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1.
Meat Sci ; 217: 109609, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39067253

RESUMEN

This study aimed to investigate the effect of lysine (Lys) on quality profile promotion and saltiness compensation in reduced­sodium salt frankfurters. The results showed that the cooking loss of reduced­sodium salt frankfurters decreased from 5.63 to 3.45% when the Lys level increased from 0.1 to 0.7%, as well as enhanced water contents and saltiness in a Lys dose-dependent manner. Moreover, the corresponding peak area percentage (A21) of reduced­sodium salt frankfurters remarkably increased from 79.63% to 81.48% with the increased level of Lys. However, a higher level of Lys (≥ 0.5%) obviously reduced the textural properties of reduced­sodium salt frankfurters, which was clearly verified by looser and rougher microstructures. Furthermore, hydrogen bonds were found to be the dominant molecular force in Lys-added reduced­sodium salt frankfurters. Meanwhile, 0.3% Lys was found to exhibit the optimal sodium salt-replacing effect due to the highest degree of quality profile promotion and saltiness compensation. Additionally, directional triangle sensory evaluation further confirmed that the reduced­sodium salt frankfurters treated with 0.3% Lys was perceived to be similar to control frankfurters, resulting a 50% salt-reduction effect. Thus, our results suggested that Lys could be applied as an efficient sodium salt alternative in reduced­sodium salt frankfurters.


Asunto(s)
Lisina , Productos de la Carne , Cloruro de Sodio Dietético , Productos de la Carne/análisis , Humanos , Animales , Cloruro de Sodio Dietético/análisis , Culinaria , Masculino , Agua , Gusto , Femenino , Adulto
2.
Medicine (Baltimore) ; 103(27): e38764, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968498

RESUMEN

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.


Asunto(s)
Antiinflamatorios no Esteroideos , Colangiopancreatografia Retrógrada Endoscópica , Quimioterapia Combinada , Nitroglicerina , Pancreatitis , Ensayos Clínicos Controlados Aleatorios como Asunto , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Nitroglicerina/uso terapéutico , Nitroglicerina/administración & dosificación , Pancreatitis/prevención & control , Pancreatitis/etiología , Vasodilatadores/uso terapéutico , Vasodilatadores/administración & dosificación
3.
Meat Sci ; 217: 109595, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39004037

RESUMEN

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.


Asunto(s)
Geles , Calor , Proteínas Musculares , Miofibrillas , Agregado de Proteínas , Animales , Geles/química , Porcinos , Miofibrillas/química , Proteínas Musculares/química , Interacciones Hidrofóbicas e Hidrofílicas , Reología , Conformación Proteica , Manipulación de Alimentos/métodos , Proteínas de la Carne/química , Tamaño de la Partícula
4.
Food Chem ; 457: 140214, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959683

RESUMEN

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.


Asunto(s)
Geles , Manihot , Transición de Fase , Reología , Almidón , Geles/química , Almidón/química , Manihot/química , Animales , Productos de la Carne/análisis , Acetilación , Proteínas Musculares/química , Miofibrillas/química
5.
Antibodies (Basel) ; 13(3)2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39051328

RESUMEN

Therapeutic antibodies play an important role in the public healthcare system to treat patients with a variety of diseases. Protein characterization using an array of analytical tools provides in-depth information for drug quality, safety, efficacy, and the further understanding of the molecule. A therapeutic antibody candidate MAB1 exhibits unique binding properties to both cation and anion exchange columns at neutral pH. This uniqueness disrupts standard purification processes and necessitates adjustments in manufacturing. This study identifies that the charge heterogeneity of MAB1 is primarily due to the N-terminal cyclization of glutamine to pyroglutamine and, to a lesser extent, succinimide intermediate, deamidation, and C-terminal lysine. Using three approaches, i.e., deferential chemical labeling, H/D exchange, and molecular modeling, the binding to anion exchange resins is attributed to negatively charged patches on the antibody's surface, involving specific carboxylic acid residues. The methodologies shown here can be extended to study protein binding orientation in column chromatography.

6.
Meat Sci ; 215: 109554, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38838569

RESUMEN

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.


Asunto(s)
Carragenina , Manipulación de Alimentos , Geles , Interacciones Hidrofóbicas e Hidrofílicas , Productos de la Carne , Reología , Carragenina/química , Animales , Geles/química , Productos de la Carne/análisis , Manipulación de Alimentos/métodos , Proteínas Musculares/química , Porcinos , Miofibrillas/química
7.
Meat Sci ; 216: 109555, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38850886

RESUMEN

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.


Asunto(s)
Manipulación de Alimentos , Microondas , Bocadillos , Animales , Vacio , Porcinos , Manipulación de Alimentos/métodos , Desecación/métodos , Digestión , Color , Microscopía Electrónica de Rastreo , Productos de la Carne/análisis
8.
J Nucl Med ; 65(Suppl 1): 38S-45S, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38719241

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor , Neoplasias , Trazadores Radiactivos , Humanos , China , Biomarcadores de Tumor/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Radiofármacos , Animales
9.
Chemistry ; 30(38): e202401350, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38700514

RESUMEN

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.

10.
Sensors (Basel) ; 24(5)2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38475180

RESUMEN

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.

11.
Front Pharmacol ; 15: 1285946, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38318142

RESUMEN

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).

12.
Int J Biol Macromol ; 257(Pt 1): 128569, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38065443

RESUMEN

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.


Asunto(s)
Proteínas Musculares , Carragenina , Geles/química , Proteínas Musculares/química , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula , Reología
13.
Nat Commun ; 14(1): 4493, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495604

RESUMEN

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.

14.
Bioorg Med Chem Lett ; 91: 129382, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37348571

RESUMEN

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.


Asunto(s)
Neoplasias de la Próstata , Urea , Masculino , Humanos , Animales , Ratones , Urea/química , Lisina/metabolismo , Radioisótopos de Galio , Tomografía de Emisión de Positrones/métodos , Ligandos , Distribución Tisular , Línea Celular Tumoral , Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo
15.
Chemistry ; 29(44): e202301105, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37243903

RESUMEN

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.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Animales , Ratones , Neoplasias de la Próstata/diagnóstico por imagen , Ligandos , Diagnóstico por Imagen , Línea Celular Tumoral
16.
Chem Sci ; 14(9): 2461-2466, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36873849

RESUMEN

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.

17.
Nat Commun ; 14(1): 974, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36810592

RESUMEN

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.


Asunto(s)
Aminoácidos , Aminoacil-ARNt Sintetasas , Animales , Ratones , Aminoácidos/metabolismo , Proteínas Recombinantes/genética , Fenilalanina , Aminoacil-ARNt Sintetasas/metabolismo
18.
Front Immunol ; 14: 1307392, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38264661

RESUMEN

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.


Asunto(s)
Lupus Eritematoso Sistémico , Transcriptoma , Animales , Ratones , Ratones Endogámicos MRL lpr , Modelos Animales de Enfermedad , Interferón-alfa , Regiones Determinantes de Complementariedad , Receptores de Antígenos de Linfocitos B
19.
Biosensors (Basel) ; 12(9)2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36140113

RESUMEN

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.


Asunto(s)
Colorantes Fluorescentes , Neoplasias Nasofaríngeas , Animales , Ratones , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/cirugía , Imagen Óptica/métodos , Péptidos
20.
Eur J Nucl Med Mol Imaging ; 49(13): 4427-4439, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35925443

RESUMEN

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.


Asunto(s)
Anhidrasas Carbónicas , Neoplasias Nasofaríngeas , Humanos , Ratones , Animales , Anhidrasa Carbónica IX/metabolismo , Carcinoma Nasofaríngeo/diagnóstico por imagen , Anhidrasas Carbónicas/análisis , Anhidrasas Carbónicas/metabolismo , Biomarcadores de Tumor/metabolismo , Pronóstico , Antígenos de Neoplasias/análisis , Metástasis Linfática , Neoplasias Nasofaríngeas/diagnóstico por imagen , Modelos Animales
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