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1.
Nat Commun ; 15(1): 5602, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961108

ABSTRACT

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.


Subject(s)
CDX2 Transcription Factor , Cell Proliferation , Cell Self Renewal , Histone Acetyltransferases , Trophoblasts , Trophoblasts/metabolism , CDX2 Transcription Factor/metabolism , CDX2 Transcription Factor/genetics , Animals , Female , Humans , Mice , Pregnancy , Cell Self Renewal/genetics , Histone Acetyltransferases/metabolism , Histone Acetyltransferases/genetics , Abortion, Habitual/metabolism , Abortion, Habitual/genetics , Mice, Knockout , Histones/metabolism , Cell Differentiation , Placentation/genetics
2.
Environ Geochem Health ; 46(8): 276, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958774

ABSTRACT

The occurrence of microplastics (MPs) and organic pollutants (OPs) residues is commonly observed in diverse environmental settings, where their interactions can potentially alter the behavior, availability, and toxicity of OPs, thereby posing risks to ecosystems. Herein, we particularly emphasize the potential for bioaccumulation and the biomagnification effect of MPs in the presence of OPs within the food chain. Despite the ongoing influx of novel information, there exists a dearth of data concerning the destiny and consequences of MPs in the context of food pollution. Further endeavors are imperative to unravel the destiny and repercussions of MPs/OPs within food ecosystems and processing procedures, aiming to gain a deeper understanding of the joint effect on human health and food quality. Nevertheless, the adsorption and desorption behavior of coexisting pollutants can be significantly influenced by MPs forming biofilms within real-world environments, including temperature, pH, and food constituents. A considerable portion of MPs tend to accumulate in the epidermis of vegetables and fruits, thus necessitating further research to comprehend the potential ramifications of MPs on the infiltration behavior of OPs on agricultural product surfaces.


Subject(s)
Food Chain , Food Contamination , Microplastics , Humans , Food Contamination/analysis , Bioaccumulation , Environmental Monitoring
3.
Sci Rep ; 14(1): 14604, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918493

ABSTRACT

The precise delineation of urban aquatic features is of paramount importance in scrutinizing water resources, monitoring floods, and devising water management strategies. Addressing the challenge of indistinct boundaries and the erroneous classification of shadowed regions as water in high-resolution remote sensing imagery, we introduce WaterDeep, which is a novel deep learning framework inspired by the DeepLabV3 + architecture and an innovative fusion mechanism for high- and low-level features. This methodology first creates a comprehensive dataset of high-resolution remote sensing images, then progresses through the Xception baseline network for low-level feature extraction, and harnesses densely connected Atrous Spatial Pyramid Pooling (ASPP) modules to assimilate multi-scale data into sophisticated high-level features. Subsequently, the network decoder amalgamates the elemental and intricate features and applies dual-line interpolation to the amalgamated dataset to extract aqueous formations from the remote images. Experimental evidence substantiates that WaterDeep outperforms its existing deep learning counterparts, achieving a stellar overall accuracy of 99.284%, FWIoU of 95.58%, precision of 97.562%, recall of 95.486%, and F1 score of 96.513%. It also excels in the precise demarcation of edges and the discernment of shadows cast by urban infrastructure. The superior efficacy of the proposed method in differentiating water bodies in complex urban environments has significant practical applications in real-world contexts.

4.
Chem Biodivers ; : e202401093, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867371

ABSTRACT

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

5.
Molecules ; 29(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38930793

ABSTRACT

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.


Subject(s)
Biological Products , Colorectal Neoplasms , Drugs, Chinese Herbal , Signal Transduction , Toll-Like Receptor 4 , Humans , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/antagonists & inhibitors , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Signal Transduction/drug effects , Biological Products/therapeutic use , Biological Products/pharmacology , Biological Products/chemistry , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Medicine, Chinese Traditional , Animals , Herbal Medicine/methods
6.
Neoplasma ; 71(2): 180-192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38766853

ABSTRACT

It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study, CALR and EIF2AK2 expression was measured in the clinical specimens of 39 patients with melanoma. Then, we constructed knockdown and overexpression cell models of CALR and EIF2AK2 and used wound healing and Transwell assays to observe cell migration and invasion. Apoptosis, EDU, and ROS assays were used to measure cell apoptosis and proliferation, as well as ROS levels. The effect of CALR on endoplasmic reticulum stress was detected using endoplasmic reticulum fluorescent probes. Western blotting was used to detect protein levels of CALR, EIF2AK2, ADAR1, and MMP14. The results indicated that CALR and EIF2AK2 expression levels were significantly higher in human melanoma tissues than in adjacent non-tumor tissue. In addition, we found a correlation between CALR and the expression of EIF2AK2 and MMP14, and the experimental results indicated that overexpression of CALR significantly upregulated the expression of EIF2AK2, MMP14, and ADAR1, while knockdown of CALR inhibited their expression. Notably, the knockdown of EIF2AK2 in the CALR overexpression group blocked the upregulation of MMP14 and ADAR1 expression by CALR, and the knockdown of both CALR and EIF2AK2 significantly inhibited MMP14 and ADAR1 expression. In conclusion, CALR and EIF2AK2 play a promoting role in melanoma progression, and knockdown of CALR and EIF2AK2 may be an effective anti-tumor target, and its mechanism may be through MMP14, ADAR1 signaling.


Subject(s)
Adenosine Deaminase , Calreticulin , Matrix Metalloproteinase 14 , Melanoma , Signal Transduction , eIF-2 Kinase , Female , Humans , Male , Middle Aged , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Apoptosis , Calreticulin/genetics , Calreticulin/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , eIF-2 Kinase/metabolism , eIF-2 Kinase/genetics , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 14/metabolism , Matrix Metalloproteinase 14/genetics , Melanoma/pathology , Melanoma/metabolism , Melanoma/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics
7.
Heliyon ; 10(9): e30354, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38726160

ABSTRACT

Background: Sex-based differences are known to be a significant feature of chronic stress; however, the morphological mechanisms of the brain underlying these differences remain unclear. The present study aimed to use magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to investigate the effects of sex on gray matter volume (GMV) changes under conditions of chronic stress. Methods: A total of 32 subjects were included for analysis in the present study: 16 participants experiencing chronic stress and 16 healthy controls. T1-weighted (T1WI) images from a 3 T MRI scanner were extracted from the OpenfMRI database. Images were segmented into gray matter using VBM analysis. A two-way analysis of variance (ANOVA) with a 2 × 2 full factorial design was used to evaluate the main and interaction effects of chronic stress and sex on GMV changes, and then post hoc testing was used to verify each simple effect. Results: Two-way ANOVA showed a chronic stress × sex interaction effect on GMV. Simple effects analysis indicated that the GMV of the bilateral pre- and post-central gyri, the right cuneus and superior occipital gyrus was decreased in males, whereas that of the bilateral pre- and post-central gyri, the right superior occipital gyrus and the left middle frontal gyrus and orbital middle frontal gyrus was increased in females, under chronic stress. Additionally, in the control group, the GMV of the bilateral pre- and post-central gyri, the right cuneus and superior occipital gyrus was greater in males than females. While in the chronic stress group, the above sex-based differences were no longer significant. Conclusions: This study preliminarily shows that there are significant differences in gray matter volume changes between males and females under chronic stress. These findings provide a basis for future studies investigating the volumetric mechanisms of sex differences under chronic stress.

8.
Article in English | MEDLINE | ID: mdl-38734936

ABSTRACT

Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1ß, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 µM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.

9.
Infect Agent Cancer ; 19(1): 25, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802946

ABSTRACT

This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

10.
World J Clin Cases ; 12(14): 2316-2323, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38765746

ABSTRACT

BACKGROUND: The exercise of limb function is the most economical and safe method to promote the maturation of arteriovenous fistula (AVF). However, due to the lack of a unified exercise standard in China, many patients have insufficient awareness of the importance of AVF, leading to poor effectiveness of limb function exercise. The self-management education model can effectively promote patients to take proactive health-related actions. This study focuses on the characteristics of patients during the peri-AVF period and conducts a phased limb function exercise under the guidance of the self-management education model to observe changes in factors such as the maturity of AVF. AIM: To assess the impact of stage-specific limb function exercises, directed by a self-management education model, on the maturation status of AVFs. METHODS: This study is a randomized controlled trial involving 74 patients with forearm AVFs from the Nephrology Department of a tertiary hospital in Sichuan Province, China. Patients were randomly divided into an observation group and a control group using a random number table method. The observation group underwent tailored stage-specific limb function exercises, informed by a self-management education model which took into account the unique features of AVF at various stages, in conjunction with routine care. Conversely, the control group was given standard limb function exercises along with routine care. The assessment involves the maturity of AVFs post-intervention, postoperative complications, and the self-management level of the fistula in both groups patients. Analyses were conducted using SPSS version 23.0. Count data were represented by frequency and percentage and subjected to chi-square test comparisons. Measurement data adhering to a normal distribution were presented as mean ± SD. The independent samples t-test was utilized for inter-group comparisons, while the paired t-test was used for intra-group comparisons. For measurement data not fitting a normal distribution, the median and interquartile range were presented and analyzed using the Wilcoxon rank sum test. RESULTS: At the 8-wk postoperative mark, the observation group demonstrated significantly higher scores in AVF symptom recognition, symptom prevention, and self-management compared to the control group (P < 0.05). However, the variance in symptom management scores between the observation and control groups lacked statistical significance (P > 0.05). At 4 wk after the operation, the observation group displayed a superior vessel diameter and depth from the skin of the drainage vessels in comparison to the control group (P < 0.05). While the observation group did manifest elevated blood flow rates in the drainage vessels relative to the control group, this distinction was not statistically significant (P > 0.05). By the 8-wk postoperative interval, the observation group outperformed the control group with notable enhancements in blood flow rates, vessel diameter, and depth from the skin of drainage vessels (P < 0.01). Seven days following the procedure, the observation group manifested significantly diminished limb swelling and an overall reduced complication rate in contrast to the control group (P < 0.05). The evaluation of infection, thrombosis, embolism, arterial aneurysm stenosis, and incision bleeding showed no notable differences between the two groups (P > 0.05). By the 4-wk postoperative juncture, complications between the observation and control groups were statistically indistinguishable (P > 0.05). CONCLUSION: Stage-specific limb function exercises, under the guidance of a self-management education model, amplify the capacity of AVF patients to discern and prevent symptoms. Additionally, they expedite AVF maturation and mitigate postoperative limb edema, underscoring their efficacy as a valuable method for the care and upkeep of AVF in hemodialysis patients.

11.
Cell Mol Life Sci ; 81(1): 180, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613672

ABSTRACT

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.


Subject(s)
Eosine Yellowish-(YS)/analogs & derivatives , Interleukin-8 , Phosphatidylethanolamines , Pre-Eclampsia , Pregnancy , Humans , Female , Interleukin-8/genetics , Phosphatidylinositol 3-Kinases , Pre-Eclampsia/genetics , Placenta , Arteries , Culture Media, Conditioned , Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins
12.
Langenbecks Arch Surg ; 409(1): 112, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587671

ABSTRACT

INTRODUCTION: Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. METHODS: Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. RESULTS: The incidence of postoperative complications was 20.8% (10/48) in the EA group and 14.6% (7/48) in the IA group respectively, with no statistical difference. Compared to the EA group, patients in the IA group revealed faster gas (40.2 + 7.8 h vs. 45.6 + 7.9 h, P = 0.001) and stool discharge (4.0 + 1.2 d vs. 4.5 + 1.1 d, P = 0.040), shorter assisted incision (5.3 + 1.3 cm vs. 7.5 + 1.2 cm, P = 0.000), and less analgesic used (3.3 + 1.3 d vs. 4.0 + 1.3 d, P = 0.012). There were no significant differences in operation time, blood loss, or postoperative hospital stays. In the IA group, the first one third of cases presented longer operation time (228.4 + 29.3 min) compared to the middle (191.0 + 35.0 min, P = 0.003) and the last one third of patients (182.2 + 20.7 min, P = 0.000). CONCLUSION: LRH with IA is feasible and safe for overweight RCC, with faster bowel function recovery and less pain. Accumulation of certain cases of LRH with IA will facilitate surgical procedures and reduce operation time.


Subject(s)
Carcinoma, Renal Cell , Colonic Neoplasms , Kidney Neoplasms , Laparoscopy , Humans , Case-Control Studies , Overweight , Colonic Neoplasms/surgery , Colectomy , Anastomosis, Surgical
13.
Nanomaterials (Basel) ; 14(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38607103

ABSTRACT

The high energy consumption of traditional water splitting to produce hydrogen is mainly due to complex oxygen evolution reaction (OER), where low-economic-value O2 gas is generated. Meanwhile, cogeneration of H2 and O2 may result in the formation of an explosive H2/O2 gas mixture due to gas crossover. Considering these factors, a favorable anodic oxidation reaction is employed to replace OER, which not only reduces the voltage for H2 production at the cathode and avoids H2/O2 gas mixture but also generates value-added products at the anode. In recent years, this innovative strategy that combines anodic oxidation for H2 production has received intensive attention in the field of electrocatalysis. In this review, the latest research progress of a coupled hydrogen production system with pollutant degradation/upgrading is systematically introduced. Firstly, wastewater purification via anodic reaction, which produces free radicals instead of OER for pollutant degradation, is systematically presented. Then, the coupled system that allows for pollutant refining into high-value-added products combined with hydrogen production is displayed. Thirdly, the photoelectrical system for pollutant degradation and upgrade are briefly introduced. Finally, this review also discusses the challenges and future perspectives of this coupled system.

14.
Acta Psychol (Amst) ; 246: 104255, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38603822

ABSTRACT

Stress can be a double-edged sword. Given the intricacy of the innovation process, the link between job stress and individual innovation behavior remains uncertain. To clarify the relationship between challenge stressors and the innovative behavior of higher education teachers, this study was based on the conservation of resources (COR) theory and adopted the structural equation modeling method to explore the impact of challenge stressors on the innovative behavior of higher education teachers and reveal its influencing mechanism and boundary conditions. By analyzing the data from 208 questionnaires of higher education teachers, the findings reveal that challenge stressors positively influence innovative behavior, with task crafting serving as a critical bridge. Additionally, a favorable employment relationship climate enhances the positive impact of challenge stressors. Gender dynamics are also explored, adding nuance to the understanding of this relationship. These results shed light on the inherent mechanisms governing the relationship between challenge stressors and innovative behavior among higher education teachers, and underscore the significance of task crafting. In addition, the discoveries provided fresh insights and ideas for investigating how organizational climate affects individual innovative behavior.


Subject(s)
Occupational Stress , Humans , Male , Female , Adult , Creativity , Surveys and Questionnaires , Faculty
15.
Food Chem ; 448: 139154, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38555687

ABSTRACT

A self-reporting molecularly-imprinted electrochemical sensor is prepared for the detection of Zearalenone (ZEA). Firstly, the reduced graphene nanoribbons and reduced graphene oxide (rGNR-rGO) were simultaneously modified onto a glassy carbon electrode (GCE) to improve the sensor's sensitivity. After electrodepositing copper nanoparticles onto the rGNR-rGO/GCE, cyclic voltammetry scanning was performed in potassium ferrocyanide solution, and copper hexacyanoferrate (CuHCF) was deposited onto rGNR-rGO/GCE to further improve the sensor's sensitivity while giving it self-reporting capability. Then, molecularly-imprinted polymer films were prepared on the CuHCF/rGNR-rGO/GCE to ensure the selectivity of the sensor. It is found that the linear range of ZEA detection by the constructed sensor is 0.25-500 ng·mL -1, with a detection limit of 0.09 ng·mL -1. This sensor shows the merits of good selectivity, high sensitivity and accurate detection, providing a great possibility for the precise detection of low concentration ZEA in food.


Subject(s)
Copper , Electrochemical Techniques , Food Contamination , Graphite , Molecular Imprinting , Zearalenone , Graphite/chemistry , Electrochemical Techniques/instrumentation , Zearalenone/analysis , Food Contamination/analysis , Copper/chemistry , Limit of Detection , Electrodes , Ferrocyanides/chemistry
16.
J Control Release ; 369: 309-324, 2024 May.
Article in English | MEDLINE | ID: mdl-38554771

ABSTRACT

Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the microsatellite stable/proficient mismatch repair (MSS/pMMR)) subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Here, a multifunctional nanodrug carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody is prepared to boost the immune checkpoint blockade (ICB)-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modify the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. First, CDKs inhibitor delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells sensitizing ICB therapy in CCLM. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft model and the patient-derived organoid model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the tumor immune microenvironment (TIME), and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.


Subject(s)
B7-H1 Antigen , Colonic Neoplasms , Immunotherapy , Liver Neoplasms , Tumor Microenvironment , Animals , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Humans , Immunotherapy/methods , Colonic Neoplasms/pathology , Colonic Neoplasms/immunology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/therapy , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Mice , Cell Membrane/metabolism , Cell Membrane/drug effects , Cyclin-Dependent Kinases/antagonists & inhibitors , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Cell Line, Tumor , Mice, Inbred BALB C , Female , Nanoparticles/administration & dosage , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use
17.
Cytokine ; 178: 156568, 2024 06.
Article in English | MEDLINE | ID: mdl-38471420

ABSTRACT

BACKGROUND: Laryngopharyngeal reflux (LPR) is one of the most common disorders in otorhinolaryngology, affecting up to 10% of outpatients visiting otolaryngology departments. In addition, 50% of hoarseness cases are related to LPR. Pepsin reflux-induced aseptic inflammation is a major trigger of LPR; however, the underlying mechanisms are unclear. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has become an important bridge between stimulation and sterile inflammation and is activated by intracellular reactive oxygen species (ROS) in response to danger signals, leading to an inflammatory cascade. In this study, we aimed to determine whether pepsin causes LPR-associated inflammatory injury via mediating inflammasome activation and explore the potential mechanism. METHODS: We evaluated NLRP3 inflammasome expression and ROS in the laryngeal mucosa using immunofluorescence and immunohistochemistry. Laryngeal epithelial cells were exposed to pepsin and analyzed using flow cytometry, western blotting, and real-time quantitative PCR to determine ROS, NLRP3, and pro-inflammatorycytokine levels. RESULTS: Pepsin expression was positively correlated with ROS as well as caspase-1 and IL-1ß levels in laryngeal tissues. Intracellular ROS levels were elevated by increased pepsin concentrations, which were attenuated by apocynin (APO)-a ROS inhibitor-in vitro. Furthermore, pepsin significantly induced the mRNA and protein expression of thioredoxin-interacting protein, NLRP3, caspase-1, and IL-1ß in a dose-dependent manner. APO and the NLRP3 inhibitor, MCC950, inhibited NLRP3 inflammasome formation and suppressed laryngeal epithelial cell damage. CONCLUSION: Our findings verified that pepsin could regulate the NLRP3/IL-1ß signaling pathway through ROS activation and further induce inflammatory injury in LPR. Targeting the ROS/NLRP3 inflammasome signaling pathway may help treat patients with LPR disease.


Subject(s)
Laryngopharyngeal Reflux , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Reactive Oxygen Species/metabolism , Pepsin A/metabolism , Signal Transduction , Inflammation/metabolism , Caspase 1/metabolism , Interleukin-1beta/metabolism
18.
iScience ; 27(2): 108757, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38313046

ABSTRACT

The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

19.
Int J Biol Macromol ; 264(Pt 1): 130004, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38325679

ABSTRACT

With the rapid development of miniaturization and integration of electronic products, its heat dissipation has become the focus of research. In order to improve the heat dissipation efficiency of electronic components, flexible thermal conduction materials are constantly studied. Cellulose has good flexibility and load capacity, which is often used in the preparation of thermal conduction materials. In this paper, carboxylated multi-walled carbon nanotubes (C-MWCNTs) were modified by metal ion coordination and hydrothermal synthesis of zinc oxide (ZnO) to prepare semi-insulating thermal conduction fillers, which were dispersed into regenerated cellulose (RC) to cast to be composite films. The results show that the two modification methods can reduce the probability of phonon scattering and block the electron transport path, so as to improve the thermal conductivity (TC) and electrical insulation properties of the composite films. Especially for the RC/C-MWCNTs@ZnO composite films, when the total filler content is 20 wt%, the in-plane TC can reach 11.89 ± 0.19 (W/(m·K)), and the surface electrical resistivity (ρs) is (5.24 ± 0.17) × 106 Ω. Compared with the RC/C-MWCNTs composite films, the in-plane TC and ρs of the RC/C-MWCNTs@ZnO composites films are increased by about 94.92 % and 555 %, respectively. Therefore, the developed RC-based composite film has broad application prospects in thermal management.


Subject(s)
Nanotubes, Carbon , Zinc Oxide , Thermal Conductivity , Cellulose , Carboxylic Acids , Ions
20.
J Hazard Mater ; 466: 133639, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38309169

ABSTRACT

The excessive usage of veterinary antibiotics has raised significant concerns regarding their environmental hazard and agricultural impact when entering surface water and soil. Animal waste serves as a primary source of organic fertilizer for intensive large-scale agricultural cultivation, including the widely utilized medicinal and edible plant, Polygonatum cyrtonem. In this study, we employed a novel plant stress tissue culture technology to investigate the toxic effects of tetracycline hydrochloride (TCH) and sulfadiazine (SDZ) on P. cyrtonema. TCH and SDZ exhibited varying degrees of influence on plant growth, photosynthesis, and the reactive oxygen species (ROS) scavenging system. Flavonoid levels increased following exposure to TCH and SDZ. The biosynthesis and signaling pathways of the growth hormones auxin and gibberellic acid were suppressed by both antibiotics, while the salicylic acid-mediated plant stress response was specifically induced in the case of SDZ. Overall, the study unveiled both common and unique responses at physiological, biochemical, and molecular levels in P. cyrtonema following exposure to two distinct types of antibiotics, providing a foundational framework for comprehensively elucidating the precise toxic effects of antibiotics and the versatile adaptive mechanisms in plants.


Subject(s)
Anti-Bacterial Agents , Polygonatum , Anti-Bacterial Agents/toxicity , Photosynthesis , Plant Growth Regulators , Polygonatum/chemistry , Sulfadiazine , Tetracycline , Transcriptome
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