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1.
Med Sci Monit ; 30: e942080, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38584384

ABSTRACT

BACKGROUND Exploring the factors that impact the time from symptom onset to first medical contact (S2FMC) is crucial for improving outcomes in elderly patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This study conducted a retrospective analysis on 282 patients who underwent emergency percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA) in Guangzhou City District to identify significant factors affecting S2FMC. MATERIAL AND METHODS A retrospective analysis was conducted on 282 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI). Descriptive statistics, univariate and multivariate Cox regression analyses were used to identify significant factors affecting S2FMC. Additionally, interactions between risk factors were examined using multivariate logistic regression and the structural equation model (SEM). RESULTS Age (HR=0.984, 95% CI: 0.975-0.993), nature of chest pain (HR=2.561, 95% CI: 1.900-3.458), admission mode (HR=1.805, 95% CI: 1.358-2.400), and vascular characteristics (HR=1.246, 95% CI: 1.069-1.451) were independent influencing factors for S2FMC. Persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) played a protective role in S2FMC. Among the influencing factors, vascular characteristics (OR=1.072, 95% CI: 1.008-1.141) had an independent effect on the nature of chest pain. Meanwhile, the nature of chest pain (OR=1.148, 95% CI: 1.015-1.298) was an independent influencing factor in the admission mode. CONCLUSIONS Patients with persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) experienced shorter S2FMC and higher compliance rate (S2FMC ≤180 min). At the same time, age and other vascular features played an inverse role. This study proposes enhancing follow-up and monitoring measures, and shows the consequences of intermittent chest pain should not be disregarded.


Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Aged , ST Elevation Myocardial Infarction/surgery , Percutaneous Coronary Intervention/adverse effects , Retrospective Studies , Treatment Outcome , Time Factors , Chest Pain/etiology
2.
Cell Signal ; 112: 110921, 2023 12.
Article in English | MEDLINE | ID: mdl-37839544

ABSTRACT

Acute myocardial infarction (AMI) is a global health threat, and programmed cell death (PCD) plays a crucial role in its occurrence and development. In this study, integrated bioinformatics tools were used to explore new biomarkers and therapeutic targets in AMI. Thirteen types of PCD-related genes were identified through literature review, KEGG, and GSEA pathways. Gene expression matrices and clinical data from AMI patients and healthy controls were obtained from the GEO database. Statistical analysis in R identified 377 differentially expressed genes in AMI patients. Intersection analysis between the differentially expressed genes and PCD-related genes revealed 24 genes positively correlated with immune cells such as Neutrophils and Monocytes, while negatively correlated with T cells CD4 memory resting and Plasma cells. Unsupervised clustering analysis divided patients into two groups (C1 and C2) based on the expression levels of these 24 genes. GSVA analysis showed that C2 patients were more active in pathways related to maintaining normal cell morphology and promoting phagocytosis, suggesting a lower programmed cell death rate and a higher tendency to maintain cell survival. Two hub genes, TNFAIP3 and TP53INP2, were identified through LASSO regression analysis and SVM-RFE, and were validated using an external dataset and RT-qPCR、Western blot and ELISA analysis. These hub genes showed significantly higher expression and protein secretion levels in AMI patients compared to healthy individuals. Overall, regulating and controlling PCD, particularly through the identified hub genes, TNFAIP3 and TP53INP2, may provide new therapeutic strategies for improving the prognosis of AMI patients and preventing heart failure.


Subject(s)
Apoptosis , Myocardial Infarction , Humans , Cell Death , Cell Survival , Cluster Analysis , Myocardial Infarction/genetics , Nuclear Proteins
3.
Clin Exp Metastasis ; 40(4): 339-356, 2023 08.
Article in English | MEDLINE | ID: mdl-37326719

ABSTRACT

Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is extensively used for clinical therapy in KRAS wild-type colorectal cancer (CRC) patients. However, some patients still cannot get benefit from the therapy, because metastasis and resistance occur frequently after cetuximab treatment. New adjunctive therapy is urgently needed to suppress metastasis of cetuximab-treated CRC cells. In this study, we used two KRAS wild-type CRC cells, HT29 and CaCo2, to investigate whether platycodin D, a triterpenoid saponin isolated from Chinese medicinal herb Platycodon grandifloras, is able to suppress the metastasis of cetuximab-treated CRC. Label-free quantitative proteomics analyses showed that platycodin D but not cetuximab significantly inhibited expression of ß-catenin in both CRC cells, and suggested that platycodin D counteracted the inhibition effect of cetuximab on cell adherence and functioned in repressing cell migration and invasion. Western blot results showed that single platycodin D treatment or combined platycodin D and cetuximab enhanced inhibition effects on expressions of key genes in Wnt/ß-catenin signaling pathway, including ß-catenin, c-Myc, Cyclin D1 and MMP-7, compared to single cetuximab treatment. Scratch wound-healing and transwell assays showed that platycodin D combined with cetuximab suppressed migration and invasion of CRC cells, respectively. Pulmonary metastasis model of HT29 and CaCo2 in nu/nu nude mice consistently showed that combined treatment using platycodin D and cetuximab inhibited metastasis significantly in vivo. Our findings provide a potential strategy to inhibit CRC metastasis during cetuximab therapy by addition of platycodin D.


Subject(s)
Colorectal Neoplasms , Saponins , Triterpenes , Humans , Animals , Mice , Cetuximab/pharmacology , Cetuximab/metabolism , Cetuximab/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Caco-2 Cells , beta Catenin , Mice, Nude , Saponins/pharmacology , Saponins/therapeutic use , Triterpenes/pharmacology , Triterpenes/therapeutic use , Wnt Signaling Pathway , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Cell Movement/genetics
4.
J Hazard Mater ; 446: 130706, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36603426

ABSTRACT

Heavy oil and petroleum refining residues usually contain high concentrations of recalcitrant hazardous organosulfur compounds, causing long-term serious global environmental pollution during leakage and combustion. Research conducted here identified a unique thermophilic bacterium Parageobacillus thermoglucosidasius W-36 with the notable ability of waste residue oil desulfurization, utilization and tolerance of multiplex hazardous organosulfur pollutants. Genome information mining revealed multiple desulfurization systems in three organosulfur-utilizing gene clusters. Enzymatic characterization, phylogenetic relationships, transcriptional performance and structural prediction indicated four novel key monooxygenases for diverse organosulfur removal. Importantly, all monooxygenases shared obvious commonalities in the predicted tertiary structure backbone and catalytic characteristics of C-S bond cleavage, implying the potential of genetic engineering for broad-spectrum hazardous organosulfur removal. Therefore, this work demonstrated the important application potential of thermophilic bacteria as a promising alternative biodesulfurization way for waste residue oil cleaning.


Subject(s)
Petroleum , Thiophenes , Phylogeny , Sulfur Compounds , Genetic Engineering
5.
Cell Rep ; 40(1): 111033, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35793624

ABSTRACT

The immune response of brain cells to invading bacteria in vivo and the mechanism used by pathogenic bacteria to escape brain immune surveillance remain largely unknown. It is believed that microglia eliminate bacteria by phagocytosis based on in vitro data. Here we find that a small percentage of microglia in the brain engulf neonatal meningitis-causing Escherichia coli (NMEC), but more microglia are activated to produce tumor necrosis factor alpha (TNFα), which activates astrocytes to secrete complement component 3 (C3) involved in anti-bacterial activity. To evade anti-bacterial activity of the immune system, NMEC senses low concentration of threonine in cerebrospinal fluid (CSF) to down-modulate the expression of flagellin and reduce microglial TNFα and astrocyte C3 production. Our findings may help develop strategies for bacterial meningitis treatment.


Subject(s)
Astrocytes , Microglia , Astrocytes/metabolism , Bacteria/metabolism , Brain/metabolism , Flagellin/metabolism , Flagellin/pharmacology , Humans , Infant, Newborn , Microglia/metabolism , Tumor Necrosis Factor-alpha/metabolism
6.
World J Gastroenterol ; 28(18): 1946-1964, 2022 May 14.
Article in English | MEDLINE | ID: mdl-35664963

ABSTRACT

BACKGROUND: Emerging evidence links gut microbiota to various human diseases including colorectal cancer (CRC) initiation and development. However, gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet, especially in a Chinese cohort. AIM: To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. METHODS: We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy controls. The patients were followed up by regular examination to determine whether tumors recurred. Triplet-paired samples from on-tumor, adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA sequencing. Next, we carried out bioinformatic analyses, Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. RESULTS: We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis. A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis, including Anaerotruncus, Bacteroidales, Coriobacteriaceae, Dialister, Eubacterium, Fusobacterium, Filifactor, Gemella, Haemophilus, Mogibacteriazeae, Pyramidobacter, Parvimonas, Porphyromonadaceae, Slackia, Schwartzia, TG5 and Treponema. CONCLUSION: Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Bacteria/genetics , Biomarkers , Colorectal Neoplasms/pathology , Gastrointestinal Microbiome/genetics , Humans , Neoplasm Recurrence, Local , RNA, Ribosomal, 16S/genetics
7.
Bioresour Technol ; 347: 126690, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35007737

ABSTRACT

Nitroalkanes are important toxic pollutants for which there is no effective removal method at present. Although genetic engineering bacteria have been developed as a promising bioremediation strategy for years, their actual performance is far lower than expected. In this study, important factors affecting the application of engineered Geobacillus for nitroalkanes degradation were comprehensively optimized. The deep-reconstructed engineered strains significantly raised the expression and activity level of catalytic enzymes, but failed to fully enhance the degradation efficiency. However, further debugging of a variety of key parameters effectively improved the performance of the engineering strains. The increased cell membrane permeability, trace supplementation of vital nutritional factors, synergy of multifunctional enzyme engineered bacteria, switch of oxygen-supply mode, and moderate initial biomass all effectively boosted the degradation efficiency. Finally, a low-cost and highly effective bioreactor test for high-concentration nitroalkanes degradation proved the multi-parameter optimization mode helps to maximize the performance of genetically engineered bacteria.


Subject(s)
Geobacillus , Wastewater , Biodegradation, Environmental , Bioreactors , Genetic Engineering , Geobacillus/genetics
8.
J Hazard Mater ; 427: 128201, 2022 04 05.
Article in English | MEDLINE | ID: mdl-34999399

ABSTRACT

Oil refining waste (ORW) contains complex, hazardous, and refractory components, causing more severe long-term environmental pollution than petroleum. Here, ORW was used to simulate the accelerated domestication of bacteria from oily sludges and polymer-flooding wastewater, and the effects of key factors, oxygen and temperature, on the ORW degradation were evaluated. Bacterial communities acclimated respectively in 30/60 °C, aerobic/anaerobic conditions showed differentiated degradation rates of ORW, ranging from 5% to 34%. High-throughput amplicon sequencing and ORW component analysis revealed significant correlation between bacterial diversity/biomass and degradation efficiency/substrate preference. Under mesophilic and oxygen-rich condition, the high biomass and abundant biodiversity with diverse genes and pathways for petroleum hydrocarbons degradation, effectively promoted the rapid and multi-component degradation of ORW. While under harsh conditions, a few dominant genera still contributed to ORW degradation, although the biodiversity was severely restricted. The typical dominant facultative anaerobes Bacillus (up to 99.8% abundance anaerobically) and Geobacillus (up to 99.9% abundance aerobically and anaerobically) showed oxygen-independent sustainable degradation ability and broad-spectrum of temperature adaptability, making them promising and competitive bioremediation candidates for future application. Our findings provide important strategies for practical bioremediation of varied environments polluted by hazardous ORW.


Subject(s)
Hazardous Waste , Petroleum , Bacteria/genetics , Biodegradation, Environmental , Hydrocarbons , Oxygen , RNA, Ribosomal, 16S , Temperature
10.
Commun Biol ; 4(1): 1232, 2021 10 28.
Article in English | MEDLINE | ID: mdl-34711923

ABSTRACT

Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.


Subject(s)
Adaptation, Biological/physiology , Desiccation , Helminth Proteins/genetics , Phosphotransferases/genetics , Tylenchida/genetics , Water/metabolism , Animals , Biological Evolution , Gene Duplication/physiology , Gene Expression Profiling , Helminth Proteins/metabolism , Humidity , Phosphotransferases/metabolism , Tylenchida/enzymology
11.
Life (Basel) ; 11(8)2021 Aug 13.
Article in English | MEDLINE | ID: mdl-34440574

ABSTRACT

Emerging evidences link gut microbiota to colorectal cancer (CRC) initiation and development. However, the CRC stage- and spatial-specific bacterial taxa were less investigated, especially in a Chinese cohort, leading to our incomplete understanding of the functional roles of gut microbiota in promoting CRC progression and recurrence. Here, we report the composition and structure of gut microbiota across CRC stages I, II and III, by analyzing the gut mucosal microbiomes of 75 triplet-paired samples collected from on-tumor, adjacent-tumor and off-tumor sites and 26 healthy controls. We observed tumor-specific pattern of mucosal microbiome profiles as CRC progressed and identified ten bacterial taxa with high abundances (>1%) as potential biomarkers for tumor initiation and development. Peptostreptococcus and Parvimonas can serve as biomarkers for CRC stage I. Fusobacterium, Streptococcus, Parvimonas, Burkholderiales, Caulobacteraceae, Delftia and Oxalobacteraceae can serve as biomarkers for CRC stage II, while Fusobacterium, Burkholderiales, Caulobacteraceae, Oxalobacteraceae, Faecalibacterium and Sutterella can serve as biomarkers for CRC stage III. These biomarkers classified CRC stages I, II and III distinguished from each other with an area under the receiver-operating curve (AUC) > 0.5. Moreover, co-occurrence and co-excluding network analysis of these genera showed strong correlations in CRC stage I, which were subsequently reduced in CRC stages II and III. Our findings provide a reference index for stage-specific CRC diagnosis and suggest stage-specific roles of Peptostreptococcus, Fusobacterium, Streptococcus and Parvimonas in driving CRC progression.

12.
Gut Pathog ; 13(1): 2, 2021 Jan 12.
Article in English | MEDLINE | ID: mdl-33436075

ABSTRACT

BACKGROUND: Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human gut microbial dysbiosis suggests that 'driver' bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by 'passenger' bacteria later on, due to their low adaptability to the on-tumor site niche. RESULTS: To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the 'passenger' bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice. CONCLUSIONS: Our findings reveal that E. rectale functions as a 'driver' bacterium and contributes to cancer initiation via promoting inflammation.

13.
Front Microbiol ; 11: 574833, 2020.
Article in English | MEDLINE | ID: mdl-33329434

ABSTRACT

Escherichia coli K1 is the leading cause of meningitis in newborns. Understanding the molecular basis of E. coli K1 pathogenicity will help develop treatment of meningitis and prevent neurological sequelae. E. coli K1 replicates in host blood and forms a high level of bacteremia to cause meningitis in human. However, the mechanisms that E. coli K1 employs to sense niche signals for survival in host blood are poorly understood. We identified one intergenic region in E. coli K1 genome that encodes a novel small RNA, sRNA-17. The expression of sRNA-17 was downregulated by ArcA in microaerophilic blood. The ΔsRNA-17 strain grew better in blood than did the wild-type strain and enhanced invasion frequency in human brain microvascular endothelial cells. Transcriptome analyses revealed that sRNA-17 regulates tens of differentially expressed genes. These data indicate that ArcA downregulates the sRNA-17 expression to benefit bacterial survival in blood and penetration of the blood-brain barrier. Our findings reveal a signaling mechanism in E. coli K1 for host adaptation.

14.
Cancer Manag Res ; 12: 11553-11561, 2020.
Article in English | MEDLINE | ID: mdl-33209059

ABSTRACT

INTRODUCTION: Besides genetic and epigenetic alterations that lead to carcinogenesis and development of colorectal cancer (CRC), intestinal microbiomes are recently recognized to play a critical role in CRC progression. The abundant species associated with human CRC have been proposed for their roles in promoting tumorigenesis. However, a recent "driver-passenger" model suggests that these CRC-associated species with high relative abundances may be passenger bacteria that take advantage of the tumor environment instead of initiating CRC, whereas the driver species that initiate CRC have been replaced by passenger bacteria due to the alteration of the intestinal niche. METHODS: Here, to reveal potential driver and passenger bacteria during CRC progression, we compare the gut mucosal microbiomes of 75 triplet-paired CRC samples collected from on-tumor site, adjacent-tumor site, and off-tumor site, and 26 healthy controls. RESULTS: Our analyses revealed potential driver bacteria in four genera and two families, and potential passenger bacteria in 14 genera or families. Bacillus, Bradyrhizobium, Methylobacterium, Streptomyces, Intrasporangiaceae and Sinobacteraceae were predicted to be potential driver bacteria. Moreover, 14 potential passenger bacteria were identified and divided into five groups. Group I passenger bacteria contain Fusobacterium, Campylobacter, Streptococcus, Schwartzia, and Parvimonas. Group II passenger bacteria contain Dethiosulfatibacter, Selenomonas, Peptostreptococus, Leptotrichia. Group III passenger bacteria contain Granulicatella. Group IV passenger bacteria contain Shewanella, Mogibacterium, and Eikenella. Group V passenger bacteria contain Anaerococus. Co-occurrence network analysis reveals a low correlation relationship between driver and passenger bacteria in CRC patients compared with healthy controls. DISCUSSION: These driver and passenger species may serve as bio-marker species for screening cohorts with high risk to initiate CRC or patients with CRC, respectively. Further functional studies will help understand the roles of driver and passenger bacteria in CRC initiation and development.

15.
Int J Mol Sci ; 20(19)2019 Oct 03.
Article in English | MEDLINE | ID: mdl-31623351

ABSTRACT

The genus Flavobacterium contains a large group of commensal bacteria identified in diverse terrestrial and aquatic habitats. We compared the genome of a new species Flavobacterium akiainvivens IK-1T to public available genomes of Flavobacterium species to reveal the genomic traits and ecological roles of IK-1T. Principle component analysis (PCA) of carbohydrate-active enzyme classes suggests that IK-1T belongs to a terrestrial clade of Flavobacterium. In addition, type 2 and type 9 secretion systems involved in bacteria-environment interactions were identified in the IK-1T genome. The IK-1T genome encodes eukaryotic-like domain containing proteins including ankyrin repeats, von Willebrand factor type A domain, and major royal jelly proteins, suggesting that IK-1T may alter plant host physiology by secreting eukaryotic-like proteins that mimic host proteins. A novel two-component system FaRpfC-FaYpdB was identified in the IK-1T genome, which may mediate quorum sensing to regulate global gene expressions. Our findings suggest that comparative genome analyses of Flavobacterium spp. reveal that IK-1T has adapted to a terrestrial niche. Further functional characterizations of IK-1T secreted proteins and their regulation systems will shed light on molecular basis of bacteria-plant interactions in environments.


Subject(s)
Adaptation, Physiological , Flavobacterium/physiology , Genome, Bacterial , Genomics , Host-Pathogen Interactions , Plants/microbiology , Bacterial Physiological Phenomena , Biological Evolution , Computational Biology/methods , Flavobacterium/classification , Genomics/methods , Plant Diseases/microbiology , Quorum Sensing , Synteny
16.
J Geriatr Cardiol ; 16(2): 156-163, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30923548

ABSTRACT

BACKGROUND: Few data on the combined effects of bifurcation and calcification on coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) are available. This study evaluated the impact of main vessel (MV) calcification on the procedural and long-term outcomes in patients with CAD who underwent provisional single stent PCI. METHODS: This is a multicenter, prospective, observational study. Patients with bifurcation lesions were enrolled at 10 PCI centers in China from January 2015 to December 2017. Intravascular ultrasound or optical coherence tomography was performed in all patients to evaluate the MV calcification. Patients were treated with provisional single stent strategy using drug eluting stents and followed-up at 1 month, 6 months and 12 months after discharge by telephone contact or outpatient visit. Repeated coronary imaging was performed within one year. We compared the procedural success rates in MV and in side branch (SB), and target lesion failure (TLF), defined as a composite of cardiac death, non-fatal myocardial infarction, definite or possible stent thrombosis and target lesion revascularization between patients with and without MV calcification. RESULTS: A total of 185 subjects were enrolled according to the inclusion and exclusion criteria of this study. MV calcification was detected in 119 (64.3%, calcification group) and not found in 66 (35.7%, non-calcification group) patients. The angiographic success rate of MV was 95.8% in the calcification group and 97.0% in the non-calcification group (P = 0.91); the angiographic success rate of SB was 32.8% in the calcification group and 53.0% in the non-calcification group (P < 0.05). During the one-year follow-up period, TLF occurred in 14 (11.8%) patients in the calcification group and in 13 (19.7%) in the non-calcification group (P = 0.31). Multivariate regression analysis showed the same result (HR = 1.23, 95% CI: 0.76-1.52, P = 0.47). Calcification on group had higher recurrent angina than non-calcification group (13.51% vs. 17.65%, P < 0.05). CONCLUSIONS: In patients with coronary bifurcation lesion treated with provisional one stent approach, calcification of MV is associated with lower SB procedural success rate, it could increase recurrence of angina; however, it was not associated with an increased risk of TLF.

17.
BMC Infect Dis ; 18(1): 608, 2018 Dec 03.
Article in English | MEDLINE | ID: mdl-30509214

ABSTRACT

BACKGROUND: Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. METHODS: We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS' ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. RESULTS: WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families' significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting's poor performance when identifying transmission in Beijing and Manila family clusters. CONCLUSIONS: This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.


Subject(s)
High-Throughput Nucleotide Sequencing/methods , Mycobacterium tuberculosis/genetics , Tuberculosis/transmission , Alleles , Asia/ethnology , Bacterial Typing Techniques/methods , Beijing/ethnology , Cluster Analysis , Diagnostic Tests, Routine , Emigrants and Immigrants/statistics & numerical data , Genomics/methods , Hawaii/epidemiology , Humans , Minisatellite Repeats , Molecular Epidemiology , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/isolation & purification , Philippines/ethnology , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Prevalence , Sensitivity and Specificity , Tuberculosis/epidemiology , Tuberculosis/genetics
18.
PLoS One ; 13(7): e0201146, 2018.
Article in English | MEDLINE | ID: mdl-30036392

ABSTRACT

While tuberculosis (TB) remains a global disease, the WHO estimates that 62% of the incident TB cases in 2016 occurred in the WHO South-East Asia and Western Pacific regions. TB in the Pacific is composed predominantly of two genetic families of Mycobacterium tuberculosis (Mtb): Beijing and Manila. The Manila family is historically under-studied relative to the families that comprise the majority of TB in Europe and North America (e.g. lineage 4), and it remains unclear why this lineage has persisted in Filipino populations despite the predominance of more globally successful Mtb lineages in most of the world. The Beijing family is of particular interest as it is increasingly associated with drug resistance throughout the world. Both of these lineages are important to the State of Hawaii, where they comprise over two-thirds of TB cases. Here, we performed whole genome sequencing on 82 Beijing family, Manila family, and outgroup clinical Mtb isolates from Hawaii to identify lineage-specific SNPs (SNPs found in all isolates from their respective families, and exclusively in those families) in established virulence factor genes. Six non-silent lineage-specific virulence factor SNPs were found in the Beijing family, including mutations in alternative sigma factor sigG and polyketide synthases pks5 and pks7. The Manila family displayed more than eleven non-silent lineage-specific and characteristic virulence factor mutations, including in genes coding for MCE-family protein Mce1B, two mutations in fatty-acid-AMP ligase FadD26, and virulence-regulating transcriptional regulator VirS. This study further identified an ancient clade that shared some virulence factor mutations with the Manila family, and investigated the relationship of those and other "Manila-like" spoligotypes to the Manila family with this SNP dataset. This work identified a set of virulence genes that are worth pursuing to determine potential differences in transmission or virulence displayed by these two Mtb families.


Subject(s)
Mycobacterium tuberculosis/genetics , Polymorphism, Single Nucleotide , Virulence Factors/genetics , Beijing , Hawaii , Mycobacterium tuberculosis/isolation & purification , Philippines , Phylogeny , Species Specificity , Whole Genome Sequencing
19.
Int J Syst Evol Microbiol ; 68(1): 35-41, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29111971

ABSTRACT

A Gram-negative, rod-shaped bacterium, designated KH87T, was isolated from a fishing hook that had been baited and suspended in seawater off O'ahu, Hawai'i. Based on a comparison of 1524 nt of the 16S rRNA gene sequence of strain KH87T, its nearest neighbours were the GammaproteobacteriaRheinheimera nanhaiensis E407-8T (96.2 % identity), Rheinheimera chironomi K19414T (96.0 %), Rheinheimera pacifica KMM 1406T (95.8 %), Rheinheimera muenzenbergensis E49T (95.7 %), Alishewanella solinquinati KMK6T (94.9 %) and Arsukibacterium ikkense GCM72T (94.6 %). Cells of KH87T were motile by a single polar flagellum, strictly aerobic, and catalase- and oxidase-positive. Growth occurred between 4 and 39 °C, and in a circumneutral pH range. Major fatty acids in whole cells of strain KH87T were cis-9-hexadecenoic acid, hexadecanoic acid and cis-11-octadecenoic acid. The quinone system contained mostly menaquinone MK-7, and a minor amount of ubiquinone Q-8. The polar lipid profile contained the major lipids phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, an unidentified aminolipid, and a lipid not containing phosphate, an amino group or a sugar moiety. Putrescine was the major polyamine. Physiological, biochemical and genomic data, including obligate halophily, absence of amylolytic activity, a quinone system dominated by MK-7 and DNA G+C content (42.0 mol%) distinguished KH87T from extant Rheinheimera species; strain KH87T was also distinguished by a multi-locus sequence analysis of aligned and concatenated 16S rRNA, gyrB, rpoB and rpoD gene sequences. Based on phenotypic and genotypic differences, the species Rheinheimera salexigens sp. nov. is proposed to accommodate KH87T as the type strain (=ATCC BAA-2715T=CIP 111115T). An emended description of the genus Rheinheimera is also proposed.


Subject(s)
Chromatiaceae/classification , Phylogeny , Seawater/microbiology , Ubiquinone/chemistry , Bacterial Typing Techniques , Base Composition , Chromatiaceae/genetics , Chromatiaceae/isolation & purification , DNA, Bacterial/genetics , Fatty Acids/chemistry , Hawaii , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry
20.
Genome Announc ; 5(42)2017 Oct 19.
Article in English | MEDLINE | ID: mdl-29051259

ABSTRACT

Most of the 24 known Chitinophaga species were originally isolated from soils. We report the draft genome sequence of a putatively novel Chitinophaga sp. from a biofilm in an air conditioner condensate pipe. The genome comprises 7,661,303 bp in one scaffold, 5,694 predicted protein-coding sequences, and a G+C content of 47.6%.

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