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1.
Angew Chem Int Ed Engl ; : e202404093, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727540

ABSTRACT

Accurate visualization of tumor microenvironment is of great significance for personalized medicine. Here, we develop a near-infrared (NIR) fluorescence/photoacoustic (FL/PA) dual-mode molecular probe (denoted as NIR-CE) for distinguishing tumors based on carboxylesterase (CE) level by an analyte-induced molecular transformation (AIMT) strategy. The recognition moiety for CE activity is the acetyl unit of NIR-CE, generating the pre-product, NIR-CE-OH, which undergoes spontaneous hydrogen atom exchange between the nitrogen atoms in the indole group and the phenol hydroxyl group, eventually transforming into NIR-CE-H. In cellular experiments and in vivo blind studies, the human hepatoma cells and tumors with high level of CE were successfully distinguished by both NIR FL and PA imaging. Our findings provide a new molecular imaging strategy for personalized treatment guidance.

2.
Curr Mol Med ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38778614

ABSTRACT

Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.

3.
Peptides ; 177: 171223, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38626843

ABSTRACT

Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.


Subject(s)
Oxytocin , Social Behavior , Oxytocin/metabolism , Oxytocin/physiology , Animals , Humans , Neuropeptides/metabolism , Mammals/metabolism , Anxiety/metabolism , Anxiety/psychology , Aggression/physiology , Empathy/physiology , Female , Maternal Behavior/physiology
4.
Cell Prolif ; : e13612, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38348888

ABSTRACT

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.

5.
iScience ; 27(3): 109144, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38380259

ABSTRACT

A micro turbine engine's thrust relies on combustion chamber efficiency, closely tied to the design of its evaporation tube. This study thoroughly investigates evaporation and atomization processes within the tube, introducing a pioneering bionic-inspired structure. Integrating a honeycomb sheet into the traditional tube, both configurations undergo a comparative analysis. Results show a direct correlation between elevated air temperatures and reduced fuel droplet diameters, leading to increased fuel evaporation rates. The bionic tube, with a 1mm-thick honeycomb sheet, 0.6 mm aperture diameter, and 3 sheets, significantly improves fuel droplet atomization and evaporation compared to the conventional design. This research holds broader significance in understanding and enhancing micro turbine engine performance.

6.
Brain Res ; 1830: 148813, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38373675

ABSTRACT

Electroencephalogram (EEG) has been widely utilized as a valuable assessment tool for diagnosing epilepsy in hospital settings. However, clinical diagnosis of patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) is challenging due to the presence of similar abnormal discharges in EEG displays compared to other types of epilepsy (non-SeLECTS) patients. To assist the diagnostic process of epilepsy, a comprehensive classification study utilizing machine learning or deep learning techniques is proposed. In this study, clinical EEG was collected from 33 patients diagnosed with either SeLECTS or non-SeLECTS, aged between 3 and 11 years. In the realm of classical machine learning, sharp wave features (including upslope, downslope, and width at half maximum) were extracted from the EEG data. These features were then combined with the random forest (RF) and extreme random forest (ERF) classifiers to differentiate between SeLECTS and non-SeLECTS. Additionally, deep learning was employed by directly inputting the EEG data into a deep residual network (ResNet) for classification. The classification results were evaluated based on accuracy, F1-score, area under the curve (AUC), and area under the precision-recall curve (AUPRC). Following a 10-fold cross-validation, the ERF classifier achieved an accuracy of 73.15 % when utilizing sharp wave feature extraction for classification. The F1-score obtained was 0.72, while the AUC and AUPRC values were 0.75 and 0.63, respectively. On the other hand, the ResNet model achieved a classification accuracy of 90.49 %, with an F1-score of 0.90. The AUC and AUPRC values for ResNet were found to be 0.96 and 0.92, respectively. These results highlighted the significant potential of deep learning methods in SeLECTS classification research, owing to their high accuracy. Moreover, feature extraction-based methods demonstrated good reliability and could assist in identifying relevant biological features of SeLECTS within EEG data.


Subject(s)
Deep Learning , Epilepsy , Humans , Child, Preschool , Child , Reproducibility of Results , Epilepsy/diagnosis , Electroencephalography/methods , Machine Learning
7.
PeerJ Comput Sci ; 10: e1760, 2024.
Article in English | MEDLINE | ID: mdl-38259885

ABSTRACT

Background: Improvement on the updating equation of an algorithm is among the most improving techniques. Due to the lack of search ability, high computational complexity and poor operability of equilibrium optimizer (EO) in solving complex optimization problems, an improved EO is proposed in this article, namely the multi-strategy on updating synthetized EO (MS-EO). Method: Firstly, a simplified updating strategy is adopted in EO to improve operability and reduce computational complexity. Secondly, an information sharing strategy updates the concentrations in the early iterative stage using a dynamic tuning strategy in the simplified EO to form a simplified sharing EO (SS-EO) and enhance the exploration ability. Thirdly, a migration strategy and a golden section strategy are used for a golden particle updating to construct a Golden SS-EO (GS-EO) and improve the search ability. Finally, an elite learning strategy is implemented for the worst particle updating in the late stage to form MS-EO and strengthen the exploitation ability. The strategies are embedded into EO to balance between exploration and exploitation by giving full play to their respective advantages. Result and Finding: Experimental results on the complex functions from CEC2013 and CEC2017 test sets demonstrate that MS-EO outperforms EO and quite a few state-of-the-art algorithms in search ability, running speed and operability. The experimental results of feature selection on several datasets show that MS-EO also provides more advantages.

8.
Biomimetics (Basel) ; 8(8)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38132530

ABSTRACT

As human-robot interaction and teleoperation technologies advance, anthropomorphic control of humanoid arms has garnered increasing attention. However, accurately translating sensor-detected arm motions to the multi-degree freedom of a humanoid robotic arm is challenging, primarily due to occlusion issues with single-sensor setups, which reduce recognition accuracy. To overcome this problem, we propose a human-like arm control strategy based on multi-sensor fusion. We defined the finger bending angle to represent finger posture and employed a depth camera to capture arm movement. Consequently, we developed an arm movement tracking system and achieved anthropomorphic control of the imitation human arm. Finally, we verified our proposed method's effectiveness through a series of experiments, evaluating the system's robustness and real-time performance. The experimental results show that this control strategy can control the motion of the humanoid arm stably, and maintain a high recognition accuracy in the face of complex situations such as occlusion.

9.
Adv Sci (Weinh) ; 10(36): e2303545, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37963851

ABSTRACT

O-GlcNAcylation functions as a cellular nutrient and stress sensor and participates in almost all cellular processes. However, it remains unclear whether O-GlcNAcylation plays a role in the establishment and maintenance of cell polarity, because mice lacking O-GlcNAc transferase (OGT) are embryonically lethal. Here, a mild Ogt knockout mouse model is constructed and the important role of O-GlcNAcylation in establishing and maintaining cell polarity is demonstrated. Ogt knockout leads to severe pulmonary fibrosis and dramatically promotes epithelial-to-mesenchymal transition. Mechanistic studies reveal that OGT interacts with pericentriolar material 1 (PCM1) and centrosomal protein 131 (CEP131), components of centriolar satellites required for anchoring microtubules to the centrosome. These data further show that O-GlcNAcylation of PCM1 and CEP131 promotes their centrosomal localization through phase separation. Decrease in O-GlcNAcylation prevents PCM1 and CEP131 from localizing to the centrosome, instead dispersing these proteins throughout the cell and impairing the microtubule-centrosome interaction to disrupt centrosome positioning and cell polarity. These findings identify a previously unrecognized role for protein O-GlcNAcylation in establishing and maintaining cell polarity with important implications for the pathogenesis of pulmonary fibrosis.


Subject(s)
Pulmonary Fibrosis , Mice , Animals , Pulmonary Fibrosis/metabolism , Cell Polarity , Centrosome/metabolism , Phenotype
10.
Curr Res Food Sci ; 7: 100607, 2023.
Article in English | MEDLINE | ID: mdl-37840701

ABSTRACT

Hydrocolloids have been widely used to adjust properties of natural starches, but related research on kudzu starch is still rare. In this study, we investigated the effects of gum arabic (AG), sodium alginate (SA), locust bean gum (LG), and guar gum (GG) on kudzu starch from the perspective of its particle size, pasting, texture, rheology, dehydration rate, thermal properties, microstructure, and sensitivity to amyloglucosidase. Results showed that GG significantly increased the particle size of starch. Addition of AG led to lower peak-, final- and holding-viscosity. SA increased the retention viscosity of kudzu starch, while LG and GG increased its peak viscosity. Addition of hydrocolloids increased the hardness, chewiness, and cohesiveness of starch-hydrocolloid complexes, and reduced the dehydration rate of complex gels. Dynamic rheological data showed that the energy storage modulus (G') was significantly higher than the loss modulus (G″). The magnitude of modulus increased with frequency, and elastic properties were better than viscous properties. Thermal analysis showed that hydrocolloids increased the starting temperature (To), and the final temperature (Tc). With addition of each of these four hydrocolloids, a more regular and porous thick-wall dense structure was formed, which effectively lowered kudzu starch's sensitivity to amyloglucosidase. It indicated that the binding of hydrocolloid to starch may slow down glucose release into blood during digestion. These results will help understand effects of natural hydrocolloid on kudzu starch, as well as expanding its application in food industry.

11.
Diabetes Metab Syndr Obes ; 16: 2875-2883, 2023.
Article in English | MEDLINE | ID: mdl-37753482

ABSTRACT

Purpose: Type 2 Diabetes mellitus (T2DM) has become a life-threatening health problem around the world. Studies have confirmed that aerobic exercise can prevent the risk of T2DM. Furthermore, recent research showed that salivary amylase gene (AMY1) copy number variation (CNV) could be one of the genetic factors that increased the risk of T2DM. To provide more evidence on how AMY1 CNV and exercise is correlated with the risk of T2DM, we designed this study to show the differences in postprandial carbohydrate metabolism between people with different AMY1 copy numbers, and how aerobic exercise can influence this process. Participants and Methods: Sixteen participants without cardiovascular disease were chosen, 8 with AMY1 CNV≥6 (High CNV group, HCNV), and 8 with AMY1 CNV ≤ 2 (Low CNV group, LCNV). All participants were Chinese, Han nationality, 18 to 40 years old, with fasting blood glucose lower than 6.1 mmol/L and normal blood pressure levels. They were asked to visit the laboratory in fasting state and drink a cup of solution with 75 grams of edible carbohydrate (glucose or starch). After carbohydrate intake, blood samples were taken at certain times at rest or after aerobic exercise. Blood glucose levels were tested with a portable blood glucose monitor, and insulin levels were tested with the enzyme-linked immunosorbent assay (ELISA). Results: The LCNV group had significantly higher resting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than the HCNV group. Compared to the HCNV group, postprandial blood glucose levels and insulin levels were insensitive to starch intake in the LCNV group. However, this difference disappeared after aerobic exercise was added as an intervention. Conclusion: Lower AMY1 CNV could be associated with higher risk of T2DM and complex carbohydrate metabolism disorder, while aerobic exercise can reduce the risk by increasing the carbohydrate utilization rate.

12.
Sensors (Basel) ; 23(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37631755

ABSTRACT

With the continuous progress and application of robotics technology, the importance of mobile robots capable of adapting to specialized work environments is gaining prominence. Among them, achieving precise and stable control of AGVs (Automated Guided Vehicles) stands as a paramount task propelling the advancement of mobile robotics. Consequently, this study devises a control system that enables AGVs to attain stable and accurate motion through equipment connection and debugging, kinematic modeling of the four-wheel steering AGV, and a selection and comparative analysis of motion control algorithms. The effectiveness of the Stanley-PID control algorithm in guiding the motion of a four-wheel steering AGV is validated through MATLAB 2021a simulation software. The simulation results illustrate the outstanding stability and precise control capabilities of the Stanley-PID algorithm.

13.
Genes Genomics ; 45(7): 935-943, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37043131

ABSTRACT

BACKGROUND: According to the WHO, about 39% of the global adult population were overweight or obese in 2016. Obesity has high heritability, with more than 1000 variants so far identified. There have been reports indicating that salivary amylase gene (AMY1) copy number was one of these variants, yet its association with obesity remains controversial. OBJECTIVE: Our research aimed to provide more evidence on the relationship of AMY1 copy number variation (CNV) with body mass index (BMI) and body composition. METHODS: We recruited 133 Chinese adults (65 males, 68 females, 18-25 years old) with normal fasting blood glucose and blood pressure levels. 19 males were selected for a 10-week intervention to change body composition. After anthropometric measurements, BMI was calculated, and body composition was measured using dual energy X-ray absorptiometry (DEXA). For the 19 selected participants, we collected their height, weight, and body composition data one more time after intervention. All participants were required to leave their saliva samples and their AMY1 copy number was determined by real-time fluorescence quantitative PCR. RESULTS: We failed to find any significant difference in BMI and body composition between different copy number groups. Only a weak correlation was found between body muscle mass and body fat mass. After adjusted for height and weight, AMY1 CNV explained 4.83% of the variance and one single increase in AMY1 CNV can increase 0.214 kg of the body muscle mass, while one single increase in AMY1 CNV can decrease 0.217 kg of the body fat mass and explained 4.69% of the variance. CONCLUSIONS: As a genetic factor, the AMY1 gene copy number variation has only a minor correlation with BMI and body composition, and its effect can easily be hidden by other factors such as individual diet and exercise habit.


Subject(s)
Body Composition , DNA Copy Number Variations , Salivary alpha-Amylases , Adolescent , Adult , Female , Humans , Male , Young Adult , Body Composition/genetics , East Asian People , Obesity/genetics , Salivary alpha-Amylases/genetics
14.
ACS Appl Mater Interfaces ; 15(15): 19002-19010, 2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37026166

ABSTRACT

High-performance metal-based catalysts are pursued to improve the sluggish reaction kinetics in lithium-sulfur batteries. However, it is challenging to achieve high catalytic activity and stability simultaneously due to the inevitable passivation of the highly active metal nanoparticles by lithium polysulfides (LiPSs). Herein, we show a design with well-balanced activity and stability to solve the above problem, that is, the cobalt (Co) nanoparticles (NPs) encapsulated with ultrathin carbon shells prepared by the one-step pyrolysis of ZIF-67. With an ultrathin carbon coating (∼1 nm), the direct exposure of Co NPs to LiPSs is avoided, but it allows the fast electron transfer from the highly active Co NPs to LiPSs for their conversion to the solid products, ensuring the efficient suppression of shuttling in long cycling. As a result, the sulfur cathode with such a catalyst exhibited good cycling stability (0.073% capacity fading over 500 cycles) and high sulfur utilization (638 mAh g-1 after 180 cycles under a high sulfur mass loading of 7.37 mg cm-2 and a low electrolyte/sulfur ratio of 5 µL mg-1). This work provides insights into the rational design of a protection layer on a metal-based catalyst to engineer both high catalytic activity and stability toward high-energy and long-life Li-S batteries.

15.
J Colloid Interface Sci ; 642: 820-828, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37060648

ABSTRACT

Boosting the energy density and safety issue of lithium-ion batteries has become ever more important to satisfy the diverse applications such as energy storage and mobile electronic devices. Herein, we present a new high voltage polyether-based electrolyte (HVPEE) by solvation structure design that can endure high-voltage operations and also possess non-flammable features. Especially, HVPEEs show better compatibility and stability with electrode than conventional electrolyte. We find that the solvent separated ion pair (SSIP) and contact ion pair (CIP) dominate the ion-solvent structure of HVPEEs, rather than the free solvent and ions. In this way, the oxidative decomposition of HVPEE on the cathode interface can be suppressed significantly due to the reduced highest occupied molecular orbital of SSIP complex structure than that of free TFSI-. As a result, the oxidation voltage can achieve as high as 5.35 V when the ether group/Li is optimized at 10/1 in the HVPEE, enabling the LiFePO4//Li full cells deliver a capacity of 165 mA h g-1 with a capacity retention of 98 % after 200 cycles. Moreover, when the cut-off voltage is 4.5 V, the discharge capacity of the LiNi0.6Mn0.2Co0.2O2//Li full cell can reach 170 mA h g-1.

16.
Adv Mater ; 35(25): e2210876, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36870077

ABSTRACT

Metallomodulation cell death strategies are extensively investigated for antitumor therapy, such as cuproptosis, ferroptosis, and chemodynamic therapy (CDT). Undoubtedly, the accurate and specific elevation of metal ions levels in cancer cells is key to boosting their therapeutic index. Herein, a programmably controllable delivery system based on croconium dye (Croc)-ferrous ion (Fe2+ ) nanoprobes (CFNPs) is developed for multiscale dynamic imaging guided photothermal primed CDT. The Croc, with kinds of electron-rich iron-chelating groups, can form the Croc-Fe2+ complex with a precise stoichiometry of 1:1 to steadily maintain the valence state of Fe2+ . The CFNPs can achieve pH-responsive visualization and accurate Fe2+ release in cancerous tissues under the coactivation of "dual-key" stimulation of "acidity and near-infrared (NIR) light". The acidic tumor microenvironment actuates NIR fluorescence/photoacoustic imaging and photothermal properties of CFNPs. Sequentially, under exogenous NIR light, the CFNPs enable in vivo accurate visualization of Croc-Fe2+ complex delivery for photothermal primed Fe2+ release, thus achieving CDT of tumors. By leveraging multiscale dynamic imaging technologies, the complicated spatiotemporal release of Fe2+ is sketched in a programmably controllable manner, and the domino effect of tumor pH level, photothermal effect, and CDT is also revealed, endowing customized feedback of the therapeutic panorama within the disease microenvironment.


Subject(s)
Nanoparticles , Neoplasms , Humans , Nanoparticles/chemistry , Phototherapy/methods , Drug Delivery Systems/methods , Neoplasms/therapy , Combined Modality Therapy , Iron , Cell Line, Tumor , Tumor Microenvironment
17.
J Cell Physiol ; 238(5): 1036-1045, 2023 05.
Article in English | MEDLINE | ID: mdl-36922748

ABSTRACT

Periodontitis is a chronic immune inflammatory disease that can lead to the destruction and loss of the tooth-supporting apparatus. During this process, the balance between bone absorption mediated by osteoclasts and bone formation mediated by osteoblasts is damaged. Consistent with previous studies, we observed that depletion of cylindromatosis (CYLD) resulted in an osteoporotic bone phenotype. However, the effect of CYLD deficiency on periodontitis is undetermined. Here, we investigated whether CYLD affects periodontal tissue homeostasis in experimental periodontitis in Cyld knockout (KO) mice, and we explored the underlying mechanisms. Interestingly, we discovered significant alveolar bone density loss and severely reduced alveolar bone height in Cyld KO mice with experimentally induced periodontitis. We observed increased osteoclast number and activity in both the femurs and alveolar bones, accompanied by the downregulation of osteogenesis genes and upregulation of osteoclastogenesis genes of alveolar bones in ligatured Cyld KO mice. Taken together, our findings demonstrate that the deletion of CYLD in mice plays a vital role in the pathogenesis of periodontal bone loss and suggest that CYLD might exert an ameliorative effect on periodontal inflammatory responses.


Subject(s)
Alveolar Bone Loss , Periodontitis , Mice , Animals , Alveolar Bone Loss/genetics , Osteogenesis , Osteoclasts/pathology , Periodontitis/genetics , Periodontitis/pathology , Bone and Bones/pathology , Deubiquitinating Enzyme CYLD/genetics
18.
Adv Mater ; 35(22): e2208097, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36893436

ABSTRACT

The development of blood-brain barrier (BBB)-crossing phototheranostic agents in second near-infrared window (NIR-II), especially in the range of 1500-1700 nm (NIR-IIb), affords great opportunities for glioblastoma (GBM) management. Herein, an organic assembly (denoted as LET-12) with the maximum absorption peak at 1400 nm and emission peak at 1512 nm with trailing over 1700 nm through the self-assembly of organic small molecule IR-1064 is designed and subsequently decorated with choline and acetylcholine analogs. The LET-12 can effectively cross BBB through the brain's choline-like receptors-mediated transcytosis and accumulated in tumor tissues, thus achieving fluorescence/photoacoustic (FL/PA) duplex imaging of orthotopic GBM with ≈3.0 mm depth and a superior tumor-to-normal tissue signal ratio (20.93 ± 0.59 for FL imaging and 32.63 ± 1.16 for PA imaging, respectively). Owing to its good photothermal conversion ability, the LET-12 also can serve as a photothermal conversion agent, achieving obvious tumor repression of orthotopic murine GBM model after once treatment. The findings indicate that the LET-12 holds great potential for BBB-crossing NIR-IIb phototheranostics of orthotopic GBM. This self-assembly strategy of organic small molecules opens a new avenue for the construction of NIR-IIb phototheranostics.


Subject(s)
Glioblastoma , Hyperthermia, Induced , Nanoparticles , Neoplasms , Mice , Animals , Glioblastoma/diagnostic imaging , Glioblastoma/therapy , Blood-Brain Barrier , Neoplasms/therapy , Fluorescence , Hyperthermia, Induced/methods , Phototherapy/methods , Theranostic Nanomedicine/methods
19.
Chem Phys Lipids ; 251: 105280, 2023 03.
Article in English | MEDLINE | ID: mdl-36634728

ABSTRACT

Antibody-functionalized targeted nanocarriers have shown great-potential for minimizing the chemoresistance and systemic toxicity of cancer chemotherapies. The combination of chemotherapy and photothermal therapy has great potential in improving therapeutic effect. However, cetuximab-modified nanoparticles based lipids for chemo-phototherapy of EGFR overexpressing colorectal carcinoma (CRC) have seldom been investigated. Hence, this study aimed to fabricate cetuximab-conjugated and near infrared (NIR) light-responsive hybrid lipid-polymer nanoparticles (abbreviated as Cet-CINPs) for targeted delivery of irinotecan. Cet-CINPs were prepared with copolymer PLGA and various lipids DSPE-PEG, DSPE-PEG-Mal, lecithin as carriers. Cetuximab was conjugated on the surface of nanoparticles to achieve targeting anti-tumor efficacy. Cet-CINPs were characterized in terms of morphology (spherical), size (119 nm), charge (-27.2 mV), drug entrapment efficiency (43.27 %), and antibody conjugation efficiency (70.87 %). Cet-CINPs showed preferable photothermal response, pH/NIR-triggered drug release behavior, enhanced cellular uptake and ROS level compared with free ICG and CINPs. Meanwhile, in vitro cytotoxicity assay showed that Cet-CINPs with NIR irradiation had a higher cytotoxicity against Lovo cells than non-targeted or non-NIR activated nanoparticles. The IC50 values of Cet-CINPs with NIR irradiation was 22.84 ± 1.11 µM for 24 h and 5.01 ± 1.06 µM for 48 h, respectively. These investigations demonstrate that Cet-CINPs with good tumor-targeting ability and enhanced antitumor activity, are a promising multifunctional nanoplatform for CRC therapy.


Subject(s)
Colorectal Neoplasms , ErbB Receptors , Molecular Targeted Therapy , Nanoparticles , Photothermal Therapy , Humans , Cell Line, Tumor , Cetuximab/administration & dosage , Cetuximab/pharmacology , Colorectal Neoplasms/drug therapy , Drug Delivery Systems , ErbB Receptors/metabolism , Lipids , Polymers
20.
Int J Mol Sci ; 24(2)2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36674446

ABSTRACT

Porcine reproductive and respiratory syndrome (PRRS) is a vertically transmitted reproductive disorder that is typically characterized by miscarriage, premature birth, and stillbirth in pregnant sows after infection. Such characteristics indicate that PRRSV can infect and penetrate the porcine placental barrier to infect fetus piglets. The porcine trophoblast is an important component of the placental barrier, and secretes various hormones, including estrogen and progesterone, to maintain normal pregnancy and embryonic development during pregnancy. It is conceivable that the pathogenic effects of PRRSV infection on porcine trophoblast cells may lead to reproductive failure; however, the underlying detailed mechanism of the interaction between porcine trophoblast (PTR2) cells and PRRSV is unknown. Therefore, we conducted genome-wide mRNA and long non-coding RNA (lncRNA) analysis profiling in PRRSV-infected PTR2. The results showed that 672 mRNAs and 476 lncRNAs were significantly different from the control group after viral infection. Target genes of the co-expression and co-location of differential mRNAs and lncRNAs were enriched by GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that most of the pathways were involved in cell nutrient metabolism, cell proliferation, and differentiation. Specifically, the estrogen signaling pathway, the PI3K (PhosphoInositide-3 Kinase)-Akt (serine/threonine kinase) signaling pathway, and the insulin secretion related to embryonic development were selected for analysis. Further research found that PRRSV inhibits the expression of G-protein-coupled estrogen receptor 1 (GPER1), thereby reducing estrogen-induced phosphorylation of AKT and the mammalian target of rapamycin (mTOR). The reduction in the phosphorylation of AKT and mTOR blocks the activation of the GPER1- PI3K-AKT-mTOR signaling pathway, consequently restraining insulin secretion, impacting PTR2 cell proliferation, differentiation, and nutrient metabolism. We also found that PRRSV triggered trophoblast cell apoptosis, interrupting the integrity of the placental villus barrier. Furthermore, the interaction network diagram of lncRNA, regulating GPER1 and apoptosis-related genes, was constructed, providing a reference for enriching the functions of these lncRNA in the future. In summary, this article elucidated the differential expression of mRNA and lncRNA in trophoblast cells infected with PRRSV. This infection could inhibit the PI3K-AKT-mTOR pathway and trigger apoptosis, providing insight into the mechanism of the vertical transmission of PRRSV and the manifestation of reproductive failure.


Subject(s)
Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , RNA, Long Noncoding , Swine , Animals , Female , Pregnancy , Porcine respiratory and reproductive syndrome virus/genetics , RNA, Long Noncoding/genetics , Trophoblasts , RNA, Messenger/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt , Placenta , Porcine Reproductive and Respiratory Syndrome/genetics , TOR Serine-Threonine Kinases , Estrogens , Mammals/genetics
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