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1.
Medicine (Baltimore) ; 103(18): e37928, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701264

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health. CASE PRESENTATION: This report examines a 39-year-old male with type 2 diabetes who developed depressive symptoms after starting liraglutide for glycemic control and weight reduction. Symptoms included poor mood, irritability, decreased interest and energy, progressing to sadness, low self-esteem, and physical discomfort. A clinical diagnosis of a depressive episode was made, coinciding with the initiation of liraglutide. INTERVENTION AND OUTCOME: The patient depressive symptoms significantly improved within a week after discontinuing liraglutide and starting antidepressant therapy. This suggests a possible link between liraglutide and depression, despite considering other factors like diabetes-related stress. DISCUSSION: The report explores potential mechanisms, such as GLP-1RA effects on glucose fluctuations and dopamine modulation, which might contribute to depressive symptoms. The influence on the brain reward system and the reduction in cravings for addictive substances after GLP-1RA use is also discussed as a factor in mood regulation. CONCLUSION: This case highlights the necessity of being vigilant about potential psychiatric side effects, particularly depression, associated with GLP-1RAs. The rarity of such reports calls for more research to investigate and understand these implications further.


Subject(s)
Depression , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Liraglutide , Humans , Liraglutide/therapeutic use , Liraglutide/adverse effects , Male , Diabetes Mellitus, Type 2/drug therapy , Adult , Depression/drug therapy , Depression/chemically induced , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use
2.
Int J Surg ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38506734

ABSTRACT

BACKGROUND: Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. METHODS: Inspired by the local use of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. RESULTS: The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. CONCLUSION: Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.

3.
Biomed Pharmacother ; 173: 116398, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458011

ABSTRACT

Breast cancer has become the most prevalent malignancy worldwide; however, therapeutic efficacy is far from satisfactory. To alleviate the burden of this disease, it is imperative to discover novel mechanisms and treatment strategies. Protein phosphatase 2 A (PP2A) comprises a family of mammalian serine/threonine phosphatases that regulate many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathologies, and plays a pivotal role in the initiation and progression of tumours. The role of PP2A as a tumour suppressor has been extensively studied, and its regulation can serve as a target for anticancer therapy. Recent studies have shown that PP2A is a tumour promotor. PP2A-mediated anticancer therapy may involve two opposing mechanisms: activation and inhibition. In general, the contradictory roles of PP2A should not be overlooked, and more work is needed to determine the molecular mechanism by which PP2A affects in tumours. In this review, the literature on the role of PP2A in tumours, especially in breast cancer, was analysed. This review describes relevant targets of breast cancer, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may lead to effective therapeutic strategies or influence drug development in breast cancer.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/drug therapy , Protein Phosphatase 2/genetics , Protein Phosphatase 2/metabolism
4.
Ambio ; 53(7): 1077-1091, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38366296

ABSTRACT

The Chinese government has pursued comprehensive ecological conservation and restoration by establishing an ecological barrier system. However, the majority of international research tends to focus on the connectivity between habitats, overlooking the functions that ecological barriers play in ecological conservation and restoration. The existing literature lacks a systematic exploration of the theory and practice of ecological barriers. This study employed the literature analysis tool CiteSpace to present the theoretical and developmental trends in ecological barriers from various perspectives, including research fields, historical evolution, research hotspots, and major research nations. By analyzing the differences in the understanding of ecological barriers between China and other countries, examining the ecological barriers construction history in China, and exploring the types and functions of ecological barriers, this study summarizes the framework of China's ecological barriers construction system as "features-functions-problems." Constructing an ecological barrier system can help achieve ecological conservation and restoration goals in China.


Subject(s)
Conservation of Natural Resources , Ecosystem , Conservation of Natural Resources/methods , China , Ecology , Environmental Restoration and Remediation/methods
5.
Ann Clin Microbiol Antimicrob ; 23(1): 13, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347529

ABSTRACT

BACKGROUND: Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. METHODS: Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. RESULTS: A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES-1 (10/47), blaVIM-2 (6/47), blaGES-14 (4/47), blaIMP-45 (2/47), blaKPC-2 (1/47), and blaNDM-14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4-O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018-2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). CONCLUSIONS: The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.


Subject(s)
Anti-Bacterial Agents , Pseudomonas Infections , Aged , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas aeruginosa/genetics , Pseudomonas Infections/epidemiology , Pseudomonas Infections/drug therapy , Bacterial Proteins/genetics , beta-Lactamases/genetics , Serogroup , China/epidemiology , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial/genetics
6.
Crit Rev Oncol Hematol ; 196: 104309, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423376

ABSTRACT

OBJECTIVE: To assess the efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy for early-stage triple-negative breast cancer (TNBC) patients with different clinical characteristics. METHODS: Randomized clinical trials for PD-1/PD-L1 inhibitors and chemotherapy combination were included. Pooled analysis of odds ratio (OR) for pathological complete response (pCR) and hazard ratio (HR) for event-free survival (EFS) was conducted overall and for predefined subgroups. RESULTS: The combination of immunotherapy and chemotherapy significantly improved pCR rate in early TNBC patients (OR, 1.77), and the incidence of events was significantly reduced by 37%. Lymph node metastasis was associated with more benefits on pCR (OR[N0], 1.29; OR[N+], 2.57; P = 0.01), while earlier T stage was related to more benefits on EFS (HR[T1-T2], 0.48; HR[T3-T4], 0.85; P = 0.05). CONCLUSION: The addition of PD-1/PD-L1 inhibitors to chemotherapy offers improved pCR and EFS in early TNBC patients. T and N stages may have implications for the efficacy.


Subject(s)
Immune Checkpoint Inhibitors , Triple Negative Breast Neoplasms , Humans , Immune Checkpoint Inhibitors/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Programmed Cell Death 1 Receptor , Prognosis
7.
Angew Chem Int Ed Engl ; 63(16): e202319907, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38391274

ABSTRACT

Encapsulating individual mammalian cells with biomimetic materials holds potential in ex vivo cell culture and engineering. However, current methodologies often present tradeoffs between homogeneity, stability, and cell compatibility. Here, inspired by bacteria that use proteins stably anchored on their outer membranes to nucleate biofilm growth, we develop a single-cell encapsulation strategy by using a DNA framework structure as a nucleator (DFN) to initiate the growth of DNA hydrogels under cell-friendly conditions. We find that among the tested structures, the tetrahedral DFN can evenly and stably reside on cell membranes, effectively initiating hybridization chain reactions which generate homogeneously dense yet flexible single-cell encapsulation for diverse cell lines. The encapsulation persists for up to 72 hours in a serum-containing cell culture environment, representing a ~70-fold improvement compared to encapsulations mediated by single-stranded DNA nucleators. The metabolism and proliferation of the encapsulated cells are suppressed, but can be restored to the original efficiencies upon release, suggesting the superior cell compatibility of the encapsulation. We also find that compared to naked cells, the encapsulated cells exhibit a lower autophagy level after undergoing mechanical stress, suggesting the protective effect of the DNA encapsulation. This method may provide a new tool for ex vivo cell engineering.


Subject(s)
Biomimetic Materials , Hydrogels , Animals , Hydrogels/chemistry , Cell Line , DNA , Mammals
8.
J Med Chem ; 67(1): 165-179, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38117948

ABSTRACT

Cytoplasmic vacuolation-associated cell death, known as methuosis, offers a promising nonapoptotic approach for cancer treatment. In this study, we outline the synthesis and evaluation of potent methuosis-inducing compounds. These compounds selectively induce cell death, characterized by extensive cytoplasmic vacuolation in HeLa and MDA-MB-231 cells. Notably, compound L22 exhibited a remarkable interaction with PIKfyve kinase, boasting a Kd value of 0.47 nM, surpassing the positive controls D-13 and MOMIPP in potency. Furthermore, it is important to highlight that cell death induced by compound L22 is unequivocally attributed to methuosis as it differs from apoptosis, necrosis, or autophagy. Importantly, when administered orally, L22 effectively inhibited tumor growth in a HeLa xenograft model without any apparent signs of toxicity. These results underscore the potential of L22 as a valuable tool for in-depth investigations into the mechanisms of methuosis and as a promising lead compound to guide structural optimization.


Subject(s)
Antineoplastic Agents , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Death , Apoptosis , Phosphatidylinositol Phosphates/pharmacology
9.
Adv Mater ; 35(45): e2302323, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37463346

ABSTRACT

Extracellular vesicles (EVs) are natural carriers for intercellular transfer of bioactive molecules, which are harnessed for wide biomedical applications. However, a facile yet general approach to engineering interspecies EV-cell communications is still lacking. Here, the use of DNA to encode the heterogeneous interfaces of EVs and cells in a manner free of covalent or genetic modifications is reported, which enables orthogonal EV-cell interkingdom interactions in complex environments. Cholesterol-modified DNA strands and tetrahedral DNA frameworks are employed with complementary sequences to serve as artificial ligands and receptors docking on EVs and living cells, respectively, which can mediate specific yet efficient cellular internalization of EVs via Watson-Crick base pairing. It is shown that based on this system, human cells can adopt EVs derived from the mouse, watermelon, and Escherichia coli. By implementing several EV-cell circuits, it shows that this DNA-programmed system allows orthogonal EV-cell communications in complex environments. This study further demonstrates efficient delivery of EVs with bioactive contents derived from feeder cells toward monkey female germline stem cells (FGSCs), which enables self-renewal and stemness maintenance of the FGSCs without feeder cells. This system may provide a universal platform to customize intercellular exchanges of materials and signals across species and kingdoms.


Subject(s)
Extracellular Vesicles , Stem Cell Niche , Humans , Animals , Mice , Cell Communication , DNA , Engineering
10.
Anal Chim Acta ; 1281: 341910, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38783745

ABSTRACT

BACKGROUND: Melanoma is a highly aggressive tumor and a significant cause of skin cancer-related death. Timely diagnosis and treatment require identification of specific biomarkers in exosomes secreted by melanoma cells. In this study, label-free surface-enhanced Raman spectroscopy (SERS) method with size-matched selectivity was used to detect membrane proteins in exosomes released from a stimulated environment of fibroblasts (L929) co-cultured with melanoma cells (B16-F10). To promote normal secretion of exosomes, micro-plasma treatment was used to gently induce the co-cultured cells and slightly increase the stress level around the cells for subsequent detection using the SERS method. RESULTS AND DISCUSSION: Firstly, changes in reactive oxygen species/reactive nitrogen species (ROS/RNS) concentrations in the cellular microenvironment and the viability and proliferation of healthy cells are assessed. Results showed that micro-plasma treatment increased extracellular ROS/RNS levels while modestly reducing cell proliferation without significantly affecting cell survival. Secondly, the particle size of secreted exosomes isolated from the culture medium of L929, B16-F10, and co-cultured cells with different micro-plasma treatment time did not increase significantly under single-cell conditions at short treatment time but might be changed under co-culture condition or longer treatment time. Third, for SERS signals related to membrane protein biomarkers, exosome markers CD9, CD63, and CD81 can be assigned to significant Raman shifts in the range of 943-1030 and 1304-1561 cm-1, while the characteristics SERS peaks of L929 and B16-F10 cells are most likely located at 1394/1404, 1271 and 1592 cm-1 respectively. SIGNIFICANCE AND NOVELTY: Therefore, this micro-plasma-induced co-culture model provides a promising preclinical approach to understand the diagnostic potential of exosomes secreted by cutaneous melanoma/fibroblasts. Furthermore, the label-free SERS method with size-matched selectivity provides a novel approach to screen biomarkers in exosomes secreted by melanoma cells, aiming to reduce the use of labeling reagents and the processing time traditionally required.


Subject(s)
Coculture Techniques , Exosomes , Fibroblasts , Spectrum Analysis, Raman , Exosomes/metabolism , Exosomes/chemistry , Fibroblasts/metabolism , Fibroblasts/cytology , Mice , Animals , Spectrum Analysis, Raman/methods , Plasma Gases/chemistry , Plasma Gases/pharmacology , Reactive Oxygen Species/metabolism , Cell Proliferation , Melanoma/metabolism , Melanoma/pathology , Cell Survival
11.
Article in English | MEDLINE | ID: mdl-36429854

ABSTRACT

This study aims to investigate the factors that affect physicians' healthcare service provision behavior on healthcare service platforms. A research model was proposed based on the related literature and uses and gratifications theory and self-determination theory. The empirical data were collected from a popular Chinese healthcare service platform, and negative binomial regression was employed to test the proposed research model. The results indicate that competence satisfaction, autonomy satisfaction, and economic benefit have positive impacts on their service provision behavior and that when physicians have a higher level of offline status, they would be less likely to provide consultation service online if they have a higher level of competence satisfaction. This study contributes to the existing literature by integrating intrinsic and extrinsic motivations to investigate how they affect physicians' healthcare service provision behavior online. Findings from this study may derive recommendations for improving the features and design of healthcare service platforms.


Subject(s)
Motivation , Physicians , Humans , Health Services , Personal Autonomy , Delivery of Health Care
12.
RSC Adv ; 12(46): 29777-29784, 2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36321098

ABSTRACT

Biomaterials have drawn considerable attention in recent years because of environmental concerns. In this paper, several different poly(lactide)-b-poly(butadiene)-b-poly(lactide) (PLA-b-PB-b-PLA) triblock copolymers were synthesized by the bulk ring-opening polymerization of lactide initiated by flexible macro-initiator hydroxyl-terminated polybutadiene (HTPB) by adjusting the ratio of HTPB to lactide and the optical isomer of lactide. Afterwards, a chain-extension reaction with hexamethylene diisocyanate (HDI) was carried out to prepare (PLA-b-PB-b-PLA) n multi-block copolymers with enhanced molecular weight. The structures and properties of these block copolymers were then characterized by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), atomic force microscope (AFM) and Fourier-transform infrared (FTIR). Toughening effect of the (PLA-b-PB-b-PLA) n multiblock copolymers on biodegradable poly(l-lactide) (PLLA) film was investigated and the blended film with higher (poly(d-lactide)-b-poly(butadiene)-b-poly(d-lactide)) n (PDLA-b-PB-b-PDLA) n loading (15 wt%) exhibited better toughness nearly without loss of the tensile strength. The mechanical properties of the (PLA-b-PB-b-PLA) n /PLLA blended film were proved to be influenced by the different isomers of PLA and rubbery PB chains.

13.
Nat Commun ; 13(1): 5413, 2022 09 15.
Article in English | MEDLINE | ID: mdl-36109526

ABSTRACT

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and hence generating an immunologically hotter microenvironment. We find that inosine directly inhibits UBA6 in tumour cells, and lower level of UBA6 makes the tumour more immunogenic and this is reflected in favourable outcome following ICB therapy in human melanomas. Transplanted mouse melanoma and breast cancer cells with genetic ablation of Uba6 show higher sensitivity to ICB than wild type tumours. Thus, we provide evidence of an inosine-regulated UBA6-dependent pathway governing tumour-intrinsic immunogenicity and hence sensitivity to immune checkpoint inhibition, which might provide targets to overcome ICB resistance.


Subject(s)
Immune Checkpoint Inhibitors , Melanoma , Animals , Combined Modality Therapy , Humans , Inosine/pharmacology , Melanoma/pathology , Mice , Radioimmunotherapy , Tumor Microenvironment , Ubiquitin-Activating Enzymes
14.
Front Immunol ; 13: 935552, 2022.
Article in English | MEDLINE | ID: mdl-35874784

ABSTRACT

The profiling of the tumor immune microenvironment (TIME) is critical for guiding immunotherapy strategies. However, how the composition of the immune landscape affects the tumor progression of gastric cancer (GC) is ill-defined. Here, we used mass cytometry to perform simultaneous in-depth immune profiling of the tumor, adjacent tissues, and blood cells from GC patients and revealed a unique GC tumor-immune signature, where CD8+ T cells were present at a lower frequency in tumor tissues compared to adjacent tissues, whereas regulatory T cells and tumor-associated macrophages (TAMs) were significantly increased, indicating strong suppressive TIME in GC. Incorporated with oncogenic genomic traits, we found that the unique immunophenotype was interactively shaped by a specific GC gene signature across tumor progression. Earlier-stage GC lesions with IFN signaling enrichment harbored significantly altered T-cell compartments while advanced GC featured by metabolism signaling activation was accumulated by TAMs. Interestingly, PD-1 expression on CD8+ T cells was relatively higher in earlier-stage GC patients, indicating that these patients may derive more benefits from PD-1 inhibitors. The dynamic properties of diverse immune cell types revealed by our study provide new dimensions to the immune landscape of GC and facilitate the development of novel immunotherapy strategies for GC patients.


Subject(s)
Stomach Neoplasms , CD8-Positive T-Lymphocytes , Humans , Immunophenotyping , Stomach Neoplasms/pathology , T-Lymphocytes, Regulatory , Tumor Microenvironment
15.
Article in English | MEDLINE | ID: mdl-35805632

ABSTRACT

The increase in predatory practices in the substance use disorder treatment industry calls for the development of measures to assess individuals' knowledge about these practices. METHODS: This study describes the development of the Knowledge of Predatory Practices Scale (KPPS), a newly developed measure designed to assess the knowledge of predatory practices within the substance use disorder treatment industry. An exploratory factor analysis was conducted to determine the factor structure of this measure. RESULTS: The final 11-item KPPS consisted of two factors-knowledge about general predatory practices (9 items) and knowledge about unethical practices (2 items). Overall, these factors explained 61.75% of the total variance. The Cronbach's alpha for the KPPS was 0.81. CONCLUSIONS: The KPPS is a reliable measure of knowledge of predatory practices within the substance use disorder treatment industry and can be used as a measurement tool to educate individuals seeking help for their loved ones who are misusing substances.


Subject(s)
Health Knowledge, Attitudes, Practice , Substance-Related Disorders , Factor Analysis, Statistical , Humans , Psychometrics , Reproducibility of Results , Substance-Related Disorders/therapy , Surveys and Questionnaires
16.
Immun Inflamm Dis ; 10(8): e626, 2022 08.
Article in English | MEDLINE | ID: mdl-35894707

ABSTRACT

INTRODUCTION: The characteristics of the tumor immune microenvironment (TIME) are closely related to immunotherapy. Breast cancer can benefit from immunotherapy, and its TIME is still unclear. METHODS: We utilized mass cytometry to explore the immune cell heterogeneity in breast cancer. Double-negative T cells (DNTs) from healthy volunteers (HBs) were enriched in vitro. Flow cytometry was used to detect the cell surface receptors of cancer cells and DNT cells. The correlation between immune checkpoints and the abundance of immune cells or prognosis of breast cancer was analyzed by the TCGA database. The messenger RNA (mRNA) expression of functional genes was performed by quantitative real-time PCR. RESULTS: We found that the frequencies of Granzyme B (GZMB)+ CD8+ T and GZMB+ DNT cells in cancer tissues (CA) of breast cancer were lower than those in blood samples of patients (PB), and the frequencies of programmed cell death protein 1 (PD1)+ CD8+ T and PD1+ DNT cells in CA were higher than those in PB. DNTs from HBs had a cytotoxic effect on MDA-MB-231. LAG3Ab could upregulate the mRNA expression of interferon gamma and perforin by increasing T-BET transcription to enhance the cytotoxicity of DNT cells in vitro. CONCLUSION: Our study revealed the suppressive status of TIME in breast cancer and supported DNT cells had the potential to be applied as a novel adoptive cell therapy for TNBC either alone or combined with LAG3Ab.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Immunotherapy, Adoptive , RNA, Messenger , T-Lymphocytes , Tumor Microenvironment
17.
J Med Chem ; 65(13): 9312-9327, 2022 07 14.
Article in English | MEDLINE | ID: mdl-35709396

ABSTRACT

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) has been demonstrated to be a promising target for treating inflammatory diseases. Herein, we describe the discovery and optimization of a series of RIPK2 inhibitors derived from an FLT3 inhibitor, CHMFL-FLT3-165. Compound 10w was identified to possess an IC50 value of 0.6 nM for RIPK2 and greater than 50,000-fold selectivity over its family homologous kinase RIPK1 (IC50 > 30 µM). It exhibited high kinase selectivity and inhibited RIPK2 to prevent NOD-induced cytokine production following muramyl dipeptide (MDP) stimulation. In an acute colitis model, compound 10w exerted better therapeutic effects than the JAK inhibitor filgotinib and the RIPK2 inhibitor WEHI-345. These robust results of in vitro and in vivo pharmacodynamic experiments demonstrate that RIPK2 as a therapeutic target shows potential abilities for the treatment of inflammatory bowel diseases.


Subject(s)
Inflammatory Bowel Diseases , Receptor-Interacting Protein Serine-Threonine Kinase 2 , Acetylmuramyl-Alanyl-Isoglutamine/metabolism , Humans , Inflammatory Bowel Diseases/drug therapy , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Receptor-Interacting Protein Serine-Threonine Kinases , Serine , Threonine
18.
J Hazard Mater ; 437: 129393, 2022 09 05.
Article in English | MEDLINE | ID: mdl-35728318

ABSTRACT

Fe0-Fe3O4 nanoparticles and cerium dioxide hollow spheres as efficient heterogeneous electro-Fenton reagents were rationally designed to be embedded in porous carbon derived from skimmed cotton for the electrocatalytic degradation of ceftriaxone sodium. Skimmed cotton porous carbon material has a hollow tubular structure, and cerium dioxide is dispersed on the surface of the carbon material in a hollow sphere structure of uniform size. Fe0-Fe3O4 nanoparticles were wrapped in irregular particle shapes on the surface of cerium dioxide hollow spheres, and the remaining part was laid flat on the surface of porous carbon material. The as-synthesized Fe0-Fe3O4/CeO2/C showed excellent degradation efficiency of 95.59 % for ceftriaxone sodium within 120 mins and obtained a COD removal rate of 95.21 % at 240 mins. The zero-valent iron as a reducing agent effectively accelerated the Fe3+/Fe2+ cycle, allowing the composites to exhibit higher catalytic activity and further reducing the possibility of secondary contamination. Moreover, the existence of cerium dioxide further promoted the redox cycle of Ce4+/Ce3+ and accelerated the electron transfer in the interface of the catalyst. The synergistic effect of iron and cerium greatly facilitated the production of hydroxyl radicals and increased the yield of hydroxyl radicals in the reaction system.


Subject(s)
Ceftriaxone , Water Pollutants, Chemical , Carbon/chemistry , Catalysis , Electrodes , Hydrogen Peroxide/chemistry , Iron/chemistry , Oxidation-Reduction , Water Pollutants, Chemical/chemistry
19.
Chemosphere ; 298: 134315, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35301999

ABSTRACT

In this work, flower-like molybdenum disulfide was constructed on the surface of ZIF-8-derived nitrogen-doped dodecahedral carbon (ZNC) for the electrocatalytic degradation of phenol. The flower-like nanostructure of MoS2@ZNC contributed to the exposure of more edge-active sites of MoS2. At the same time, Mo4+ and Mo6+ co-existed in MoS2@ZNC, which promoted the generation of H2O2 and •OH, and improved the catalytic activity of composite materials. In addition, electrochemical performance analysis showed that MoS2 loaded on the surface of ZNC significantly improved the redox capacity of the material, and the composite ratio of MoS2 and ZNC affected the structure and properties of MoS2@ZNC composites. Moreover, the electrochemical performance of prepared MoS2@ZNC was evaluated by the generation of hydroxyl (•OH) and the degradation efficiency of phenol. The results showed that MoS2@ZNC-2 had an excellent phenol degradation efficiency (98.8%) and COD removal efficiency (86.8%) within 120 min. Furthermore, MoS2@ZNC cathode still maintained good performance after being experimented with 20 times, indicated the excellent stability of MoS2@ZNC.


Subject(s)
Carbon , Molybdenum , Disulfides , Hydrogen Peroxide/chemistry , Molybdenum/chemistry , Nitrogen , Phenol , Phenols
20.
Small ; 18(36): e2107640, 2022 09.
Article in English | MEDLINE | ID: mdl-35119201

ABSTRACT

The cell microenvironment plays a crucial role in regulating cell behavior and fate in physiological and pathological processes. As the fundamental component of the cell microenvironment, extracellular matrix (ECM) typically possesses complex ordered structures and provides essential physical and chemical cues to the cells. Hydrogels have attracted much attention in recapitulating the ECM. Compared to natural and synthetic polymer hydrogels, DNA hydrogels have unique programmable capability, which endows the material precise structural customization and tunable properties. This review focuses on recent advances in programmable DNA hydrogels as artificial extracellular matrix, particularly the pure DNA hydrogels. It introduces the classification, design, and assembly of DNA hydrogels, and then summarizes the state-of-the-art achievements in cell encapsulation, cell culture, and tissue engineering with DNA hydrogels. Ultimately, the challenges and prospects for cellular applications of DNA hydrogels are delivered.


Subject(s)
Extracellular Matrix , Hydrogels , DNA/chemistry , Extracellular Matrix/chemistry , Hydrogels/chemistry , Polymers/analysis , Tissue Engineering
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