuscular injections per week per rat. Group C was further given daily intraperitoneal injections of rHuEPO during this period. Group A received only injection of saline at the same schedule. 12 weeks after the initial drug administration, the rats' femoral tissues were harvested for HE staining, immunohistochemistry studies for PECAM-1(also CD31) expression and Western Blotting for VEGF expression. RESULTS: Histology studies showed that compared with the disease group, EPO group had significant improvement and bone morphology being much closer to the negative control group. Immunohistochemical studies revealed that EPO group had statistically much more expression of PECAM-1 than the other groups did. Western Blot demonstrated that the EPO group had significantly higher VEGF expression than the disease group. CONCLUSION: Results suggested that simultaneous injection of EPO could partially prevent steroid-induced ANFH.
Subject(s)
Erythropoietin/pharmacology , Femur Head Necrosis/prevention & control , Femur Head/drug effects , Methylprednisolone , Animals , Disease Models, Animal , Female , Femur Head/metabolism , Femur Head/pathology , Femur Head Necrosis/chemically induced , Femur Head Necrosis/metabolism , Femur Head Necrosis/pathology , Male , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolismABSTRACT
A Gram-negative, strictly aerobic, yellow-pigmented and rod-shaped bacterium, designated strain NSL10(T), was isolated from the waste surface soil of a chemical factory in Hongan, China. Strain NSL10(T) was found to grow optimally at pH 7.0, 30 °C and in the absence of NaCl in modified LB medium. Cells were found to be positive for catalase and oxidase. The G+C content of the total DNA was determined to be 66.8 mol%. The 16S rRNA gene sequence of strain NSL10(T) showed the highest similarity to that of Devosia albogilva IPL15(T) (96.80 %), followed by Devosia geojensis BD-c194(T) (96.46 %) and Devosia chinhatensis IPL18(T) (96.27 %). The major cellular fatty acids of strain NSL10(T) were identified as C18:1 ω7c/C18:1 ω6c (48.2 %) and C16:0 (17.7 %). The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and an unidentified compound. Minor amounts of unidentified glycolipids and unidentified polar lipids were also detected. These chemotaxonomic data supported the affiliation of strain NSL10(T) to the genus Devosia. In conclusion, on the basis of biochemical, physiological characteristics and molecular properties, strain NSL10(T) represents a novel species within the genus Devosia, for which the name Devosia honganensis sp. nov., is proposed. The type strain is NSL10(T) (=KCTC 42281(T) = ACCC 19737(T)).
Subject(s)
Hyphomicrobiaceae/classification , Hyphomicrobiaceae/isolation & purification , Soil Microbiology , Aerobiosis , Base Composition , China , Cluster Analysis , Cytosol/chemistry , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Fatty Acids/analysis , Glycolipids/analysis , Hydrogen-Ion Concentration , Hyphomicrobiaceae/genetics , Hyphomicrobiaceae/physiology , Industrial Waste , Molecular Sequence Data , Phospholipids/analysis , Phylogeny , Pigments, Biological/analysis , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Sodium Chloride/metabolism , TemperatureABSTRACT
A rapid and sensitive hydrophilic interaction ultra high performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry method was validated for the simultaneous determination of 20 nucleobases, nucleosides, and nucleotides (within 3.5 min), and then was employed to test the functional food of Luo-Han-Guo samples. The analysis showed that the Luo-Han-Guo was rich in guanosine and uridine, but contained trace levels of the other target compounds. Chemometrics methods were employed to identify 40 batches of Luo-Han-Guo samples from different cultivated forms, regions and varieties. Unsupervised hierarchical cluster analysis and principal component analysis were used to classify Luo-Han-Guo samples based on the level of the 20 target compounds, and the supervised learning method of counter propagation artificial neural network was utilized to further separate clusters and validate the established model. As a result, the samples could be clustered into three primary groups, in which correlation with cultivated varieties was observed. The present strategy could be applied to the investigation of other edible plants containing nucleobases, nucleosides, or nucleotides.
Subject(s)
Drugs, Chinese Herbal/chemistry , Fruit/chemistry , Neural Networks, Computer , Nucleosides/analysis , Nucleotides/analysis , Principal Component Analysis , Chromatography, High Pressure Liquid , Cluster Analysis , Hydrophobic and Hydrophilic Interactions , Ions/chemistry , Tandem Mass SpectrometryABSTRACT
Radix Inulae is endemic to China and has been used in traditional medicine to treat upper body pain, emesis and diarrhoea, and to eliminate parasites. Here, an UPLC-MS/MS method was developed and applied to study the pharmacokinetics, distribution and excretion of isoalantolactone and alantolactone, which are two main active sesquiterpene lactones in Radix Inulae, in Sprague-Dawley rats following oral administration of total Radix Inulae extract. Isoalantolactone, alantolactone and osthole (internal standard) were prepared using acetonitrile precipitation, and the separation of isoalantolactone and alantolactone was achieved by isocratic elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase using a ZORBAX Eclipse Plus C18 column. The total run time was 6.4 min. The present study showed poor absorption of isoalantolactone and alantolactone in vivo. The apparent Cmax, Tmax, T1/2 and total exposure (AUC0-12h) in rat plasma were 37.8 ng/mL, 120 min, 351.7 min and 6112.3 ng-min/mL for isoalantolactone and 25.9 ng/mL, 90 min, 321.0 min and 4918.9 ng-min/mL for alantolactone, respectively. It was shown that the highest concentration was achieved in the small intestine and feces clearance was shown to be the dominant elimination pathway of the lactones.
Subject(s)
Gastropoda/metabolism , Lactones/metabolism , Lactones/pharmacokinetics , Sesquiterpenes, Eudesmane/metabolism , Sesquiterpenes, Eudesmane/pharmacokinetics , Sesquiterpenes/metabolism , Sesquiterpenes/pharmacokinetics , Administration, Oral , Animals , Chromatography, Liquid , Male , Medicine, Chinese Traditional , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Tissue Extracts/administration & dosage , Tissue Extracts/metabolism , Tissue Extracts/pharmacokineticsABSTRACT
OBJECTIVE: To compare the clinical application in the percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. METHODS: One hundred forty three elderly patients with Osteoporotic vertebral compression fractures (OVCFs) underwent percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. The number of pulsed imagings, the time of operation and the incidence of cement leakage were recorded. RESULTS: The average number of pulsed imagings was 16.00±1.58 vs 13.07±2.00 per patient under the guidance of one vs two C-arm fluoroscopes. The average time of operation was 48.42±5.00 minutes vs 39.70±7.42 minutes per patient under the guidance of one vs two C-arm fluoroscopes. The incidence of cement leakage was 20% vs 15.7% of the patients under the guidance of one vs two C-arm fluoroscopes. The differences in the number of pulsed imagings and the time of operation were statistically significant. The difference in incidence of cement leakage was not statistically significant. CONCLUSION: The two-fluoroscopic technique reduce the labor cost, the radiation, the time of operation and the operation risk.