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1.
Meat Sci ; 217: 109595, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39004037

RESUMO

The purpose of the present study was to investigate the mechanism of gel deterioration of myofibrillar proteins (MP) gels induced by high-temperature treatments based on the protein aggregation and conformation. The results showed that the gel strength and water holding capacity of MP obviously increased and then decreased as the temperature increased, reaching the maximum value at 80 °C (P < 0.05). The microstructure analysis revealed that appropriate temperature (80 °C) contributed to the formation of a more homogeneous, denser, and smoother three-dimensional mesh structure when compared other treatment temperatures, whereas excessive temperature (95 °C) resulted in the formation of heterogeneous and large protein aggregates of MP, decreasing the continuity of gel networks. This was verified by the rheological properties of MP gels. The particle size (D4,3 and D3,2) of MP obviously increased with larger clusters at excessive temperature, and the surface hydrophobicity of MP decreased (P < 0.05), which has been linked to the formation of soluble or insoluble protein aggregates. Tertiary structure and secondary structure results revealed that the proteins had a tendency to be more stretched under higher temperature treatments, which resulted in a decrease in covalent interactions and non-covalent interactions, fostering the over-aggregation of MP. Therefore, our present study indicated that the degradation of MP gels treated at high temperatures was explained by protein aggregation and conformational changes in MP.

2.
Food Chem ; 457: 140214, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38959683

RESUMO

This study investigated the gelling properties, rheological behaviour, and microstructure of heat-induced, low-salt myofibrillar protein (MP) gels containing different levels (2%, 4%, 6%, and 8%, w/w) of cross-linked (CTS) or acetylated (ATS) tapioca starch. The results indicated that either CTS or ATS significantly enhanced the gel strength and water-holding capacity of low-salt MP gels (P < 0.05), an outcome verified by the rheological behaviour test results under different modes. Furthermore, iodine-staining images indicated that the MP-dominated continuous phase gradually transited to a starch-dominated phase with increasing CTS or ATS levels, and 4% was the critical point for this phase transition. In addition, hydrophobic interactions and disulphide bonds constituted the major intermolecular forces of low-salt MP gels, effectively promoting phase transition. In brief, modified tapioca starches possess considerable potential application value in low-salt meat products.

3.
Medicine (Baltimore) ; 103(27): e38764, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968498

RESUMO

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.


Assuntos
Anti-Inflamatórios não Esteroides , Colangiopancreatografia Retrógrada Endoscópica , Quimioterapia Combinada , Nitroglicerina , Pancreatite , Ensaios Clínicos Controlados Aleatórios como Assunto , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Nitroglicerina/uso terapêutico , Nitroglicerina/administração & dosagem , Pancreatite/prevenção & controle , Pancreatite/etiologia , Vasodilatadores/uso terapêutico , Vasodilatadores/administração & dosagem
4.
Meat Sci ; 215: 109554, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38838569

RESUMO

This study investigated the effect of ultrasound (US) combined with pre- and post-addition of κ-carrageenan (KC) on the gelling properties, structural characteristics and rheological behavior of myofibrillar proteins (MP) under low-salt conditions. The results showed that US combined with either pre- or post-addition of KC rendered higher gel strength and water holding capacity (WHC) of MP gels than those treated with US alone and added with KC alone (P < 0.05). US combined with pre-addition of KC facilitated the binding between MP and KC, which enhanced the gel strength and WHC of the mixed MP gels and significantly improved the rheological behavior of MP. This was also confirmed by the highest surface hydrophobicity, disulfide bonds and ß-sheet content of the MP gels with US combined with pre-addition of KC. Moreover, microstructural results reflected a denser structure for the pre-addition of KC in combination with US. However, US combined with post-addition of KC resulted in limited MP unfolding and relatively weak hydrophobic interactions in the composite gels, which were less effective in improving the gel properties of the MP gels. This study provides potential strategies for enhancing the gelling properties of low-salt meat products via application of US and KC.


Assuntos
Carragenina , Manipulação de Alimentos , Géis , Interações Hidrofóbicas e Hidrofílicas , Produtos da Carne , Reologia , Carragenina/química , Animais , Géis/química , Produtos da Carne/análise , Manipulação de Alimentos/métodos , Proteínas Musculares/química , Suínos , Miofibrilas/química
5.
Meat Sci ; 216: 109555, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38850886

RESUMO

In present study, the quality profiles, microstructures and in vitro digestibility of pork chip snacks (PCS) prepared by microwave vacuum drying (MVD) under different drying times (20, 21, 22, 23, and 24 min) were investigated. The results revealed significant decreases in the moisture content and L*-value of PCS, while the protein/ash contents, a*-value, and b*-value of PCS markedly increased with prolonged MVD time (P < 0.05). Additionally, as MVD time extended from 20 to 24 min, the textural characteristics of PCS, particularly brittleness and crunchiness, initially increased and then gradually decreased (P < 0.05). Scanning electron microscopy (SEM) images showed that a moderate MVD time (22 min) resulted in the formation of larger pores in PCS, enhancing brittleness and crunchiness. However, excessive MVD time (24 min) led to the melting of these pores, subsequently reducing the brittleness and crunchiness of PCS. Furthermore, in vitro protein digestibility of PCS gradually decreased with increasing MVD time, primarily attributed to increased protein aggregation, as indicated by changes in sulfhydryl contents. In summary, our findings highlight that PCS subjected to 22 min of MVD exhibited the highest overall acceptability. This study provides a novel strategy for the application of MVD in the processing of meat snacks.

6.
J Nucl Med ; 65(Suppl 1): 38S-45S, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719241

RESUMO

Radiopharmaceuticals play a critical role in nuclear medicine, providing novel tools for specifically delivering radioisotopes for the diagnosis and treatment of cancers. As the starting point for developing radiopharmaceuticals, cancer-specific biomarkers are important and receive worldwide attention. This field in China is currently experiencing a rapid expansion, with multiple radiotracers targeting novel targets being developed and translated into clinical studies. This review provides a brief overview of the exploration of novel imaging targets, preclinical evaluation of their targeting ligands, and translational research in China from 2020 to 2023, for detecting cancer, guiding targeted therapy, and visualizing the immune microenvironment. We believe that China will play an even more important role in the development of nuclear medicine in the world in the future.


Assuntos
Biomarcadores Tumorais , Neoplasias , Traçadores Radioativos , Humanos , China , Biomarcadores Tumorais/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Compostos Radiofarmacêuticos , Animais
7.
Chemistry ; 30(38): e202401350, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38700514

RESUMO

An unprecedented 1,5-addition/N-1,4-addition cascade reaction is established via palladium hydride catalysis. A variety of polysubstituted dihydropyrrole skeletons are constructed in high yield and with exclusively >20 : 1 diastereoselectivity. An enantioselective protocol of this design is also developed to provide a novel access to enantioenriched dihydropyrroles.

8.
Sensors (Basel) ; 24(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38475180

RESUMO

In this study, an electric oil and gas actuator based on fractional-order PID position feedback control is proposed, through which the damping coefficient of the suspension system is adjusted to realize the active control of the suspension. An FOPID algorithm is used to control the motor's rotational angle to realize the damping adjustment of the suspension system. In this process, the road roughness is collected by the sensors as the criterion of damping adjustment, and the particle swarm algorithm is utilized to find the optimal objective function under different road surface slopes, to obtain the optimal cornering value. According to the mathematical and physical model of the suspension system, the simulation model and the corresponding test platform of this type of suspension system are built. The simulation and experimental results show that the simulation results of the fractional-order nonlinear suspension model are closer to the actual experimental values than those of the traditional linear suspension model, and the accuracy of each performance index is improved by more than 18.5%. The designed active suspension system optimizes the body acceleration, suspension dynamic deflection, and tire dynamic load to 89.8%, 56.7%, and 73.4% of the passive suspension, respectively. It is worth noting that, compared to traditional PID control circuits, the FOPID control circuit designed for motors has an improved control performance. This study provides an effective theoretical and empirical basis for the control and optimization of fractional-order nonlinear suspension systems.

9.
Front Pharmacol ; 15: 1285946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318142

RESUMO

Objective: To compare the intervention effects and pharmacoeconomic advantages of Fufang Huangbai Fluid (FFHB) hydropathic compress versus Antimicrobial Calcium Alginate Wound Dressing (ACAWD) in the treatment of diabetic foot infections (DFI). Methods: Patients with DF who were hospitalized in the peripheral vascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2020 to February 2022 and met the inclusion and excluding criteria were allocated into the experimental group and control group through minimization randomization. The experimental group was treated with FFHB hydropathic compress for 2 weeks, while the control group was treated with ACAWD for the same duration. The wound healing of both groups was monitored for 1 month post-discharge. Clinical data from all eligible patients were collected, and differences in various indices between cohorts were analyzed. Results: 22 in the experimental group (including two fell off) and 20 in the control group. After the treatment, the negative rate of wound culture in the experimental group was 30% and that in the control group was 10%, There was no significant difference in the negative rate of wound culture and change trend of minimum inhibitory concentration (MIC) value of drug sensitivity (p > 0.05). The infection control rate of the experimental group was 60%, and that of the control group was 25%. The difference between the two groups was statistically significant (χ2 = 5.013, p = 0.025). The median wound healing rate of the experimental group was 34.4% and that of the control group was 33.3%. There was no significant difference between the two groups (p > 0.05). During the follow-up 1 month later, the wound healing rate in the experimental group was higher, and the difference was statistically significant (p = 0.047). Pharmacoeconomic evaluations indicated that the experimental group had greater cost-effectiveness compared to the control group. Conclusion: In the preliminary study, FFHB demonstrated comparable pathogenic and clinical efficacy to ACAWD in the treatment of mild DF infection, and exhibited superior pharmacoeconomic advantages. With the aid of infection control, the wound healing rate in the FFHB group showed notable improvement. Nevertheless, due to the limited sample size, larger-scale studies are warranted to further validate these findings. Clinical Trial Registration: (https://www.chictr.org.cn/showproj.aspx?proj=66175), identifier (ChiCTR2000041443).

10.
Int J Biol Macromol ; 257(Pt 1): 128569, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065443

RESUMO

This work aimed to investigate the combined effect of ultrasound (US) treatment and κ-carrageenan (KC) addition on the gelling properties and rheological behaviors of myofibrillar protein (MP). Without US treatment, the KC incorporation promoted the gel strength and water-holding capacity (WHC) of MP gels. These properties were further improved by 20 min US treatment with gel strength of 98.61 g and WHC of 79.87 %, which was mainly attributed to changes associated with hydrophobic interactions and disulfide bonds and the transformation from α-helix to ß-sheet in MP gels. In addition, US treatment for 20 min effectively resulted in a more homogeneous polymer distribution of the MP-KC mixed system, leading to lower particle size and the largest G' and G″ values of the MP-KC mixed gels. However, longer US treatment times (30, 40 and 50 min) rendered lower gel strength, WHC, storage modulus and loss modulus of MP-KC mixed gels, which was mainly due to the formation of loose and disordered gel structures. Our present results indicated that the application of US to MP for an intermediate treatment time (20 min) combined with KC provides a potential and novel strategy to promote the gel qualities of heat-induced MP gels.


Assuntos
Proteínas Musculares , Carragenina , Géis/química , Proteínas Musculares/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Reologia
11.
Nat Commun ; 14(1): 4493, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495604

RESUMO

Atomic-scale precision alignment is a bottleneck in the fabrication of next-generation nanoelectronics. In this study, a redox-coupled inherently selective atomic layer deposition (ALD) is introduced to tackle this challenge. The 'reduction-adsorption-oxidation' ALD cycles are designed by adding an in-situ reduction step, effectively inhibiting nucleation on copper. As a result, tantalum oxide exhibits selective deposition on various oxides, with no observable growth on Cu. Furthermore, the self-aligned TaOx is successfully deposited on Cu/SiO2 nanopatterns, avoiding excessive mushroom growth at the edges or the emergence of undesired nucleation defects within the Cu region. The film thickness on SiO2 exceeds 5 nm with a selectivity of 100%, marking it as one of the highest reported to date. This method offers a streamlined and highly precise self-aligned manufacturing technique, which is advantageous for the future downscaling of integrated circuits.

12.
Bioorg Med Chem Lett ; 91: 129382, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37348571

RESUMO

Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synthesized seven ODAP-Urea-Lys derivatives characterized with p-bromobenzyl group conjugated to lysine. The ligands showed medium-to-high potency, with Ki values ranging from 27.9 nM to 0.94 nM. The ligands could be efficiently radiolabeled with 68Ga, in high purity. Radioligands were stable and showed PSMA specific cellular uptake, in PSMA++ LNCaP cells and PSMA+ 22Rv1 cells over PSMA- PC3 cells. MicroPET imaging was performed in 22Rv1 tumor-bearing mice and 68Ga-ligand-1 showed the best characteristics among the seven ligands, with the highest tumor uptake (SUVmax: 0.56 ± 0.07). A biodistribution study was also performed. ODAP-Urea-Lys-p-bromobenzyl could be used to image prostate cancer in vivo, and the ligands could have high binding potency. The future investigation is still necessary to improve the tumor-specific uptake of this class of ligands and reducing the non-specific uptake in normal organs.


Assuntos
Neoplasias da Próstata , Ureia , Masculino , Humanos , Animais , Camundongos , Ureia/química , Lisina/metabolismo , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons/métodos , Ligantes , Distribuição Tecidual , Linhagem Celular Tumoral , Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo
13.
Chemistry ; 29(44): e202301105, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37243903

RESUMO

An expanding body of evidence suggests that specifically targeting hydrogen sulfide (H2 S) might potentially benefit both tumor diagnosis and treatment, but there is still a lack of cancer-targeted molecular tools for in vivo applications. Here, we report the first ligand-directed H2 S-specific near-infrared fluorescent sensor PSMA-Cy7-NBD and scavenger PSMA-Py-NBD that target the prostate-specific membrane antigen (PSMA). PSMA-Cy7-NBD displays a 53-fold off-on fluorescence response to H2 S at 803 nm with high specificity. PSMA-Py-NBD can scavenge H2 S fast (k2 =30.8 M-1 s-1 at 25 °C) without interference from biothiols. Both tools are highly water-soluble and can be transported selectively into PSMA-expressing prostate cancer cells. Endogenous H2 S levels in murine 22Rv1 tumor models can be imaged and downregulated by intravenous injection of PSMA-Cy7-NBD and PSMA-Py-NBD, respectively. These tools could potentially help to investigate H2 S cancer biology and with related therapies.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Neoplasias da Próstata/diagnóstico por imagem , Ligantes , Diagnóstico por Imagem , Linhagem Celular Tumoral
14.
Chem Sci ; 14(9): 2461-2466, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36873849

RESUMO

A conceptually new methodology to give unusual cyclization products from usual migration substrates was disclosed. The highly complex and structurally important and valuable spirocyclic compounds were produced through radical addition, intramolecular cyclization and ring opening instead of usual migration to the di-functionalization products of olefins. Furthermore, a plausible mechanism was proposed based on a series of mechanistic studies including radical trapping, radical clock, verification experiments of intermediates, isotope labeling and KIE experiments.

15.
Nat Commun ; 14(1): 974, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810592

RESUMO

Genetic encoding of noncanonical amino acid (ncAA) for site-specific protein modification has been widely applied for many biological and therapeutic applications. To efficiently prepare homogeneous protein multiconjugates, we design two encodable noncanonical amino acids (ncAAs), 4-(6-(3-azidopropyl)-s-tetrazin-3-yl) phenylalanine (pTAF) and 3-(6-(3-azidopropyl)-s-tetrazin-3-yl) phenylalanine (mTAF), containing mutually orthogonal and bioorthogonal azide and tetrazine reaction handles. Recombinant proteins and antibody fragments containing the TAFs can easily be functionalized in one-pot reactions with combinations of commercially available fluorophores, radioisotopes, PEGs, and drugs in a plug-and-play manner to afford protein dual conjugates to assess combinations of tumor diagnosis, image-guided surgery, and targeted therapy in mouse models. Furthermore, we demonstrate that simultaneously incorporating mTAF and a ketone-containing ncAA into one protein via two non-sense codons allows preparation of a site-specific protein triconjugate. Our results demonstrate that TAFs are doubly bio-orthogonal handles for efficient and scalable preparation of homogeneous protein multiconjugates.


Assuntos
Aminoácidos , Aminoacil-tRNA Sintetases , Animais , Camundongos , Aminoácidos/metabolismo , Proteínas Recombinantes/genética , Fenilalanina , Aminoacil-tRNA Sintetases/metabolismo
16.
Front Immunol ; 14: 1307392, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264661

RESUMO

Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Anti-B-cell-activating factor (BAFF) therapy effectively depletes B cells and reduces SLE disease activity. This research aimed to evaluate the effect of BAFF blockade on B cell receptor (BCR) repertoire and gene expression. Methods: Through next-generation sequencing, we analyzed gene expression and BCR repertoire in MRL/lpr mice that received long-term anti-BAFF therapy. Based on gene expression profiles, we predicted the relative proportion of immune cells using ImmuCellAI-mouse, validating our predictions via flow cytometry and FluoroSpot. Results: The loss of BCR repertoire diversity and richness, along with increased clonality and differential frequency distribution of the immunoglobulin heavy chain variable (IGHV) segment gene usage, were observed in BAFF-blockade mice. Meanwhile, the distribution of complementarity-determining region 3 (CDR3) length and CDR3 amino acid usage remained unaffected. BAFF blockade resulted in extensive changes in gene expression, particularly that of genes related to B cells and immunoglobulins. Besides, the tumor necrosis factor (TNF)-α responses and interferon (IFN)-α/γ were downregulated, consistent with the decrease in IFN-γ and TNF-α serum levels following anti-BAFF therapy. In addition, BAFF blockade significantly reduced B cell subpopulations and plasmacytoid dendritic cells, and caused the depletion of antibody-secreting cells. Discussion: Our comparative BCR repertoire and transcriptome analyses of MRL/lpr mice subjected to BAFF blockade provide innovative insights into the molecular pathophysiology of SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Transcriptoma , Animais , Camundongos , Camundongos Endogâmicos MRL lpr , Modelos Animais de Doenças , Interferon-alfa , Regiões Determinantes de Complementaridade , Receptores de Antígenos de Linfócitos B
17.
Biosensors (Basel) ; 12(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36140113

RESUMO

Detecting residual nasopharyngeal carcinoma (rNPC) can be difficult because of the coexistence of occult tumours and post-chemoradiation changes, which poses a challenge for both radiologists and surgeons using current imaging methods. Currently, molecular imaging that precisely targets and visualises particular biomarkers in tumours may exceed the specificity and sensitivity of traditional imaging techniques, providing the potential to distinguish tumours from non-neoplastic lesions. Here, we synthesised a HER2/SR-BI-targeted tracer to efficiently position NPC and guide surgery in living mice. This bispecific tracer contained the following two parts: IRDye 800 CW, as an imaging reagent for both optical and optoacoustic imaging, and a fusion peptide (FY-35), as the targeting reagent. Both in vitro and in vivo tests demonstrated that the tracer had higher accumulation and longer retention (up to 48 h) in tumours than a single-targeted probe, and realised sensitive detection of tumours with a minimum size of 3.9 mm. By visualising the vascular network via a customised handheld optoacoustic scan, our intraoperative fluorescence molecular imaging system provides accurate guidance for intraoperative tumour resection. Integrating the advantages of both optical and optoacoustic scanning in an intraoperative image-guided system, this method holds promise for depicting rNPC and guiding salvage surgery.


Assuntos
Corantes Fluorescentes , Neoplasias Nasofaríngeas , Animais , Camundongos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia , Imagem Óptica/métodos , Peptídeos
18.
Eur J Nucl Med Mol Imaging ; 49(13): 4427-4439, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35925443

RESUMO

PURPOSE: Accurate identification of nodal status enables adequate neck irradiation for nasopharyngeal carcinoma (NPC). However, most conventional techniques are unable to pick up occult metastases, leading to underestimation of tumor extensions. Here we investigate the clinical significance of carbonic anhydrase IX (CAIX) in human NPC samples, and develop a CAIX-targeted imaging strategy to identify occult lymph node metastases (LNMs) and extranodal extension (ENE) in animal studies. METHODS: A total of 211 NPC samples are performed CAIX staining, and clinical outcomes are analyzed. The metastatic murine models are generated by foot pad injection of NPC cells, and a CAIX-targeted imaging agent (CAIX-800) is intravenously administered. We adopt fluorescence molecular tomography and ultrasonography (US)-guided spectroscopic photoacoustic (sPA) imaging to perform in vivo studies. Histological and immunohistochemical characterization are carried out via node-by-node analysis. RESULTS: For clinical samples, 90.1% (91/101) primary tumors, 73.3% (66/90) metastases, and 100% (20/20) local recurrences are CAIX positive. In metastases group, 84.7% (61/72) nodal metastases and 22.2% (4/18) organ metastases are CAIX positive. CAIX expression in primary tumors is significantly associated with NPC stage and prognosis. For animal studies, CAIX-800-based fluorescence imaging achieves 81.3% sensitivity and 93.8% specificity in detecting occult LNMs in vivo, with a minimum detectable diameter of 1.7 mm. Coupled with CAIX-800, US-guided sPA imaging could not only detect subcapsular deposits of metastatic cancer cells 2 weeks earlier than conventional techniques, but also successfully track pathological ENE. CONCLUSION: CAIX remarkably expresses in human NPCs and stratifies patient prognosis. In preclinical studies, CAIX-800-based imaging successfully identifies occult LNMs and tracks early stage of pathological ENE. This attractive method shows potential in clinic, allowing medical workers to longitudinally monitor nodal status and helping to reduce unnecessary nodal biopsy for patients with NPC. The schematic diagram for the study. CAIX, carbonic anhydrase IX; NPC, nasopharyngeal carcinoma; US, ultrasonography; sPA, spectroscopic photoacoustic.


Assuntos
Anidrases Carbônicas , Neoplasias Nasofaríngeas , Humanos , Camundongos , Animais , Anidrase Carbônica IX/metabolismo , Carcinoma Nasofaríngeo/diagnóstico por imagem , Anidrases Carbônicas/análise , Anidrases Carbônicas/metabolismo , Biomarcadores Tumorais/metabolismo , Prognóstico , Antígenos de Neoplasias/análise , Metástase Linfática , Neoplasias Nasofaríngeas/diagnóstico por imagem , Modelos Animais
19.
Drug Des Devel Ther ; 16: 1885-1896, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747442

RESUMO

Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide tigecycline dosing in different patient subpopulations through comparing the published population pharmacokinetic models of tigecycline, as well as summarizing and determining the potential covariates that markedly influence tigecycline pharmacokinetics. In this review, literature was systematically searched from the PubMed database from inception to March 2022. The articles focusing on population pharmacokinetics for tigecycline in healthy volunteers or patients were included; finally, a total of eight studies were included in this review. NONMEM methods were used in five studies to generate the population pharmacokinetic models. Tigecycline pharmacokinetics were mostly described by a two-compartment model in these included studies. Estimated clearance and volumes of distribution of tigecycline at steady state (Vss) varied widely in different target patient populations, with a range of 7.5-23.1 L/h and 212.7-1087.7 L, respectively. Body-weight and creatinine clearance were the most important predictors of clearance in these studies, while other predictors include age, gender, bilirubin and aspartate aminotransferase. In conclusion, this review showed the large variability of tigecycline population pharmacokinetics, which can provide guide dosing in different target populations. For clinicians, the individual dosing adjustment should be based not only on the indication and pathogen susceptibility but also on the potential important predictors. However, more studies were needed to confirm the necessity of modified dosage regimens in different patient subpopulations.


Assuntos
Antibacterianos , Modelos Biológicos , Antibacterianos/uso terapêutico , Peso Corporal , Bases de Dados Factuais , Humanos , Tigeciclina
20.
Bioorg Med Chem ; 66: 116810, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35580538

RESUMO

Prostate-specific membrane antigen (PSMA) is emerging as a promising target to specifically image prostate cancer. Dual-modality probe combining radionuclide imaging and near-infrared fluorescence navigation targeting PSMA would enable both the preoperative staging and intraoperative detection of the tumor lesions. To overcome one of the key barriers for achieving high contrast imaging at both early and late time points, we optimized the pharmacokinetics of dual-modality probes based on oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA inhibitors recently developed. Four dual-modality probes with variable hydrophilicity were synthesized and evaluated. They displayed good optical properties (λem max = 835 nm, QY = 0.67%-1.50%), high affinity to PSMA (Ki = 2.09 ± 1.71-4.15 ± 2.20 nM) and PSMA specific cellular uptake (0.48 ± 0.01% - 0.64 ± 0.04% IA/105 LNCaP cells) upon labeled with 68Ga. In vivo studies showed that [68Ga]Ga-P3 exhibited an optimum pharmacokinetic property with high specific tumor uptake (SUVmax = 1.88 ± 0.36, at 1 h) in medium level PSMA expressing 22Rv1 tumor model and high tumor-to-muscle ratio (12.56 ± 2.63, at 1 h). Specific fluorescence imaging could also be achieved with high contrast for later time points (tumor-to-background ratio = 11.63 ± 4.16 at 24 h). This study demonstrates that ODAP-Urea-based P3 has the potential for PET imaging and intraoperative optical imaging of prostate cancer.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Diamino Aminoácidos , Linhagem Celular Tumoral , Radioisótopos de Gálio , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Distribuição Tecidual , Ureia
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