RESUMO
Frailty is a dynamic condition encompassing physical, psychological, and social domains. While certain factors are associated with overall or specific frailty domains, research on the correlations between physical, psychological, and social frailty is lacking. This study aims to investigate the associations between physical, psychological, and social frailty in European older adults. The study involved 1781 older adults from the Urban Health Centres Europe project. Baseline and 1-year follow-up data were collected on physical, psychological, and social frailty, along with covariates. Linear regression analyzed unidirectional associations, while cross-lagged panel modeling assessed bi-directional associations. Participants' mean age was 79.57 years (SD = 5.54) and over half were female (61.0%). Physical and psychological frailty showed bi-directional association (effect of physical frailty at baseline on psychological frailty at follow-up: ß = 0.14, 95%CI 0.09, 0.19; reversed direction: ß = 0.05, 95%CI 0.01, 0.09). Higher physical frailty correlated with increased social frailty (ß = 0.05, 95%CI 0.01, 0.68), but no association was found between social and psychological frailty. This longitudinal study found a reciprocal relationship between physical and psychological frailty in older adults. A relatively higher level of physical frailty was associated with a higher level of social frailty. There was no association between social and psychological frailty. These findings underscore the multifaceted interplay between various domains of frailty. Public health professionals should recognize the implications of these interconnections while crafting personalized prevention and care strategies. Further research is needed to confirm these findings and investigate underlying mechanisms.
Assuntos
Idoso Fragilizado , Fragilidade , Vida Independente , Humanos , Idoso , Feminino , Masculino , Estudos Longitudinais , Europa (Continente)/epidemiologia , Idoso de 80 Anos ou mais , Idoso Fragilizado/psicologia , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Fragilidade/psicologia , Avaliação GeriátricaRESUMO
BACKGROUND: Polypharmacy can be defined as using five or more medications simultaneously. "Medication-related problems", an extension of polypharmacy, includes inappropriate prescribing, poor adherence, overdosage, underdosage, inappropriate drug selection, inadequate monitoring, adverse drug effects, and drug interactions. Polypharmacy and the high risk of medication-related problems among older people are associated with adverse health consequences due to drug-drug interactions, drug-disease interactions, and adverse drug effects. This study aims to assess the factors associated with polypharmacy and the high risk of medication-related problems among community-dwelling older people in the Netherlands, Greece, Croatia, Spain, United Kingdom. METHOD: This longitudinal study used baseline and follow-up data from 1791 participants of the Urban Health Center European project. Polypharmacy and the risk of medication-related problems were evaluated at baseline and follow-up using the Medication Risk Questionnaire. We studied factors in the domains (a) sociodemographic characteristics, (b) lifestyle and nutrition, and (c) health and health care use. Hierarchical logistic regression analyses were used to examine the factors associated with polypharmacy and the high risk of medication-related problems. RESULTS: Mean age was 79.6 years (SD ± 5.6 years); 60.8% were women; 45.2% had polypharmacy, and 41.8% had a high risk of medication-related problems. Women participants had lower odds of polypharmacy (OR = 0.55;95%CI:0.42-0.72) and a high risk of medication-related problems (OR = 0.50; 95%CI:0.39-0.65). Participants with a migration background (OR = 1.67;95%CI:1.08-2.59), overweight (OR = 1.37; 95%CI:1.04-1.79) and obesity (OR = 1.78;95%CI:1.26-2.51) compared to 'normal weight', with lower physical HRQoL (OR = 0.96, 95%CI:0.95-0.98), multi-morbidity (OR = 3.73, 95%CI:2.18-6.37), frailty (OR = 1.69, 95%CI:1.24-2.30), visited outpatient services (OR = 1.77, 95%CI: 1.09-2.88) had higher odds of polypharmacy. The associations with the high risk of medication-related problems were similar. CONCLUSIONS: Multiple factors in demography, lifestyle, nutrition, and health care use are associated with polypharmacy and the high risk of medication-related problems. Polypharmacy is a single element that may reflect the number of medications taken. The broader content of medication-related problems should be considered to assess the context of medication use among older people comprehensively. These provide starting points to improve interventions to reduce polypharmacy and high risk of medication-related problems. In the meantime, health professionals can apply these insights to identify subgroups of patients at a high risk of polypharmacy and medication-related problems. TRIAL REGISTRATION: The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Polimedicação , Humanos , Feminino , Idoso , Masculino , Vida Independente , Estudos Longitudinais , Europa (Continente)/epidemiologia , Prescrição Inadequada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
BACKGROUND: Frailty is an age-related condition resulting in a state of increased vulnerability regarding functioning across multiple systems. It is a multidimensional concept referring to physical, psychological and social domains. The purpose of this study is to identify factors (demographic characteristics, lifestyle factors and health indicators) associated with overall frailty and physical, psychological and social frailty in community-dwelling older people from five European countries. METHODS: This cross-sectional study used baseline data from 2289 participants of the Urban Health Center European project in five European countries. Multivariable logistic regression models were used to assess associations of the factors with overall frailty and the three frailty domains. RESULTS: The mean age was 79.7 (SD = 5.7). Participants who were older, were female, had secondary or equivalent education, lived alone, not at risk of alcohol use, were less physically active, had multi-morbidity, were malnourished or with a higher level of medication risk, had higher odds of overall frailty (all P < 0.05). Age was not associated with psychological and social frailty; sex was not associated with social frailty; smoking and migration background was not associated with overall frailty or any of its domains. There existed an interaction effect between sex and household composition regarding social frailty (P < 0.0003). CONCLUSIONS: The present study contributed new insights into the risk factors for frailty and its three domains (physical, psychological and social frailty). Nurses, physicians, public health professionals and policymakers should be aware of the risk factors of each type of frailty. Furthermore, examine these risk factors more comprehensively and consider overall frailty as well as its three domains in order to further contribute to decision-making more precisely on the prevention and management of frailty. TRIAL REGISTRATION: The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952 . The date of registration is 13/03/2017.
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Fragilidade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Vida Independente , Saúde da População UrbanaRESUMO
Limbs originated from paired fish fins are an important innovation in Gnathostomata. Many studies have focused on limb development-related genes, of which the T-box transcription factor 4 gene (tbx4) has been considered as one of the most essential factors in the regulation of the hindlimb development. We previously confirmed pelvic fin loss in tbx4-knockout zebrafish. Here, we report a high-quality genome assembly of the Japanese eel (Anguilla japonica), which is an economically important fish without pelvic fins. The assembled genome is 1.13 Gb in size, with a scaffold N50 of 1.03 Mb. In addition, we collected 24 tbx4 sequences from 22 teleost fishes to explore the correlation between tbx4 and pelvic fin evolution. However, we observed complete exon structures of tbx4 in several pelvic-fin-loss species such as Ocean sunfish (Mola mola) and ricefield eel (Monopterus albus). More interestingly, an inversion of a special tbx4 gene cluster (brip1-tbx4-tbx2b- bcas3) occurred twice independently, which coincides with the presence of fin spines. A nonsynonymous mutation (M82L) was identified in the nuclear localization sequence (NLS) of the Japanese eel tbx4. We also examined variation and loss of hindlimb enhancer B (HLEB), which may account for pelvic fin loss in Tetraodontidae and Diodontidae. In summary, we generated a genome assembly of the Japanese eel, which provides a valuable genomic resource to study the evolution of fish tbx4 and helps elucidate the mechanism of pelvic fin loss in teleost fishes. Our comparative genomic studies, revealed for the first time a potential correlation between the tbx4 gene cluster and the evolutionary development of toxic fin spines. Because fin spines in teleosts are usually venoms, this tbx4 gene cluster may facilitate the genetic engineering of toxin-related marine drugs.
Assuntos
Anguilla/genética , Proteínas de Peixes/genética , Família Multigênica/genética , Proteínas com Domínio T/genética , Nadadeiras de Animais , Animais , Evolução Molecular , Feminino , Genoma , Genômica/métodos , Japão , Anotação de Sequência Molecular , Mutação , Filogenia , Alinhamento de Sequência , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Healthcare services worldwide are transforming themselves into value-based organizations. Integrated care is an important aspect of value-based healthcare (VBHC), but practical evidence-based recommendations for the successful implementation of integrated care within a VBHC context are lacking. This systematic review aims to identify how value-based integrated care (VBIC) is defined in literature, and to summarize the literature regarding the effects of VBIC, and the facilitators and barriers for its implementation. METHODS: Embase, Medline ALL, Web of Science Core Collection, and Cochrane Central Register of Controlled Trails databases were searched from inception until January 2022. Empirical studies that implemented and evaluated an integrated care intervention within a VBHC context were included. Non-empirical studies were included if they described either a definition of VBIC or facilitators and barriers for its implementation. Theoretical articles and articles without an available full text were excluded. All included articles were analysed qualitatively. The Rainbow Model of Integrated Care (RMIC) was used to analyse the VBIC interventions. The quality of the articles was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: After screening 1328 titles/abstract and 485 full-text articles, 24 articles were included. No articles were excluded based on quality. One article provided a definition of VBIC. Eleven studies reported-mostly positive- effects of VBIC, on clinical outcomes, patient-reported outcomes, and healthcare utilization. Nineteen studies reported facilitators and barriers for the implementation of VBIC; factors related to reimbursement and information technology (IT) infrastructure were reported most frequently. CONCLUSION: The concept of VBIC is not well defined. The effect of VBIC seems promising, but the exact interpretation of effect evaluations is challenged by the precedence of multicomponent interventions, multiple testing and generalizability issues. For successful implementation of VBIC, it is imperative that healthcare organizations consider investing in adequate IT infrastructure and new reimbursement models. Systematic Review Registration: PROSPERO (CRD42021259025).
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Prestação Integrada de Cuidados de Saúde , Prestação Integrada de Cuidados de Saúde/organização & administração , HumanosRESUMO
This study aimed to identify the factors associated with health-related quality of life (HRQOL) among community-dwelling older adults. Physical and mental HRQOL were measured by the 12-item Short Form Health Survey (SF-12) at baseline and follow-up. Linear regression models were used to evaluate associations between socio-demographic, health, and lifestyle factors and HRQOL. The sample included 661 participants (mean age = 77.4 years). Frailty was negatively associated with physical HRQOL (B = - 5.56; P < 0.001) and mental HRQOL (B = - 6.65; P < 0.001). Participants with a higher score on activities of daily living (ADL) limitations had lower physical HRQOL (B = - 0.63; P < 0.001) and mental HRQOL (B = - 0.18; P = 0.001). Female sex (B = - 2.38; P < 0.001), multi-morbidity (B = - 2.59; P = 0.001), and a high risk of medication-related problems (B = - 2.84; P < 0.001) were associated with lower physical HRQOL, and loneliness (B = - 3.64; P < 0.001) with lower mental HRQOL. In contrast, higher age (B = 2.07; P = 0.011) and living alone (B = 3.43; P < 0.001) were associated with better mental HRQOL in the multivariate models. Future interventions could be tailored to subpopulations with relatively poor self-reported HRQOL, such as frail or lonely older adults to improve their HRQOL.
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Atividades Cotidianas , Vida Independente , Qualidade de Vida , Humanos , Feminino , Idoso , Masculino , Vida Independente/psicologia , Idoso de 80 Anos ou mais , Fragilidade/psicologia , Solidão/psicologia , Idoso Fragilizado/psicologia , Nível de SaúdeRESUMO
A simple anaerobic upflow column system (15 cm long, 5 cm inner diameter) for complete pentachlorophenol (PCP) mineralization has been established using a microbial consortium requiring only lactate as the external nutrient. With lactate as an electron donor, PCP was dechlorinated to 3-chlorophenol (3-CP) and phenol. The degradation of 3-CP and phenol proceeded without an external electron acceptor, indicating fermentative or syntrophic characteristics. A tracer experiment using (14)C-U-ring-labeled PCP confirmed the conversion of PCP into CO(2) (54.1%), CH(4) (48.1%), and biomass (0.6%). The nitrogen required for degradation was supplied by N(2)-fixation, evidenced from the nitrogen balance and an acetylene reduction assay. A 16S rRNA gene library analysis showed that bottom of the upflow column harbored the potential dechlorinators, Dehalobacter and Desulfitobacterium, and the phenol/3-CP fermentative or syntrophic degraders, Cryptanaerobacter and Syntrophus. The nitrogen-fixing facultative anaerobes, Rhizobiales, were detected in the top of the upflow column, with other possible nitrogen-fixers at both bottom and top of the upflow column. The mineralization rate reached 1.96 µmoles L(-1) d(-1) for 50 µM of the initial PCP concentration: one of the highest efficiencies reported. This compact anaerobic mineralization system requiring no external supply of an electron acceptor would be useful for the remediation of chlorinated aromatic compounds under anaerobic conditions.
Assuntos
Recuperação e Remediação Ambiental/métodos , Ácido Láctico/farmacologia , Minerais/metabolismo , Pentaclorofenol/metabolismo , Anaerobiose/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Sequência de Bases , Técnicas de Cultura Celular por Lotes , Biodegradação Ambiental/efeitos dos fármacos , Biomassa , Reatores Biológicos/microbiologia , Carbono/análise , Isótopos de Carbono , Clorofenóis/metabolismo , Dados de Sequência Molecular , Nitrogênio/análise , Filogenia , Porosidade , RNA Ribossômico 16S/genética , Reologia/efeitos dos fármacos , Fatores de Tempo , Eliminação de Resíduos LíquidosRESUMO
miRNA is considered a novel biomarker for cancer diagnosis and due to its low level in vivo, the development of new detection methods for it has become a research hotspot in recent years. Here, we firstly found that miR-625-5p was significantly upregulated in colorectal cancer tissues by means of differential expression analysis of the dbDEMC database and clinical validation. Subsequently, it was found that miR-625-5p promoted cell proliferation and migration but inhibited apoptosis through phenotypic experiments; thus, we initially identified miR-625-5p as a potential biomarker for colorectal cancer. Moreover, in order to monitor slight changes in the miR-625-5p level, we developed a novel detection method for it based on strand displacement amplification (SDA). In this system, a hairpin was designed to recognize and pair with miR-625-5p, which was used as a primer to initiate SDA, and a large number of complementary DNAs were generated via cyclic amplification, followed by the addition of SYBR Gold to achieve quantitative analysis of miR-625-5p. Moreover, this method showed a good response to miR-625-5p with a detection limit of 8.6 pM and a dynamic range of 0.01 to 200 nM, and the specificity of it was verified using a set of other miRNAs as an interference. Finally, we set up different concentrations of biologic samples for detection to verify the practicability of the method. The results of this study indicate that this detection method has great potential in clinical diagnosis.
Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Biomarcadores Tumorais , MicroRNAs/metabolismo , DNA Complementar , Apoptose , Neoplasias Colorretais/diagnósticoRESUMO
Colorectal cancer (CRC) becomes the second leading cause of cancer-related deaths in 2020. Emerging studies have indicated that microRNAs (miRNAs) play a key role in tumorigenesis and progression. The dysfunctions of miR-455-3p are observed in many cancers. However, its biological function in CRC remains to be confirmed. By sequencing serum sample, miR-455-3p was found to be up-regulated in CRC patients. RT-qPCR demonstrated that the miR-455-3p expression was both higher in the serum and tumor tissues of CRC patients. Furthermore, it indicated that miR-455-3p had the ability in promoting cell proliferation, suppressing cell apoptosis, and stimulating cell migration. In vivo experiments also showed that miR-455-3p promoted tumor growth. Additionally, H2AFZ was proved as the direct gene target of miR-455-3p by dual-luciferase assay. Taken together, miR-455-3p functioned as a tumor promoter in CRC development by regulating H2AFZ directly. Thus, it has enormous potential as a biomarker in the diagnosis of CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Neoplasias Colorretais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Apoptose/genética , Carcinogênese/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Studies revealed unidirectional associations between frailty and medication-related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi-directional association between frailty and the risk of MRPs in community-dwelling older adults in five European countries. METHODS: Participants were 1785 older adults in the population-based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one-year follow-up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross-lagged panel modeling was used to assess bi-directional associations. RESULTS: The unidirectional association between frailty at baseline and the risk of MRPs at follow-up remained statistically significant after adjusting for covariates (ß = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow-up shows similar trends. The bi-directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow-up than reversed path (Wald test for comparing lagged effects: p < 0.05). CONCLUSION: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways.
Assuntos
Fragilidade , Humanos , Idoso , Fragilidade/epidemiologia , Vida Independente , Estudos Longitudinais , Idoso Fragilizado , Europa (Continente)/epidemiologia , Avaliação GeriátricaRESUMO
Introduction: We aimed to assess the associated factors for adolescent depression, problem behavior and cognitive level in China. Methods: A total of 2,584 adolescents aged from 10 to 15 years old in 2018 were included for analyses. Information on a comprehensive set of potential determinants was collected by the questionnaire, including demographic, health-, school- and family-related factors. Differences in average scores of depression, problem behavior, and cognitive level across subgroups were assessed by two independent sample t-tests and one-way analysis of variance (ANOVA). The clinical relevance among subgroups was assessed by the effect size. Multivariate linear regression models were applied to identify the statistically significant determinants. Results: School-related factors and parental depressive status were strongly associated with depression. Low maternal education, poor/bad health of adolescents, high academic pressure, and parental depression were significantly associated with behavior problems. The socioeconomic factors, poor academic performance and father's depression were significantly associated with adolescent cognitive level. Discussion: Multiple associated factors were identified for depression, problem behavior, and cognition of Chinese adolescents, which will provide insights into developing more targeted public health policies and interventions to improve their mental health.
RESUMO
Background: Falls are a leading cause of disability. Previous studies have identified various risk factors for falls. However, contemporary novel research is needed to explore these and other factors associated with falls among a diverse older adult population. This study aims to identify the factors associated with falls among hospitalized and community-dwelling older adults. Methods: Cross-sectional data from the 'Appropriate care paths for frail elderly people: a comprehensive model' (APPCARE) study were analyzed. The study sample consisted of hospitalized and community-dwelling older adults. Falling was assessed by asking whether the participant had fallen within the last 12 months. Multivariable logistic regression models were used to evaluate associations between socio-demographic characteristics, potential fall risk factors and falls. Results: The sample included 113 hospitalized (mean age = 84.2 years; 58% female) and 777 community-dwelling (mean age = 77.8 years; 49% female) older adults. Among hospitalized older adults, loneliness was associated with an increased risk of falls. Associations between female sex, secondary education lever or lower, multimorbidity, a higher score on limitations with activities of daily living (ADL), high risk of malnutrition and falling were found among community-dwelling participants. Conclusion: The results of this study confirm the multi-factorial nature of falling and the complex interaction of risk factors. Future fall prevention programs could be tailored to the needs of vulnerable subpopulations at high risk for falls.
Assuntos
Acidentes por Quedas , Vida Independente , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Acidentes por Quedas/prevenção & controle , Atividades Cotidianas , Estudos Transversais , Idoso FragilizadoRESUMO
BACKGROUND: Insufficient sleep duration among university students was commonly associated with many detrimental effects. University students experience substantial environmental and psychological changes. Female and male university students may differ in many spheres. However, most research on sleep duration of university students is based on an aggregate sample rather than digging the sex-specific profiles. The objective of this study is to examine potential sex differences in the correlates of sleep duration and explore the underlying mechanism of correlations. METHODS: This is a large-scale university-based mental health survey, which was conducted in university students in Qinghai Province in Northwest China in December 2019. A multi-stage logistic regression was separately fitted by sex to examine the factors associated with short sleep duration in university students. RESULTS: A total of 5,552 university students with an average sleep duration of 6.88 h (SDâ¯=â¯1.04) were included, among which 35.0% of the participants may currently be sleeping less than the optimal duration. Female students (6.84 h, SDâ¯=â¯1.00) slept shorter than males (6.94 h, SDâ¯=â¯1.09). The only parallel between sexes was that both female and male students with 3-5 times weekly breakfast were less likely to have short sleep duration. Adjusting for depressive symptoms in the following step eliminated the association between anxiety symptoms and short sleep duration in the model for female students. Female-specific associated factors with short sleep duration were age, grade, academic pressure, weekly physical exercise, depressive symptoms. Male-specific characteristics were current smoking tobacco cigarette, self-perceived health, duration of daily Internet use. CONCLUSION: Characteristic profiles of sleep duration differed between female and male university students; only a few male-specific factors were identified. Psychological guidance and education courses as well as other interventions to improve university students' sleep and related health should be designed and implemented based on sex differences.
Assuntos
Caracteres Sexuais , Universidades , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Sono , Estudantes , Inquéritos e QuestionáriosRESUMO
Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid-leucine-arginine sequence-contained chemokines CXCs (ELR+ CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block CXCLs/CXCR2 axis, and are widely used in regulating immune cell migration, tumor metastasis, apoptosis and angiogenesis. Herein, two series of new CXCR2 small-molecule inhibitors, including 1,2,4-triazol-3-one derivatives 1-11 and pyridazinone derivatives 12-22 were designed and synthesized based on the proof-to-concept. The pyridazinone derivative 18 exhibited good CXCR2 antagonistic activity (69.4 ± 10.5 %Inh at 10 µM) and demonstrated its significant anticancer metastasis activity in MDA-MB-231 cells and remarkable anti-angiogenesis activity in HUVECs. Furthermore, noteworthy was that 18 exhibited an obvious synergistic effect with Sorafenib in anti-proliferation assay in MDA-MB-231 cells. Moreover, 18 showed a distinct reduction of the phosphorylation levels of both PI3K and AKT proteins in MDA-MB-231 cells, and also affected the expression levels of other PI3K/AKT signaling pathway-associated proteins. The molecular docking studies of 18 with CXCR2 also verified the rationality of our design strategy. All of these results revealed pyridazinone derivative 18 as a promising CXCR2 antagonist for future cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Piridazinas/farmacologia , Receptores de Interleucina-8B/antagonistas & inibidores , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Piridazinas/síntese química , Piridazinas/química , Receptores de Interleucina-8B/metabolismo , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
Multi-microRNA (miRNA) detection would greatly facilitate early diagnosis of colorectal cancer (CRC). Here a convenient cascade isothermal amplification approach incorporating a G-quadruplex molecular beacon (G4MB) was established for achieving one-pot detection of multiple CRC miRNAs (miRNA-21, miRNA-92a, miRNA-31); this strategy incorporated a Bsu DNA polymerase (Bsu pol)-induced strand-displacement reaction and a Lambda exonuclease (λexo)-aided recycling reaction. In the presence of target miRNA, the G-rich stem structure was opened and became available for hybridization with the primer to initiate synthesis of Bsu pol-catalyzed double-stranded DNA (dsDNA) that displaced the miRNA target and released it, allowing it to participate in subsequent amplification cycles. Meanwhile, the dsDNA was gradually digested into fragments by λexo from the 5' phosphorylated end, releasing the newly synthesized DNA strand for participation in subsequent cycles that led to amplification of the fluorescent signal. This approach provided a low limit of detection (LOD) of zeptomolar-level, 85.8 zM, 77.6 zM, 78.9 zM for miRNA-21, miRNA-92a, miRNA-31, respectively. It could distinguish the mismatched targets and achieved three miRNA targets detection run in parallel in one-pot within 2 h. Thus, this fast, simple, and convenient strategy holds great promise as a clinical application for the detection of multiple miRNAs in clinical CRC samples.
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Técnicas Biossensoriais , MicroRNAs , Neoplasias , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico , Hibridização de Ácido NucleicoRESUMO
The purpose of this study was the enrichment and phylogenetic identification of bacteria that dechlorinate 4,5,6,7-tetrachlorophthalide (commercially designated "fthalide"), an effective fungicide for rice blast disease. Sequential transfer culture of a paddy soil with lactate and fthalide produced a soil-free enrichment culture (designated the "KFL culture") that dechlorinated fthalide by using hydrogen, which is produced from lactate. Phylogenetic analysis based on 16S rRNA genes revealed the dominance of two novel phylotypes of the genus Dehalobacter (FTH1 and FTH2) in the KFL culture. FTH1 and FTH2 disappeared during culture transfer in medium without fthalide and increased in abundance with the dechlorination of fthalide, indicating their growth dependence on the dechlorination of fthalide. Dehalobacter restrictus TEA is their closest relative, with 97.5% and 97.3% 16S rRNA gene similarities to FTH1 and FTH2, respectively.
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Benzofuranos/metabolismo , Peptococcaceae/isolamento & purificação , Peptococcaceae/metabolismo , Microbiologia do Solo , Biotransformação , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Genes de RNAr , Hidrogênio/metabolismo , Dados de Sequência Molecular , Peptococcaceae/classificação , Filogenia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Biodegradable plastics (BPs) were evaluated for their applicability as sustainable and solid H(2) donors for microbial reductive dechlorination of 4,5,6,7-tetrachlorophthalide (fthalide). After a screening test of several BPs, the starch-based plastic (SP) that produced the highest levels of H(2) was selected for its use as the sole H(2) donor in this reaction. Fthalide dechlorination was successfully accomplished by combining an H(2)-producing SP culture and a KFL culture containing Dehalobacter species, supplemented with 0.13% and 0.5% SP, respectively. The efficiency of H(2) use in dechlorination was evaluated in a combined culture containing the KFL culture and strain Clostridium sp. Ma13, a new isolate that produces H(2) from SP. Results obtained with this culture indicated increased H(2)-fraction for fthalide dechlorination much more in this culture than in compared with a KFL culture supplemented with 20mM lactate, which are 0.75 H(2)·glucose(-1) and 0.015 H(2)·lactate(-1) in mol ratio, respectively.
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Bactérias Anaeróbias/metabolismo , Benzofuranos/metabolismo , Hidrogênio/metabolismo , Plásticos/química , Clostridium , OxirreduçãoRESUMO
Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant on the market. It has been detected in various environmental samples, and a growing body of evidence has demonstrated its toxic effects on living organisms. In this study, we report the enrichment and phylogenetic identification of bacteria that debrominate TBBPA to bisphenol A in the presence of humin. Incubation experiments indicated that humin was required for this debromination activity. Of the five compounds examined for inclusion in the TBBPA-debrominating culture, formate was the optimal electron donor. A 16S rRNA gene library showed that the culture was dominated by three known dehalogenator genera: Dehalobacter, Geobacter, and Sulfurospirillum. Further investigation indicated that Dehalobacter was responsible for the debromination of TBBPA. PCR-denaturing gradient gel electrophoresis analysis showed that Dehalobacter grew in the culture by utilizing TBBPA. Moreover, the copy number of the Dehalobacter 16S rRNA genes increased by about two orders of magnitude in the cultures without the addition of TBBPA, whereas it increased by approximately four orders of magnitude when TBBPA was present. The incubation experiments showed that Dehalobacter was reliant on humin for its debromination activity, indicating a new type of metabolism in Dehalobacter that is linked to humin respiration.
Assuntos
Poluentes Ambientais/metabolismo , Retardadores de Chama/metabolismo , Substâncias Húmicas/análise , Peptococcaceae/metabolismo , Bifenil Polibromatos/metabolismo , Biodegradação Ambiental , Poluentes Ambientais/isolamento & purificação , Retardadores de Chama/isolamento & purificação , Halogenação , Peptococcaceae/genética , Filogenia , Bifenil Polibromatos/isolamento & purificação , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genéticaRESUMO
Two soil-free anaerobic dechlorinating cultures (3-CP and 35-DCP) were enriched from a pentachlorophenol (PCP)-to-phenol dechlorinating soil-dependent culture, using 3-chlorophenol (3-CP) and 3,5-dichlorophenol (3,5-DCP) as specific respective substrates, and characterized polyphasically. Physiological characterization indicated that the 3-CP and 35-DCP cultures had similar features, but with some variations. Both cultures utilized formate or acetate preferably as optimum electron donors for reductive dechlorination, and they shared similar patterns of dechlorination spectra for chlorophenols ranging from mono-CPs to a tetra-CP, with preferred dechlorination pathways in the ortho and meta positions. Alternative electron acceptors such as NO(3)(-) but not SO(4)(2-) inhibited the dechlorination activity in both cultures, while amorphous iron oxides (FeOOH) suppressed dechlorination activity only in the 35-DCP culture. Complete inhibition of dechlorination was observed in both cultures supplemented with chloramphenicol and vancomycin. The addition of 2-bromoethanesulfonate resulted in delayed dechlorination activity in the 35-DCP culture but not in the 3-CP culture; molybdate did not exert any inhibitory effect in either culture. Phylogenetic analysis based on 16S rRNA genes confirmed that the two cultures exhibited similar bacterial species but with varied responsible dechlorinators. Dehalobacter spp. were the likely dechlorinators in the 3-CP culture versus Sulfurospirillum spp. in the 35-DCP culture, with Clostridium and Clostridium-like spp. as candidate dechlorinators in both cultures.
Assuntos
Clorofenóis/metabolismo , Consórcios Microbianos , Ácidos Alcanossulfônicos/farmacologia , Bactérias Anaeróbias/classificação , Bactérias Anaeróbias/genética , Bactérias Anaeróbias/metabolismo , Elétrons , Pentaclorofenol/metabolismo , Filogenia , Microbiologia do SoloRESUMO
The dechlorination of polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins was examined in an enrichment culture (KFL culture) that contained two phylotypes of Dehalobacter, FTH1 and FTH2. The KFL culture dechlorinated 2,3,4,5-tetrachlorobiphenyl, 2,3,4-trichorobiphenyl (2,3,4-TriCB), and 1,2,3-trichlorodibenzo-p-dioxin (1,2,3-TriCDD). Quantitative real-time PCR targeting FTH1 and FTH2 revealed significant increases with the addition of PCBs and 1,2,3-TriCDD, suggesting halorespiring growth of the Dehalobacter species in the KFL culture. This study demonstrated the reductive dechlorination of PCBs and 1,2,3-TriCDD by Dehalobacter species in a sediment-free culture and a novel dechlorination pathway, the conversion of 2,3,4-TriCB to 4-monochlorobiphenyl via 3,4-dichlorobiphenyl.