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1.
Curr Drug Deliv ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38847256

RESUMO

PURPOSE: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier. METHODS: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C. RESULTS: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 µm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres. CONCLUSION: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner.

2.
Int J Nanomedicine ; 19: 5071-5094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846644

RESUMO

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.


Assuntos
Disponibilidade Biológica , Docetaxel , Estabilidade de Medicamentos , Nanopartículas , Tamanho da Partícula , Soroalbumina Bovina , Docetaxel/farmacocinética , Docetaxel/química , Docetaxel/administração & dosagem , Animais , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/administração & dosagem , Nanopartículas/química , Taxoides/farmacocinética , Taxoides/química , Taxoides/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratos Sprague-Dawley , Masculino , Composição de Medicamentos/métodos , Ratos
3.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38887599

RESUMO

Tobacco consumption in China remains the primary cause of preventable mortality, with Shanghai being particularly affected by issues related to secondhand smoke exposure. This study explores the role of the public service hotline 12345, a grassroots initiative in Shanghai, in capturing public sentiment and assessing the effectiveness of anti-smoking regulations. Our research aims to accurately and deeply understand the implementation and feedback of smoking control policies: by identifying high-frequency points and prominent issues in smoking control work based on the smoking control work order data received by the health hotline 12320. The results of this study will assist government enforcement agencies in improving smoking monitoring and clarify the direction for improving smoking control measures. Text-mining techniques were employed to analyze a dataset comprising 78011 call sheets, all related to tobacco control and collected from the hotline between 1 January 2015 and 31 December 2019. This methodological approach aims to uncover prevalent themes and sentiments in the public discourse on smoking and its regulation, as reflected in the hotline interactions. Our study identified hotspots and the issues of greatest concern to citizens. Additionally, it provided recommendations to enforcement agencies to enhance their capabilities, optimize the allocation of human resources for smoking control monitoring, reduce enforcement costs and support for anti-smoking campaigns, thereby contributing to more effective tobacco control policies in the region.

4.
Sci Total Environ ; 945: 173993, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879026

RESUMO

A total of 17 groups of wastewaters from the chemical industrial parks and matched receiving river waters were collected in the east of China. The measured total concentrations of 21 analyzed PFAS analogues (∑21PFAS) in the influents and effluents of the wastewater treatment plants (WWTPs) were in the range of 0.172-20.6 µg/L (mean: 18.2 µg/L, median: 3.9 µg/L) and 0.167-93.6 µg/L (mean: 10.8 µg/L, median: 1.12 µg/L), respectively, which were significantly higher than those observed in the upstream (range: 0.0158-7.05 µg/L, mean: 1.09 µg/L, median: 0.482 µg/L) and downstream (range: 0.0237-1.82 µg/L, mean: 0.697 µg/L, median: 0.774 µg/L) receiving waters. Despite the concentrations and composition profiles of PFAS varied in the water samples from different sampling sites, PFOA was generally the major PFAS analogue in the research areas, mainly due to the history of PFOA production and usage as well as the specific exemptions. The calculated concentration ratios of the short-chain PFCAs and PFSAs to their respective predecessors (PFOA and PFOS) in most of the samples far exceeded 1, indicating a shift from legacy PFOA and PFOS to short-chain PFAS in the research areas. Correlation network analysis and the calculated concentration ratios of PFAS in the effluents versus influents indicated transformation may have occurred during the water treatment processes and PFAS could not be efficiently removed in the WWTPs. Wastewater discharge of chemical industrial parks is a vital source of PFAS dispersed into the aquatic environment.

6.
J Org Chem ; 89(12): 8397-8406, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38825774

RESUMO

[(p-Cymene)Ru(2,2'-bpyO)(H2O)] was proven to be an efficient catalyst for the synthesis of amino-(N-alkyl)benzenesulfonamides via selective N-alkylation of aminobenzenesulfonamides with alcohols. It was confirmed that functional groups in the bpy ligand are crucial for the activity of catalysts. Furthermore, the utilization of this catalytic system for the preparation of a biologically active compound was presented.

7.
Front Cardiovasc Med ; 11: 1339094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803667

RESUMO

Objective: To investigate the causal role of venous thrombolism mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in death due to cardiac causes using Mendelian randomization (MR). Methods: A two-sample two-step MR was used to determine (1) the causal effects of SGLT2 inhibition on death due to cardiac causes; (2) the causal effects of venous thrombolism on death due to cardiac causes; and (3) the mediation effects of venous thrombolism. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Additionally, employing MR to investigate the causal association between SGLT2 inhibition and cardiac arrest as well as coronary heart disease (CHD). Results: SGLT2 inhibition was associated with a lower risk of death due to cardiac causes (odds ratio [OR] = 0.983, [95% CI = 0.972, 0.993], P = 0.0016). Venous thrombolism was associated with death due to cardiac causes ([OR] = 1.031, [95% CI = 1.005, 1.057], P = 0.0199). Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on death due to cardiac causes through venous thrombolism [ß = -0.0015, (95% CI = -0.0032 -0.0002), P = 0.042], with a mediated proportion of 8.9% (95% CI = 1.2%, 18.7%) of the total. Furthermore, SGLT2 inhibition was linked to a lower risk of cardiac arrest ([OR] = 0.097, [95% CI = 0.013, 0.742], P = 0.025). SGLT2 inhibition was linked to a lower risk of CHD ([OR] = 0.957, [95% CI = 0.932, 0.982], P = 0.0009). Conclusions: Our study identified the causal roles of SGLT2 inhibition in venous thrombolism. SGLT2 inhibition may influence death due to cardiac causes through venous thrombolism. Additionally, SGLT2 inhibition was associated with reduced risk of cardiac arrest and CHD.

8.
Small ; : e2400267, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805747

RESUMO

Developing synergistic targeted therapeutics to improve treatment efficacy while reducing side effects has proven promising for anticancer therapies, but how to conveniently modulate multidrug cooperation remains a challenge. Here, a novel synergistic strategy using a G-quadruplex-programmed versatile nanorobot (G4VN) containing two subunits of DNAzyme (DzG4) and ligand-drug conjugates (LDCs) is proposed to precisely target tumors and then execute both gene silencing and chemotherapy. As the core module of this nanorobot, a well-designed G4 responding to a high level of K+ in tumor microenvironment smartly kills three birds with one stone, which makes two TfR aptamers proximate to improve their efficiency of targeting tumor cells, and in situ activates a split 10-23 DNAzyme to downregulate target mRNA expression, meanwhile promotes the cell uptake of a GSH-responsive LDCs to enhance drug efficacy. Such a design enables a potently synergistic anticancer therapy with low side effects in vivo, showing great promise for broad applications in precision disease treatment.

9.
Cell Mol Life Sci ; 81(1): 228, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777955

RESUMO

Diabetic cardiomyopathy (DCM) is a prevalent complication of type 2 diabetes (T2D). 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a glycolysis regulator. However, the potential effects of PFKFB3 in the DCM remain unclear. In comparison to db/m mice, PFKFB3 levels decreased in the hearts of db/db mice. Cardiac-specific PFKFB3 overexpression inhibited myocardial oxidative stress and cardiomyocyte apoptosis, suppressed mitochondrial fragmentation, and partly restored mitochondrial function in db/db mice. Moreover, PFKFB3 overexpression stimulated glycolysis. Interestingly, based on the inhibition of glycolysis, PFKFB3 overexpression still suppressed oxidative stress and apoptosis of cardiomyocytes in vitro, which indicated that PFKFB3 overexpression could alleviate DCM independent of glycolysis. Using mass spectrometry combined with co-immunoprecipitation, we identified optic atrophy 1 (OPA1) interacting with PFKFB3. In db/db mice, the knockdown of OPA1 receded the effects of PFKFB3 overexpression in alleviating cardiac remodeling and dysfunction. Mechanistically, PFKFB3 stabilized OPA1 expression by promoting E3 ligase NEDD4L-mediated atypical K6-linked polyubiquitination and thus prevented the degradation of OPA1 by the proteasomal pathway. Our study indicates that PFKFB3/OPA1 could be potential therapeutic targets for DCM.


Assuntos
Cardiomiopatias Diabéticas , GTP Fosfo-Hidrolases , Miócitos Cardíacos , Fosfofrutoquinase-2 , Ubiquitinação , Fosfofrutoquinase-2/metabolismo , Fosfofrutoquinase-2/genética , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/genética , Camundongos , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Masculino , Estresse Oxidativo , Apoptose/genética , Miocárdio/metabolismo , Miocárdio/patologia , Camundongos Endogâmicos C57BL , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Glicólise , Humanos , Estabilidade Proteica
10.
Front Cardiovasc Med ; 11: 1371513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725835

RESUMO

Objective: To investigate the causal contributions of Sodium-glucose cotransporter 2 (SGLT2) inhibition on Heart Failure (HF) and identify the circulating proteins that mediate SGLT2 inhibition's effects on HF. Methods: Applying a two-sample, two-step Mendelian Randomization (MR) analysis, we aimed to estimate: (1) the causal impact of SGLT2 inhibition on HF; (2) the causal correlation of SGLT2 inhibition on 4,907 circulating proteins; (3) the causal association of SGLT2 inhibition-driven plasma proteins on HF. Genetic variants linked to SGLT2 inhibition derived from the previous studies. The 4,907 circulating proteins were derived from the deCODE study. Genetic links to HF were obtained through the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium. Results: SGLT2 inhibition demonstrated a lower risk of HF (odds ratio [OR] = 0.44, 95% CI [0.26, 0.76], P = 0.003). Among 4,907 circulating proteins, we identified leucine rich repeat transmembrane protein 2 (LRRTM2), which was related to both SGLT2 inhibition and HF. Mediation analysis revealed that the impact of SGLT2 inhibition on HF operates indirectly through LRRTM2 [ß = -0.20, 95% CI (-0.39, -0.06), P = 0.02] with a mediation proportion of 24.6%. Colocalization analysis provided support for the connections between LRRTM2 and HF. Conclusion: The study indicated a causative link between SGLT2 inhibition and HF, with plasma LRRTM2 potentially serving as a mediator.

11.
Nat Commun ; 15(1): 4009, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740761

RESUMO

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

12.
Sleep Med ; 119: 480-487, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795402

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) initially emerged as oral antidiabetic medication but were subsequently discovered to exhibit pleiotropic actions. Insomnia is a prevalent and debilitating sleep disorder. To date, the causality between SGLT2 inhibitors and insomnia remains unclear. This study aims to evaluate the causality between SGLT2 inhibitors and insomnia and identify potential plasma protein mediators. METHODS: Using a two-sample Mendelian Randomization (MR) analysis, we estimated the causality of SGLT2 inhibition on insomnia and sleep duration. Additionally, employing a two-step and proteome-wide MR analysis, we evaluated the causal link of SGLT2 inhibition on 4907 circulating proteins and the causality of SGLT2 inhibition-driven plasma proteins on insomnia. We applied a false discovery rate (FDR) correction for multiple comparisons. Furthermore, mediation analyses were used to identify plasma proteins that mediate the effects of SGLT2 inhibition on insomnia. RESULTS: SGLT2 inhibition was negatively correlated with insomnia (odds ratio [OR] = 0.791, 95 % confidence interval [CI] [0.715, 0.876], P = 5.579*10^-6) and positively correlated with sleep duration (ß = 0.186, 95 % CI [0.059, 0.314], P = 0.004). Among the 4907 circulating proteins, diadenosine tetraphosphatase (Ap4A) was identified as being linked to both SGLT2 inhibition and insomnia. Mediation analysis indicated that the effect of SGLT2 inhibition on insomnia partially operates through Ap4A (ß = -0.018, 95 % CI [-0.036, -0.005], P = 0.023), with a mediation proportion of 7.7 %. CONCLUSION: The study indicated a causality between SGLT2 inhibition and insomnia, with plasma Ap4A potentially serving as a mediator.


Assuntos
Análise da Randomização Mendeliana , Distúrbios do Início e da Manutenção do Sono , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Proteínas Sanguíneas
13.
Radiology ; 311(1): e230459, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563669

RESUMO

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.


Assuntos
Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Hospitalização , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia
14.
Wei Sheng Yan Jiu ; 53(2): 229-236, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38604958

RESUMO

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Sobrepeso , Obesidade Infantil , Receptor Tipo 4 de Melanocortina , Pré-Escolar , Humanos , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença , Genótipo , Sobrepeso/genética , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética
15.
Eur J Pharmacol ; 976: 176619, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38679119

RESUMO

AIMS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors offer a novel therapeutic avenue for myocardial infarction (MI). However, the exact nature of this relationship and the underlying mechanisms are not fully understood. METHODS: Utilizing a two-sample Mendelian Randomization (MR) analysis, we elucidated the causal effects stemming from the inhibition of SGLT2 on MI. Then, The pool of 4907 circulating proteins within the plasma proteome were utilized to explore the mediators of SGLT2 inhibitors on MI. Protein-protein network and enrichment analysis were conducted to clarify the potential mechanism. Finally, employing MR analysis and meta-analysis techniques, we systematically assessed the causal associations between SGLT2 inhibition and coronary heart diseases (CHD). RESULTS: SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of MI (odds ratio [OR] = 0.462, [95% CI 0.222, 0.958], P = 0.038). Among 4907 circulating proteins, we identified APOB and CCL17 which were related to both SGLT2 inhibition and MI. Mediation analysis showed evidence of the indirect effect of SGLT2 inhibition on MI through APOB (ß = -0.557, 95%CI [-1.098, -0.155]) with a mediated proportion of 72%, and CCL17 (ß = -0.176, 95%CI [-0.332, -0.056]) with a mediated proportion of 17%. The meta-analysis result showed that SGLT2 inhibition was associated with a lower risk of CHD. CONCLUSION: Based on proteome-wide mendelian randomization, APOB and CCL17 were seen as mediators in the protective effect of SGLT2 inhibition against myocardial infarction.


Assuntos
Apolipoproteínas B , Análise da Randomização Mendeliana , Infarto do Miocárdio , Proteoma , Inibidores do Transportador 2 de Sódio-Glicose , Infarto do Miocárdio/prevenção & controle , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Proteoma/metabolismo , Apolipoproteínas B/sangue , Apolipoproteínas B/genética
16.
Toxicol Res (Camb) ; 13(2): tfae025, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38496381

RESUMO

Objective: The purpose of this study was to assess the safety of transgenic maize CC-2 through a 90-day feeding study in Sprague-Dawley rats. Methods: Transgenic maize CC-2 and its parental counterpart maize Zhengdan 958 were respectively incorporated into diets at levels of 70%, 35% or 17.5% (w/w) and were administrated to rats (n = 10/sex/group) for 90 days. An additional control group of rats (n = 10/sex/group) were fed with the AIN93 breeding diet. All formulated diets were nutritionally balanced. Results: There was no death and obvious toxic symptom in all rats. Food consumption, body weight, total food consumption rate, hematology, urinalysis, organ weight and organ coefficient were comparable between transgenic groups and the corresponding dose parental groups. There were significant differences of food consumption rate on some timepoint between high dose transgenic group and high dose parental group; male rats in high dose transgenic group showed significantly higher ALT/AST than high dose parental group on the middle or end of the experiment; but the differences showed no biological significance. There were no significant differences of other serum biochemistry parameters and pathological changes. Conclusion: The results in this study demonstrated that the transgenic maize CC-2 didn't cause any related toxicity in rats.

17.
World J Diabetes ; 15(2): 232-239, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38464372

RESUMO

BACKGROUND: Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important. AIM: To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM. METHODS: For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), etc. were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve. RESULTS: The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels (P < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels (P < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c (r = 0.308, 0.426, and 0.551, respectively) and FBG levels (r = 0.236, 0.231, and 0.298, respectively). CONCLUSION: As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.

18.
Front Pharmacol ; 15: 1327033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469409

RESUMO

Ginsenoside Rg3, a compound derived from Panax ginseng C. A. Mey., is increasingly recognized for its wide range of pharmacological effects. Under the worldwide healthcare challenges posed by heart diseases, Rg3 stands out as a key subject in modern research on Chinese herbal medicine, offering a novel approach to therapy. Mental illnesses are significant contributors to global disease mortality, and there is a well-established correlation between cardiac and psychiatric conditions. This connection is primarily due to dysfunctions in the sympathetic-adrenomedullary system (SAM), the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, and brain-derived neurotrophic factor impairment. This review provides an in-depth analysis of Rg3's therapeutic benefits and its pharmacological actions in treating cardiac and mental health disorders respectively. Highlighting its potential for the management of these conditions, Rg3 emerges as a promising, multifunctional therapeutic agent.

19.
Nat Commun ; 15(1): 2179, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467684

RESUMO

Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.


Assuntos
Ecossistema , Metagenoma , Silicatos , Metagenoma/genética , Metagenômica/métodos
20.
Arch Toxicol ; 98(6): 1629-1643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38536500

RESUMO

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.


Assuntos
Nanopartículas , Organelas , Fibrose Pulmonar , Fuligem , Fuligem/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Humanos , Nanopartículas/toxicidade , Organelas/efeitos dos fármacos , Organelas/metabolismo , Animais , Tamanho da Partícula , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/patologia
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