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1.
ACS Sustain Chem Eng ; 12(32): 12161-12170, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39148516

RESUMEN

Nonisocyanate polyurethanes (NIPUs) show promise as more sustainable alternatives to conventional isocyanate-based polyurethanes (PUs). In this study, polyhydroxyurethane (PHU) and nonisocyanate polythiourethane (NIPTU) production and reprocessing models inform the results of a techno-economic analysis and a life cycle assessment. The profitability of selling PHU and NIPTU is rationalized by identifying significant production costs, indicating that raw materials drive the costs of PHU and NIPTU production and reprocessing. After stepping along a path of process improvements, PHU and NIPTU can achieve minimum selling prices (MSPs) of 3.15 and 4.39 USD kg-1, respectively. Depolymerization yields need to be optimized, and polycondensation reactions need to be investigated for the reprocessing of NIPUs into secondary (2°) NIPUs. Of the NIPUs examined here, PHU has a low depolymerization yield and NIPTU has a high depolymerization yield. Fossil energy use, greenhouse gas (GHG) emissions, and water consumption are reported for the biobased production of PHU, NIPTU, 2° PHU, and 2° NIPTU and compared with baseline values for fossil-based PU production. There are options for reducing environmental impacts, which could make these pathways more sustainable. If barriers to implementation are overcome, 2° NIPUs can be manufactured at lower cost and environmental impacts than those of virgin NIPUs.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39136893

RESUMEN

BACKGROUND: Gastric cancer (GC) poses a significant global health challenge. This study is aimed at elucidating the role of the immune system, particularly T cells and their subtypes, in the pathogenesis and progression of intestinal-type gastric carcinoma (GC), and at evaluating the predictive utility of a T cell marker gene-based risk score for overall survival. METHODS: We performed an extensive analysis using single-cell RNA sequencing data to map the diversity of immune cells and identify specific T cell marker genes within GC. Pseudotime trajectory analysis was employed to observe the expression patterns of tumor-related pathways and transcription factors (TFs) at various disease stages. We developed a risk score using data from The Cancer Genome Atlas (TCGA) as a training set and validated it with the GSE15459 dataset. RESULTS: Our analysis revealed distinct patterns of T cell marker gene expression associated with different stages of GC. The risk score, based on these markers, successfully stratified patients into high-risk and low-risk groups with significantly different overall survival prospects. High-risk patients exhibited poorer survival outcomes compared to low-risk patients (p < 0.05). Additionally, the risk score was capable of identifying patients across a spectrum from chronic atrophic gastritis to early GC. CONCLUSION: The findings enhance the understanding of the tumor immune microenvironment in GC and propose new immunotherapeutic targets. The T cell marker gene-based risk score offers a potential tool for gastroenterologists to tailor treatment plans more precisely according to the cancer's severity.

3.
ACS Macro Lett ; : 1147-1155, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150319

RESUMEN

We synthesized covalent adaptable networks (CANs) made from chain-growth comonomers using nonisocyanate thiourethane chemistry. We derivatized glycidyl methacrylate with cyclic dithiocarbonate (GMA-DTC), did a free-radical polymerization of n-hexyl methacrylate with GMA-DTC to obtain a statistical copolymer with 8 mol % GMA-DTC, and cross-linked it with difunctional amine. The dynamic covalent thionourethane and disulfide bonds lead to CAN reprocessability with full recovery of the cross-link density; the temperature dependence of the rubbery plateau modulus indicates that associative character dominates the dynamic response. The CAN exhibits complete self-healing at 110 °C with tensile property recovery and excellent creep resistance at 90-100 °C. Stress relaxation at 140-170 °C reveals an activation energy of 105 ± 6 kJ/mol, equal to the activation energy (Ea) of the CAN poly(n-hexyl methacrylate) backbone α-relaxation. We hypothesize that CANs with exclusively or predominantly associative dynamics have their stress-relaxation Ea defined by the α-relaxation Ea. This hypothesis is supported by stress relaxation studies on a similar poly(n-lauryl methacrylate)-based CAN.

4.
Macromol Rapid Commun ; : e2400460, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39047164

RESUMEN

Catalyst-free, radical-based reactive processing is used to transform low-density polyethylene (LDPE) into polyethylene covalent adaptable networks (PE CANs) using a dialkylamino disulfide crosslinker, BiTEMPS methacrylate (BTMA). Two versions of BTMA are used, BTMA-S2, with nearly exclusively disulfide bridges, and BTMA-Sn, with a mixture of oligosulfide bridges, to produce S2 PE CAN and Sn PE CAN, respectively. The two PE CANs exhibit identical crosslink densities, but the S2 PE CAN manifests faster stress relaxation, with average relaxation times ∼4.5 times shorter than those of Sn PE CAN over a 130 to 160 °C temperature range. The more rapid dynamics of the S2 PE CAN translate into a shorter compression-molding reprocessing time at 160 °C of only 5 min (vs 30 min for the Sn PE CAN) to achieve full recovery of crosslink density. Both PE CANs are melt-extrudable and exhibit full recovery within experimental uncertainty of crosslink density after extrusion. Both PE CANs are self-healable, with a crack fully repaired and the original tensile properties restored after 30 min for the S2 PE CAN or 60 min for the Sn PE CAN at a temperature slightly above the LDPE melting point and without the assistance of external forces.

5.
Chin J Cancer Res ; 36(3): 240-256, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38988488

RESUMEN

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

6.
J Immunol Res ; 2024: 1117796, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081632

RESUMEN

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high-throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune-mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230.


Asunto(s)
Lactancia Materna , Neutrófilos , Femenino , Humanos , Recién Nacido , Masculino , Factores de Edad , Citometría de Flujo , Gambia , Recuento de Leucocitos , Monocitos/inmunología , Neutrófilos/inmunología , Papúa Nueva Guinea , Vacunación
7.
Sci Total Environ ; 948: 174462, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-38992374

RESUMEN

This comprehensive study unveils the vast global potential of microalgae as a sustainable bioenergy source, focusing on the utilization of marginal lands and employing advanced machine learning techniques to predict biomass productivity. By identifying approximately 7.37 million square kilometers of marginal lands suitable for microalgae cultivation, this research uncovers the extensive potential of these underutilized areas, particularly within equatorial and low-latitude regions, for microalgae bioenergy development. This approach mitigates the competition for food resources and conserves freshwater supplies. Utilizing cutting-edge machine learning algorithms based on robust datasets from global microalgae cultivation experiments spanning 1994 to 2017, this study integrates essential environmental variables to map out a detailed projection of potential yields across a variety of landscapes. The analysis further delineates the bioenergy and carbon sequestration potential across two effective cultivation methods: Photobioreactors (PBRs), and Open Ponds, with PBRs showcasing exceptional productivity, with a global average daily biomass productivity of 142.81mgL-1d-1, followed by Open Ponds at 122.57mgL-1d-1. Projections based on optimal PBR conditions suggest an annual yield of 99.54 gigatons of microalgae biomass. This yield can be transformed into 64.70 gigatons of biodiesel, equivalent to 58.68 gigatons of traditional diesel, while sequestering 182.16 gigatons of CO2, equating to approximately 4.5 times the global CO2 emissions projected for 2023. Notably, Australia leads in microalgae biomass production, with an annual output of 16.19 gigatons, followed by significant contributions from Kazakhstan, Sudan, Brazil, the United States, and China, showcasing the diverse global potential for microalgae bioenergy across varying ecological and geographical landscapes. Through this rigorous investigation, the study emphasizes the strategic importance of microalgae cultivation in achieving sustainable energy solutions and mitigating climate change, while also acknowledging the scalability challenges and the necessity for significant economic and energy investments.


Asunto(s)
Biocombustibles , Biomasa , Secuestro de Carbono , Aprendizaje Automático , Microalgas , Microalgas/crecimiento & desarrollo
8.
Foods ; 13(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38928771

RESUMEN

Sea buckthorn juice has high nutritional value and a rich flavor that consumers enjoy. Traditional sea buckthorn thermal processing (TP) technology has problems such as low juice yield, poor quality, and poor flavor. Sea buckthorn berries are processed using a technique combining pulsed electric field (PEF) and high-pressure processing (HPP) to increase juice yield and study its impact on the quality and volatile aroma of sea buckthorn juice. Results have show that, compared with TP, under the condition of PEF-HPP, the juice yield of sea buckthorn significantly increased by 11.37% (p > 0.05); TP and PEF-HPP treatments could effectively kill microorganisms in sea buckthorn juice, but the quality of sea buckthorn juice decreased significantly after TP treatment (p > 0.05), whereas PEF-HPP coupling technology could maximally retain the nutrients of sea buckthorn juice while inhibiting enzymatic browning to improve color, viscosity, and particle size. The flavor of sea buckthorn juice is analyzed using electronic nose (E-nose) and gas chromatography-ion mobility spectrometer (GC-IMS) techniques, and it has been shown that PEF-HPP retains more characteristic volatile organic compounds (VOCs) of sea buckthorn while avoiding the acrid and pungent flavors produced by TP, such as benzaldehyde, (E)-2-heptenal, and pentanoic acid, among others, which improves the sensory quality of sea buckthorn juice. PEF-HPP technology is environmentally friendly and efficient, with significant economic benefits. Research data provide information and a theoretical basis for the sea buckthorn juice processing industry.

9.
Cell Biol Int ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886911

RESUMEN

Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF-HDAC complex (BHC) components in cells. The transcriptome of GSE1-knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p-value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel-like factor 6). Indeed, quantitative reverse-transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non-small cell lung cancer cells through the downregulation of KLF6 expression.

10.
Opt Express ; 32(11): 20230-20241, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859138

RESUMEN

A low-complexity multi-subcarrier pulse generation scheme is proposed to suppress the interference fading in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) based distributed acoustic sensor (DAS) with heterodyne coherent detection. The multi-subcarrier pulse is generated in the digital domain based on the proper clipping operation of a sine signal. The localization and recovery of the disturbance signal are realized by the spectrum extraction and rotated vector sum (SERVS) method. The experimental results show that the occurrences of interference fading can be significantly reduced. The intensity fluctuation is reduced from ∼75 dB to ∼25 dB. Multiple disturbance signals are successfully demodulated to verify the effectiveness of the proposed method.

11.
Membranes (Basel) ; 14(6)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38921504

RESUMEN

The shape of a cell as defined by its membrane can be closely associated with its physiological state. For example, the irregular shapes of cancerous cells and elongated shapes of neuron cells often reflect specific functions, such as cell motility and cell communication. However, it remains unclear whether and which cell shape descriptors can characterize different cellular physiological states. In this study, 12 geometric shape descriptors for a three-dimensional (3D) object were collected from the previous literature and tested with a public dataset of ~400,000 independent 3D cell regions segmented based on fluorescent labeling of the cell membranes in Caenorhabditis elegans embryos. It is revealed that those shape descriptors can faithfully characterize cellular physiological states, including (1) cell division (cytokinesis), along with an abrupt increase in the elongation ratio; (2) a negative correlation of cell migration speed with cell sphericity; (3) cell lineage specification with symmetrically patterned cell shape changes; and (4) cell fate specification with differential gene expression and differential cell shapes. The descriptors established may be used to identify and predict the diverse physiological states in numerous cells, which could be used for not only studying developmental morphogenesis but also diagnosing human disease (e.g., the rapid detection of abnormal cells).

14.
J Transl Med ; 22(1): 489, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778315

RESUMEN

OBJECTIVE: Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia-reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia-reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia-reperfusion injury and the O-GlcNAcylation level of COX10. METHODS: We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia-reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. RESULTS: Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia-reperfusion injury. In vivo, MTH effectively alleviates ischemia-reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. CONCLUSIONS: In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia-reperfusion injury, which provides important theoretical basis for the clinical application of MTH.


Asunto(s)
Hipotermia Inducida , Daño por Reperfusión Miocárdica , Regulación hacia Arriba , Animales , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Masculino , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Ratas Sprague-Dawley , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Mitocondrias/metabolismo , Glicosilación , Acilación
15.
Bioact Mater ; 39: 41-58, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38800718

RESUMEN

Natural fracture healing is most efficient when the fine-tuned mechanical force and proper micromotion are applied. To mimick this micromotion at the fracture gap, a near-infrared-II (NIR-II)-activated hydrogel was fabricated by integrating two-dimensional (2D) monolayer Nb2C nanosheets into a thermally responsive poly(N-isopropylacrylamide) (NIPAM) hydrogel system. NIR-II-triggered deformation of the NIPAM/Nb2C hydrogel was designed to generate precise micromotion for co-culturing cells. It was validated that micromotion at 1/300 Hz, triggering a 2.37-fold change in the cell length/diameter ratio, is the most favorable condition for the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, mRNA sequencing and verification revealed that micromotion-induced augmentation was mediated by Piezo1 activation. Suppression of Piezo1 interrupts the mechano-sensitivity and abrogates osteogenic differentiation. Calvarial and femoral shaft defect models were established to explore the biocompatibility and osteoinductivity of the Micromotion Biomaterial. A series of research methods, including radiography, micro-CT scanning, and immunohistochemical staining have been performed to evaluate biosafety and osteogenic efficacy. The in vivo results revealed that tunable micromotion strengthens the natural fracture healing process through the sequential activation of endochondral ossification, promotion of neovascularization, initiation of mineral deposition, and combinatory acceleration of full-thickness osseous regeneration. This study demonstrated that Micromotion Biomaterials with controllable mechanophysical characteristics could promote the osteogenic differentiation of BMSCs and facilitate full osseous regeneration. The design of NIPAM/Nb2C hydrogel with highly efficient photothermal conversion, specific features of precisely controlled micromotion, and bionic-mimicking bone-repair capabilities could spark a new era in the field of regenerative medicine.

16.
Biol Psychol ; 190: 108807, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38703810

RESUMEN

Attentional bias toward weight-related stimuli plays a crucial role in the development and maintenance of body image disturbances. However, the temporal dynamics of attentional biases responsible for the previously reported behavioral effects caused by the task-irrelevant but spatial-relevant weight-related stimuli presented in the peripheral visual field among females with high weight dissatisfaction (HWD) remain unclear. The present study combined the modified dot-probe task and event-related potentials to explore the temporal dynamics of spatial attentional biases toward weight-related words among females with HWD. The results showed significantly larger N2pc amplitudes were elicited by fat-related and thin-related words than neutral words only in the HWD group. Moreover, only fat-related words elicited a significant PD for the HWD group, and the PD amplitudes were larger in the HWD group than in the control group. These findings revealed that weight-related words initially captured spatial allocation among females with HWD, and then fat-related words were actively suppressed after the initial capturing.


Asunto(s)
Sesgo Atencional , Electroencefalografía , Potenciales Evocados , Humanos , Femenino , Adulto Joven , Sesgo Atencional/fisiología , Potenciales Evocados/fisiología , Peso Corporal/fisiología , Insatisfacción Corporal/psicología , Adulto , Tiempo de Reacción/fisiología , Percepción Espacial/fisiología , Estimulación Luminosa/métodos , Atención/fisiología
17.
Neurobiol Dis ; 196: 106505, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38642715

RESUMEN

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.


Asunto(s)
Enfermedad de Alzheimer , Metabolismo de los Lípidos , Enfermedad de Parkinson , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Animales
18.
Clin Transl Med ; 14(4): e1656, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38664597

RESUMEN

BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.


Asunto(s)
Inmunoterapia , Neoplasias , Organoides , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Organoides/efectos de los fármacos , Medicina de Precisión/métodos
19.
Apoptosis ; 29(7-8): 1070-1089, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38615305

RESUMEN

The mortality and therapeutic failure in cutaneous melanoma (CM) are mainly caused by wide metastasis and chemotherapy resistance. Meanwhile, immunotherapy is considered a crucial therapy strategy for CM patients. However, the efficiency of currently available methods and biomarkers in predicting the response of immunotherapy and prognosis of CM is limited. Programmed cell death (PCD) plays a significant role in the occurrence, development, and therapy of various malignant tumors. In this research, we integrated fourteen types of PCD, multi-omics data from TCGA-SKCM and other cohorts in GEO, and clinical CM patients to develop our analysis. Based on significant PCD patterns, two PCD-related CM clusters with different prognosis, tumor microenvironment (TME), and response to immunotherapy were identified. Subsequently, seven PCD-related features, especially CD28, CYP1B1, JAK3, LAMP3, SFN, STAT4, and TRAF1, were utilized to establish the prognostic signature, namely cell death index (CDI). CDI accurately predicted the response to immunotherapy in both CM and other cancers. A nomogram with potential superior predictive ability was constructed, and potential drugs targeting CM patients with specific CDI have also been identified. Given all the above, a novel CDI gene signature was indicated to predict the prognosis and exploit precision therapeutic strategies of CM patients, providing unique opportunities for clinical intelligence and new management methods for the therapy of CM.


Asunto(s)
Inmunoterapia , Aprendizaje Automático , Melanoma Cutáneo Maligno , Melanoma , Neoplasias Cutáneas , Microambiente Tumoral , Humanos , Melanoma/terapia , Melanoma/inmunología , Melanoma/patología , Melanoma/genética , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/tratamiento farmacológico , Pronóstico , Microambiente Tumoral/inmunología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica
20.
J Sci Food Agric ; 104(11): 6531-6540, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38517196

RESUMEN

BACKGROUND: With the increasing popularity of plant protein-based diets, soy proteins are favored as the most important source of plant protein worldwide. However, potential food allergy risks limit their use in the food industry. This work aims to reveal the mechanism of ß-conglycinin-induced food allergy, and to explore the regulatory mechanism of heat treatment and high hydrostatic pressure (HHP) treatment in a BALB/c mouse model. RESULTS: Our results showed that oral administration of ß-conglycinin induced severe allergic symptoms in BALB/c mice, but these symptoms were effectively alleviated through heat treatment and HHP treatment. Moreover, ß-conglycinin stimulated lymphocyte proliferation and differentiation; a large number of cytokines interleukin (IL)-4, IL-5, IL-10, IL-12 and IL-13 were released and interferon γ secretion was inhibited, which disrupted the Th1/Th2 immune balance and promoted the differentiation and proliferation of naive T cells into Th2-type cells. CONCLUSION: Heat/non-heat treatment altered the conformation of soybean protein, which significantly reduced allergic reactions in mice. This regulatory mechanism may be associated with Th1/Th2 immune balance. Our results provide data support for understanding the changes in allergenicity of soybean protein within the food industry. © 2024 Society of Chemical Industry.


Asunto(s)
Antígenos de Plantas , Modelos Animales de Enfermedad , Hipersensibilidad a los Alimentos , Globulinas , Calor , Ratones Endogámicos BALB C , Proteínas de Almacenamiento de Semillas , Proteínas de Soja , Células TH1 , Células Th2 , Animales , Hipersensibilidad a los Alimentos/inmunología , Globulinas/química , Globulinas/inmunología , Globulinas/administración & dosificación , Proteínas de Soja/química , Proteínas de Soja/inmunología , Proteínas de Almacenamiento de Semillas/química , Proteínas de Almacenamiento de Semillas/inmunología , Proteínas de Almacenamiento de Semillas/administración & dosificación , Ratones , Antígenos de Plantas/inmunología , Antígenos de Plantas/química , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células Th2/inmunología , Femenino , Humanos , Balance Th1 - Th2/efectos de los fármacos , Citocinas/inmunología , Citocinas/metabolismo , Glycine max/química
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