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Keywords = immune-fragile profile

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19 pages, 2858 KB  
Article
An Immuno-Fragile Profile Is Associated with Mortality Risk in Patients with Chronic Kidney Disease
by Noemí Ceprián, Irene Martínez de Toda, Paula Jara Caro, Claudia Yuste, Gemma Valera-Arévalo, Ignacio González de Pablos, Andrea Figuer, Matilde Alique, Rafael Ramírez, Enrique Morales and Julia Carracedo
Biomedicines 2025, 13(10), 2370; https://doi.org/10.3390/biomedicines13102370 - 27 Sep 2025
Abstract
Background/Objectives: Patients with chronic kidney disease (CKD) face higher risks of infections, poor vaccine responses, and cardiovascular diseases, leading to increased morbidity and mortality due to immune dysfunction and frailty. This study aims to evaluate immune status and frailty in CKD patients across [...] Read more.
Background/Objectives: Patients with chronic kidney disease (CKD) face higher risks of infections, poor vaccine responses, and cardiovascular diseases, leading to increased morbidity and mortality due to immune dysfunction and frailty. This study aims to evaluate immune status and frailty in CKD patients across different treatments, examine the influence of frailty on immune status, and link these factors to mortality. Methods: A total of 174 participants were included (end-stage renal disease, ESRD n = 40; hemodialysis, HD n = 40; peritoneal dialysis, n = 36; kidney transplant patients, n = 40; healthy subjects n = 18). Immunophenotyping of lymphocyte and monocyte subpopulations was performed, and frailty was assessed using the Edmonton Frail Scale. Principal component analysis (PCA) integrated immune and frailty variables to define an “immuno-fragile profile,” and survival was monitored for up to six years. Results: CKD patients, especially those on HD, showed decreased lymphocyte counts and proinflammatory monocyte subpopulations with increased expression of costimulatory molecules (B7.2/CD86 and ICAM-1/CD54). Frailty was most prevalent in HD patients (53%), with notable sex differences. PCA identified three components—lymphocyte counts, monocyte co-stimulatory expression, and frailty—that together explained 70% of the variance. Survival analysis revealed that patients with lower lymphocyte counts and higher frailty scores had increased mortality risk, especially in the HD and ESRD groups. Cox regression confirmed that the immuno-fragile profile independently predicted mortality. Conclusions: The integration of immune alterations and frailty defines an immuno-fragile profile strongly associated with mortality in CKD patients, which may serve as a robust prognostic tool to improve risk stratification and guide personalized interventions in clinical practice. Full article
(This article belongs to the Special Issue Pharmaceutical Treatments for Typical CKD Comorbidities)
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14 pages, 3376 KB  
Article
A Study of Ultra-Thin Surface-Mounted MEMS Fibre-Optic Fabry–Pérot Pressure Sensors for the In Situ Monitoring of Hydrodynamic Pressure on the Hull of Large Amphibious Aircraft
by Tianyi Feng, Xi Chen, Ye Chen, Bin Wu, Fei Xu and Lingcai Huang
Photonics 2025, 12(7), 627; https://doi.org/10.3390/photonics12070627 - 20 Jun 2025
Viewed by 455
Abstract
Hydrodynamic slamming loads during water landing are one of the main concerns for the structural design and wave resistance performance of large amphibious aircraft. However, current existing sensors are not used for full-scale hydrodynamic load flight tests on complex models due to their [...] Read more.
Hydrodynamic slamming loads during water landing are one of the main concerns for the structural design and wave resistance performance of large amphibious aircraft. However, current existing sensors are not used for full-scale hydrodynamic load flight tests on complex models due to their large size, fragility, intrusiveness, limited range, frequency response limitations, accuracy issues, and low sampling frequency. Fibre-optic sensors’ small size, immunity to electromagnetic interference, and reduced susceptibility to environmental disturbances have led to their progressive development in maritime and aeronautic fields. This research proposes a novel hydrodynamic profile encapsulation method using ultra-thin surface-mounted micro-electromechanical system (MEMS) fibre-optic Fabry–Pérot pressure sensors (total thickness of 1 mm). The proposed sensor exhibits an exceptional linear response and low-temperature sensitivity in hydrostatic calibration tests and shows superior response and detection accuracy in water-entry tests of wedge-shaped bodies. This work exhibits significant potential for the in situ monitoring of hydrodynamic loads during water landing, contributing to the research of large amphibious aircraft. Furthermore, this research demonstrates, for the first time, the proposed surface-mounted pressure sensor in conjunction with a high-speed acquisition system for the in situ monitoring of hydrodynamic pressure on the hull of a large amphibious prototype. Following flight tests, the sensors remained intact throughout multiple high-speed hydrodynamic taxiing events and 12 full water landings, successfully acquiring the complete dataset. The flight test results show that this proposed pressure sensor exhibits superior robustness in extreme environments compared to traditional invasive electrical sensors and can be used for full-scale hydrodynamic load flight tests. Full article
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17 pages, 3686 KB  
Article
Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa
by Hélène Ragot, Sonia Gaucher, Mathilde Bonnet des Claustres, Justine Basset, Rose Boudan, Maxime Battistella, Emmanuelle Bourrat, Alain Hovnanian and Matthias Titeux
Cancers 2024, 16(13), 2476; https://doi.org/10.3390/cancers16132476 - 6 Jul 2024
Cited by 2 | Viewed by 2598
Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There [...] Read more.
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs. Full article
(This article belongs to the Section Cancer Biomarkers)
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16 pages, 1671 KB  
Review
Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer
by Olivia G. Huffman, Danielle B. Chau, Andreea I. Dinicu, Robert DeBernardo and Ofer Reizes
Cancers 2023, 15(5), 1402; https://doi.org/10.3390/cancers15051402 - 22 Feb 2023
Cited by 18 | Viewed by 5834
Abstract
Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy, yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal [...] Read more.
Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy, yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer, though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage, impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients. Full article
(This article belongs to the Collection Hyperthermia in Cancer Therapy)
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13 pages, 1251 KB  
Article
Safety Monitoring of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years by Using EudraVigilance Pharmacovigilance Database: The CoVaxChild Study
by Alessia Zinzi, Mario Gaio, Valerio Liguori, Rosanna Ruggiero, Marina Tesorone, Francesco Rossi, Concetta Rafaniello and Annalisa Capuano
Vaccines 2023, 11(2), 401; https://doi.org/10.3390/vaccines11020401 - 9 Feb 2023
Cited by 12 | Viewed by 3101
Abstract
Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 [...] Read more.
Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 vaccines in children by analysing the pharmacovigilance data of the European spontaneous reporting system database EudraVigilance (EV) in the period from 1 January 2021, to 1 October 2022. During our study period, overall 4838 ICSRs related to mRNA COVID-19 vaccines referring to 5–11-year-old subjects were retrieved from EV, of which 96.9% were related to BNT162b2 and 49.3% were related to males. A total of 12,751 Adverse Events Following Immunization (AEFIs) were identified, of which 38.7% were serious. The most frequently reported AEFIs were pyrexia, headache, and vomiting. Only 20 Individual Case Safety Reports (ICSRs) reported Multisystem Inflammatory Syndrome (MIS) as an AEFI, all related to BNT162b2. The majority of MIS cases were females, and six cases were completely resolved at the time of reporting. Our results show a favourable risk–benefit profile for all mRNA COVID-19 vaccines in this paediatric sub-population, supporting their use in children. Considering the peculiarity and fragility of children, continuous safety monitoring of COVID-19 vaccines is required. Full article
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20 pages, 9377 KB  
Article
Gene Expression Profiling of Trematomus bernacchii in Response to Thermal and Stabling Stress
by Samuele Greco, Anastasia Serena Gaetano, Gael Furlanis, Francesca Capanni, Chiara Manfrin, Piero Giulio Giulianini, Gianfranco Santovito, Paolo Edomi, Alberto Pallavicini and Marco Gerdol
Fishes 2022, 7(6), 387; https://doi.org/10.3390/fishes7060387 - 13 Dec 2022
Cited by 4 | Viewed by 3325
Abstract
The Antarctic continent is one of the most pristine environments on planet Earth, yet one of the most fragile and susceptible to the effects of the ongoing climate change. The overwhelming majority of the components of Antarctic marine trophic chain are stenotherm organisms, [...] Read more.
The Antarctic continent is one of the most pristine environments on planet Earth, yet one of the most fragile and susceptible to the effects of the ongoing climate change. The overwhelming majority of the components of Antarctic marine trophic chain are stenotherm organisms, highly adapted to the extreme, but extremely stable, freezing temperatures of the Antarctic ocean, which have not changed significantly during the past fifteen million years. Notothenioid fishes are the most abundant representatives of ichthyofauna at these latitudes, being ubiquitously found in coastal areas across the entire continent. While different Antarctic fish species have been previously subjected to studies aimed at defining their range of thermal tolerance, or at studying the response to acute thermal stress, just a handful of authors have investigated the effects of the exposure to a moderate increase of temperature, falling within the expected forecasts for the next few decades in some areas of the Antarctica. Here, the emerald rockcod Trematomus bernacchii was used as a model species to investigate the effects of a 20-day long exposure to a +1.5 °C increase in the brain, gills and skeletal muscle, using a RNA-sequencing approach. In parallel, the experimental design also allowed for assessing the impact of stabling (including acclimation, the handling of fishes and their confinement in tanks during the experimental phase) on gene expression profiling. The results of this study clearly identified the brain as the most susceptible tissue to heat stress, with evidence of a time-dependent response dominated by an alteration of immune response, protein synthesis and folding, and energy metabolism-related genes. While the gills displayed smaller but still significant alterations, the skeletal muscle was completely unaffected by the experimental conditions. The stabling conditions also had an important impact on gene expression profiles in the brain, suggesting the presence of significant alterations of the fish nervous system, possibly due to the confinement to tanks with limited water volume and of the restricted possibility of movement. Besides providing novel insights in the molecular mechanisms underlying thermal stress in notothenioids, these findings suggest that more attention should be dedicated to an improved design of the experiments carried out on Antarctic organism, due to their extreme susceptibility to the slightest environmental alterations. Full article
(This article belongs to the Special Issue Impacts of Anthropogenic Stressors on Fish Physiology)
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16 pages, 5571 KB  
Article
An fMRI Compatible Smart Device for Measuring Palmar Grasping Actions in Newborns
by Daniela Lo Presti, Sofia Dall’Orso, Silvia Muceli, Tomoki Arichi, Sara Neumane, Anna Lukens, Riccardo Sabbadini, Carlo Massaroni, Michele Arturo Caponero, Domenico Formica, Etienne Burdet and Emiliano Schena
Sensors 2020, 20(21), 6040; https://doi.org/10.3390/s20216040 - 23 Oct 2020
Cited by 11 | Viewed by 4151
Abstract
Grasping is one of the first dominant motor behaviors that enable interaction of a newborn infant with its surroundings. Although atypical grasping patterns are considered predictive of neuromotor disorders and injuries, their clinical assessment suffers from examiner subjectivity, and the neuropathophysiology is poorly [...] Read more.
Grasping is one of the first dominant motor behaviors that enable interaction of a newborn infant with its surroundings. Although atypical grasping patterns are considered predictive of neuromotor disorders and injuries, their clinical assessment suffers from examiner subjectivity, and the neuropathophysiology is poorly understood. Therefore, the combination of technology with functional magnetic resonance imaging (fMRI) may help to precisely map the brain activity associated with grasping and thus provide important insights into how functional outcomes can be improved following cerebral injury. This work introduces an MR-compatible device (i.e., smart graspable device (SGD)) for detecting grasping actions in newborn infants. Electromagnetic interference immunity (EMI) is achieved using a fiber Bragg grating sensor. Its biocompatibility and absence of electrical signals propagating through the fiber make the safety profile of the SGD particularly favorable for use with fragile infants. Firstly, the SGD design, fabrication, and metrological characterization are described, followed by preliminary assessments on a preterm newborn infant and an adult during an fMRI experiment. The results demonstrate that the combination of the SGD and fMRI can safely and precisely identify the brain activity associated with grasping behavior, which may enable early diagnosis of motor impairment and help guide tailored rehabilitation programs. Full article
(This article belongs to the Special Issue Smart Sensors for Healthcare and Medical Applications)
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29 pages, 709 KB  
Review
Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches
by Carolina Ferreira, Sofia D. Viana and Flávio Reis
Microorganisms 2020, 8(10), 1514; https://doi.org/10.3390/microorganisms8101514 - 1 Oct 2020
Cited by 55 | Viewed by 11553
Abstract
Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients present a complex clinical picture that, in severe cases, evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. The [...] Read more.
Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients present a complex clinical picture that, in severe cases, evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. The underlying pathophysiological mechanisms are complex and multifactorial and have been summarized as a hyperresponse of the immune system that originates an inflammatory/cytokine storm. In elderly patients, particularly in those with pre-existing cardiovascular, metabolic, renal, and pulmonary disorders, the disease is particularly severe, causing prolonged hospitalization at intensive care units (ICU) and an increased mortality rate. Curiously, the same populations have been described as more prone to a gut microbiota (GM) dysbiosis profile. Intestinal microflora plays a major role in many metabolic and immune functions of the host, including to educate and strengthen the immune system to fight infections, namely of viral origin. Notably, recent studies suggest the existence of GM dysbiosis in COVID-19 patients. This review article highlights the interplay between the triad GM dysbiosis–immune hyperresponse–inflammation in the individual resilience/fragility to SARS-CoV-2 infection and presents the putative impact of pharmacological and nutraceutical approaches on the triumvirate, with focus on GM. Full article
(This article belongs to the Special Issue Gut Microbiota Dysbiosis 2.0)
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18 pages, 2961 KB  
Article
Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction
by Douâa Moussa Agha, Redouane Rouas, Mehdi Najar, Fatima Bouhtit, Hussein Fayyad-Kazan, Laurence Lagneaux, Dominique Bron, Nathalie Meuleman, Philippe Lewalle and Makram Merimi
Cells 2020, 9(9), 2053; https://doi.org/10.3390/cells9092053 - 8 Sep 2020
Cited by 15 | Viewed by 3437
Abstract
Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy in which antitumor immunity is impaired. The therapeutic management of AML requires understanding the mechanisms involved in the fragility and immune dysfunction of AML T lymphocytes. Methods: In this study, T lymphocytes from healthy [...] Read more.
Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy in which antitumor immunity is impaired. The therapeutic management of AML requires understanding the mechanisms involved in the fragility and immune dysfunction of AML T lymphocytes. Methods: In this study, T lymphocytes from healthy donors (HD) and AML patients were used. Extracellular vesicles (EVs) from leukemic cells were screened for their microRNA content and impact on T lymphocytes. Flow cytometry, transcriptomic as well as lentiviral transduction techniques were used to carry out the research. Results: We observed increased cell death of T lymphocytes from AML patients. EVs from leukemia myeloid cell lines harbored several miRNAs, including miR-21, and were able to induce T lymphocyte death. Compared to that in HD, miR-21 was overexpressed in both the bone marrow fluid and infiltrating T lymphocytes of AML patients. MiR-21 induces T lymphocyte cell death by upregulating proapoptotic gene expression. It also increases the immunosuppressive profile of T lymphocytes by upregulating the IL13, IL4, IL10, and FoxP3 genes. Conclusions: Our results demonstrate that miR-21 plays a significant role in AML T lymphocyte dysfunction and apoptosis. Targeting miR-21 may be a novel approach to restore the efficacy of the immune response against AML. Full article
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15 pages, 2325 KB  
Article
The Impact of Moyamoya Disease and RNF213 Mutations on the Spectrum of Plasma Protein and MicroRNA
by Ming-Jen Lee, Shannon Fallen, Yong Zhou, David Baxter, Kelsey Scherler, Meng-Fai Kuo and Kai Wang
J. Clin. Med. 2019, 8(10), 1648; https://doi.org/10.3390/jcm8101648 - 10 Oct 2019
Cited by 14 | Viewed by 4231
Abstract
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by occlusion of bilateral internal carotid and intracerebral arteries with the compensatory growth of fragile small vessels. MMD patients develop recurrent infarctions in the basal ganglia and subcortical regions. Symptoms include transient ischemic attack [...] Read more.
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by occlusion of bilateral internal carotid and intracerebral arteries with the compensatory growth of fragile small vessels. MMD patients develop recurrent infarctions in the basal ganglia and subcortical regions. Symptoms include transient ischemic attack or stroke, seizures, and headaches, which may occur suddenly or in a stepwise progression. Mutations in Ring Finger Protein 213 (RNF213), a Zinc ring finger protein, have been identified in some MMD patients but the etiology of MMD is still largely unknown. To gain insight into the pathophysiology of MMD, we characterized the impact of the RNF213 mutations on plasma protein and RNA profiles. Isobaric tags for relative and absolute quantitation and proximity extension assay were used to characterize the plasma proteome. Next generation sequencing-based small RNAseq was used to analyze the cell-free small RNAs in whole plasma and RNA encapsulated in extracellular vesicles. The changes of miRNAs and proteins identified are associated with signaling processes including angiogenesis and immune activities which may reflect the pathology and progression of MMD. Full article
(This article belongs to the Section Cardiology)
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16 pages, 4156 KB  
Article
Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling
by Zu-Quan Hu, Hui Xue, Jin-Hua Long, Yun Wang, Yi Jia, Wei Qiu, Jing Zhou, Zong-Yao Wen, Wei-Juan Yao and Zhu Zeng
Int. J. Mol. Sci. 2016, 17(11), 1756; https://doi.org/10.3390/ijms17111756 - 31 Oct 2016
Cited by 25 | Viewed by 5333
Abstract
Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation [...] Read more.
Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors. Full article
(This article belongs to the Section Biochemistry)
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