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1.
Xenobiotica ; 53(12): 644-652, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38054840

ABSTRACT

Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.Cmax, tmax, and AUC0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t1/2, AUC0-t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology.In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.


Subject(s)
Berberine , Cardiovascular Diseases , Hyperlipidemias , Humans , Rats , Animals , Atorvastatin/pharmacology , Berberine/pharmacology , Hyperlipidemias/drug therapy , Lipids
2.
Anal Chem ; 95(44): 16426-16432, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37874622

ABSTRACT

Rapid antimicrobial susceptibility testing (AST) with the ability of bacterial identification is urgently needed for evidence-based antibiotic prescription. Herein, we propose an enzymatic AST (enzyAST) that employs ß-d-glucuronidase as a biomarker to identify pathogens and profile phenotypic susceptibilities simultaneously. EnzyAST enables to offer binary AST results within 30 min, much faster than standard methods (>16 h). The general applicability of enzyAST was verified by testing the susceptibility of two Escherichia coli strains to three antibiotics with different action mechanisms. The pilot study also shows that the minimal inhibitory concentrations can be determined by enzyAST with the statistical analysis of enzymatic activity of the bacteria population exposed to varying antibiotic concentrations. With further development of multiple bacteria and sample treatment, enzyAST could be able to evaluate the susceptibility of pathogens in clinical samples directly to facilitate the evidence-based therapy.


Subject(s)
Anti-Bacterial Agents , Bacteria , Pilot Projects , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Escherichia coli
3.
Small ; 19(49): e2303398, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37612816

ABSTRACT

Digital nucleic acid detection based on microfluidics technology can quantify the initial amount of nucleic acid in the sample with low equipment requirements and simple operations, which can be widely used in clinical and in vitro diagnosis. Recently, isothermal amplification technologies such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats-CRISPR associated proteins (CRISPR-Cas) assisted technologies have become a hot spot of attention and state-of-the-art digital nucleic acid chips have provided a powerful tool for these technologies. Herein, isothermal amplification technologies including RPA, LAMP, and CRISPR-Cas assisted methods, based on digital nucleic acid microfluidics chips recently, have been reviewed. Moreover, the challenges of digital isothermal amplification and possible strategies to address them are discussed. Finally, future directions of digital isothermal amplification technology, such as microfluidic chip and device manufacturing, multiplex detection, and one-pot detection, are outlined.


Subject(s)
Nucleic Acids , Recombinases , CRISPR-Cas Systems/genetics , Biological Assay , Nucleic Acid Amplification Techniques
4.
BMC Microbiol ; 23(1): 201, 2023 07 29.
Article in English | MEDLINE | ID: mdl-37516855

ABSTRACT

BACKGROUND: The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients. RESULTS: The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients. CONCLUSIONS: Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.


Subject(s)
Sinusitis , Humans , Adult , RNA, Ribosomal, 16S/genetics , Nose , Bacteroidetes , Firmicutes
5.
J Ultrasound Med ; 42(10): 2331-2338, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37255035

ABSTRACT

OBJECTIVES: We herein evaluated the effects of gestational weight gain (GWG) on postpartum pelvic floor function using transperineal ultrasound (TPUS). METHODS: We analyzed retrospectively the data from 228 primiparous women with singleton pregnancies who were evaluated for postpartum pelvic floor function between February 2022 and October 2022. According to the 2009 Institute of Medicine guidelines regarding GWG, subjects were separated into three groups: inadequate GWG, recommended GWG, and excessive GWG. All underwent TPUS 6-10 weeks postpartum to assess bladder neck descent between rest and Valsalva (BND), retrovesical angle at Valsalva (RVA), urethral rotation angle between rest and Valsalva (URA), the area of levator hiatus at Valsalva (LHA), and abnormal pelvic floor function. Univariate and multivariate regression analyses were applied to explore the association measures between GWG and the pelvic floor. A P-value <.05 was considered statistically significant. RESULTS: Of the 228 primiparous women, 113 (49.6%) showed excessive GWG. Univariate analysis revealed that there were no statistical differences in ultrasonic parameters of the pelvic floor among the three groups (P > .05). After adjusting for potential confounders and using the recommended GWG group as a reference group, inadequate GWG was significantly associated with BND ≥25 mm (OR = 0.36, 95% CI = 0.14-0.93), and excessive GWG was significantly associated with uterine prolapse (OR = 2.79, 95% CI = 1.13-6.92). CONCLUSIONS: GWG was associated with the ultrasonic parameters of the female pelvic floor in the early postpartum period.


Subject(s)
Gestational Weight Gain , Pelvic Floor , Pregnancy , Female , Humans , Pelvic Floor/diagnostic imaging , Retrospective Studies , Postpartum Period , Urethra , Ultrasonography
6.
Anal Chem ; 95(10): 4744-4752, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36867551

ABSTRACT

Rapid and sensitive pathogen detection methods are critical for disease diagnosis and treatment. RPA-CRISPR/Cas12 systems have displayed remarkable potential in pathogen detection. A self-priming digital PCR chip is a powerful and attractive tool for nucleic detection. However, the application of the RPA-CRISPR/Cas12 system to the self-priming chip still has great challenges due to the problems of protein adsorption and two-step detection mode of RPA-CRISPR/Cas12. In this study, an adsorption-free self-priming digital chip was developed and a direct digital dual-crRNAs (3D) assay was established based on the chip for ultrasensitive detection of pathogens. This 3D assay combined the advantages of rapid amplification of RPA, specific cleavage of Cas12a, accurate quantification of digital PCR, and point-of-care testing (POCT) of microfluidics, enabling accurate and reliable digital absolute quantification of Salmonella in POCT. Our method can provide a good linear relationship of Salmonella detection in the range from 2.58 × 101 to 2.58 × 104 cells/mL with a limit of detection ∼0.2 cells/mL within 30 min in a digital chip by targeting the invA gene of Salmonella. Moreover, the assay could directly detect Salmonella in milk without nucleic acid extraction. Therefore, the 3D assay has the significant potential to provide accurate and rapid pathogen detection in POCT. This study provides a powerful nucleic detection platform and facilitates the application of CRISPR/Cas-assisted detection and microfluidic chips.


Subject(s)
CRISPR-Cas Systems , RNA, Guide, CRISPR-Cas Systems , CRISPR-Cas Systems/genetics , Adsorption , Biological Assay , Cell Nucleus , Nucleic Acid Amplification Techniques
7.
Colloids Surf B Biointerfaces ; 219: 112806, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36088828

ABSTRACT

The poor bacteriostasis and osseointegration properties of bioinert polyetheretherketone (PEEK) hinder its clinical application. This work reports a simple and versatile strategy for fabricating dual-functional coating with programmed sequential drug release properties on porous PEEK surfaces. The dual-drug-loaded composite coating composed of drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and drug-loaded polyvinyl alcohol (PVA) gel can be immobilized on the surface of sulfonated PEEK by a cyclic freeze-thaw method. Based on the swelling of PVA and the slow degradation of PLGA, the composite coating can realize rapid release of antibacterial drugs and sustained release of osteogenic drugs. The in vitro antibacterial evaluations show that the porous PEEK modified with drug-loaded composite gel coating exhibits an early effective fight against Staphylococcus aureus (S.aureus). The results of in vitro cell experiments show that the PEEK materials modified by the composite gel coating can well support the normal growth, adhesion and proliferation of cells. In addition, the PEEK material coated with the drug-loaded composite gel is found to have positive effects on the osteogenic differentiation of cells in detections of alkaline phosphatase (ALP) activity of cells and the amount of calcium deposition on the surface of the material. The results demonstrate that the proposed porous PEEK modified with dual-drug-loaded composite gel coating simultaneously exhibits excellent osseointegration and exerts early effective antibacterial activity. This dual-functional PEEK material has great application potential in clinical bone tissue repair.

8.
Biosensors (Basel) ; 12(7)2022 Jun 26.
Article in English | MEDLINE | ID: mdl-35884261

ABSTRACT

Food poisoning and infectious diseases caused by Salmonella typhimurium (S. typhimurium) are serious public health concerns for human health and food safety. The diversity and complexity of food matrices pose great challenges for rapid and ultra-sensitive detection of S. typhimurium in food samples. A method capable of identification, detection, and quantification of S. typhimurium is essential for addressing these issues. In this study, aptamer-coated magnetic beads (Apt-MBs) are employed as capture bio-probes to specifically and selectively concentrate S. typhimurium in food samples. A self-priming chip-based digital PCR was then presented as another biosensor for on-site detection and quantification of S. typhimurium cells. The chip we developed was robust and did not require any external power for sample loading. The combination of Apt-MBs with an on-chip digital detection realized the integration into lab-on-a-chip-based biosensors for on-site monitoring of foodborne pathogens. It was possible to capture and detect S. typhimurium cells as low as 90 CFU/reaction with a capture efficiency of 94.5%. Additionally, the whole process only took about 2 h. This unique platform could also be used to monitor other target bacteria with high specificity and sensitivity by utilizing different aptamers. Furthermore, the platform has potential applications in point-of-care testing in the future.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Biosensing Techniques/methods , Food Microbiology , Humans , Immunomagnetic Separation/methods , Polymerase Chain Reaction , Salmonella typhimurium/genetics
9.
Analyst ; 147(14): 3305-3314, 2022 Jul 12.
Article in English | MEDLINE | ID: mdl-35762329

ABSTRACT

The rapid and accurate detection of viable bacteria is of great importance in food quality monitoring and clinical diagnosis. Escherichia coli (E. coli) is a major pathogenic bacterium, which causes potential threats to food safety and human health. Therefore, rapid and portable methods for preventing E. coli outbreaks are needed. Single cell analysis can be performed at the single-cell level, which has great advantages for analysis and diagnosis. Herein, we employed a thermosetting oil to generate a large-scale pico-droplet array for viable bacteria digital counting and dynamic tracking. In this array, the droplets can be solidified without any inducers due to the cross-linking reaction of the hydrosilation of vinyl silicone oil and hydrosilicone oil. Single E. coli cells were encapsulated in solidified droplets to form a microcolony. Resazurin was used as a fluorescent indicator to achieve amplification of bacterial growth signals. This method can achieve digital counting of viable E. coli cells in 4 h. We achieved real-time monitoring of E. coli cell growth and division in droplets. It is rapid, simple, and does not require a pre-enrichment process when compared to the traditional plate counting method. We successfully applied the method for the enumeration of E. coli in milk. In conclusion, the thermosetting oil enables the immobilization of droplets to achieve real-time monitoring and digital counting of bacterial growth without impairing the flexibility of droplet microfluidics, and it has the potential to provide dynamic information at high resolution in this process.


Subject(s)
Escherichia coli Infections , Escherichia coli , Cell Count , Humans , Microfluidics , Single-Cell Analysis
10.
Int Immunopharmacol ; 99: 107985, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34435584

ABSTRACT

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting IL-4Rα, has demonstrated rapid and sustained improvements in clinical outcomes in patients with atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps. METHODS: In a phase 1, double-blind, ascending-dose study, 30 healthy Chinese adults were randomized to single subcutaneous doses of dupilumab 200, 300, 600 mg, or placebo. In a phase 3, double-blind study, 165 Chinese adults with AD were randomized to dupilumab 300 mg or placebo every 2 weeks. RESULTS: Following single doses of dupilumab 200, 300, and 600 mg in the phase 1 study, mean serum maximum concentrations (Cmax) were 25.4 ± 4.0, 37.2 ± 14.5, and 77.3 ± 19.0 mg/L, respectively. For a 1.5-fold increase in dupilumab dose, 1.31-, 1.73-, and 1.66-fold increases in Cmax, area under the curve to real time (AUClast), and extrapolated to infinity (AUC) were observed, respectively, while a 2-fold dose increase resulted in 2.17-, 2.81-, and 2.80-fold increases, respectively. In the phase 3 study, mean dupilumab trough concentrations were 78.8 ± 32.0 and 86.4 ± 33.6 mg/L at weeks 12 and 16, respectively. CONCLUSIONS: Cmax increased approximately proportionally to dose, while AUC and AUClast increased greater than proportionally. Dupilumab pharmacokinetics were generally comparable between Chinese and non-Asian healthy subjects (single dose) and between Chinese and non-Asian AD patients (repeated doses), with differences accounted for by body weight. As differences in exposure by weight are unlikely to be clinically relevant based on late-stage study results, no dose adjustment by ethnic origin or weight is required.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacokinetics , Dermatitis, Atopic/metabolism , Dermatologic Agents/pharmacokinetics , Adult , Anti-Allergic Agents/pharmacokinetics , Area Under Curve , Asian People , Dose-Response Relationship, Drug , Double-Blind Method , Female , Healthy Volunteers , Humans , Injections, Subcutaneous , Male
11.
Shanghai Kou Qiang Yi Xue ; 28(4): 373-377, 2019 Aug.
Article in Chinese | MEDLINE | ID: mdl-31792476

ABSTRACT

PURPOSE: To study the effects of miR-218 on cell proliferation, apoptosis and invasion of human tongue cancer cell line SCC-4 and SCC-9 cells. METHODS: SCC-4 and SCC-9 cells were transfected with negative control, miR-218 mimics and inhibitor, then cell proliferation was detected by MTT assay, cell cycle and cell apoptosis were measured by flow cytometry, cell invasion ability was tested by Transwell assay. The data were analyzed using GraphPad 7.0 software package. RESULTS: Compared with control cells, there was no significant difference for cell proliferation, cell cycle, cell apoptosis and invasion ability in cells transfected with miR-218 inhibitor. However, decreased cell proliferation and invasion ability and increased apoptosis ratio were found in cells transfected with miR-218 mimics. CONCLUSIONS: The expression level of miR-218 in tongue cancer cell lines may be correlated with cell proliferation, apoptosis and invasion.


Subject(s)
MicroRNAs , Tongue Neoplasms , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness
12.
Medicine (Baltimore) ; 98(46): e17965, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31725659

ABSTRACT

To investigate the value of transvaginal three-dimensional (3D) power Doppler ultrasound in the diagnosis of benign and malignant endometrial diseases.A total of 144 patients with endometrial thickness ≥4 mm were enrolled. Endometrial thickness was measured by transvaginal 3D B-mode ultrasound, while blood signals were detected by 3D power Doppler ultrasound. Endometrial volume (EV), vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI) were calculated. All histopathological diagnoses of endometrium were obtained.There were 86 benign and 58 malignant cases. There were statistically significant differences between two groups in endometrial thickness [1.50 (1.30, 1.80) vs 2.30 (1.80, 3.20), P < .001], EV [10.62 (7.14, 17.36) vs 28.94 (9.59, 67.96), P < .001], VI [6.07 (3.61, 10.33) vs 12.01 (7.50, 19.87), P = .001], FI [27.42 (24.45, 31.33) vs 32.98 (30.22, 35.40), P < .001], and VFI [1.58 (0.92, 3.32) vs 4.28 (2.24, 6.41), P < 0.001]. Sensitivity and specificity of endometrial thickness were relatively high [endometrial thickness (86.2%, 76.1%), EV (48.3%, 97.7%), VI (72.4%, 69.8%), FI (72.4%, 74.4%), and VFI (72.4%, 74.4%)]. There was no significant difference in any parameters of the endometrium between different stages (Ia, Ib, II, and above) or phases (G1, G2, and G3) of Ia phase of endometrial cancer (all P > .05).Transvaginal 3D power Doppler ultrasound is valuable in the differentiating benign and malignant endometrial lesions.


Subject(s)
Ultrasonography, Doppler/methods , Uterine Diseases/diagnosis , Uterine Diseases/pathology , Adult , Aged , Endometrium/pathology , Female , Humans , Middle Aged , Prospective Studies , Sensitivity and Specificity , Uterine Diseases/diagnostic imaging
13.
Sci Rep ; 9(1): 5638, 2019 04 04.
Article in English | MEDLINE | ID: mdl-30948762

ABSTRACT

Porcine circovirus 2 (PCV2) is the main pathogen of porcine circovirus diseases and porcine circovirus-associated diseases, which are widespread in swine-producing countries. However, there is controversy regarding the susceptibility of human cells to PCV2 infection. In this study, human cell lines were infected with PCV2 and blind passaged several times. PCV2 entered and replicated in human cells, and infectious virions were generated, indicating that human cell lines were permissive to PCV2 replication. Furthermore, PCV2 replication in human cell lines was enhanced by D-glucosamine or concanavalin A (ConA). However, the infection efficiency of PCV2 was lower in human cells than in PK-15 cells, suggesting that PCV2 infection was limited in human cells. Our study reveals that human cells are permissive for the productive infection of porcine circovirus type 2 in vitro.


Subject(s)
Circovirus/growth & development , Circovirus/isolation & purification , Animals , Cell Line , Circoviridae Infections/virology , Concanavalin A/metabolism , Glucosamine/metabolism , Humans , Swine , Swine Diseases/virology , Virus Replication
14.
Leukemia ; 32(7): 1670, 2018 07.
Article in English | MEDLINE | ID: mdl-29891936

ABSTRACT

At the time of publication the funding information was omitted from the article - this has now been corrected in both the HTML and the PDF.

15.
Leukemia ; 32(7): 1575-1586, 2018 07.
Article in English | MEDLINE | ID: mdl-29467489

ABSTRACT

The presence, within the human bone marrow, of cells with both endothelial and hemogenic potential has been controversial. Herein, we identify, within the human fetal bone marrow, prior to establishment of hematopoiesis, a unique APLNR+, Stro-1+ cell population, co-expressing markers of early mesodermal precursors and/or hemogenic endothelium. In adult marrow, cells expressing similar markers are also found, but at very low frequency. These adult-derived cells can be extensively culture expanded in vitro without loss of potential, they preserve a biased hemogenic transcriptional profile, and, upon in vitro induction with OCT4, assume a hematopoietic phenotype. In vivo, these cells, upon transplantation into a fetal microenvironment, contribute to the vasculature, and generate hematopoietic cells that provide multilineage repopulation upon serial transplantation. The identification of this human somatic cell population provides novel insights into human ontogenetic hematovascular potential, which could lead to a better understanding of, and new target therapies for, malignant and nonmalignant hematologic disorders.

16.
Dose Response ; 15(4): 1559325817739760, 2017.
Article in English | MEDLINE | ID: mdl-29200986

ABSTRACT

INTRODUCTION: Nicotine is a key biologically active compound of cigarettes. Although nicotine is a risk factor for various health issues, it may also be beneficial when treated at moderate concentrations. Nicotine has been shown to bidirectionally regulate stem cell proliferation and differentiation depending on the doses applied. It is not clear whether or how nicotine regulates mouse embryonic stem cell (mESC) survival and proliferation. METHODS: Mouse embryonic stem cells were cultured in the presence of 0.01, 0.1, 1, or 10 µM nicotine. The effects of nicotine on cell survival and proliferation were examined. The signaling pathway that mediated these effects was analyzed. RESULTS: Cell viability was not affected by nicotine at all 4 concentrations examined. The proliferation of mESCs was promoted by 0.01 and 0.1 µM nicotine and suppressed by 1 and 10 µM. This dose-dependent regulation was mediated through the Wnt/ß-catenin pathway. Modulation of Wnt/ß-catenin activity either worsens or reverses the effects of nicotine. CONCLUSIONS: We have identified a bidirectional function of nicotine on mESC proliferation through regulation of the Wnt/ß-catenin pathway and this is associated with different doses. This study suggests that concentration of nicotine is a crucial aspect for consideration when designing research or therapeutic strategies.

17.
Medicine (Baltimore) ; 96(21): e6652, 2017 May.
Article in English | MEDLINE | ID: mdl-28538366

ABSTRACT

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. METHODS: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. RESULTS: A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). CONCLUSION: Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.


Subject(s)
Enterocolitis, Necrotizing/diet therapy , Enterocolitis, Necrotizing/prevention & control , Food Additives/administration & dosage , Food Additives/adverse effects , Humans , Infant, Newborn , Infant, Premature , Network Meta-Analysis
18.
Mol Ther Methods Clin Dev ; 2014(1)2014 Sep.
Article in English | MEDLINE | ID: mdl-25279386

ABSTRACT

Mesenchymal stromal cells (MSC) constitutively express low levels of human leukocyte antigen-G (HLA-G), which has been shown to contribute to their immunomodulatory and anti-inflammatory properties. Here, we hypothesized that overexpression of HLA-G on bone marrow-derived MSC would improve their immunomodulatory function, thus increasing their therapeutic potential. Therefore, we investigated which gene transfer system is best suited for delivering this molecule while maintaining its immuno-modulatory effects. We performed a side-by-side comparison between three nonviral plasmid-based platforms (pmax-HLA-G1; MC-HLA-G1; pEP-HLA-G1) and a viral system (Lv-HLA-G1) using gene transfer parameters that yielded similar levels of HLA-G1-expressing MSC. Natural killer (NK) cell-mediated lysis assays and T cell proliferation assays showed that MSC modified with the HLA-G1 expressing viral vector had significantly lower susceptibility to NK-lysis and significantly reduced T cell proliferation when compared to nonmodified cells or MSC modified with plasmid. We also show that, in plasmid-modified MSC, an increase in Toll-like receptor (TLR)9 expression is the mechanism responsible for the abrogation of HLA-G1's immunomodulatory effect. Although MSC can be efficiently modified to overexpress HLA-G1 using viral and nonviral strategies, only viral-based delivery of HLA-G1 is suitable for improvement of MSC's immunomodulatory properties.

19.
Arthritis Rheumatol ; 66(8): 2201-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24664641

ABSTRACT

OBJECTIVE: To determine the effects of aging and oxidative stress on the response of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1). METHODS: Chondrocytes isolated from normal articular cartilage obtained from tissue donors were cultured in alginate beads or monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both. Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate incorporation was used to measure proteoglycan synthesis, and immunoblotting of cell lysates was performed to analyze cell signaling. Confocal microscopy was performed to measure nuclear translocation of Smad4. RESULTS: Chondrocytes isolated from the articular cartilage of tissue donors ranging in age from 24 years to 81 years demonstrated an age-related decline in proteoglycan synthesis stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while increasing phosphorylation of ERK, and that these effects were greater in cells from older donors. Oxidative stress also increased p38 phosphorylation, which resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1-stimulated nuclear translocation of Smad4. CONCLUSION: These results demonstrate an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1, which are 2 important anabolic factors in cartilage, and suggest that oxidative stress may be a contributing factor by altering IGF-1 and OP-1 signaling.


Subject(s)
Aging/metabolism , Bone Morphogenetic Protein 7/physiology , Chondrocytes/physiology , Insulin-Like Growth Factor I/physiology , Oxidative Stress , Cartilage, Articular/cytology , Cells, Cultured , Humans
20.
Zhonghua Yan Ke Za Zhi ; 49(1): 22-6, 2013 Jan.
Article in Chinese | MEDLINE | ID: mdl-23601461

ABSTRACT

OBJECTIVE: Autologous labial salivary gland transplantation has been a promising alternative for the treatment of severe dry eye. In this article, we describe the results of the ocular surface changes after labial salivary gland transplantation and investigate the feasibility of this treatment. METHODS: The results of this technique in 8 patients (eyes) who suffered from severe dry eye were prospectively analyzed after surgery (follow-up of 6 months). The best-corrected visual acuity, Schirmer I test, degree of discomfort, usage of pharmaceutical tear substitutes, tear interferometry and slit lamp examination were investigated at different time before and after surgery. RESULTS: All grafts remained viable and the survival rate is 100%. All patients showed significant increase in the Schirmer's test and they expressed great improvement in their ocular discomfort. The use of artificial tear substitutes was reduced because of the increased ocular surface lubrication. CONCLUSION: Although the authors' long-term experience still is limited, we believe that the procedure is a promising alternative approach for severe dry eye.


Subject(s)
Dry Eye Syndromes/surgery , Salivary Glands/transplantation , Adolescent , Adult , Female , Humans , Male , Middle Aged , Mouth Mucosa , Transplantation, Autologous , Treatment Outcome , Young Adult
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