RESUMO
Lab-on-a-chip systems (LOCs), characterized by their high sensitivity, low sample consumption, and portability, have significantly advanced the field of on-site testing. Despite the evolution of integrated LOCs from qualitative to quantitative analyses, on-chip full integration of sample preparation, purification, and multiplexed detection remains a challenge. Here, we propose a strategy for the heterogeneous integration of a set of complementary metal oxide semiconductor-compatible devices including acoustic resonator, thin-film resistors, and temperature/photosensors as a new type of LOC for nucleic acid testing (NAT). Programmed acoustic streaming-based particles and fluid manipulations largely simplify the nucleic acid extraction process including cell lysis, nucleic acid capture, and elution. The design of the acoustic microextraction module and extraction process was thoroughly studied. Benefitted by the microelectromechanical system approach, the conventional mechanical actions and complex flow control are avoided, which enables a compact hand-held NAT instrument without complicated peripherals. Validation experiments conducted on plasma-harboring mutations in the epidermal growth factor receptor (EGFR) gene confirmed the robustness of the system, achieving an impressive nucleic acid (NA) extraction efficiency of approximately 90% within 5 min and a limit of detection of the target NA in the plasma of 1 copy/µL.
Assuntos
Acústica , Vidro , Vidro/química , Humanos , Dispositivos Lab-On-A-Chip , Receptores ErbB/genética , Ácidos Nucleicos/análise , Ácidos Nucleicos/isolamento & purificação , Semicondutores , DNA/análise , DNA/químicaRESUMO
The global concern over arsenic contamination in water due to its natural occurrence and human activities has led to the development of innovative solutions for its detection and remediation. Microbial metabolism and mobilization play crucial roles in the global cycle of arsenic. Many microbial arsenic-resistance systems, especially the ars operons, prevalent in bacterial plasmids and genomes, play vital roles in arsenic resistance and are utilized as templates for designing synthetic bacteria. This review novelty focuses on the use of these tailored bacteria, engineered with ars operons, for arsenic biosensing and bioremediation. We discuss the advantages and disadvantages of using synthetic bacteria in arsenic pollution treatment. We highlight the importance of genetic circuit design, reporter development, and chassis cell optimization to improve biosensors' performance. Bacterial arsenic resistances involving several processes, such as uptake, transformation, and methylation, engineered in customized bacteria have been summarized for arsenic bioaccumulation, detoxification, and biosorption. In this review, we present recent insights on the use of synthetic bacteria designed with ars operons for developing tailored bacteria for controlling arsenic pollution, offering a promising avenue for future research and application in environmental protection.
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Arsênio , Bactérias , Biodegradação Ambiental , Técnicas Biossensoriais , Óperon , Técnicas Biossensoriais/métodos , Arsênio/metabolismo , Bactérias/genética , Bactérias/metabolismo , Biologia Sintética/métodos , Engenharia GenéticaRESUMO
Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.
Assuntos
Elementos Alu , Distrofina , Distrofia Muscular de Duchenne , Mutagênese Insercional , Distrofia Muscular de Duchenne/genética , Humanos , Elementos Alu/genética , Distrofina/genética , Masculino , Sequência de Bases , Cabelo/metabolismo , Feminino , Éxons/genética , Criança , Dados de Sequência MolecularRESUMO
Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.
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Monitoramento Biológico , Chumbo , Adsorção , Transporte Biológico , BiomineralizaçãoRESUMO
Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50â µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40â µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.
Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Solanum , Humanos , Solanum/química , Fármacos Neuroprotetores/química , Simulação de Acoplamento Molecular , Estereoisomerismo , Estrutura MolecularRESUMO
Thioredoxin (Trx) is a central component of the redox control system that maintains the redox homeostasis critical for organism survival. Owing to its central role in survival, Trx is a prospective target for novel antimicrobial agents. Herein, we report a 1.45 Å high-resolution structure of Trx1 of Acinetobacter baumannii (abTrx1), an antibiotic-resistant pathogenic superbug. Although abTrx1 exhibited the canonical Trx fold, which consists of a four-stranded ß-sheet surrounded by four α-helices, structural differences were detected in the loop forming the C-X-X-C redox center and the C-terminal. The unique CAPC sequence of the C-X-X-C motif in the abTrx1 redox center was characterized by mutagenesis. This study contributes to the field of drug designing against superbugs.
Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/metabolismo , Sequência de Aminoácidos , Oxirredução , Estudos Prospectivos , Tiorredoxinas/metabolismoRESUMO
INTRODUCTION: The purpose of this article was to determine the prevalence of inner ear symptoms in patients with blunt head trauma and to explore whether the severity of head trauma was associated with the incidence of such symptoms. METHODS: We performed a retrospective review of 56 patients admitted with blunt head trauma who underwent audiovestibular evaluation within 1 month after injury. Two scales were used to measure the severity of trauma; these were the Glasgow Coma Scale (GCS) and the Head Abbreviated Injury Scale (H-AIS). Patients with sensorineural-type hearing loss, or dizziness with nystagmus, were considered to have inner ear symptoms. RESULTS: About half of all patients (45%) with blunt head trauma showed trauma-related inner ear symptoms. Patients with inner ear symptoms were significantly more likely to have H-AIS scores ≥4 than those without inner ear symptoms (p = 0.004), even without concomitant temporal bone fracture (p > 0.05). Also, patients with inner ear symptoms required a statistically significantly longer time (measured from admission) before undergoing their ontological evaluations than did those without such symptoms (p = 0.002), possibly due to prolonged bed rest and use of sedatives. CONCLUSION: Thus, detailed history-taking and early evaluation using trauma scales are essential for all patients suffering from severe head trauma. It may be necessary to initiate early treatment of traumatic inner ear diseases.
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Traumatismos Craniocerebrais , Orelha Interna , Perda Auditiva Neurossensorial , Escala Resumida de Ferimentos , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/epidemiologia , Escala de Coma de Glasgow , Humanos , Estudos RetrospectivosRESUMO
RING finger protein 6 (RNF6), a RING finger protein, has been identified as a potential tumor promoter in several cancers. However, the exact mechanism of RNF6 in cancer remains elusive. As in various diseases, RNF6 may be involved in regulating cell growth, cell proliferation, invasion, cell cycle progression, apoptosis and cell adhesion through E3 ligase-mediated ubiquitination. Thus, the research on RNF6 is mainly focused on the ubiquitination of RNF6 in recent years. This article summarizes the role of RNF6 ubiquitination in various physiological and pathological mechanisms, such as Akt/mTOR signaling pathway, Wnt/ß-catenin pathway, RNF6/ERα/Bcl-xL axis, and provides knowledge and understanding for the treatment of diseases.
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Carcinogênese/genética , Proteínas de Ligação a DNA/genética , Neoplasias/genética , Transcrição Gênica , Proliferação de Células/genética , Receptor alfa de Estrogênio/genética , Humanos , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética , Ubiquitinação/genética , Proteína bcl-X/genéticaRESUMO
BACKGROUND: Carbon monoxide poisoning (COP), resulting from accidental and intentional exposure, is a leading cause of fatal poisoning worldwide. Except for early death, neurological sequelae are common and impose a large burden on patients, caregivers, and the society. MATERIALS AND METHODS: This retrospective study included patients who visited the emergency departments (EDs) of the medical institutes of Chang Gung Memorial Hospital after COP with a carboxyhemoglobin level > 10% between January 2009 and October 2018. Patients who experienced out-of-hospital cardiac arrest (OHCA) were excluded. Poor outcome was defined as mortality or a Glasgow coma scale (GCS) <13 at discharge. Stepwise regression analysis was performed, and a receiver operating characteristic (ROC) curve was applied to analyze our newly created scoring system for prognosis prediction. RESULTS: This study enrolled 1171 patients. Fire scene (F) (aOR, 20.635; 95% CI, 8.345-51.023), intentional CO exposure (I) (aOR, 2.634; 95% CI, 1.335-5.196), respiratory failure (R) (aOR, 9.944; 95% CI, 5.533-17.873), every point of reduced GCS (E) (aOR, 1.253; 95% CI, 1.186-1.323), and diabetes mellitus (D) (aOR, 2.749; 95% CI, 1.201-6.292) were identified as predictors of poor outcomes. The FIRED score was created. CONCLUSION: The FIRED score could predict the outcomes of non-OHCA patients with a carboxyhemoglobin level > 10% after COP using five factors that can be obtained by history taking and basic examination. An FIRED score ≥ 10 was associated with a poor outcome (sensitivity, 89.6%; specificity, 82.4%; AUC0.930).
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Intoxicação por Monóxido de Carbono , Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/diagnóstico , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/análise , Escala de Coma de Glasgow , Humanos , Curva ROC , Estudos RetrospectivosRESUMO
During the last few decades, whole-cell biosensors have attracted increasing attention for their enormous potential in monitoring bioavailable heavy metal contaminations in the ecosystem. Visual and measurable output signals by employing natural pigments have been demonstrated to offer another potential choice to indicate the existence of bioavailable heavy metals in recent years. The biosynthesis of the blue pigment indigoidine has been achieved in E. coli following heterologous expression of both BpsA (a single-module non-ribosomal peptide synthetase) and PcpS (a PPTase to activate apo-BpsA). Moreover, we demonstrated herein the development of the indigoidine-based whole-cell biosensors to detect bioavailable Hg(II) and Pb(II) in water samples by employing metal-responsive transcriptional regulator MerR and PbrR as the sensory elements, and the indigoidine biosynthesis gene cluster as a reporter element. The resulting indigoidine-based biosensors presented a good selectivity and high sensitivity to target metal ions. High concentration of target metal exposure could be clearly recognized by the naked eye due to the color change by the secretion of indigoidine, and quantified by measuring the absorbance of the culture supernatants at 600 nm. Dose-response relationships existed between the exposure concentrations of target heavy metals and the production of indigoidine. Although fairly good linear relationships were obtained in a relatively limited concentration range of the concentrations of heavy metal ions, these findings suggest that genetically controlled indigoidine biosynthesis triggered by the MerR family transcriptional regulator can enable a sensitive, visual, and qualitative whole-cell biosensor for bioindicating the presence of bioaccessible heavy metal in environmental water samples. KEY POINTS: ⢠Biosynthesis pathway of indigoidine reconstructed in a high copy number plasmid in E. coli. ⢠Visual and colorimetric detection of Hg(II) and Pb(II) by manipulation of indigoidine biosynthesis through MerR family metalloregulator. â¢Enhanced detection sensitivity toward Hg(II) and Pb(II) achieved using novel pigment-based whole-cell biosensors.
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Técnicas Biossensoriais , Metais Pesados , Ecossistema , Escherichia coli/genética , PiperidonasRESUMO
Previous work has shown that the lignans from the twigs and leaves of Archidendron clypearia (Jack) I.C.N. possess anti-ß-amyloid aggregation activity. Here we report a new dilignan, archidendronin A (1), along with one known sesquilignan (2). Their structures were determined by extensive spectroscopic methods, including UV, HRESIMS, 1 D and 2 D NMR data. The inhibitory activity on Aß1-42 aggregation was screened by ThT assay with curcumin as the positive control, and compounds 1 and 2 showed inhibition rate of 60.0% and 64.4% at 20 µM, respectively.[Formula: see text].
Assuntos
Fabaceae , Lignanas , Estrutura Molecular , Extratos Vegetais , Folhas de PlantaRESUMO
Cadmium (Cd) pollution has become a global environmental issue because Cd gets easily accumulated and translocated in the food chain, threatening human health. Considering the detrimental effects and non-biodegradability of environmental Cd, this is an urgent issue that needs to be addressed through the development of robust, cost-effective, and eco-friendly green routes for monitoring and remediating toxic levels of Cd. This article attempts to review various bacterial approaches toward biosensing and bioremediation of Cd in the environment. This review focuses on the recent development of bacterial cell-based biosensors for the detection of bioavailable Cd and the bioremediation of toxic Cd by natural or genetically-engineered bacteria. The present limitations and future perspectives of these available bacterial approaches are outlined. New trends for integrating synthetic biology and metabolic engineering into the design of bacterial biosensors and bioadsorbers are additionally highlighted.
Assuntos
Bactérias/metabolismo , Cádmio/análise , Bactérias/genética , Biodegradação Ambiental , Técnicas Biossensoriais , Engenharia GenéticaRESUMO
BACKGROUND AND OBJECTIVES: Acute acalculous cholecystitis (AAC) often occurs in critically ill patients, especially in those that have experienced trauma, surgery, shock, and prolonged fasting. Early enteral nutrition has been shown to significantly reduce morbidity and mortality compared to other nutritional support strategies. The purpose of this study was to evaluate the effect of early enteral nutrition on the incidence of AAC among trauma patients. METHODS AND STUDY DESIGN: Multi-strategy nutritional protocol was implemented in the intensive care unit (ICU) in 2016 for early enteral nutrition and proper nutritional support. The traumatized critically-ill patients without volitional intake who were admitted to ICU between 2015 and 2017 were included. Basic characteristics, duration of fasting, and the incidence of percutaneous cholecystostomy (PC) due to AAC were analyzed according to the year. RESULTS: Enteral nutrition was indicated in 552 trauma patients (28.2%). The mean duration of fasting was shortened from 6.5 days in 2015 to 5.4 days in 2017 (p=0.202). The incidence of PC was significantly decreased from 2015 to 2017 [6/171 (3.5%) vs. 6/204 (2.9%) vs. 0/177 (0%), p=0.023]. The provision of central parenteral nutrition (p=0.001) and fasting over 7 days (p=0.014) proved to be a risk factor of AAC. CONCLUSIONS: This study showed that the incidence of PC due to AAC was decreased significantly after the implementation of a nutritional protocol among traumatized critically ill patients. Early enteral nutrition may be effective in reducing the AAC among trauma patients who are at high risk of AAC.
Assuntos
Colecistite Acalculosa/prevenção & controle , Colecistostomia/estatística & dados numéricos , Nutrição Enteral , Adulto , Idoso , Estado Terminal , Feminino , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Ferimentos e LesõesRESUMO
BACKGROUND: FOXD3 is aberrantly regulated in several tumors, but its underlying mechanisms in ovarian cancer (OC) remains largely unknown. The present study aimed to explore the role and associated mechanisms of FOXD3 in OC. METHODS: Microarray data from GEO was used to analyze differential CpG sites and differentially methylated regions (DMR) in tumor tissues and Illumina 450 genome-wide methylation data was employed. The FOXD3 expression level was determined through qRT-PCR and western blot analysis. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, proliferation abilities, cell cycle and cell apoptosis, respectively. Finally, the effect of FOXD3 on tumor growth was investigated through in vivo xenograft experiments. RESULTS: GEO data analysis showed that FOXD3 was hypermethylated in OC tissues. Also, qRT-PCR revealed that FOXD3 was low expressed and methylation-specific PCR (MSP) confirmed that the methylation level of FOXD3 was hypermethylated. Combined treatment of 5-aza-2'-deoxycytidine (5-Aza-dC) could synergistically restored FOXD3 expression. Finally, in vitro and in vivo experiments showed that demethylated FOXD3 decreased cell proliferation and migration abilities, and increased the cell apoptosis. In vivo experiment detected that demethylated FOXD3 restrained tumor growth. CONCLUSIONS: FOXD3 could act as a tumor suppressor to inhibit cell proliferation, migration and promote cell apoptosis in OC cells.
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OBJECTIVES: An efficient bacterial surface display system based on the anchoring motif derived from Escherichia coli (E. coli) outer membrane protease OmpT was developed in this study. RESULTS: Referring to the classical Lpp-OmpA (LOA) display system, the signal peptide and nine amino acids of mature Lpp were fused to the transmembrane domain comprising five ß-strands of truncated OmpT to generate a novel Lpp-OmpT (LOT) display system. The C-terminal fusion strategy was used to fuse a small peptide (His tag) and red fluorescent protein (mCherry) to the C-terminus of LOT. Cell surface exposure of His tag and mCherry were compared between the LOA and LOT display systems. E. coli expressing LOT-His tag adsorbed more Cu2+ than E. coli expressing LOA-His tag. E. coli expressing both LOT-mCherry-His tag and LOA-mCherry-His tag adhered to Cu2+ chelating sepharose beads, and adhered cells could be dissociated from the beads after excess Cu2+ treatment. More importantly, compared with the LOA system, a higher amount of LOT-mCherry-His tag hybrid protein was demonstrated to be localized at the outer membrane by both fluorescence spectrophotometric determination of cell fractions and cell-surface immunofluorescence assay. CONCLUSIONS: These results suggest that genetically modified OmpT can be used as a potential anchoring motif to efficiently and stably display polypeptides and proteins, and that the LOT system could be used in a variety of biotechnological and industrial processes.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Técnicas de Visualização da Superfície Celular/métodos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Engenharia Metabólica/métodosRESUMO
BACKGROUND: To determine the most appropriate pancreatic drainage method, by investigating differences in 12-month clinical outcomes in patients implanted with external and internal pancreatic stents as an extension to a previous study on short-term outcome. METHODS: This prospective randomized controlled trial enrolled 213 patients who underwent pancreaticoduodenectomy with duct to mucosa pancreaticojejunostomy between August 2010 and January 2014 (NCT01023594). Of the 185 patients followed-up for 12 months, 97 underwent external and 88 underwent internal stenting. Their long-term clinical outcomes were compared. RESULTS: Overall late complication rates were similar in the external and internal stent groups (P = 0.621). The percentage of patients with >50% atrophy of the remnant pancreatic volume after 12 months was similar in both groups (P = 0.580). Factors associated with pancreatic exocrine or endocrine function, including stool elastase level (P = 0.571) and rate of new-onset diabetes (P = 0.179), were also comparable. There were no significant between-group differences in quality of life, as evaluated by the EORTC QLQ-C30 and QLQ PAN26 questionnaires. CONCLUSION: External and internal stents showed comparable long-term, as well as short-term clinical outcomes, including late complication rates, preservation of pancreatic duct diameters, pancreatic volume changes with functional derangements, and quality of life after surgery.
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Neoplasias do Sistema Digestório/cirurgia , Drenagem/instrumentação , Pancreaticoduodenectomia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Digestório/diagnóstico por imagem , Neoplasias do Sistema Digestório/patologia , Drenagem/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Desenho de Prótese , Qualidade de Vida , Fatores de Risco , Seul , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS: Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy. METHODS: The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPß, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis. RESULTS: At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn't statistically significant difference between the SHR and intervention groups. Staining with Masson's trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPß expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks. CONCLUSION: This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPß/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy.
Assuntos
Atorvastatina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/patologia , Transdução de Sinais/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Atorvastatina/uso terapêutico , Fator Natriurético Atrial/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Ecocardiografia , Hipertensão/complicações , Hipertrofia/diagnóstico por imagem , Hipertrofia/tratamento farmacológico , Hipertrofia/etiologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Proteína Desacopladora 3/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Various anthropometric indices can be used to estimate obesity, and it is important to determine which one is the best in predicting the risk of coronary heart disease (CHD) and to define the optimal cut-off point for the best index. METHODS: This cross-sectional study investigated a consecutive sample of 11,247 adults, who had lived in rural areas of China and were older than 35 years of age. Eight obesity indices, including the body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), abdominal volume index (AVI), body adiposity index (BAI), body roundness index (BRI) and a body shape index (ABSI) were investigated. The risk of CHD was evaluated by the 10-year coronary event risk (Framingham risk score). Receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive ability of the obesity indices for CHD risk. RESULTS: Of the whole population, 3636 (32.32%) participants had a risk score higher than 10%. Those who suffered medium or high CHD risk were more likely to have higher mean anthropometric indices, except for BMI in males. In the multivariate-adjusted logistic regression, all these anthropometric measurements were statistically associated with CHD risk in males. After adjusting for all the possible confounders, these anthropometric measurements, except for ABSI, remained as independent indicators of CHD risk in females. According to the ROC analyses, ABSI provided the largest area under the curve (AUC) value in males, and BMI showed the lowest AUC value, with AUC varying from 0.52 to 0.60. WHtR and BRI provided the largest AUC value in female, and similarly, BMI showed the lowest AUC value, with AUC varying from 0.59 to 0.70. The optimal cut-off values were as follows: WHtR (females: 0.54), BRI (females: 4.21), and ABSI (males: 0.078). CONCLUSIONS: ABSI was the best anthropometric index for estimating CHD risk in males, and WHtR and BRI were the best indicators in females. Males should maintain an ABSI of less than 0.078, and females should maintain a WHtR of less than 0.54 or a BRI of less than 4.21.
Assuntos
Antropometria/métodos , Doença das Coronárias/epidemiologia , Obesidade/diagnóstico , Adulto , Área Sob a Curva , Distribuição de Qui-Quadrado , China/epidemiologia , Doença das Coronárias/diagnóstico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Saúde da População Rural , Fatores SexuaisRESUMO
BACKGROUND: Despite current interest in the unfavorable impact of nontraditional lipid profiles on cardiovascular disease, information regarding its relations to abnormal left ventricular (LV) geometry has not been systemically elucidated. This study sought to understand predictive implication of nontraditional lipid profiles in specific LV geometric patterns in the general population of rural China. METHODS: Analyses were based upon a cross-sectional study of 10,756 participants (mean age 53.8 years; 54.0% females) who underwent assessment of biochemical, anthropometric, and blood pressure variables in rural areas of China. Participants were classified into four groups of LV morphologic pattern according to left ventricular mass index (LVMI) and relative wall thickness with quantitative echocardiographic data. RESULTS: By multivariable-adjusted linear regression models, nontraditional lipid profiles were positive determinants of concentricity index and LV wall thickness (all P < 0.05), with modest effects on LVMI. Non-high-density lipoprotein cholesterol (non-HDL-C) emerged as an independent correlate of concentric LV hypertrophy (LVH) (adjusted odds ratio [OR]: 1.174 per 1 SD increment in non-HDL-C, 95% confidence interval [CI]: 1.075-1.281), followed by low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (1.158 [1.059-1.266]), total cholesterol (TC)/HDL-C ratio (1.150 [1.050-1.260]), and triglyceride (TG)/HDL-C ratio (1.134 [1.030-1.249]). The ORs for concentric LVH by tertiles further provided insight into that excess risk was associated with the highest tertile of nontraditional lipid profiles. The areas under the ROC curves to predict concentric LVH were statistically identical among nontraditional lipid parameters. CONCLUSION: Nontraditional lipid profiles, easily measured in the everyday routine examination, were responsible for increased risk of concentric LVH, potentially providing enhanced clinical utility at no additional cost, which emphasized the beneficial effect of these markers to supplement and improve CVD risk stratification.
Assuntos
Dislipidemias/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Lipídeos/sangue , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Saúde da População RuralRESUMO
BACKGROUND: The trilobed flap is a useful repair option for distal nasal defects. In certain cases, however, the placement of its quaternary defect may risk compression of the internal nasal valve or induction of ectropion. In this study, we propose a modified design of the trilobed flap, which uses unequal external interlobe angles. OBJECTIVE: To present the design principles and results of our modified trilobed flap for the reconstruction of difficult distal nasal Mohs defects. MATERIALS AND METHODS: Mohs defects of 26 patients were reconstructed (21 with long-term follow-up) using our modified trilobed flap over 1 year. Two independent masked raters graded postoperative photographs for alar symmetry and overall cosmesis. RESULTS: Median alar symmetry scores were excellent and overall cosmesis grades were between excellent and very good. CONCLUSION: The modified trilobed flap with unequal external angles offers an excellent option for reconstruction of Mohs defect of the distal nose that may not be well-suited for other repairs. Over 1 year, 21 modified trilobed repairs were performed with overall excellent outcomes.