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1.
Front Oncol ; 14: 1355559, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737905

RESUMO

Objective: The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. Methods: Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis. Data from TCGA, GTEx and GEO databases were retrieved for gastric cancer patients, and bioinformatics analysis was utilized to investigate the association between MCU expression and clinical pathological features. Furthermore, we conducted an in-depth analysis of the role of MCU in GC patients. We investigated the correlation between MCU expression in GC and its impact on mitochondrial function, metabolism, biosynthesis, and immune cells. Additionally, we studied the proteins or molecules that interact with MCU. Results: Our research revealed high expression of MCU in the GC tissues. This high expression was associated with poorer T and N staging, and indicated a worse disease-free survival period. MCU expression was positively correlated with mitochondrial function, mitochondrial metabolism, nucleotide, amino acid, and fatty acid synthesis metabolism, and negatively correlated with nicotinate and nicotinamide metabolism. Furthermore, the MCU also regulates the function of the mitochondrial oxidative respiratory chain. The MCU influences the immune cells of GC patients and regulates ROS generation, cell proliferation, apoptosis, and resistance to platinum-based drugs in gastric cancer cells. Conclusion: High expression of MCU in GC indicates poorer clinical outcomes. The expression of the MCU are affected through impacts the function of mitochondria, energy metabolism, and cellular biosynthesis in gastric cancer cells, thereby influencing the growth and metastasis of gastric cancer cells. Therefore, the mitochondrial changes regulated by MCU could be a new focus for research and treatment of GC.

2.
J Agric Food Chem ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738910

RESUMO

Pectin lyases (PNLs) can enhance juice clarity and flavor by degrading pectin in highly esterified fruits, but their inadequate acid resistance leads to rapid activity loss in juice. This study aimed to improve the acid resistance of Aspergillus niger PNL pelA through surface charge design. A modification platform was established by fusing pelA with a protein tag and expressing the fusion enzyme in Escherichia coli. Four single-point mutants were identified to increase the surface charge using computational tools. Moreover, the combined mutant M6 (S514D/S538E) exhibited 99.8% residual activity at pH 3.0. The M6 gene was then integrated into the A. niger genome using a multigene integration system to obtain the recombinant PNL AM6. Notably, AM6 improved the light transmittance of orange juice to 45.3%, which was 8.39 times higher than that of pelA. In conclusion, AM6 demonstrated the best-reported acid resistance, making it a promising candidate for industrial juice clarification.

3.
Int J Biol Macromol ; 267(Pt 1): 131690, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688790

RESUMO

In the current study, how pectin retards the digestibility of wheat gluten was investigated using a static in vitro gastric-duodenal model. The degree of protein hydrolysis was estimated using the o-phthaldialdehyde method, while the in vitro digestograms were mathematically fitted using a single first-order kinetics model. Peptides' profile, free amino acids compositions, gluten-pectin interactions and their effects on enzymatic activities of proteolytic enzymes as well as on the gluten secondary structures under digestive conditions were studied using combined techniques. Results showed that pectin could retard gluten digestibility through 1). preferential absorption to insoluble gluten aggregates by electrostatic interactions; 2). increasing the helix and reducing the ß-sheet content of the solubilized gluten protein fractions in terms of their secondary molecular structures; 3). reducing pepsin activity by forming negatively charged pectin-gluten mixtures which then interacted with the positively charged pepsin molecules. The deeper insight into gluten-pectin interactions and their influences on gluten digestibility under gastrointestinal conditions provides important clues for developing effective forms of dietary fiber to improve the nutritional benefits of plant protein in individuals.


Assuntos
Digestão , Glutens , Pectinas , Pepsina A , Pectinas/química , Pectinas/farmacologia , Glutens/química , Digestão/efeitos dos fármacos , Hidrólise , Pepsina A/química , Pepsina A/metabolismo , Duodeno/metabolismo , Duodeno/efeitos dos fármacos , Triticum/química , Proteólise , Aminoácidos/química , Cinética
4.
Int J Biol Macromol ; 266(Pt 2): 131366, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580020

RESUMO

A functional starch (TPS-E) was designed and constructed by incorporating epoxy soybean oil (ESO) and an antibacterial agent polyhexamethylene guanidine hydrochloride (PHMG), then the film was prepared by reaction extrusion and blow molding using TPS-E and poly(butylene adipate-co-terephthalate) (PBAT). The micro-crosslinking structure, forming through ring-opening reaction between the epoxy active site of TPS-E and the end group of PBAT, improved the compatibility of starch/PBAT blend and reduce the dispersed starch phase size, leading to significantly increase the tensile strength. Compared to starch/PBAT films, the tensile strength of TPS-E/PBAT in the longitudinal direction increase by 112% with the same starch content of 30%. Furthermore, these TPS-E/PBAT films demonstrated long-lasting antibacterial performance with a 98% inhibition ratio even after 10 cycles, without any observed leaching of the antibacterial agent, highlighting the high coupling efficiency of PHMG. TPS-E with the degradable ESO also promotes the degradation of PBAT. Thus, an important method of synergistic improving the mechanical, degradable and antibacterial properties of blown films through the design of reactive micro-crosslinked starch structures was established.


Assuntos
Antibacterianos , Amido , Resistência à Tração , Amido/química , Antibacterianos/química , Antibacterianos/farmacologia , Poliésteres/química , Escherichia coli/efeitos dos fármacos , Fenômenos Mecânicos , Reagentes de Ligações Cruzadas/química , Staphylococcus aureus/efeitos dos fármacos
5.
Acta Pharm Sin B ; 14(3): 1457-1466, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38487010

RESUMO

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition. In this study, we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01 (a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative) that exhibits both anti-depression effects and improvements in cognition. D01 inhibits serotonin transporters (Ki = 30.1 ± 6.9 nmol/L) and M channels (IC50 = 10.1 ± 2.4 µmol/L). D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion. Intragastric administrations of D01 (20 and 40 mg/kg) can significantly shorten the immobility time in a mouse model of chronic restraint stress (CRS)-induced depression-like behavior. Additionally, D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice, but not fluoxetine. Furthermore, D01 reverses the long-term potentiation (LTP) inhibition induced by scopolamine. Taken together, our findings demonstrate that D01, a dual-target serotonin reuptake and M channel inhibitor, is highly effective in the treatment-resistant depression and cognitive deficits, thus holding potential for development as therapy of depression with cognitive deficits.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38507385

RESUMO

We exploit the potential of the large-scale Contrastive Language-Image Pretraining (CLIP) model to enhance scene text detection and spotting tasks, transforming it into a robust backbone, FastTCM-CR50. This backbone utilizes visual prompt learning and cross-attention in CLIP to extract image and text-based prior knowledge. Using predefined and learnable prompts, FastTCM-CR50 introduces an instance-language matching process to enhance the synergy between image and text embeddings, thereby refining text regions. Our Bimodal Similarity Matching (BSM) module facilitates dynamic language prompt generation, enabling offline computations and improving performance. FastTCM-CR50 offers several advantages: 1) It can enhance existing text detectors and spotters, improving performance by an average of 1.6% and 1.5%, respectively. 2) It outperforms the previous TCM-CR50 backbone, yielding an average improvement of 0.2% and 0.55% in text detection and spotting tasks, along with a 47.1% increase in inference speed. 3) It showcases robust few-shot training capabilities. Utilizing only 10% of the supervised data, FastTCM-CR50 improves performance by an average of 26.5% and 4.7% for text detection and spotting tasks, respectively. 4) It consistently enhances performance on out-of-distribution text detection and spotting datasets, particularly the NightTime-ArT subset from ICDAR2019-ArT and the DOTA dataset for oriented object detection. The code is available at https://github.com/wenwenyu/TCM.

7.
Adv Sci (Weinh) ; : e2309852, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504470

RESUMO

Biosynthesis is the application of enzymes in microbial cell factories and has emerged as a promising alternative to chemical synthesis. However, natural enzymes with limited catalytic performance often need to be engineered to meet specific needs through a time-consuming trial-and-error process. This study presents a quantum mechanics (QM)-incorporated design-build-test-learn (DBTL) framework to rationally design phosphatase BT4131, an enzyme with an ambiguous substrate spectrum involved in N-acetylglucosamine (GlcNAc) biosynthesis. First, mutant M1 (L129Q) is designed using force field-based methods, resulting in a 1.4-fold increase in substrate preference (kcat /Km ) toward GlcNAc-6-phosphate (GlcNAc6P). QM calculations indicate that the shift in substrate preference is caused by a 13.59 kcal mol-1 reduction in activation energy. Furthermore, an iterative computer-aided design is conducted to stabilize the transition state. As a result, mutant M4 (I49Q/L129Q/G172L) with a 9.5-fold increase in kcat-GlcNAc6P /Km-GlcNAc6P and a 59% decrease in kcat-Glc6P /Km-Glc6P is highly desirable compared to the wild type in the GlcNAc-producing chassis. The GlcNAc titer increases to 217.3 g L-1 with a yield of 0.597 g (g glucose)-1 in a 50-L bioreactor, representing the highest reported level. Collectively, this DBTL framework provides an easy yet fascinating approach to the rational design of enzymes for industrially viable biocatalysts.

8.
Oncol Lett ; 27(5): 194, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38495832

RESUMO

Apatinib plus chemotherapy demonstrates good efficacy in multiple advanced carcinomas; however, its use in patients with advanced lung adenocarcinoma (LUAD) has not yet been assessed. The present study evaluated the potential benefits of apatinib plus chemotherapy in patients with advanced LUAD. A total of 145 patients with advanced LUAD and negative driver genes who received apatinib plus chemotherapy (n=65) or chemotherapy alone (n=80) were analyzed. The overall response rate was significantly improved by apatinib plus chemotherapy vs. chemotherapy alone (53.8 vs. 36.3%; P=0.034). Moreover, progression-free survival (PFS) was significantly longer in patients who received apatinib plus chemotherapy, compared with those who received chemotherapy alone [median (95% CI), 13.4 months (11.5-15.3) vs. 8.2 months (6.9-9.5); P<0.001], as was overall survival (OS) [median (95% CI), 23.1 months (not reached) vs. 17.0 months (14.6-19.4; P=0.001). Following adjustment by multivariate Cox regression analysis, apatinib plus chemotherapy was associated with a significantly longer PFS [hazard ratio (HR), 0.444; P<0.001] and OS (HR, 0.347; P<0.001), compared with chemotherapy alone. Subgroup analyses revealed that PFS and OS were significantly improved following apatinib plus chemotherapy vs. chemotherapy alone (all P<0.05) in patients receiving first- or second-line treatment. Notably, the incidence of hypertension was significantly increased following apatinib plus chemotherapy vs. chemotherapy alone (43.1 vs. 25.0%; P=0.021), whereas the incidence of other adverse events was not significantly different between the two treatment groups (all P>0.05). In conclusion, apatinib plus chemotherapy is associated with an improved treatment response and survival compared with chemotherapy alone, with a tolerable safety profile in patients with advanced LUAD.

9.
Front Immunol ; 15: 1302903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500886

RESUMO

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.


Assuntos
Neoplasias Colorretais , Receptor de Morte Celular Programada 1 , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Prognóstico , Imunoterapia/métodos
10.
iScience ; 27(3): 109155, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425845

RESUMO

Although the impact of sleep loss on social behaviors has been widely observed in recent years, the mechanisms underpinning these impacts remain unclear. In this study, we explored the detrimental effects of sleep deprivation on reciprocity behavior as well as its underlying psychological and neuroimaging mechanisms by combining sleep manipulation, an interpersonal interactive game, computational modeling and neuroimaging. Our results suggested that after sleep deprivation, individuals showed reduced reciprocity behavior, mainly due to their reduced weights on communal concern when making social decisions. At neural level, we demonstrated that sleep deprivation's effects were observed in the precuneus (hyperactivity) and temporoparietal junction, dorsal lateral prefrontal cortex (DLPFC) (both hypoactivity), and reduced reciprocity was also accounted for by increased precuneus-thalamus connectivity and DLPFC-thalamus connectivity. Our findings contributed to the understanding of the psychological and neuroimaging bases underlying the deleterious impact of sleep deprivation on social behaviors.

11.
J Leukoc Biol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478709

RESUMO

Triple-negative breast cancer (TNBC) is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in TNBC is affected by immunocyte infiltration in the tumor microenvironment (TME). Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism; however, its role in the TME remains unclear. In this study, we aimed to investigate the role of PGAM1 in TNBC and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in TNBC and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, significantly remodeling the TME and leading to an increase in anti-tumor immunocytes, such as CD8+ T cells and M1-macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2-macrophage, and Tregs. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti-PD-1 immunotherapy, providing a novel treatment strategy for TNBC.

12.
J Pathol ; 262(4): 517-528, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38361487

RESUMO

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell-cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Linfócitos T CD8-Positivos , Linfócitos T Reguladores , Prognóstico , Adenocarcinoma de Pulmão/patologia , Reino Unido , Microambiente Tumoral , Neoplasias Pulmonares/patologia
13.
Front Immunol ; 15: 1302751, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384466

RESUMO

Background: The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods: Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results: Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells. Conclusions: These results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.


Assuntos
Melanoma , Estruturas Linfoides Terciárias , Humanos , Animais , Camundongos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Linfócitos T CD8-Positivos , Gencitabina , Estruturas Linfoides Terciárias/patologia , Morte Celular Imunogênica , Camundongos Endogâmicos C57BL , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/metabolismo , Desoxicitidina , Proteínas Reguladoras de Apoptose/metabolismo , Microambiente Tumoral
14.
Foods ; 13(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38397494

RESUMO

Chinese steamed bread (CSB), which is widely consumed in East Asia, usually undergoes storage before consumption, but it is unclear how different storage temperatures affect CSB starch retrogradation and digestion properties, which are important for consumers. CSB was stored for 2 days at 25 °C, 4 °C, -18 °C, 4 °C/25 °C temperature cycling (i.e., 24 h at 4 °C, followed by 24 h at 25 °C) and -18 °C/ 25 °C temperature cycling. The results revealed for the first time that more orderly starch double helices are formed when CSB was stored at 4 °C or 4 °C/25 °C. Storage under -18 °C produced lower amounts of, but more heterogenous, starch double helices, with fewer B-type, but more V-type, crystallites. Compared to other storage temperatures, more long-range intermolecular interactions formed between the starch and protein at 4 °C or 4 °C/25 °C. CSB samples showed the slowest starch digestibility when stored at 4 °C. The impact of storage temperature on the starch retrogradation properties and digestibility of CSB also depended on the wheat variety, attributed to differences in the starch molecular structure. These results have significance and practical applications to help the CSB food industry to control starch retrogradation and digestibility. For example, CSB could be stored at 4 °C for 2 days in order to reduce its starch digestibility.

15.
BMC Bioinformatics ; 25(1): 75, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365583

RESUMO

BACKGROUND: High-performance computing plays a pivotal role in computer-aided drug design, a field that holds significant promise in pharmaceutical research. The prediction of drug-target affinity (DTA) is a crucial stage in this process, potentially accelerating drug development through rapid and extensive preliminary compound screening, while also minimizing resource utilization and costs. Recently, the incorporation of deep learning into DTA prediction and the enhancement of its accuracy have emerged as key areas of interest in the research community. Drugs and targets can be characterized through various methods, including structure-based, sequence-based, and graph-based representations. Despite the progress in structure and sequence-based techniques, they tend to provide limited feature information. Conversely, graph-based approaches have risen to prominence, attracting considerable attention for their comprehensive data representation capabilities. Recent studies have focused on constructing protein and drug molecular graphs using sequences and SMILES, subsequently deriving representations through graph neural networks. However, these graph-based approaches are limited by the use of a fixed adjacent matrix of protein and drug molecular graphs for graph convolution. This limitation restricts the learning of comprehensive feature representations from intricate compound and protein structures, consequently impeding the full potential of graph-based feature representation in DTA prediction. This, in turn, significantly impacts the models' generalization capabilities in the complex realm of drug discovery. RESULTS: To tackle these challenges, we introduce GLCN-DTA, a model specifically designed for proficiency in DTA tasks. GLCN-DTA innovatively integrates a graph learning module into the existing graph architecture. This module is designed to learn a soft adjacent matrix, which effectively and efficiently refines the contextual structure of protein and drug molecular graphs. This advancement allows for learning richer structural information from protein and drug molecular graphs via graph convolution, specifically tailored for DTA tasks, compared to the conventional fixed adjacent matrix approach. A series of experiments have been conducted to validate the efficacy of the proposed GLCN-DTA method across diverse scenarios. The results demonstrate that GLCN-DTA possesses advantages in terms of robustness and high accuracy. CONCLUSIONS: The proposed GLCN-DTA model enhances DTA prediction performance by introducing a novel framework that synergizes graph learning operations with graph convolution operations, thereby achieving richer representations. GLCN-DTA does not distinguish between different protein classifications, including structurally ordered and intrinsically disordered proteins, focusing instead on improving feature representation. Therefore, its applicability scope may be more effective in scenarios involving structurally ordered proteins, while potentially being limited in contexts with intrinsically disordered proteins.


Assuntos
Proteínas Intrinsicamente Desordenadas , Desenvolvimento de Medicamentos , Descoberta de Drogas , Sistemas de Liberação de Medicamentos , Desenho de Fármacos
16.
J Leukoc Biol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373017

RESUMO

Murine cytokine-induced killer (CIK) cells are heterologous cells that kill various allogeneic and isogenic tumors and have functional and phenotypic characteristics of natural killer cells and T lymphocytes. However, the effect of CIK alone on solid tumor therapy is only limited. To enhance the therapeutic effect, it is vital to discover a mix of several therapy approaches. Immune cell function is inhibited by abnormal tumor vessels and the tumor microenvironment, which block lymphocyte entry into tumor tissue. To increase the effectiveness of CIK cells' anti-tumor activity, anti-vascular therapy and CIK cell therapy can be combined. Furthermore, anlotinib is a tiny drug with multi-target tyrosine kinase inhibitors (TKI) that can block cell migration, delay angiogenesis, and decrease blood vessel density. Compared with other anti-angiogenesis drugs, anlotinib stands out due to the wider target of action and lower effective dose. In this work, anlotinib and murine CIK cells were coupled to boost CD3+ T cell infiltration, CD3 + CD4+ T cell infiltration, and expression of granzyme B and IFN-γ from CD3 + CD8+ T cells, which increased the anti-tumor activity. Through the generation of cytotoxic cytokines by T lymphocytes, the therapeutic group using anti-PD-1 monoclonal antibodies (anti-PD-1 mAbs) in conjunction with anlotinib and CIK cells was more successful than the group receiving dual therapy. The preclinical study contributes to exploring the therapeutic alternatives for patients with lung adenocarcinoma, thus prolonging their lives.

17.
Food Res Int ; 176: 113845, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163735

RESUMO

How different dietary fibers including pectin, cellulose and lignin affect casein digestibility was studied using in vitro static protocols. Peptides' profile, free amino acids (AAs) content, casein-DF interactions and their influences on enzymatic activities of proteolytic enzymes were studied using combined techniques. Under gastric and intestinal digestive conditions, while pectin could reduce casein digestibility (with an averaged decrease of 12.15% and 7.83, respectively) through both depletion flocculation and hydrogen-binding interactions, lignin inhibited the digestion of casein straightly through reducing the enzymatic activity of proteolytic enzymes, thereby altering the production of free AAs. Although cellulose showed the least detrimental effects, it still significantly reduced the content of Thr, Glu, Val, Leu, Phe, Lys, and no Arg was released. Deeper insight into casein-DF interactions and their influences on casein digestibility improves the development of more effective forms of DF for improving AA homeostasis in individuals.


Assuntos
Caseínas , Lignina , Humanos , Caseínas/metabolismo , Ração Animal/análise , Digestão , Aminoácidos/metabolismo , Fibras na Dieta/metabolismo , Celulose/farmacologia , Pectinas/farmacologia , Peptídeo Hidrolases/farmacologia
18.
J Sci Food Agric ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284773

RESUMO

BACKGROUND: Pickering emulsions stabilized by multicomponent particles have attracted increasing attention. Research on characterizing the digestion and health benefit effects of these emulsions in the human gastrointestinal tract are quite limited. This work aims to reveal the digestive characteristics of media-milled purple sweet potato particle-stabilized Pickering emulsions (PSPP-Es) during in vitro digestion and colonic fermentation. RESULTS: The media-milling process improved the in vitro digestibility and fermentability of PSPP-Es by reaching afree fatty acids release rate of 43.11 ± 4.61% after gastrointestinal digestion and total phenolic content release of 101.00 ± 1.44 µg gallic acid equivalents/mL after fermentation. In addition, PSPP-Es exhibited good antioxidative activity (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays), α-glucosidase inhibitory activity (half-maximal inhibitory concentration: 6.70%, v/v), and prebiotic effects, reaching a total short-chain fatty acids production of 9.90 ± 0.12 mol L-1 , boosting the growth of Akkermansia, Bifidobacterium, and Blautia and inhibiting the growth of Escherichia-Shigella. CONCLUSIONS: These findings indicate that the media-milling process enhances the potential health benefits of purple sweet potato particle-stabilized Pickering emulsions, which is beneficial for their application as a bioactive component delivery system in food and pharmaceutical products. © 2024 Society of Chemical Industry.

19.
Carbohydr Polym ; 329: 121779, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286529

RESUMO

While cooked rice is widely consumed as a whole food, the specific characteristics and impact of its resistant starch (RS) on gut microbiota are largely unexplored. In this study, three rice varieties with distinct starch molecular structures were used to prepare RS from cooked rice. All three types of RS had a crystalline structure characterized as B + V type, with the V type being the predominant crystalline polymorph. Distinct differences in chain-length distributions were observed among different RSs, with rapidly fermentable starch fractions comprising short amylopectin and long amylose chains, while the degrees of polymerization (DPs) âˆ¼ 10, 37, 65, and 105 fractions comprised the slowly fermentable starch. Jasmine rice RS showed the highest proportion of this slowly fermentable starch fraction, which appeared to be specifically utilized by Megasphaera_elsdenii_DSM_20460 OTU198. The fermentation of Jasmine RS resulted in the highest production of butyrate after 24 h, which was positively correlated with the relative abundance of Megasphaera_elsdenii_DSM_20460 OTU198. These findings collectively indicate that RS in cooked rice with a higher V type crystallinity and DPs âˆ¼ 10, 37, 65, and 105 fractions promote butyrate production and stimulate the growth of butyrate-producing bacteria in the human gut, thereby conferring beneficial effects on gut health.


Assuntos
Microbioma Gastrointestinal , Oryza , Humanos , Amido Resistente , Oryza/química , Amido/química , Amilose/química , Butiratos
20.
Carbohydr Polym ; 329: 121768, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286543

RESUMO

In the current study, the effects of extrusion using a haake rheometer with a twin-roll mixer, with and without FA addition, on the structures and in vitro digestibility of starches from different sources were investigated. After extruding for 15 min at 90 °C with a moisture content of 40 %, no matter FA was added or not, lager Ap molecules were preferentially debranched, while Am with longer CL were depolymerized simultaneously, resulting to reduced averaged molecular size of Ap and shortened Am chains. Of all starches, regardless of their botanical backgrounds, although synergic effects were found between extrusion and FA addition on reducing their relative crystallinity and the ordered structures, distinctly different effects on the in vitro digestibility of these starches have also been observed especially regarding the digestion of starch branches with DP > 10 Particularly, the Am chains with DP 10-1000 was remaining undigested when FA was added. This study provides important information concerning how to adjust starch digestibility into a healthy range through altering the starch structures using extrusion technique with the addition of phytochemicals or not.


Assuntos
Ácidos Cumáricos , Amido , Amido/química , Digestão
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