ABSTRACT
Transglutaminase (TGase)-catalyzed crosslinking has gained substantial traction as a novel strategy for reducing allergenic risk in food proteins, particularly within the realm of hypoallergenic food production. This study explored the impact of TGase crosslinking on conformational changes in a binary protein system composed of soy protein isolate (SPI) and sodium caseinate (SC) at varying mass ratios (10:0, 7:3, 5:5, 3:7 (w/w)). Specifically, the immunoglobulin E (IgE) binding capacity of soy proteins within this system was examined. Prolonged TGase crosslinking (ranging from 0 h to 15 h) resulted in a gradual reduction in IgE reactivity across all SPI-SC ratios, with the order of IgE-binding capability as follows: SPI > SPI5-SC5 > SPI7-SC3 > SPI3-SC7. These alterations in protein conformation following TGase crosslinking, as demonstrated by variable intrinsic fluorescence, altered surface hydrophobicity, increased ultraviolet absorption and reduced free sulfhydryl content, were identified as the underlying causes. Additionally, ionic bonds were found to play a significant role in maintaining the structure of the dual-protein system after crosslinking, with hydrophobic forces and hydrogen bonds serving as supplementary forces. Generally, the dual-protein system may exhibit enhanced efficacy in reducing the allergenicity of soy protein.
Subject(s)
Immunoglobulin E , Protein Conformation , Soybean Proteins , Transglutaminases , Transglutaminases/chemistry , Transglutaminases/metabolism , Soybean Proteins/chemistry , Soybean Proteins/immunology , Immunoglobulin E/immunology , Immunoglobulin E/metabolism , Cross-Linking Reagents/chemistry , Hydrophobic and Hydrophilic Interactions , Humans , Caseins/chemistry , Caseins/metabolism , Caseins/immunologyABSTRACT
BACKGROUND: Food allergies are a growing concern worldwide, with soy proteins being important allergens that are widely used in various food products. This study investigated the potential of transglutaminase (TGase) and lactic acid bacteria (LAB) treatments to modify the allergenicity and structural properties of soy protein isolate (SPI), aiming to develop safer soy-based food products. RESULTS: Treatment with TGase, LAB or their combination significantly reduced the antibody reactivity of ß-conglycinin and the immunoglobulin E (IgE) binding capacity of soy protein, indicating a decrease in allergenicity. TGase treatment led to the formation of high-molecular-weight aggregates, suggesting protein crosslinking, while LAB treatment resulted in partial protein hydrolysis. These structural changes were confirmed by Fourier transform infrared spectroscopy, which showed a decrease in ß-sheet content and an increase in random coil and ß-turn contents. In addition, changes in intrinsic fluorescence and ultraviolet spectroscopy were also observed. The alterations in protein interaction and the reduction in free sulfhydryl groups highlighted the extensive structural modifications induced by these treatments. CONCLUSION: The synergistic application of TGase and LAB treatments effectively reduced the allergenicity of SPI through significant structural modifications. This approach not only diminished antibody reactivity of ß-conglycinin and IgE binding capacity of soy protein but also altered the protein's primary, secondary and tertiary structures, suggesting a comprehensive alteration of SPI's allergenic potential. These findings provide a promising strategy for mitigating food allergy concerns and lay the foundation for future research on food-processing techniques aimed at allergen reduction. © 2024 Society of Chemical Industry.
ABSTRACT
BACKGROUND: The main challenge in follow-up duration of patients with brain metastases after stereotactic radiotherapy is to distinguish between pseudo-progression and tumor recurrence. The objective of this study is to retrospectively analyze the predictive factors. METHODS: The study included 123 patients with enlarged brain metastases after hypo-fractionated radiotherapy in our center from March 2009 to October 2019, and the baseline clinical features, radiotherapy planning parameters, and enhanced magnetic resonance imaging before and after radiation therapy were analyzed. Logistic regression was performed to compare the differences between groups. Independent risk factors with P < 0.05 and associated with recurrence were used to establish a nomogram prediction model and validated by Bootstrap repeated sampling, which was validated in an internal cohort (n = 23) from October 2019 to December 2021. RESULTS: The median follow-up time was 68.4 months (range, 8.9-146.2 months). A total of 76 (61.8%) patients were evaluated as pseudo-progression, 47 patients (38.2%) were evaluated as tumor recurrence. The median time to pseudo-progression and tumor recurrence were 18.3 months (quartile range, 9.4-27.8 months) and 12.9 months (quartile range, 8.7-19.6 months) respectively. Variables associated with tumor recurrence included: gross tumor volume ≥ 6 cc, biological effective dose < 60 Gy, target coverage < 96% and no targeted therapy. The area under curve values were 0.730 and 0.967 in the training and validation cohorts, respectively. Thirty-one patients received salvage therapy in the tumor recurrence group. The survival time in pseudo-progression and tumor recurrence groups were 66.3 months (95% CI 56.8-75.9 months) and 39.6 months (95% CI 29.2-50.0 months, respectively; P = 0.001). CONCLUSIONS: Clinical and dosimetry features of hypo-fractionated radiation therapy based on enhanced brain magnetic resonance can help distinguish pseudo-progression from tumor recurrence after hypo-fractionated radiotherapy for brain metastases. Gross tumor volume, biological effective dose, target coverage, and having received targeted therapy or not were factors associated with the occurrence of tumor recurrence, and the individual risk could be estimated by the nomogram effectively.
Subject(s)
Brain Neoplasms , Radiosurgery , Humans , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/etiology , Retrospective Studies , Treatment Outcome , Brain Neoplasms/secondary , Radiosurgery/methods , Dose Fractionation, RadiationABSTRACT
With rapid urbanization, contradictions between rapid economic development and a lack of spiritual culture become increasingly complicated. Accessibility is a useful spatial quantitative index to evaluate the spiritual and cultural construction of the city. Amongst various accessibility methods, the two-step floating catchment area (2SFCA) method is suitable for evaluating cultural urban land use (CULU) based on its advantage of flexibility and rationality. This study selects Xi'an as the representative ancient city. Based on comparing accessibility results between different travel modes (walk, bus, subway, and total), and analyzing through statistics, Z-score, and comparison of classification, comparison of a particular area, we obtain the characteristics of CULU accessibility in Xi'an. Firstly, for different travel modes, the distribution of CULU accessibility value in Xi'an is imbalanced, and the accessibility value of bus and subway is closely related to public transport resources. Secondly, CULU in Xi'an has apparent features of being dense in the center, sparse in the suburbs, and lack edge, which correspond to the development of the city. Finally, about 60% accessibility value is contributed by historical CULU, which reflects the typical characteristics of Xi'an as an ancient city with rich historical resources. This study profoundly analyses the attributes of CULU in Xi'an and provides essential data for decision-makers. Furthermore, it gives a significant exploration for building a CULU evaluation system in the future.
ABSTRACT
Esophageal carcinosarcoma is a rare type of esophageal cancer; however, few studies have investigated the effects of radiotherapy in locally advanced patients. This study aimed to report experience of the safety and efficacy of intensity-modulated radiotherapy for locally advanced esophageal carcinosarcoma and review the literature. By searching the institutional database between January 2010 and December 2020, along with the literature review, 25 patients were eligible for the study. The clinical and radiologic information of all patients with esophageal carcinosarcoma who underwent radiotherapy were collected. Survival outcomes were calculated using Kaplan-Meier plots. In our series, 5 patients were in the curative/neoadjuvant radiotherapy group and 10 patients were in the adjuvant group. Most tumors were protruding (n = 10, 66.7%). All patients underwent intensity-modulated radiotherapy. In the curative/neoadjuvant radiotherapy group, 2 patients underwent concurrent chemoradiotherapy before surgery, and the other three received radiotherapy alone as the initial treatment. The median follow-up time was 43.1 months. All patients showed a partial response at the efficacy evaluation. The median time of overall survival and progression-free survival were 40.2 months (95% confidence interval [CI], 13.1-67.3 months) and 19.0 months (95% CI, 13.9 months-24.1 months) for the entire cohort, but were not reached for curative/neoadjuvant radiotherapy group. Overall survival (hazard ratio [HR] 0.81, 95% CI, 0.15-4.43; P = .805) and progression-free survival (HR 1.68, 95% CI, 0.35-8.19; P = .514) did not differ significantly between the 2 groups. When considering the literature review data in the final analysis, overall survival (HR 0.84, 95% CI, 0.25-2.81; P = .779) and progression-free survival (HR, 0.68; 95% CI, 0.26-1.76; P = .425) were also not different between the 2 groups. Treatment based on intensity-modulated radiotherapy with neoadjuvant or curative intent may be an option for patients with unresectable esophageal carcinosarcoma. Further research with a larger sample size is needed to validate the reliability.
Subject(s)
Carcinosarcoma , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Radiotherapy, Intensity-Modulated , Humans , Disease-Free Survival , Reproducibility of Results , Esophageal Neoplasms/pathology , Carcinosarcoma/radiotherapyABSTRACT
PURPOSE: Fast and accurate delineation of organs on treatment-fraction images is critical in magnetic resonance imaging-guided adaptive radiotherapy (MRIgART). This study proposes a personalized auto-segmentation (AS) framework to assist online delineation of prostate cancer using MRIgART. METHODS: Image data from 26 patients diagnosed with prostate cancer and treated using hypofractionated MRIgART (5 fractions per patient) were collected retrospectively. Daily pretreatment T2-weighted MRI was performed using a 1.5-T MRI system integrated into a Unity MR-linac. First-fraction image and contour data from 16 patients (80 image-sets) were used to train the population AS model, and the remaining 10 patients composed the test set. The proposed personalized AS framework contained two main steps. First, a convolutional neural network was employed to train the population model using the training set. Second, for each test patient, the population model was progressively fine-tuned with manually checked delineations of the patient's current and previous fractions to obtain a personalized model that was applied to the next fraction. RESULTS: Compared with the population model, the personalized models substantially improved the mean Dice similarity coefficient from 0.79 to 0.93 for the prostate clinical target volume (CTV), 0.91 to 0.97 for the bladder, 0.82 to 0.92 for the rectum, and 0.91 to 0.93 for the femoral heads, respectively. CONCLUSIONS: The proposed method can achieve accurate segmentation and potentially shorten the overall online delineation time of MRIgART.
Subject(s)
Prostatic Neoplasms , Radiotherapy, Image-Guided , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Neural Networks, Computer , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/methods , Retrospective StudiesABSTRACT
PURPOSE: The high intracranial efficacy of targeted therapeutic agents poses a challenge in determining the optimal sequence of local radiation therapy (RT) and systemic treatment with tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). Therefore, we conducted a cohort study to elucidate the appropriate treatment strategy, either upfront RT or deferred RT including a toxicity assessment, in these patients. PATIENTS AND METHODS: We retrospectively evaluated patients with gene-driven BMs from a single institution and divided them into deferred and upfront RT groups. Survival was estimated using a log-rank test. Intracranial progression was estimated using Fine-Gray competing risks model. Cox proportional hazards regression was performed for multivariable analysis in the entire group and subgroups. RESULTS: Among the 198 eligible patients, 94 and 104 patients received deferred and upfront RT, respectively. The upfront RT group showed a lower intracranial progression risk with an adjusted sub-distribution hazard ratios of 0.41 (95% CI, 0.30-0.57) than did the deferred RT group (median intracranial progression-free survival [iPFS], 19.9 months vs. 11.1 months; p < 0.001). The median overall survival (OS; 43.2 months vs. 49.1 months, p = 0.377) and BM-specific survival (92.1 months vs. 82.9 months, p = 0.810) after salvage therapy were not significantly different between the upfront and deferred groups. Among patients with progressed extracranial disease, the deferred RT group showed significantly better OS than did the upfront RT group (44.0 vs. 28.1 months, p = 0.022). Grade 3-4 treatment-related adverse events were rare, and similar toxicities were observed between the two groups. CONCLUSION: Compared to the deferred RT group, the upfront RT group achieved longer iPFS and similar survival outcomes in most patients with gene-driven NSCLC BM, although patients with progression of extracranial disease might benefit from deferred RT. Both groups showed well-tolerated toxicities. TRIAL REGISTRATION ID: NCT04832672.
ABSTRACT
OBJECTIVE: To investigate the clinical outcomes of hypofractionated radiotherapy for adrenal metastases. MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with adrenal metastases and treated with hypofractionated radiotherapy, who did not receive adrenalectomy or have disease progression after chemotherapy, from 2007 to 2019. The Kaplan-Meier method was used to estimate local control rate (LCR), progression-free survival (PFS), and overall survival (OS). Univariate analysis was performed using Log rank test. RESULTS: Thirty-five patients with 42 lesions were enrolled, and the lung was the most common primary site (80.0%). The median follow-up time was 46.4 months. The median volume of GTV and PTV was 23.2 cm3 (range: 3.5-97.8 cm3) and 38.3 cm3 (range: 10.2-135.6 cm3), respectively. The main dose regimens were 60 Gy delivered in 4-15 fractions, with the median dose of PTV being 60 Gy (range: 40-66.3 Gy) and the biologically effective dose (BED) being 84 Gy (range: 56-110 Gy). The 1-year and 2-year LCR, OS, and PFS were 92.7% and 88.1%, 76.9% and 45.4%, and 25.1% and 14.4%, respectively. Univariate analysis showed that chemotherapy, disease-free interval from primary disease diagnosis to adrenal metastases diagnosis, and age were significant factors for LCR, OS, and PFS, respectively (p=0.017, 0.049, and 0.004, respectively). No more than grade III toxicities were observed. CONCLUSION: As a non-invasive approach, hypofractionated radiotherapy is safe and effective for metastatic adrenal lesions, without serious complications.
ABSTRACT
PURPOSE: Complex brain metastases (BMs), such as large lesions, lesions within or close to eloquent locations, or multiple recurrent/progressive BMs, remain the most challenging forms of brain cancer because of decreased intracranial control rates and poor survival. In the present study, we report the results from a single institutional phase II trial of concurrent temozolomide (TMZ) with hypofractionated stereotactic radiotherapy (HFSRT) in patients with complex brain metastases, including assessment of its feasibility and toxicity. PATIENTS AND METHODS: Fifty-four patients with histologically proven primary cancer and complex BMs were enrolled between 2010 and 2015. All the patients were treated with concurrent HFSRT and TMZ (administrated orally at a dosage of 75 mg/m2 per day for at least 20 days). The primary endpoint was overall survival (OS). RESULTS: The median follow-up time was 30.6 months. The local control rates at 1 and 2 years were 96% and 82%, respectively. The median OS was 17.4 months (95% confidence interval [CI], 12.6-22.2), and the OS rates at 1 and 2 years were 65% (95% CI, 52%-78%) and 33% (19%-47%). Only six patients (15.8%) died of intracranial disease. The median brain metastasis-specific survival was 46.9 months (95% CI, 35.5-58.4). Treatment-related grade 3-4 adverse events were rare and included one grade 3 hematological toxicity and two grade 3 liver dysfunctions. CONCLUSION: Treatment using HFSRT concurrent with TMZ was well tolerated and could significantly extend OS compared with historical controls in complex BMs. Large randomized clinical trials are warranted. Trial registration ID: NCT02654106. IMPLICATIONS FOR PRACTICE: The treatment using hypofractionated stereotactic radiotherapy concurrent with temozolomide appeared to be safe and could significantly extend overall survival compared with historical control in complex brain metastases. Large randomized clinical trials are warranted to verify our results.
Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Drug-Related Side Effects and Adverse Reactions/pathology , Temozolomide/administration & dosage , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Combined Modality Therapy , Disease-Free Survival , Dose Fractionation, Radiation , Drug-Related Side Effects and Adverse Reactions/classification , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Radiosurgery/adverse effects , Temozolomide/adverse effects , Treatment OutcomeABSTRACT
Adulteration of meat products and costly animal-derived commodities with their inferior/cheaper counterparts is a grievous global problem. Species authentication is still technical challenging, especially to those deep processed products. The present study described the design of seven sets of species-specific primer based on a high heterozygous region of mitochondrial cytochrome c oxidase subunit I (COI) gene. These primers were proven to have high species specificity and no cross-reactions and unexpected products to different DNA source. Multiplex PCR assay was achieved for rapid and economical identification of four commonly consumed meats (pork, beef, chicken, and mutton). The conventional PCR assay was sensitive down to 0.001 ng of DNA template in the reactant. The developed method was also powerful in detecting as low as 0.1-mg adulterated pork (0.05 % in wt/wt) in an artificial counterfeited mutton. Validation test showed that the assay is specific, reproducible, and robust in commercial deep processed meats, leatherware, and feather commodities. This proposed method will be greatly beneficial to the consumers, food industry, leather, and feather commodity manufacture.