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2.
Environ Geochem Health ; 46(10): 384, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167116

RESUMO

In recent times, biochar has emerged as a novel approach for environmental remediation due to its exceptional adsorption capacity, attributed to its porous structure formed by the pyrolysis of biomass at elevated temperatures in oxygen-restricted conditions. This characteristic has driven its widespread use in environmental remediation to remove pollutants. When biochar is introduced into ecosystems, it usually changes the makeup of microbial communities by offering a favorable habitat. Its porous structure creates a protective environment that shields them from external pressures. Consequently, microorganisms adhering to biochar surfaces exhibit increased resilience to environmental conditions, thereby enhancing their capacity to degrade pollutants. During this process, pollutants are broken down into smaller molecules through the collaborative efforts of biochar surface groups and microorganisms. Biochar is also often used in conjunction with composting techniques to enhance compost quality by improving aeration and serving as a carrier for slow-release fertilizers. The utilization of biochar to support sustainable agricultural practices and combat environmental contamination is a prominent area of current research. This study aims to examine the beneficial impacts of biochar application on the absorption and breakdown of contaminants in environmental and agricultural settings, offering insights into its optimization for enhanced efficacy.


Assuntos
Carvão Vegetal , Recuperação e Remediação Ambiental , Carvão Vegetal/química , Recuperação e Remediação Ambiental/métodos , Poluentes Ambientais/química , Adsorção , Agricultura/métodos , Biodegradação Ambiental , Compostagem/métodos
3.
Molecules ; 29(16)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39202952

RESUMO

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used around the world in both agricultural and non-agricultural fields due to its high activity. However, the heavy use of 2,4-D has resulted in serious environmental contamination, posing a significant risk to non-target organisms, including human beings. This has raised substantial concerns regarding its impact. In addition to agricultural use, accidental spills of 2,4-D can pose serious threats to human health and the ecosystem, emphasizing the importance of prompt pollution remediation. A variety of technologies have been developed to remove 2,4-D residues from the environment, such as incineration, adsorption, ozonation, photodegradation, the photo-Fenton process, and microbial degradation. Compared with traditional physical and chemical remediation methods, microorganisms are the most effective way to remediate 2,4-D pollution because of their rich species, wide distribution, and diverse metabolic pathways. Numerous studies demonstrate that the degradation of 2,4-D in the environment is primarily driven by enzymatic processes carried out by soil microorganisms. To date, a number of bacterial and fungal strains associated with 2,4-D biodegradation have been isolated, such as Sphingomonas, Pseudomonas, Cupriavidus, Achromobacter, Ochrobactrum, Mortierella, and Umbelopsis. Moreover, several key enzymes and genes responsible for 2,4-D biodegradation are also being identified. However, further in-depth research based on multi-omics is needed to elaborate their role in the evolution of novel catabolic pathways and the microbial degradation of 2,4-D. Here, this review provides a comprehensive analysis of recent progress on elucidating the degradation mechanisms of the herbicide 2,4-D, including the microbial strains responsible for its degradation, the enzymes participating in its degradation, and the associated genetic components. Furthermore, it explores the complex biochemical pathways and molecular mechanisms involved in the biodegradation of 2,4-D. In addition, molecular docking techniques are employed to identify crucial amino acids within an alpha-ketoglutarate-dependent 2,4-D dioxygenase that interacts with 2,4-D, thereby offering valuable insights that can inform the development of effective strategies for the biological remediation of this herbicide.


Assuntos
Ácido 2,4-Diclorofenoxiacético , Biodegradação Ambiental , Herbicidas , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/química , Herbicidas/metabolismo , Herbicidas/química , Bactérias/metabolismo , Bactérias/genética , Microbiologia do Solo , Fungos/metabolismo , Fungos/genética
4.
Front Oncol ; 14: 1421651, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39148902

RESUMO

Background: Body composition is recognized to be associated with clinical outcomes in patients with locally advanced rectal cancer (LARC). This study aimed to determine the prognostic role of regional adipose tissue distribution in patients with resectable LARC treated with or without neoadjuvant chemoradiotherapy (nCRT). Methods: This retrospective study included 281 consecutive patients who underwent radical surgery for LARC with or without preoperative nCRT between 2013 and 2019. Patients underwent contrast-enhanced CT scans before nCRT and before surgery. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and gluteal subcutaneous adipose tissue (gSAT) were quantified on the CT images. The association of adipose tissue distribution with progression-free survival (PFS) was analyzed using Cox proportional hazards analysis. Results: A total of 102 nCRT-treated and 179 primarily resected patients were included. During a median follow-up period of 24 months, 74 (26.3%) patients experienced local recurrence or metastasis. Multivariable analysis showed that VAT was associated with PFS in all patients (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.04-1.57; P = 0.021). This association was only maintained in primarily resected patients (HR 1.31, 95% CI 1.02-1.69; P = 0.037). For patients receiving preoperative nCRT, VAT was not significantly associated with PFS, while the dynamic change in gSAT (ΔgSAT) between nCRT and surgery was associated with PFS (HR 0.43, 95%CI 0.27-0.69, P = 0.001). Conclusion: Visceral obesity is an adverse prognostic factor in patients with resectable LARC treated by primary resection, while increased gluteal subcutaneous adiposity during preoperative nCRT may indicate favorable clinical outcomes.

5.
Emerg Microbes Infect ; 13(1): 2396875, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39178194

RESUMO

We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , SARS-CoV-2/imunologia , Estudos Retrospectivos , Masculino , Adulto , Feminino , Imunização Secundária , Pessoa de Meia-Idade , Inquéritos e Questionários , Vacinação , Idoso , Eficácia de Vacinas , Aerossóis , Adulto Jovem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia
6.
Chin Med J (Engl) ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030074

RESUMO

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (Ptrend = 0.011) and MCEs (Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction = 0.037). CONCLUSIONS: Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.

7.
Environ Geochem Health ; 46(9): 356, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083106

RESUMO

Acetochlor is a selective pre-emergent herbicide that is widely used to control annual grass and broadleaf weeds. However, due to its stable chemical structure, only a small portion of acetochlor exerts herbicidal activity in agricultural applications, while most of the excess remains on the surfaces of plants or enters ecosystems, such as soil and water bodies, causing harm to the environment and human health. In recent years, researchers have become increasingly focused on the repair of acetochlor residues. Compared with traditional physical and chemical remediation methods, microorganisms are the most effective way to remediate chemical pesticide pollution, such as acetochlor, because of their rich species, wide distribution, and diverse metabolic pathways. To date, researchers have isolated and identified many high-efficiency acetochlor-degrading strains, such as Pseudomonas oleovorans, Klebsiella variicola, Bacillus subtilus, Rhodococcus, and Methylobacillus, among others. The microbial degradation pathways of acetochlor include dechlorination, hydroxylation, N-dealkylation, C-dealkylation, and dehydrogenation. In addition, the microbial enzymes, including hydrolase (ChlH), debutoxylase (Dbo), and monooxygenase (MeaXY), responsible for acetochlor biodegradation are also being investigated. In this paper, we review the migration law of acetochlor in the environment, its toxicity to nontarget organisms, and the main metabolic methods. Moreover, we summarize the latest progress in the research on the microbial catabolism of acetochlor, including the efficient degradation of microbial resources, biodegradation metabolic pathways, and key enzymes for acetochlor degradation. At the end of the article, we highlight the existing problems in the current research on acetochlor biodegradation, provide new ideas for the remediation of acetochlor pollution in the environment, and propose future research directions.


Assuntos
Biodegradação Ambiental , Herbicidas , Toluidinas , Toluidinas/toxicidade , Toluidinas/metabolismo , Herbicidas/metabolismo , Herbicidas/toxicidade , Herbicidas/química , Bactérias/metabolismo , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Recuperação e Remediação Ambiental/métodos
8.
J Vasc Access ; : 11297298241251507, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38800939

RESUMO

AIM: The use of central venous catheters as hemodialysis vascular access is a major contributor to high bloodstream infection rate. In our dialysis unit in Shenzhen Guangdong Province China, we have developed and used our own dialysis catheter care protocol since May 2013 with good results. In this study, we would like to share our experience with the other units. METHODS: We have undertaken a 5-year retrospective analysis to determine our tunneled dialysis catheter-related blood stream infection rate by adding the number of infections divided by total number of catheter days × 1000. The results were compared with another study carried out in Henan Province China. Demographic data were summarized using descriptive statistics. Continuous and categorical variables were compared using t-test and χ2 test respectively. RESULTS: Between 2017 and 2021, a total of 216 tunneled dialysis catheters were managed by following our own dialysis access pathway and catheter care protocol. The tunneled dialysis catheter-related bloodstream infection rate was 0.0229 per 1000 catheter days in the 5-year period. CONCLUSION: Comparing with other published studies in China, our unit has achieved a very low rate of tunneled dialysis catheter-related bloodstream infection which has been sustained over time. This paper explores how our protocol and implementation might have contributed to the results.

9.
J Matern Fetal Neonatal Med ; 37(1): 2352089, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38812363

RESUMO

OBJECTIVE: Deep vein thrombosis (DVT) is a common complication in obstetrics that needs early interaction. The study examined the expression change and clinical value of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in DVT early diagnosis. METHODS: One hundred patients with DVT after delivery and 100 healthy parturients without DVT were enrolled. Serum samples were collected one day before delivery and received qRT-PCR for mRNA detection. Prenatal coagulation markers including prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (FIB) and thrombin time (TT), D-dimer (D-D), thrombomodulin (TM), and peroxidase anti-peroxidase soluble complex (PAP) were tested. The receiver operating characteristic (ROC) curve was drawn for the diagnostic value assessment. RESULTS: LncRNA CRNDE levels increased remarkably in the serum of DVT patients compared with the healthy controls, which were negatively correlated with serum concentration of PT, APTT, and TT while positively correlated with FIB, D-D, TM, and PAP. Serum CRNDE (HR = 5.973, 95% CI = 2.990-11.933, p < .001) was independently related to the occurrence of DVT after delivery. Then, ROC curve using serum CRNDE showed a good diagnostic value for DVT with the AUC of 0.899. ROC curve of ultrasonography combined with CRNDE produced an AUC of 0.968, and both sensitivity and specificity were enhanced compared to a single indicator. CONCLUSIONS: The increase of CRNDE level was an independent risk factor for postpartum DVT. Prenatal ultrasonography combined with CRNDE can improve the predictive efficacy for DVT.


Assuntos
Valor Preditivo dos Testes , RNA Longo não Codificante , Ultrassonografia Pré-Natal , Trombose Venosa , Humanos , Feminino , RNA Longo não Codificante/sangue , Gravidez , Adulto , Trombose Venosa/genética , Trombose Venosa/diagnóstico , Trombose Venosa/sangue , Estudos de Casos e Controles , Período Pós-Parto/sangue , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Biomarcadores/sangue , Curva ROC
10.
J Biol Chem ; 300(6): 107376, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38762176

RESUMO

Liver fibrosis/cirrhosis is a pathological state caused by excessive extracellular matrix deposition. Sustained activation of hepatic stellate cells (HSC) is the predominant cause of liver fibrosis, but the detailed mechanism is far from clear. In this study, we found that long noncoding RNA Fendrr is exclusively increased in hepatocytes in the murine model of CCl4- and bile duct ligation-induced liver fibrosis, as well as in the biopsies of liver cirrhosis patients. In vivo, ectopic expression of Fendrr aggravated the severity of CCl4-induced liver fibrosis in mice. In contrast, inhibiting Fendrr blockaded the activation of HSC and ameliorated CCl4-induced liver fibrosis. Our mechanistic study showed that Fendrr binds to STAT2 and enhances its enrichment in the nucleus, which then promote the expression of interleukin 6 (IL-6), and, ultimately, activates HSC in a paracrine manner. Accordingly, disrupting the interaction between Fendrr and STAT2 by ectopic expression of a STAT2 mutant attenuated the profibrotic response inspired by Fendrr in the CCl4-induced liver fibrosis. Notably, the increase of Fendrr in patient fibrotic liver is positively correlated with the severity of fibrosis and the expression of IL-6. Meanwhile, hepatic IL-6 positively correlates with the extent of liver fibrosis and HSC activation as well, thus suggesting a causative role of Fendrr in HSC activation and liver fibrosis. In conclusion, these observations identify an important regulatory cross talk between hepatocyte Fendrr and HSC activation in the progression of liver fibrosis, which might represent a potential strategy for therapeutic intervention.


Assuntos
Hepatócitos , Interleucina-6 , Cirrose Hepática , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Tetracloreto de Carbono/toxicidade , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Interleucina-6/metabolismo , Interleucina-6/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT2/metabolismo , Fator de Transcrição STAT2/genética
11.
Mol Genet Metab Rep ; 39: 101088, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38736698

RESUMO

Isovaleric acidemia (IVA) is a rare autosomal recessive disorder that manifests as a deficiency of isovaleryl-CoA dehydrogenase (IVD), a key enzyme in leucine metabolism. The clinical presentations associated with IVD deficiency are variable and include feeding intolerance, vomiting, metabolic acidosis, ketonemia, "sweaty feet" odor, lethargy, coma and even death. Tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS) methods were used to perform organic acid analysis of blood and urine samples from IVA patients, and the genetic analysis included next generation sequencing (NGS) and Sanger sequencing of the IVD gene. Here, we report the case of an almost seven-year-old male patient from a Chinese family who was asymptomatic during the newborn period, including the clinical manifestations and examination results. Genetic analysis revealed a previously unreported compound heterozygous variant in the IVD gene: c.593G > C (p.W198S) and c.859C > T (p.R287W).

12.
Acta Pharmacol Sin ; 45(6): 1224-1236, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38467717

RESUMO

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.


Assuntos
Proteínas Quinases Ativadas por AMP , Aconitina , Cardiotoxicidade , Histona Desacetilases , Animais , Camundongos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/etiologia , Histona Desacetilases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Humanos , Aconitum/química , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Medicamentos de Ervas Chinesas/farmacologia
13.
Huan Jing Ke Xue ; 45(2): 837-843, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471922

RESUMO

The Yellow River water of an urban area located in the middle and lower reaches of the Yellow River was taken as the research object, in which the seasonal and along-range distribution of total culturable bacteria, typical antibiotic resistant bacteria (amoxicillin resistant bacteria and sulfamethoxazole-resistant bacteria), and their corresponding typical resistance genes ï¼»ß-lactam resistance gene (blaCTX-M) and sulfamamide resistance genes (sulI and sulⅡ), as well as intⅠ1 were investigated. The results showed that the total culturable bacteria, ß-lactam-resistant bacteria and sulfonamide-resistant bacteria in the Yellow River Basin were significantly affected by temperature and human activities. The composition and quantity of their genera had obvious spatiotemporal distribution characteristics, in which Bacillus and Pseudomonas were dominant in the composition and number of bacteria. The abundance of resistance genes decreased with the decrease in temperature. The proportion of ß-lactam resistance genes in the total genes was higher than that of sulfanilamide genes, and sulI was the dominant gene in sulfanilamide genes. Correlation analysis showed that class Ⅰ integron played an important role in accelerating the spread of resistance genes. This study offers insight into the status quo of water resistance pollution in the Yellow River and provides theoretical support for the risk assessment of resistance genes in the middle and lower reaches of the Yellow River Basin.


Assuntos
Rios , Água , Humanos , Rios/microbiologia , Antibacterianos/análise , Bactérias/genética , Sulfametoxazol , China
14.
J Biomed Res ; 38(2): 175-188, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38438134

RESUMO

Deterministic compartment models (CMs) and stochastic models, including stochastic CMs and agent-based models, are widely utilized in epidemic modeling. However, the relationship between CMs and their corresponding stochastic models is not well understood. The present study aimed to address this gap by conducting a comparative study using the susceptible, exposed, infectious, and recovered (SEIR) model and its extended CMs from the coronavirus disease 2019 modeling literature. We demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and simulations. Based on this equivalence, we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter adjustment. The advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of epidemics. However, it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time CMs. Additionally, we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of agents. This model offered a balance between computational efficiency and accuracy. The results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic modeling. Furthermore, the results had implications for the development of hybrid models that integrated the strengths of both frameworks. Overall, the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

15.
Clin Cardiol ; 47(1): e24213, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269631

RESUMO

BACKGROUND: Usual measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. We aimed to demonstrate the effect of a novel time-weighted BP on cardiovascular outcomes using a post hoc analysis of two published randomized trials. HYPOTHESIS: Time-weighted blood pressure is associated with cardiovascular risk among patients with or without diabetes. METHODS: The limited-access ACCORD and SPRINT data sets were used for the current study. Time-weighted BP is obtained by dividing cumulative BP by the total follow-up time. Time-weighted BP burden above a threshold is also determined after deriving the time-weighted BP by re-zeroing the interpolated pressure values at two different hypertension thresholds (>140/90 and >130/80 mmHg). RESULTS: Eighteen thousand five hundred forty-one patients from the two clinical trials were enrolled in this study. A J-curve relation was observed between time-weighted BP and major cardiovascular events (MACE). The systolic blood pressure (SBP) burden independently predicted MACE across the two trials at different thresholds (ACCORD: SBP > 130 mmHg, HR = 1.05 [1.03-1.06]; SBP > 140 mmHg, HR = 1.06 [1.04-1.08]; SPRINT: SBP > 130 mmHg, HR = 1.04 [1.03-1.05]; SBP > 140 mmHg, HR = 1.05 [1.04-1.07]). Consistent results were found for diastolic blood pressure (DBP) burden (ACCORD: DBP > 80 mmHg, HR = 1.10 [1.06-1.15]; DBP > 90 mmHg, HR = 1.20 [1.11-1.30]. SPRINT: DBP > 80 mmHg, HR = 1.06 [1.02-1.09]; DBP > 90 mmHg, HR = 1.12 [1.06-1.18]). Significant associations were also observed for stroke, myocardial infarction, cardiovascular death, and all-cause mortality. CONCLUSION: Both time-weighted SBP and DBP independently influenced the risk of adverse cardiovascular events among patients with and without diabetes, regardless of the definition of hypertension (130/80 or <140/90 mmHg).


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , Humanos , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Fatores de Risco de Doenças Cardíacas
16.
Angew Chem Int Ed Engl ; 63(13): e202318887, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38237082

RESUMO

Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.

17.
Nutr Cancer ; 76(1): 137-148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37897077

RESUMO

Sulforaphane (SFN) is a compound derived from cruciferous plants. It has received considerable attention in recent years due to its effectiveness in cancer prevention and anti-inflammatory properties. The purpose of this study was to evaluate the antitumor potential of sulforaphane on colitis-associated carcinogenesis (CAC) through the establishment of a mouse model with AOM/DSS. First, AOM/DSS and DSS-induced model were established and administered SFN for 10 wk, and then the severity of colitis-associated colon cancer was examined macroscopically and histologically. Subsequently, immune cells and cytokines in the tumor microenvironment (TME) were quantified. Finally, the influence of sulforaphane was also investigated using different colon cell lines. We found that sulforaphane treatment decreased tumor volume, myeloid-derived suppressor cells (MDSC) expansion, the expression of the proinflammatory cytokine IL-1ß, and the level of IL-10 in serum. Also, it enhanced the antitumor activities of CD8+ T cells and significantly reduced tumorigenesis as induced by AOM/DSS. SFN also attenuated intestinal inflammation in DSS-induced chronic colitis by reshaping the inflammatory microenvironment. This work demonstrates that sulforaphane suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression.


Assuntos
Colite , Neoplasias Colorretais , Animais , Camundongos , Azoximetano/efeitos adversos , Carcinogênese , Transformação Celular Neoplásica , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Inflamação/patologia , Neoplasias Colorretais/patologia , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Microambiente Tumoral
18.
Radiol Med ; 129(2): 175-187, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37982937

RESUMO

PURPOSE: Accurately predicting the treatment response in patients with Crohn's disease (CD) receiving infliximab therapy is crucial for clinical decision-making. We aimed to construct a prediction model incorporating radiomics and body composition features derived from computed tomography (CT) enterography for identifying individuals at high risk for infliximab treatment failure. METHODS: This retrospective study included 137 patients with CD between 2015 and 2021, who were divided into a training cohort and a validation cohort with a ratio of 7:3. Patients underwent CT enterography examinations within 1 month before infliximab initiation. Radiomic features of the intestinal segments involved were extracted, and body composition features were measured at the level of the L3 lumbar vertebra. A model that combined radiomics with body composition was constructed. The primary outcome was the occurrence of infliximab treatment failure within 1 year. The model performance was evaluated using discrimination, calibration, and decision curves. RESULTS: Fifty-two patients (38.0%) showed infliximab treatment failure. Eight significant radiomic features were used to develop the radiomics model. The model incorporating radiomics model score, skeletal muscle index (SMI), and creeping fat showed good discrimination for predicting infliximab treatment failure, with an area under the curve (AUC) of 0.88 (95% CI 0.81, 0.95) in the training cohort and 0.83 (95% CI 0.66, 1.00) in the validation cohort. The favorable clinical application was observed using decision curve analysis. CONCLUSIONS: We constructed a comprehensive model incorporating radiomics and muscle volume, which could potentially be used to facilitate the individualized prediction of infliximab treatment response in patients with CD.


Assuntos
Doença de Crohn , Humanos , Infliximab/uso terapêutico , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Radiômica , Estudos Retrospectivos , Composição Corporal
19.
J Nanobiotechnology ; 21(1): 423, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964381

RESUMO

Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects.


Assuntos
Nanofibras , Ratos , Humanos , Animais , Nanofibras/química , Gelatina/química , Células Endoteliais , Regeneração Óssea , Durapatita/química , Crânio , Poliésteres/química , Alicerces Teciduais , Proliferação de Células , Engenharia Tecidual/métodos
20.
J Glob Health ; 13: 04100, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37681671

RESUMO

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) from the US and the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial from China have consistently demonstrated clinical benefits from intensive blood pressure (BP) treatment among elderly adults with hypertension. However, we have little data on the generalisability and potential implications of a scale-up of intensive BP treatment to all eligible elderly in the US and China. Methods: We used two nationally representative data sets from China (Health and Retirement Longitudinal Study (CHALRS), 2011-2012) and the US (National Health and Nutrition Examination Survey (NHANES), 2007-2012) and linked them with CHARLS follow-up data (2013) and the National Death Index (1999-2015), respectively. We estimated the percentage, number, and characteristics of elderly (≥60 years old) meeting the STEP and SPRINT eligibility criteria, and deaths that would be prevented or postponed with the implementation of intensive BP treatment. Results: Among the Chinese adults aged 60 years and over, 38.89% (95% confidence interval (CI) = 36.97-40.84) or 85.39 (95% CI = 81.14-89.64) million subjects met the STEP criteria, and 40.90 million (47.90%) adults were not taking antihypertensive medications. In the US, 23.77% (95% CI = 22.32%-25.28) or 12.46 (95% CI = 11.68-13.24) million elderly were eligible for the SPRINT, and 5.78 million (46.36%) were untreated. Overall, 0.07 (95% CI = 0.06-0.08) million deaths in the US and 0.31 (95% CI = 0.25-0.39) in China would be averted annually if intensive BP treatment was implemented, while 120 000 and 680 000 of hypotension cases would be identified yearly inthe US and China, respectively. Conclusions: A substantial percentage of Chinese and the US elderly meet the eligibility criteria for STEP and SPRINT. If intensive BP treatment was adopted, 70 000 and 310 000 deaths would be prevented or postponed yearly in the US and China, respectively.


Assuntos
Hipertensão , Adulto , Humanos , Idoso , Pessoa de Meia-Idade , Pressão Sanguínea , Estudos Transversais , Estudos Longitudinais , Inquéritos Nutricionais , China/epidemiologia , Hipertensão/tratamento farmacológico
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