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2.
J Cell Mol Med ; 28(16): e70005, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39159135

RESUMO

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.


Assuntos
Fibrilação Atrial , Cálcio , Átrios do Coração , Camundongos Knockout , Miócitos Cardíacos , Fatores de Transcrição , Animais , Miócitos Cardíacos/metabolismo , Camundongos , Fibrilação Atrial/metabolismo , Fibrilação Atrial/genética , Cálcio/metabolismo , Átrios do Coração/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Sinalização do Cálcio , Potenciais de Ação , Potenciais da Membrana , Masculino
3.
Org Lett ; 26(29): 6225-6229, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39004828

RESUMO

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

4.
Mol Pharm ; 21(8): 4147-4156, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39008899

RESUMO

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [18F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [18F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [18F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [18F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [18F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [18F]FNA-N-CooP to be used for in vivo applications.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Proteína 3 Ligante de Ácido Graxo , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Feminino , Camundongos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Proteína 3 Ligante de Ácido Graxo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Radioisótopos de Flúor/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Linhagem Celular Tumoral , Peptídeos/química , Distribuição Tecidual , Compostos de Sulfidrila/química , Camundongos Nus
5.
J Org Chem ; 89(12): 9098-9102, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38861461

RESUMO

We report the first total synthesis of scleropentaside D, a unique C-glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C-acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.


Assuntos
Taninos Hidrolisáveis , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/síntese química , Estrutura Molecular , Glicosídeos/química , Glicosídeos/síntese química , Glicosídeos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Catálise
6.
Sleep Med Rev ; 77: 101967, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38936220

RESUMO

The quality of sleep plays a significant role in determining human well-being, and studying sleep and sleep disorders using various methods can aid in the prevention and treatment of diseases. Positron emission tomography (PET) is a noninvasive and highly sensitive medical imaging technique that has been widely adopted in the clinic. This review article provides data on research activity related to sleep and sleep apnea and discusses the use of PET in investigating sleep apnea and other sleep disorders. We conducted a statistical analysis of the number of original research articles published on sleep and sleep apnea between 1965 and 2021 and found that there has been a dramatic increase in publications since 1990. The distribution of contributing countries and regions has also undergone significant changes. Although there is an extensive body of literature on sleep research (256,399 original research articles during 1965-2021), PET has only been used in 54 of these published studies, indicating a largely untapped area of research. Nonetheless, PET is a useful tool for identifying connections between sleep disorders and pathological changes in various diseases, including neurological, metabolic, and cardiovascular disorders, as well as cancer. To facilitate the broader use of PET in sleep apnea research, further studies are needed in both clinical and preclinical settings.

7.
Chemistry ; 30(43): e202401501, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38806409

RESUMO

Visible-light-mediated [2+2] photocycloaddition reaction can be considered an ideal solution due to its green and sustainable properties, and is one of the most efficient methods to synthesize four-membered ring motifs. Although research on the [2+2] photocycloaddition of alkynes is challenging because of the diminished reactivity of alkynes, and the more significant ring strain of the products, remarkable achievements have been made in this field. In this article, we highlight the recent advances in visible-light-mediated [2+2] photocycloaddition reactions of alkynes, with focus on the reaction mechanism and the late-stage synthetic applications. Advances in obtaining cyclobutenes, azetines, and oxetene active intermediates continue to be breakthroughs in this fascinating field of research.

8.
Carbohydr Res ; 541: 109166, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815341

RESUMO

Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster comprising ß-1,2-linked mannobioses that in humans induces TNF in vitro and in vivo. The purpose of this study was to analyze whether uptake of acetylated glycoclusters of such ß-1,2-linked mannobioses by human macrophages is dependent on the mannose receptor (CD206) or if it is mediated by transmembrane activation. In mannose receptor blocking assays, monocyte-derived polarized macrophages were incubated with carbohydrate test-compounds and their binding to the mannose receptor was demonstrated as inhibition of FITC-Dextran binding. For 1H NMR spectroscopy, macrophages were incubated with TADM. The cells were collected at 6 and 24 h of incubation, centrifuged and washed twice with PBS. We found dose-dependent blocking of the mannose receptor in macrophage carbohydrate constructs containing free hydroxyl groups, but not by the trivalent acetylated glycocluster molecules. NMR spectroscopic analyses demonstrated that TADM was found in washed cellular pellets after 6-h co-culture, while after 24-h co-culture TADM was no more detectable, suggesting cleavage of the acetyl groups in vitro. The Type 1 immune response enhancing effects of TADM and other, stereochemically and structurally similar, trivalent acetylated glycoclusters may be due to transmembrane uptake of macrophages independent of the mannose receptor.


Assuntos
Lectinas Tipo C , Macrófagos , Receptor de Manose , Lectinas de Ligação a Manose , Receptores de Superfície Celular , Lectinas Tipo C/metabolismo , Lectinas Tipo C/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Receptores de Superfície Celular/metabolismo , Lectinas de Ligação a Manose/metabolismo , Lectinas de Ligação a Manose/química , Humanos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Acetilação
9.
Adv Mater ; : e2403766, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780131

RESUMO

Inspired by intriguing color changeable ability of natural animals, the design and fabrication of artificial mechanochromic materials capable of changing colors upon stretching or pressing have attracted intense scientific interest. Liquid crystal (LC) is a self-organized soft matter with anisotropic molecular alignment. Due to the sensitivity to various external stimulations, LC has been considered as an emerging and appealing responsive building block to construct intelligent materials and advanced devices. Recently, mechanochromic LC materials have becoming a hot topic in multi fields from flexible artificial skins to visualized sensors and smart biomimetic devices. In this review, the recent progress of mechanochromic LCs is comprehensively summarized. Firstly, the mechanism and functionalities of mechanochromic LC is introduced, followed by preparation of various functional materials based on mechanochromic LCs. Then the applications of mechanochromic LCs are provided. Finally, the conclusion and outlooks of this field is given. This overview is hoped to provide inspiration in fabrication of advanced functional soft materials for scientists and engineers from multidisciplines including materials science, elastomers, chemistry and physical science. This article is protected by copyright. All rights reserved.

10.
EJNMMI Radiopharm Chem ; 9(1): 42, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753262

RESUMO

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This selection of highlights provides commentary on 24 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

11.
Front Mol Neurosci ; 17: 1289476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646099

RESUMO

Social memory is the ability to discriminate between familiar and unknown conspecifics. It is an important component of social cognition and is therefore essential for the establishment of social relationships. Although the neural circuit mechanisms underlying social memory encoding have been well investigated, little focus has been placed on the regulatory mechanisms of social memory processing. The dopaminergic system, originating from the midbrain ventral tegmental area (VTA), is a key modulator of cognitive function. This study aimed to illustrate its role in modulating social memory and explore the possible molecular mechanisms. Here, we show that the activation of VTA dopamine (DA) neurons is required for the formation, but not the retrieval, of social memory. Inhibition of VTA DA neurons before social interaction, but not 24 h after social interaction, significantly impaired social discrimination the following day. In addition, we showed that the activation of VTA DA neurons was regulated by the serine/threonine protein kinase liver kinase B1 (Lkb1). Deletion of Lkb1 in VTA DA neurons reduced the frequency of burst firing of dopaminergic neurons. Furthermore, Lkb1 plays an important role in regulating social behaviors. Both genetic and virus-mediated deletions of Lkb1 in the VTA of adult mice impaired social memory and subsequently attenuated social familiarization. Altogether, our results provide direct evidence linking social memory formation to the activation of VTA DA neurons in mice and illustrate the crucial role of Lkb1 in regulating VTA DA neuron function.

12.
Nat Commun ; 15(1): 3401, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649350

RESUMO

N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, and stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N-glycosides by leveraging copper metallaphotoredox catalysis, in which stable and readily available 1-hydroxy carbohydrates are activated for direct N-glycosylation. Our method employs inexpensive photo- and copper- catalysts and can tolerate some extent of water. The reaction exhibits a broad substrate scope, encompassing 76 examples, and demonstrates high stereoselectivity, favoring 1,2-trans selectivity for furanoses and α-selectivity for pyranoses. It also exhibits high site-selectivity for substrates containing multiple N-atoms. The synthetic utility is showcased through the late-stage functionalization of bioactive compounds and pharmaceuticals like Olaparib, Axitinib, and Metaxalone. Mechanistic studies prove the presence of glycosyl radicals and the importance of copper metallaphotoredox catalysis.

13.
Foods ; 13(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611353

RESUMO

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

14.
Phys Rev Lett ; 132(11): 110801, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563910

RESUMO

Reducing the average resource consumption is the central quest in discriminating non-orthogonal quantum states for a fixed admissible error rate ϵ. The globally optimal fixed local projective measurement for this task is found to be different from that for previous minimum-error discrimination tasks [S. Slussarenko et al., Phys. Rev. Lett. 118, 030502 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.030502]. To achieve the ultimate minimum average consumption, here we develop a general globally optimal adaptive strategy (GOA) by subtly using the updated posterior probability, which works under any error rate requirements and any one-way measurement restrictions, and can be solved by a convergent iterative relation. First, under the local measurement restrictions, our GOA is solved to serve as the local bound, which saves 16.6 copies (24%) compared with the previously best globally optimal fixed local projective measurement. When the more powerful two-copy collective measurements are allowed, our GOA is experimentally demonstrated to beat the local bound by 3.9 copies (6.0%). By exploiting both adaptivity and collective measurements, our Letter marks an important step toward minimum-consumption quantum state discrimination.

15.
Eur J Nucl Med Mol Imaging ; 51(8): 2216-2228, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38532026

RESUMO

PURPOSE: Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[18F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer's ability to target the macrophage mannose receptor CD206. METHODS: First, the uptake of intravenously (i.v.) administered Al[18F]F-NOTA-D10CM was compared between wild-type (WT) and CD206-/- knockout (KO) mice. C57BL/6N mice were injected with complete Freund's adjuvant (CFA) in the left hind leg and the uptake of Al[18F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14 days after CFA induction of inflammation. Healthy C57BL/6N mice were studied as controls. Mice underwent PET/CT on consecutive days with [18F]FDG, i.v. Al[18F]F-NOTA-D10CM, and i.d. Al[18F]F-NOTA-D10CM. After the last imaging, Al[18F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[18F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining. RESULTS: Compared with WT mice, the uptake of Al[18F]F-NOTA-D10CM was significantly lower in several CD206-/- KO mice tissues, including liver (SUV 8.21 ± 2.51 vs. 1.06 ± 0.16, P < 0.001) and bone marrow (SUV 1.63 ± 0.37 vs. 0.22 ± 0.05, P < 0.0001). The uptake of i.v. injected Al[18F]F-NOTA-D10CM was significantly higher in inflamed ankle joint (SUV 0.48 ± 0.13 vs. 0.18 ± 0.05, P < 0.0001) and inflamed foot pad skin (SUV 0.41 ± 0.10 vs. 0.04 ± 0.01, P < 0.0001) than in the corresponding tissues in healthy mice. The i.d.-injected Al[18F]F-NOTA-D10CM revealed differences between CFA-induced lymph node activation and lymph nodes in healthy mice. Ex vivo γ-counting, autoradiography, and immunohistochemistry supported the results, and a decrease of ~ 80% in the binding of Al[18F]F-NOTA-D10CM in the displacement study with excess NOTA-D10CM confirmed that tracer binding was specific. At 60 min after i.v. injection, an average 96.70% of plasma radioactivity was derived from intact Al[18F]F-NOTA-D10CM, indicating good in vivo stability. The uptake of Al[18F]F-NOTA-D10CM into inflamed tissues was positively associated with the area percentage of CD206-positive staining. CONCLUSION: The uptake of mannosylated dextran derivative Al[18F]F-NOTA-D10CM correlated with CD206 expression and the tracer appears promising for inflammation imaging.


Assuntos
Dextranos , Radioisótopos de Flúor , Lectinas Tipo C , Receptor de Manose , Lectinas de Ligação a Manose , Receptores de Superfície Celular , Animais , Camundongos , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Lectinas de Ligação a Manose/metabolismo , Distribuição Tecidual , Dextranos/química , Manose/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Marcação por Isótopo , Compostos Heterocíclicos com 1 Anel
16.
Phys Rev Lett ; 132(8): 080202, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38457709

RESUMO

Quantum measurements based on mutually unbiased bases (MUBs) play crucial roles in foundational studies and quantum information processing. It is known that there exist inequivalent MUBs, but little is known about their operational distinctions, not to say experimental demonstration. In this Letter, by virtue of a simple estimation problem, we experimentally demonstrate the operational distinctions between inequivalent triples of MUBs in dimension 4 based on high-precision photonic systems. The experimental estimation fidelities coincide well with the theoretical predictions with only 0.16% average deviation, which is 25 times less than the difference (4.1%) between the maximum estimation fidelity and the minimum estimation fidelity. Our experiments clearly demonstrate that inequivalent MUBs have different information extraction capabilities and different merits for quantum information processing.

17.
EJNMMI Radiopharm Chem ; 9(1): 16, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393497

RESUMO

BACKGROUND: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression. RESULTS: The prosthetic compound 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6-[18F]fluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S-acylation instead of the expected N-acylation, and the chemical identity of the product [18F]FNA-S-ACooP was confirmed. In the in vitro binding experiments, [18F]FNA-S-ACooP exhibited heterogeneous and high focal binding in malignant tissue sections, where we also observed abundant FABP3 positivity by immunofluorescence staining. Blocking study further confirmed the [18F]FNA-S-ACooP binding specificity. CONCLUSIONS: FABP3 targeted ACooP peptide was successfully radiolabeled by S-acylation using 6-[18F]fluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed [18F]FNA-S-ACooP binding specificity. Further preclinical studies of [18F]FNA-S-ACooP are warranted.

18.
J Nucl Med ; 65(1): 132-138, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37973184

RESUMO

[68Ga]Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvß3 integrin, which is upregulated during angiogenesis soon after acute myocardial infarction (AMI). We prospectively evaluated determinants of myocardial uptake of [68Ga]Ga-NODAGA-RGD and its associations with left ventricular (LV) function in patients after AMI. Methods: Myocardial blood flow and [68Ga]Ga-NODAGA-RGD uptake (60 min after injection) were evaluated by PET in 31 patients 7.7 ± 3.8 d after primary percutaneous coronary intervention for ST-elevation AMI. Transthoracic echocardiography of LV function was performed on the day of PET and at the 6-mo follow-up. Results: PET images showed increased uptake of [68Ga]Ga-NODAGA-RGD in the ischemic area at risk (AAR), predominantly in injured myocardial segments. The SUV in the segment with the highest uptake (SUVmax) in the ischemic AAR was higher than the SUVmean of the remote myocardium (0.73 ± 0.16 vs. 0.51 ± 0.11, P < 0.001). Multivariable predictors of [68Ga]Ga-NODAGA-RGD uptake in the AAR included high peak N-terminal pro-B-type natriuretic peptide (P < 0.001), low LV ejection fraction, low global longitudinal strain (P = 0.01), and low longitudinal strain in the AAR (P = 0.01). [68Ga]Ga-NODAGA-RGD uptake corrected for myocardial blood flow and perfusable tissue fraction in the AAR predicted improvement in global longitudinal strain at follow-up (P = 0.002), independent of peak troponin, N-terminal pro-B-type natriuretic peptide, and LV ejection fraction. Conclusion: [68Ga]Ga-NODAGA-RGD uptake shows increased αvß3 integrin expression in the ischemic AAR early after AMI that is associated with regional and global systolic dysfunction, as well as increased LV filling pressure. Increased [68Ga]Ga-NODAGA-RGD uptake predicts improvement of global LV function 6 mo after AMI.


Assuntos
Integrina beta3 , Infarto do Miocárdio , Humanos , Peptídeo Natriurético Encefálico , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Gálio , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/metabolismo , Oligopeptídeos , Integrina alfaVbeta3/metabolismo
19.
China Occupational Medicine ; (6): 116-120, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1038738

RESUMO

ObjectiveTo analyze the causes of occupational acute 1,2-dichloroethane (1,2-DCE) poisoning accident during the use of polyurethane grouting materials for waterproof plugging operation in the construction industry. Methods By combining the clinical symptoms of the patient, worksite survey of occupational health and workplace occupational hazards monitoring method, the cause of an occupational acute 1,2-DCE poisoning accident was investigated at a construction site during the use of polyurethane grouting material for waterproofing and plugging operations. Results The patient was engaged in waterproof grouting work using polyurethane grouting material. The main volatile organic components in the raw materials were 1,2-DCE, with traces of dichloromethane, methyl acetate and others. The result of post-incident on-site investigation showed that the short-term exposure concentration of 1,2-DCE in the workplace air was 578.70 mg/m3, which was more than 30 times higher than the national occupational health standard limit. The mass concentration of 1,2-DCE in the patient's blood was 230 μg/L. Combined with the patient's occupational hazard exposure history, clinical manifestations, worksite survey of occupational health, and laboratory test results, according to GBZ 39-2016 Diagnosis of Occupational Acute 1,2-Dichloroethane Poisoning, this incident was diagnosed as a severe occupational acute 1,2-DCE poisoning event caused by the use of inferior polyurethane grouting material. Conclusion The excessive concentration of 1,2-DCE in the workplace air is the main cause of this poisoning accident. Construction sites with confined space operations should improve various occupational health management systems, occupational health engineering protective facilities, and personal protective equipment must be provided for workers.

20.
Journal of Clinical Hepatology ; (12): 351-355, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1007251

RESUMO

ObjectiveTo investigate the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) combined with electrohydraulic lithotripsy under the direct view of eyeMax biliary-pancreatic imaging system in the treatment of difficult choledocholithiasis. MethodsA retrospective analysis was performed for the clinical data of 12 patients with difficult choledocholithiasis who underwent ERCP and electrohydraulic lithotripsy under the direct view of eyeMax biliary-pancreatic imaging system in Department of Gastroenterology, Jilin People’s Hospital, from May to November 2022. The clinical effect of lithotripsy and lithotomy was observed, and postoperative complications and time of surgical operation were assessed. ResultsAmong the 12 patients, 11 (91.67%) were successfully treated by electrohydraulic lithotripsy under direct view, 9 (75.00%) achieved first-attempt success in lithotripsy, and 11 (91.67%) had complete removal of calculi; 1 patient was found to have stenosis of the bile ducts caused by multiple biliary tract surgeries, and grade Ⅱ intrahepatic bile duct stones above the sites of stenosis were removed under direct view, but there were still residues of grade Ⅲ intrahepatic bile duct stones, which led to the fact that complete calculus removal was not achieved. The mean time of ERCP operation was 91.3±26.2 minutes, including a time of 41.8±22.2 minutes for energy lithotripsy. There were 2 cases of postoperative biliary tract infection which were improved after anti-infective therapy, 2 cases of hyperamylasemia which were not given special treatment, and 3 cases of mild pancreatitis which were improved after symptomatic medication, and there were no complications such as bleeding and perforation. ConclusionERCP combined with electrohydraulic lithotripsy under the direct view of eyeMax biliary-pancreatic imaging system is safe, effective, and feasible in the treatment of difficult choledocholithiasis.

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