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1.
Complement Med Res ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560980

RESUMO

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

2.
Cell Oncol (Dordr) ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592610

RESUMO

PURPOSE: α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown. METHODS: We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism. RESULTS: RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner. CONCLUSION: DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.

3.
Ecotoxicol Environ Saf ; 276: 116308, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38593496

RESUMO

BACKGROUND: Impact of outdoor and household air pollution on physical function remains unelucidated. This study examined the influence of various ambient particulate sizes (PM1, PM2.5, and PM10) and household fuel usage on physical function. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 and 2015 were utilized. The physical functional score was computed by summing scores from four tests: grip strength, gait speed, chair stand test, and balance. Multivariate linear and linear mixed-effects models were used to explore the separate and combined effects of PM1, PM2.5, PM10 and household fuel use on physical function in the cross-sectional and longitudinal analyses, respectively, and to further observe the effects of fuel cleanup on physical function in the context of air pollution exposure. RESULTS: Both cross-sectional and longitudinal analyses revealed negative correlations between PM1 (ß = -0.044; 95% CI: -0.084, -0.004), PM2.5 (ß = -0.024; 95% CI: -0.046, -0.001), PM10 (ß = -0.041; 95% CI: -0.054, -0.029), and physical function, with a more pronounced impact observed for fine particulate matter (PM1). Cleaner fuel use was associated with enhanced physical function compared to solid fuels (ß = 0.143; 95% CI: 0.070, 0.216). The presence of air pollutants and use of solid fuels had a negative impact on physical function, while cleaner fuel usage mitigated the adverse effects of air pollutants, particularly in areas with high exposure. CONCLUSION: This study underscores the singular and combined detrimental effects of air pollutants and solid fuel usage on physical function. Addressing fine particulate matter, specifically PM1, and prioritizing efforts to improve household fuel cleanliness in regions with elevated air pollution levels are crucial for preventing physical disability.

4.
BMC Genomics ; 25(1): 330, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565995

RESUMO

Plant growth and development can be significantly impacted by drought stress. Plants will adjust the synthesis and accumulation of secondary metabolites to improve survival in times of water constraint. Simultaneously, drought stress can lead to modifications in the DNA methylation status of plants, and these modifications can directly impact gene expression and product synthesis by changing the DNA methylation status of functional genes involved in secondary metabolite synthesis. However, further research is needed to fully understand the extent to which DNA methylation modifies the content of secondary metabolites to mediate plants' responses to drought stress, as well as the underlying mechanisms involved. Our study found that in Eleutherococcus senticosus (E. senticosus), moderate water deprivation significantly decreased DNA methylation levels throughout the genome and at the promoters of EsFPS, EsSS, and EsSE. Transcription factors like EsMYB-r1, previously inhibited by DNA methylation, can re-bind to the EsFPS promotor region following DNA demethylation. This process promotes gene expression and, ultimately, saponin synthesis and accumulation. The increased saponin levels in E. senticosus acted as antioxidants, enhancing the plant's adaptability to drought stress.


Assuntos
Eleutherococcus , Saponinas , Metilação de DNA , Eleutherococcus/genética , Eleutherococcus/metabolismo , Metabolismo Secundário , Secas
5.
Int J Gen Med ; 17: 1369-1379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601195

RESUMO

Background: The elderly patients are at increased high risk of myocardial injury and mortality after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aims to investigate the prevalence, predictors and prognostic implications of myocardial injury in the elderly patients with SARS-CoV-2 infection. Methods: Patients aged over 65 years were consecutively recruited between April to May, 2022. Myocardial injury was assessed using the high-sensitivity cardiac troponin T (hs-cTnT) assay. The primary endpoint was in-hospital mortality. Results: A total of 347 patients were recruited with a median age of 81 years. 45.8% were male and 18 (5.2%) deceased before discharge. Myocardial injury (hs-cTnT over 99% upper reference limit [URL]) was detected in 202 (58.2%) of patients. Predictors of myocardial injury included age (per 5-year increase), hypertension, vaccination, creatine, and neutrophil-to-lymphocyte ratio. hs-cTnT over 3 × URL was independently correlated with in-hospital mortality (adjusted odds ratio [adOR], 13.21; 95% confidence interval [CI], 2.11-87.1; p = 0.005) in comparison to hs-cTnT > URL (adOR, 0.66; 95% CI, 0.09-5.92; p = 0.680). Conclusion: Myocardial injury was a common phenomenon and prognostic predictor in elder patients after SARS-CoV-2 infection. Higher threshold of myocardial injury may be considered to improve risk stratification.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38607211

RESUMO

Objective: To explore the application value of transabdominal ultrasonography in the diagnosis of gastrointestinal malignant tumors. Methods: This study retrospectively analyzed the transabdominal ultrasound imaging data of 284 patients with gastrointestinal tumors admitted to our hospital from April 2019 to March 2022 and assessed the accuracy of transabdominal ultrasound in diagnosing different types of gastrointestinal tumor diseases. The diagnostic accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was calculated. Results: The sensitivity and specificity of transabdominal ultrasonography in the diagnosis of gastric cancer were (82.40% and 83.72%, respectively), colon cancer (77.78% and 88.35%, respectively), gastric stromal tumor (95.45% and 93.65%, respectively), gastric lymphoma (72.22% and 94.66%, respectively), colorectal lymphoma (80.00% and 95.42%, respectively), gastric mucosal hypertrophy (85.71% and 96.69%, respectively), and pyloric hypertrophy (92.59% and 97.79%, respectively). Among the 284 patients included, 152 patients had malignant tumors, including 34 patients with stage I, 30 patients with stage II, 51 patients with stage III, and 37 patients with stage IV. The accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was 85.53% (130/152). Conclusion: Transabdominal ultrasonography shows promise as a diagnostic tool for gastrointestinal malignant tumors; however, it is recommended to be used in conjunction with other detection methods such as fibrous gastrointestinal tract examination to minimize the risk of missed diagnoses and misdiagnoses. The study highlights the potential of transabdominal ultrasonography as a non-invasive and accessible diagnostic method for gastrointestinal malignancies. Further research and advancements in imaging technologies are crucial for enhancing diagnostic capabilities and improving patient outcomes in the future.

7.
J Affect Disord ; 356: 204-214, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599254

RESUMO

BACKGROUND: Major depressive disorder is a prevalent psychiatric illness characterized by mood disturbances and influenced by various environmental and genetic factors, yet its etiology remains largely unknown. METHODS: We profiled a self-reported depressive population in Japan with a focus on sociodemographic background, lifestyle, comorbidities, and genetic background, using data from two cohorts, a population-based cohort and a three-generation cohort, recruited by the Tohoku Medical Megabank Organization until December 2021. RESULTS: Our findings revealed that depression in the Japanese population is strongly associated with certain sociocultural features prevalent in Japan, such as social isolation, neuroticism, and introversion, as well as with well-known risk factors that include age and gender. Environmental factors related to the Great East Japan Earthquake, considered as cohort characteristics, were also strongly associated with the onset of depression. Moreover, using GWAS analysis of whole-genome sequencing data, we identified novel candidate genetic risk variants located on chromosomes 21 and 22 that are associated with depression in Japanese individuals; further validation of these risk variants is warranted. LIMITATIONS: Our study has limitations, including uncertain clinical relevance resulting from the use of self-reported questionnaires for depression assessment. Additionally, the cohort exhibited a population bias, with greater representation of women than men. CONCLUSIONS: Our results provide holistic insights into depression risk factors in Japanese adults, although their associations with depression are correlations. This supports the idea that targeted interventions and individualized approaches are important for addressing depression in the Japanese population.

8.
Phytochemistry ; : 114093, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615927

RESUMO

Nine 3-arylisoquinoline alkaloids including five undescribed ones, hypectumines A-E (1-5), were isolated from the whole herb of Hypecoum erectum L. with the guidance of 1H-NMR. Their structures were established by a combination of 1D, 2D NMR, and HRESIMS spectrometry. Among them, hypectumines A and B possessed rare urea moieties while hypectumines C and D were characterized by 3-(methylamino)propanoic acid scaffolds. Biological assay demonstrated that alkaloids hypectumine B and 2,3-dimethoxy-N-formylcorydamine had anti-inflammatory effects by inhibiting NO production on LPS-induced RAW264.7 cells with IC50 values of 24.4 and 44.2 µM, respectively. Furthermore, hypectumine B could reduce the expression of pro-inflammatory cytokines TNF-α and IL-6, suggesting it might be a potential candidate for treating inflammatory disease.

10.
Atherosclerosis ; 391: 117491, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471264

RESUMO

BACKGROUND AND AIMS: NLRP3 inflammasome plays a key role in vascular inflammation and atherosclerosis. Circular RNAs (circRNAs) are involved in disease development by regulating gene expression, and have emerged as promising novel disease biomarkers. This study aimed to identify the NLRP3 inflammasome-associated circRNA biomarkers of carotid atherosclerosis. METHODS: Based on the differential expression profiles of circRNAs in patients with carotid artery plaque (CAP) and healthy controls, hsa_circ_0043621, hsa_circ_0051995, and hsa_circ_0123388 were screened and validated using real-time quantitative polymerase chain reaction (RT-qPCR). Potential circRNA-miRNA-mRNA interactions were explored using a luciferase assay. The biological roles of the validated circRNAs were investigated in human umbilical vein endothelial cells (HUVECs) using Western blotting, transwell, and CCK-8 assays. Clinical significance was assessed using receiver operating characteristic (ROC) curves and logistic regression analysis. RESULTS: The expression levels of all candidate circRNAs were significantly higher in patients with CAP than in controls (p<0.05), which was consistent with the results of the microarray analysis. Overexpression of hsa_circ_0043621 significantly increased the expression of NLRP3, induced migration of HUVECs, and inhibited cell proliferation. hsa_circ_0043621 demonstrated reasonable diagnostic accuracy for CAP detection and increased intima-media thickness (IMT). hsa_circ_0043621 upregulation was an independent predictor of an increased risk of CAP and increased IMT. CONCLUSIONS: hsa_circ_0043621 is a valuable circulating biomarker of carotid atherosclerosis and may contribute to its pathogenesis by regulating the NLRP3 inflammasome.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , MicroRNAs , Humanos , RNA Circular/genética , Inflamassomos/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espessura Intima-Media Carotídea , MicroRNAs/genética , Biomarcadores/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/metabolismo , Estenose das Carótidas/metabolismo
11.
Acta Crystallogr D Struct Biol ; 80(Pt 4): 232-246, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38488730

RESUMO

Single-particle cryo-electron microscopy has become a widely adopted method in structural biology due to many recent technological advances in microscopes, detectors and image processing. Before being able to inspect a biological sample in an electron microscope, it needs to be deposited in a thin layer on a grid and rapidly frozen. The VitroJet was designed with this aim, as well as avoiding the delicate manual handling and transfer steps that occur during the conventional grid-preparation process. Since its creation, numerous technical developments have resulted in a device that is now widely utilized in multiple laboratories worldwide. It features plasma treatment, low-volume sample deposition through pin printing, optical ice-thickness measurement and cryofixation of pre-clipped Autogrids through jet vitrification. This paper presents recent technical improvements to the VitroJet and the benefits that it brings to the cryo-EM workflow. A wide variety of applications are shown: membrane proteins, nucleosomes, fatty-acid synthase, Tobacco mosaic virus, lipid nanoparticles, tick-borne encephalitis viruses and bacteriophages. These case studies illustrate the advancement of the VitroJet into an instrument that enables accurate control and reproducibility, demonstrating its suitability for time-efficient cryo-EM structure determination.


Assuntos
Proteínas de Membrana , Manejo de Espécimes , Microscopia Crioeletrônica/métodos , Reprodutibilidade dos Testes , Manejo de Espécimes/métodos , Processamento de Imagem Assistida por Computador
12.
Blood Cancer J ; 14(1): 38, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38443358

RESUMO

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.


Assuntos
Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Plasmócitos , Prognóstico , Análise de Sequência de RNA , Microambiente Tumoral
13.
Heliyon ; 10(5): e26741, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449651

RESUMO

Background: Monocytes play an essential role in developing autoimmune diseases; however, their association with myasthenia gravis (MG) development is unclear. Methods: We performed a two-sample Mendelian randomization analysis to assess the causal relationship between monocyte-associated traits and MG, reviewing summary statistics of genome-wide association studies (GWAS). Results: Using the inverse variance weighted method, the following were found to be causally associated with MG: HLA-DR on monocytes (OR, 1.363; 95% CI, 1.158-1.605; P = 2E-04), HLA-DR on CD14+ monocytes (OR, 1.324; 95% CI, 1.183-1.482; P = 1.08E-06), HLA-DR on CD14+CD16- monocytes (OR, 1.313; 95% CI, 1.177-1.465; P = 1.07E-06), CD40 on monocytes (OR, 1.135; 95% CI, 1.012-1.272; P < 0.05), CD40 on CD14+CD16- monocytes (OR, 1.142; 95% CI, 1.015-1.285; P < 0.05), CD40 on CD14+CD16+ monocytes (OR, 1.142; 95% CI, 1.021-1.278; P < 0.05), CD64 on CD14+CD16+ monocytes (OR, 1.286; 95% CI, 1.019-1.623; P < 0.05). Conclusions: The present study suggests a causal relationship between the upregulation of CD40, HLA-DR, and CD64 on monocytes and the development of MG. Altered monocyte function may potentially be a risk factor for MG and a therapeutic target.

14.
Nat Commun ; 15(1): 2077, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453947

RESUMO

Ultrastrong and deep-strong coupling are two coupling regimes rich in intriguing physical phenomena. Recently, hybrid magnonic systems have emerged as promising candidates for exploring these regimes, owing to their unique advantages in quantum engineering. However, because of the relatively weak coupling between magnons and other quasiparticles, ultrastrong coupling is predominantly realized at cryogenic temperatures, while deep-strong coupling remains to be explored. In our work, we achieve both theoretical and experimental realization of room-temperature ultrastrong magnon-magnon coupling in synthetic antiferromagnets with intrinsic asymmetry of magnetic anisotropy. Unlike most ultrastrong coupling systems, where the counter-rotating coupling strength g2 is strictly equal to the co-rotating coupling strength g1, our systems allow for highly tunable g1 and g2. This high degree of freedom also enables the realization of normalized g1 or g2 larger than 0.5. Particularly, our experimental findings reveal that the maximum observed g1 is nearly identical to the bare frequency, with g1/ω0 = 0.963, indicating a close realization of deep-strong coupling within our hybrid magnonic systems. Our results highlight synthetic antiferromagnets as platforms for exploring unconventional ultrastrong and even deep-strong coupling regimes, facilitating the further exploration of quantum phenomena.

15.
BMC Pharmacol Toxicol ; 25(1): 26, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504370

RESUMO

Browning of white adipose tissue (WAT) is become an appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Dapagliflozin is widely used in the treatment of type 2 diabetes, and it is also found that the drug exhibits regulate systemic metabolism such as obesity, insulin resistance and hepatic steatosis. However, the precise role of dapagliflozin on WAT remodeling remains to be elucidated. The current study aimed to explore the role of dapagliflozin on WAT browning in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice (n = 6 per group) were used to establish obesity model by following feeding with HFD for 6 weeks. The mice were randomly treated with or without dapagliflozin for the experimental observation. The volume and fat fraction of WAT were quantified, H&E, UCP-1 staining and immunohistochemistry were conducted to investigate the white-to-brown fat conversion and angiogenesis in WAT respectively. Quantitative real-time polymerase chain reaction (qPCR) was employed to explore the mRNA expression levels of genes related to fat browning and angiogenesis in WAT. Subsequently, 3T3-L1 cells were used to explore the effect of dapagliflozin on preadipocytes differentiation in vitro. Our results demonstrated that dapagliflozin could reduce body weight gain and promote WAT browning in HFD induced obese mice via regulating lipogenesis and angiogenesis in WAT. Furthermore, dapagliflozin reduce cells differentiation, up-regulate the expression of WAT browning and angiogenesis genes in 3T3-L1 adipocytes in vitro. In conclusion, dapagliflozin can potentially promote WAT browning in HFD induced obese mice via improving lipogenesis and angiogenesis in WAT.


Assuntos
60489 , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Masculino , Camundongos , Animais , Camundongos Obesos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos
16.
J Chromatogr A ; 1721: 464827, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38520985

RESUMO

Some bile acids (BAs) were considered as biomarkers or have therapeutical effect on metabolic diseases. However, due to the existence of isomers and limitations in sensitivity, simultaneous quantification of multiple BAs remains a challenge. The aim of this study is to establish an accurate and sensitive method for the determination of multiple BAs with similar polarity. A LC-MS/MS analytical method capable of quantifying forty-five BAs simultaneously using nine stable isotope internal standards was developed and fully validated based on key isomers-oriented separation strategy. The method was further applied to analyze plasma samples to describe the dynamic profile of BAs after high glucose intake. The chromatography and mass spectrum conditions were optimized to enable the accurate quantification of forty-five BAs, while ensuring the lower limit of quantification between 0.05-10 ng/mL. The results of system suitability, linearity, dilution integrity, accuracy and precision demonstrated the good quantitative capacity and robustness of the method. A total of thirty-five BAs were quantified in plasma samples from twelve healthy Chinese individuals. The established method featured superior sensitivity and better separation efficiency compared to previous studies. Meanwhile, BAs exhibited correlations with glucose and insulin, suggesting their potential as biomarkers for metabolic disorders.


Assuntos
Ácidos e Sais Biliares , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Biomarcadores , Glucose , Cromatografia Líquida de Alta Pressão/métodos
17.
Front Cell Infect Microbiol ; 14: 1298202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524181

RESUMO

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolations have rapidly increased in pediatric patients. To investigate a possible health care-associated infections of CRKP in a tertiary pediatric hospital, the circulating clones and carbapenem-resistant pattern between CRKP and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were compared to classify their epidemiological characteristics. The results will help to identify the epidemic pattern of the CRKP transmission in the hospital. Methods: Ninety-six CRKP and forty-eight CRAB isolates were collected in Kunming Children's Hospital from 2019 through 2022. These isolates were genotyped using repetitive extragenic palindromic-PCR (REP-PCR). Carbapenemase phenotypic and genetic characterization were investigated using a disk diffusion test and singleplex PCR, respectively. In addition, these characteristics of the two pathogens were compared. Results: The rates of CRKP and CRAB ranged from 15.8% to 37.0% at the hospital. Forty-nine and sixteen REP genotypes were identified among the 96 and 48 CRKP and CRAB isolates tested, respectively. The CRKP isolates showed more genetic diversity than the CRAB isolates. Of the 96 CRKP isolates, 69 (72%) produced Class B carbapenemases. However, all 48 CRAB isolates produced Class D carbapenemase or extended-spectrum ß-lactamases (ESBL) combined with the downregulation of membrane pore proteins. Furthermore, the carbapenemase genes bla KPC, bla IMP, and bla NDM were detected in CRKP isolates. However, CRAB isolates were all positive for the bla VIM, bla OXA-23, and bla OXA-51 genes. Conclusions: These CRKP isolates exhibited different biological and genetic characteristics with dynamic changes, suggesting widespread communities. Continuous epidemiological surveillance and multicenter research should be carried out to strengthen the prevention and control of infections.


Assuntos
Acinetobacter baumannii , Enterobacteriáceas Resistentes a Carbapenêmicos , Humanos , Criança , Antibacterianos/farmacologia , Klebsiella pneumoniae , Genótipo , Hospitais Pediátricos , Farmacorresistência Bacteriana , beta-Lactamases/genética , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana
18.
Fitoterapia ; 174: 105867, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382891

RESUMO

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.


Assuntos
Doença de Alzheimer , Butirilcolinesterase , Fenóis , Humanos , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Desenho de Fármacos
19.
Bioorg Chem ; 144: 107166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308998

RESUMO

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.


Assuntos
Alcaloides , Corydalis , Corydalis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Alcaloides/química , Espectroscopia de Ressonância Magnética , Autofagia
20.
RSC Adv ; 14(8): 5370-5379, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38348300

RESUMO

Nitrate contamination in water sources poses a substantial environmental and health risk. However, accurate detection of nitrate in water, particularly in the presence of dissolved organic carbon (DOC) interference, remains a significant analytical challenge. This study investigates a novel approach for the reliable detection of nitrate in water samples with varying levels of DOC interference based on the equivalent concentration offset method. The characteristic wavelengths of DOC were determined based on the first-order derivatives, and a nitrate concentration prediction model based on partial least squares (PLS) was established using the absorption spectra of nitrate solutions. Subsequently, the absorption spectra of the nitrate solutions were subtracted from that of the nitrate-DOC mixed solutions to obtain the difference spectra. These difference spectra were introduced into the nitrate prediction model to calculate the equivalent concentration offset values caused by DOC. Finally, a DOC interference correction model was established based on a binary linear regression between the absorbances at the DOC characteristic wavelengths and the DOC-induced equivalent concentration offset values of nitrate. Additionally, a modeling wavelength selection algorithm based on a sliding window was proposed to ensure the accuracy of the nitrate concentration prediction model and the equivalent concentration offset model. The experimental results demonstrated that by correcting the DOC-induced offsets, the relative error of nitrate prediction was reduced from 94.44% to 3.36%, and the root mean square error of prediction was reduced from 1.6108 mg L-1 to 0.1037 mg L-1, which is a significant correction effect. The proposed method applied to predict nitrate concentrations in samples from two different water sources shows a certain degree of comparability with the standard method. It proves that this method can effectively correct the deviations in nitrate measurements caused by DOC and improve the accuracy of nitrate measurement.

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