ABSTRACT
Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.
Subject(s)
MicroRNAs , Neuroblastoma , Animals , Mice , Down-Regulation , Gene Expression Regulation , Hypoxia/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neuroblastoma/geneticsABSTRACT
Past research supports the detrimental effects of parental psychological control on adolescent school adjustment in both emotional and academic domains. However, how psychological control changes during adolescence, and how such developmental course is related to adolescent psychological well-being and academic functioning are unclear. The direction of effects between parenting and child behaviors is also inconclusive. This 3-year longitudinal study addressed these research gaps by using five waves of survey data on 710 Chinese adolescents of high school ages (Mean age at T1 = 15.54 years, SD = 0.45, 50% males). Using latent growth curve models and latent class growth analysis, the majority of adolescents (about 63%) reported gradual increases of parental psychological control in the first 2 years of high school but a slight decline afterwards, while the other 37% perceived low and stable levels. Results from parallel latent growth modeling suggested that trajectories of psychological control were positively related to developmental trends of internalizing problems (i.e., depression and anxiety) and maladaptive academic functioning, but negatively associated with the trajectory of adaptive academic functioning, as indexed by intercept-intercept and slope-slope associations. The random-intercept cross-lagged models further revealed that psychological control was predictive of adolescent anxiety and lower adaptive academic functioning, and bidirectionally associated with maladaptive academic-related beliefs and behaviors at the within-person level. Taken together, these findings highlight the crucial role of parental psychological control on adolescent school adjustment in the Chinese cultural context and support the reciprocal model of parent-child interactions.
Subject(s)
Parent-Child Relations , Parenting , Humans , Adolescent , Female , Male , Longitudinal Studies , China , Parenting/psychology , Adolescent Behavior/psychology , Social Adjustment , Schools , Depression/psychology , Adaptation, Psychological , Anxiety/psychology , East Asian PeopleABSTRACT
The mycotoxin Ochratoxin A (OTA) causes serious health risks and is found in food products throughout the world. The most promising method to detoxify this compound is biodegradation. In this study, Aspergillus oryzae strain M30011 was isolated and characterized based on its considerable capacity to degrade OTA. The degradation product (compound I) of A. oryzae-treated OTA was isolated, and its toxicity response was also evaluated. Furthermore, the relationships between three key cultivation condition factors affecting the OTA degradation rate were examined using the response surface methodology (RSM). Compound I was identified as ochratoxin α (C11H9O5Cl), and the toxicity response experiments indicated that A. oryzae detoxified OTA to a great extent. A maximum degradation rate of 94% was observed after 72h. This study demonstrates the potential for using A. oryzae to detoxify OTA and suggests that it could be applied in the food industry to improve food safety and quality.
Subject(s)
Aspergillus oryzae , Mycotoxins , Ochratoxins , Biodegradation, Environmental , Food ContaminationABSTRACT
Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1ß, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.
Subject(s)
Biomarkers/blood , Cytokines/blood , Schizophrenia/blood , Adult , Age of Onset , Female , Humans , Interleukin-10/blood , Interleukin-4/blood , Least-Squares Analysis , Male , Middle AgedABSTRACT
The Medial Habenular (MHb) and the Lateral Habenular nuclei are 2 main parts of the habenular complex (Hb). Recent studies showed that MHb plays an important role in memory, and in the expression of ErbB4. However, the expression of MHb ErbB4 receptor and its role in fear memory is not well understood. In this study, western blotting and quantitative real-time polymerase chain reaction were used to assess the protein and mRNA levels of ErbB4 in the process of contextual fear conditioning. A pharmacological approach was used to block and stimulate the ErbB4 receptor. Contextual fear conditioning tests induced a significant increase on the expression of ErbB4 at various times in the Hb and the MHb. Moreover, the blockade and stimulation of MHb ErbB4 receptors did not affect the fear formation but impaired and improved the contextual-dependent fear expression. Furthermore, in vitro electrophysiological recordings showed that the blockade of the MHb ErbB4 receptor reduced the presynaptic gamma-amino butyric acid release. ErbB4 is a susceptible gene for schizophrenia and the above findings may provide new insights into the mechanisms of fear-related responses.
Subject(s)
Fear/physiology , Habenula/metabolism , Memory/physiology , Receptor, ErbB-4/metabolism , Animals , Behavior Rating Scale , Conditioning, Classical , Fear/psychology , Freezing Reaction, Cataleptic/drug effects , Habenula/drug effects , Habenula/physiology , Male , Memory/drug effects , Mice , Mice, Inbred C57BL , Miniature Postsynaptic Potentials/drug effects , Neuregulin-1/pharmacology , Pyrimidines/pharmacology , Quinazolines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, ErbB-4/agonists , Receptor, ErbB-4/antagonists & inhibitors , Receptor, ErbB-4/genetics , Tyrphostins/pharmacologyABSTRACT
Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.
Subject(s)
Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Insulin-Like Growth Factor I/administration & dosage , Solanaceous Alkaloids/administration & dosage , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic/drug effects , Glycogen Synthase Kinase 3 beta/genetics , Humans , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Signal Transduction/drug effects , bcl-2-Associated X Protein/geneticsABSTRACT
A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.
Subject(s)
Endothelial Cells/metabolism , Genetic Therapy/methods , Intercellular Adhesion Molecule-1/metabolism , MicroRNAs/metabolism , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , 3' Untranslated Regions , Animals , Cell Adhesion , Coculture Techniques , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/pathology , Female , Gene Expression Regulation , HL-60 Cells , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intercellular Adhesion Molecule-1/genetics , Leukocytes/metabolism , Macrophages/metabolism , Mice, Inbred BALB C , MicroRNAs/genetics , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardium/pathology , RNA, Messenger/metabolism , Time Factors , Transfection , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.
Subject(s)
Antigens, Bacterial/cerebrospinal fluid , Bacterial Proteins/cerebrospinal fluid , Leukocytes/microbiology , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Meningeal/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/cerebrospinal fluid , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mycobacterium tuberculosis/immunology , Prospective Studies , Sensitivity and Specificity , Staining and Labeling , Tuberculosis, Meningeal/cerebrospinal fluid , Young AdultABSTRACT
OBJECTIVE: To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis. METHODS: The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of F12 gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure. RESULTS: The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure. CONCLUSION: The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.
Subject(s)
Factor XII Deficiency , Factor XII , Heterozygote , Pedigree , Humans , Factor XII Deficiency/genetics , Factor XII/genetics , Exons , Mutation, Missense , Mutation , Partial Thromboplastin Time , Phenotype , Male , FemaleABSTRACT
BACKGROUND: A rare autosomal recessive genetic disorder, 3M syndrome, is characterized by severe intrauterine and postnatal growth retardation. Children with 3M syndrome typically exhibit short stature, facial deformities, long tubular bones, and high vertebral bodies but generally lack mental abnormalities or other organ damage. Pathogenic genes associated with 3M syndrome include CUL7, OBSL1 and CCDC8. The clinical and molecular characteristics of patient with 3M syndrome are unique and serve as important diagnostic indicators. CASE SUMMARY: In this case, the patient displayed square shoulders, scoliosis, long slender tubular bones, and normal neurological development. Notably, the patient did not exhibit the typical dysmorphic facial features, relative macrocephaly, or growth retardation commonly observed in individuals with 3M syndrome. Whole exon sequencing revealed a novel heterozygous c.56681+1G>C (Splice-3) variant and a previously reported nonsense heterozygous c.3341G>A (p.Trp1114Ter) variant of OBSL1. Therefore, it is important to note that the clinical features of 3M syndrome may not always be observable, and genetic confirmation is often required. Additionally, the identification of the c.5683+1G>C variant in OBSL1 is noteworthy because it has not been previously reported in public databases. CONCLUSION: Our study identified a new variant (c.5683+1G>C) of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.
ABSTRACT
Tuberculous meningitis leads to a devastating outcome, and early diagnosis and rapid chemotherapy are vital to reduce morbidity and mortality. Since Mycobacterium tuberculosis is a kind of cytozoic pathogen and its numbers are very few in cerebrospinal fluid, detecting M. tuberculosis in cerebrospinal fluid from tuberculous meningitis patients is still a challenge for clinicians. Ziehl-Neelsen stain, the current feasible microbiological method for the diagnosis of tuberculosis, often needs a large amount of cerebrospinal fluid specimen but shows a low detection rate of M. tuberculosis. Here, we developed a modified Ziehl-Neelsen stain, involving cytospin slides with Triton processing, in which only 0.5 ml of cerebrospinal fluid specimens was required. This method not only improved the detection rate of extracellular M. tuberculosis significantly but also identified intracellular M. tuberculosis in the neutrophils, monocytes, and lymphocytes clearly. Thus, our modified method is more effective and sensitive than the conventional Ziehl-Neelsen stain, providing clinicians a convenient yet powerful tool for rapidly diagnosing tuberculous meningitis.
Subject(s)
Coloring Agents/chemistry , Mycobacterium tuberculosis , Staining and Labeling/methods , Tuberculosis, Meningeal/cerebrospinal fluid , Tuberculosis, Meningeal/diagnosis , Humans , Lymphocytes/microbiology , Neutrophils/microbiology , Sensitivity and Specificity , Tuberculosis, Meningeal/microbiologyABSTRACT
OBJECTIVE: To detect and compare the transcriptional activities of prostate-specific membrane antigen (PSMA) promoter and enhancer and survivin promoter in different human prostate cancer cell lines, and to search for some evidence for the targeting gene therapy of human prostate cancer. METHODS: The fragments of the PSMA promoter and enhancer and survivin promoter were amplified by PCR and inserted into pGL3-Basic. The recombinant plasmids were transiently transfected into human prostate cancer cell lines and normal Chang liver cells, and, their transcriptional activities in various cells were determined by measuring the expression of luciferase. RESULTS: The survivin promoter exhibited a higher transcriptional activity than PSMA promoter and enhancer in tumor cell lines, and the S2pro promoter showed the highest activity, reaching one third of that of the CMV promoter. CONCLUSION: The survivin promoter is highly activated in prostate cancer cell lines and may serve as a new tool for the transcriptional targeting gene therapy of prostate cancer.
Subject(s)
Antigens, Surface/genetics , Glutamate Carboxypeptidase II/genetics , Inhibitor of Apoptosis Proteins/genetics , Prostatic Neoplasms/genetics , Transcription Initiation Site , Cell Line, Tumor , Humans , Male , Plasmids , Promoter Regions, Genetic , Prostatic Neoplasms/therapy , Survivin , Transcriptional Activation , TransfectionABSTRACT
A simple and unique conjugation of norvancomycin-fluorescein (VanF) has been achieved. It was characterized by UV-vis and fluorescence spectra and confirmed by MALDI-TOF mass spectrum. The photodynamic assay indicated that VanF effectively inactivated the Gram-positive Bacillus subtilis (ATCC 6633) from clinic with inactivation rate of 30-70% within 1-7.5 µM. In vitro, VanF showed low antimicrobial activity with value of >128 µg/mL, binding affinity with value of 180 nM per 10(8) cells/mL against the bacteria strains. The fluorescence imaging showed that VanF could label the B. subtilis strain, but not the Escherichia coli (ATCC 25922), Enterococcus faecalis (ATCC 51299, VanD), and VRE strains from clinic.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Fluorescein/chemistry , Photochemistry/methods , Vancomycin/analogs & derivatives , Enterococcus faecalis/drug effects , Escherichia coli/drug effects , Light , Microbial Sensitivity Tests , Molecular Structure , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Vancomycin/chemistry , Vancomycin/pharmacologyABSTRACT
Vibrio alginolyticus, a Gram-negative rod bacterium found in marine environments, is known to cause opportunistic infections in humans, including ear infections, which can be difficult to diagnose. We investigated the microbiological and otopathogenic characteristics of a V. alginolyticus strain isolated from an ear exudate specimen obtained from a patient with chronic otitis externa to provide a basis for the future diagnosis of V. alginolyticus-associated infections. The identification of V. alginolyticus was accomplished using a combination of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), classical biochemical identification methods, and the use of Vibrio-selective media and advanced molecular identification methodologies. Antimicrobial susceptibility testing revealed that the strain was resistant to ampicillin and sensitive to ß-lactam, aminoglycosides, fluoroquinolones, and sulfonamide antibiotics. The potential otopathogenic effects of V. alginolyticus were determined through the performance of cell viability, cell apoptosis, and cell death assays in tympanic membrane (TM) keratinocytes and HEI-OC1 cells treated with V. alginolyticus-conditioned medium using cell-counting kit (CCK)-8 assay, a wound-healing migration assay, Annexin V/propidium iodide (PI) flow cytometric analysis, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL staining). The results indicated that the identified V. alginolyticus strain exerts cytotoxic effects on keratinocytes and HEI-OC1 cells by inhibiting cell proliferation and migration and inducing apoptosis and cell death. To evaluate the ototoxicity of V. alginolyticus, the cell density and morphological integrity of hair cells (HCs) and spiral ganglion neurons (SGNs) were analyzed after exposing cochlear organotypic explants to the bacterial supernatant, which revealed the pre-dominant susceptibility and vulnerability of HCs and SGNs in the basal cochlear region to the ototoxic insults exerted by V. alginolyticus. Our investigation highlights the challenges associated with the identification and characteristic analysis of the Vibrio strain isolated in this case and ultimately aims to increase the understanding and awareness of clinicians and microbiologists for the improved diagnosis of V. alginolyticus-associated ear infections and the recognition of its potential otopathogenic and ototoxic effects.
ABSTRACT
Urokinase plasminogen activator (uPA) correlates closely with breast cancer metastasis via triggering the degradation of divergent matrix proteins. Here, uPA was selectively knocked down in breast carcinoma MDA-MB-231 cells by siRNAs. The in vitro migration of MDA-MB-231 cells was effectively suppressed accompanied by a decrease in extracellular MMP-9 activities. The colony formation ability of MDA-MB-231 cells was inhibited following uPA knockdown, while the proliferation was not affected. The uPA knockdown in MDA-MB-231 cells caused significantly suppressed tumor metastasis in nude mice. Thus, siRNAs targeted to uPA have implications in the development of novel approaches to preventing breast cancer metastasis.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , RNA, Small Interfering/pharmacology , Urokinase-Type Plasminogen Activator/genetics , Animals , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis/prevention & controlABSTRACT
OBJECTIVES: Commensal bacteria in the nasal cavity may act as opportunistic pathogens that cause infections under certain conditions. Screening for commensal bacteria in the nasal cavity may aid in understanding their roles in microbiota balance and preventing potential infections. METHODS: Nasal samples were collected from healthy preclinical medical students and used to inoculate various bacterial culture media, by means of the WaspLab microbiology automated system. Bacterial colonies were then identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antibiotic resistance phenotypes of Staphylococcus aureus were determined by antibiotic susceptibility tests. RESULTS: In total, 549 bacterial strains were isolated from 161 participants. These strains included the following genera: Staphylococcus, Streptococcus, Corynebacterium, Dolosigranulum, Bacillus, Micrococcus, Haemophilus, Neisseria, Moraxella, Pseudomonas, and members of Enterobacteriaceae (e.g., Escherichia, Klebsiella, Citrobacter, Enterobacter, and Serratia). Approximately 25.5% of students were carriers of S. aureus; most S. aureus isolates were resistant to penicillin, erythromycin, and clindamycin. The prevalence of methicillin-resistant S. aureus in nasal samples was 4.3%. CONCLUSIONS: A diverse group of nasal commensal bacteria inhabited our population of healthy volunteers. These data can improve comprehension of the potential roles of these nasal commensal bacteria in regulating microbiota balance and promoting or mitigating potential future infections.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Students, Medical , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/genetics , Humans , Microbial Sensitivity Tests , Prevalence , Staphylococcal Infections/drug therapy , Staphylococcus aureusABSTRACT
OBJECTIVES: Adductor canal block (ACB) could provide effective postoperative pain control for patients after total knee arthroplasty (TKA). However, some authors pointed out that the ACB as originally described may be more similar to a femoral triangle block (FTB). Recent neuroanatomic evidences made the authors conjecture that the "true" ACB would provide superior analgesia compared with FTB. Therefore, the study was designed to determine the hypothesis that postoperative analgesia after TKA could be improved by a "true" ACB compared with FTB. MATERIALS AND METHODS: Patients undergoing unilateral, primary TKA were randomized into the ACB group or FTB group. The primary outcome was postoperative pain during active flexion at 8 hours after surgery measured by the visual analog scale (VAS). In addition, pain scores at other time points, quadriceps strength, morphine consumption, satisfaction of the patient, and side effects of morphine were also evaluated. RESULTS: Sixty participants completed the research. The VAS scores were lower in the ACB group than the FTB group at 8 and 24 hours at rest (P<0.05). The VAS scores were lower in the ACB group than the FTB group at 4, 8, 24, and 48 hours during active flexion (P<0.05). The quadriceps strength was superior in the ACB group than the FTB group at 4, 8, and 24 hours (P<0.05). The consumption of morphine was lower in the ACB group than the FTB group (P<0.05). However, there were no significant differences for both patient satisfaction and the incidence of adverse reactions (P>0.05). DISCUSSION: ACB can provide superior analgesia and preserve more quadriceps strength than FTB. ACB facilitates functional recovery in the early stages and is compatible with the highly recognized concept of rapid rehabilitation, which should be promoted in the clinic.
Subject(s)
Arthroplasty, Replacement, Knee , Nerve Block , Analgesics, Opioid , Femoral Nerve , Humans , Pain, Postoperative/drug therapyABSTRACT
Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). "Cell RevealTM system" is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e.g., de novo pathogenic copy number changes) were tested for the capture of circulating fetal nucleated red blood cells (fnRBCs). Captured cells were subjected to fluorescent in situ hybridization (FISH) on chip or recovered by an automated cell picker for molecular genetic analyses. The capture rate for the spiking tests is estimated as 88.1%. For the prenatal study, 2â»71 fnRBCs were successfully captured from 2 mL of maternal blood in all pregnant women. The captured fnRBCs were verified to be from fetal origin. Our results demonstrated that the Cell RevealTM system has a high capture efficiency and can be used for fnRBC capture that is feasible for the genetic diagnosis of fetuses without invasive procedures.
ABSTRACT
OBJECTIVE: To clone DNA sequence of the survivin promoter and study is transcriptional activities in human prostate cancer cells and normal Chang liver cells. METHODS: The fragment of the survivin promoter was acquired by PCR amplification and inserted into pPRIME vectors to reconstruct a recombinant plasmid named pPRIME-S1pro and pPRIME-S2pro. Then the reconstructed plasmid was transiently transfected into human prostate cancer cells lines LNCaP and normal Chang liver cells. The transcriptional activities of the survivin promoter in various cells was determined by measuring the expression of green fluorescent protein (GFP). RESULTS: The survivin promoter had transcriptional activities in LNCaP cells and the transcriptional activity of the S2pro was much higher that of the S1pro, reaching a level of 39% of the transcriptional activity of the CMV promoter. CONCLUSION: The survivin promoter cloned in the therapy for prostate cancer.
Subject(s)
Microtubule-Associated Proteins/genetics , Neoplasm Proteins/genetics , Promoter Regions, Genetic , Prostatic Neoplasms/metabolism , Cell Line, Tumor , Humans , Inhibitor of Apoptosis Proteins , Male , Microtubule-Associated Proteins/biosynthesis , Neoplasm Proteins/biosynthesis , Plasmids , Polymerase Chain Reaction , Prostatic Neoplasms/genetics , Survivin , TransfectionABSTRACT
Colorectal cancer is one of the major health problems, with invade surrounding tissues, and migrate to distant organs being the most critical concern, thus identified metastasis associated hallmarks and more efficacious treatment are urgently needed. It found that forkhead box q1 (FOXQ1) is aberrant expression in variety of human cancers and FOXQ1 is involved in oncogenic pathways. However, the role of FOXQ1 has been unexplored in colorectal cancer metastasis to date. Here, expression of FOXQ1 was higher in colorectal cancer tissue samples and cancer cell lines than in normal colorectal tissue and cell lines. Further research suggested that FOXQ1 positively regulated cell proliferation in colorectal cancer and down-regulation of CDK6, extracellular regulated protein kinases 1/2 (ERK1/2) and mammalian target of rapamycin (mTOR). In corresponding to this result, over-expression of FOXQ1 significantly promoted colorectal cancer growth in vivo. Moreover, down regulation of FOXQ1 expression in colorectal carcinoma cell HCT116 and LOVO strikingly inhibits tumor growth in vivo. Finally, FOXQ1-dependent inhibition of colorectal cancer cell migration and invasion and down-regulation of focal adhesion kinase (FAK), phosphatidyl inositol 3-kinase (PI3K) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation and matrix metalloproteinase-2/9 (MMP-2/9) expression. These integrated efforts have identified FOXQ1 as a tumor promoter and might provide promising approaches for colorectal cancer metastasis treatment.