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1.
Proc Natl Acad Sci U S A ; 120(1): e2209062120, 2023 01 03.
Article in English | MEDLINE | ID: mdl-36577070

ABSTRACT

Hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous group of cells with expansion, differentiation, and repopulation capacities. How HSPCs orchestrate the stemness state with diverse lineage differentiation at steady condition or acute stress remains largely unknown. Here, we show that zebrafish mutants that are deficient in an epigenetic regulator Atf7ip or Setdb1 methyltransferase undergo excessive myeloid differentiation with impaired HSPC expansion, manifesting a decline in T cells and erythroid lineage. We find that Atf7ip regulates hematopoiesis through Setdb1-mediated H3K9me3 modification and chromatin remodeling. During hematopoiesis, the interaction of Atf7ip and Setdb1 triggers H3K9me3 depositions in hematopoietic regulatory genes including cebpß and cdkn1a, preventing HSPCs from loss of expansion and premature differentiation into myeloid lineage. Concomitantly, loss of Atf7ip or Setdb1 derepresses retrotransposons that instigate the viral sensor Mda5/Rig-I like receptor (RLR) signaling, leading to stress-driven myelopoiesis and inflammation. We find that ATF7IP or SETDB1 depletion represses human leukemic cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation. These findings establish that Atf7ip/Setdb1-mediated H3K9me3 deposition constitutes a genome-wide checkpoint that impedes the myeloid potential and maintains HSPC stemness for diverse blood cell production, providing unique insights into potential intervention in hematological malignancy.


Subject(s)
Hematopoietic Stem Cells , Histone-Lysine N-Methyltransferase , Zebrafish , Animals , Humans , Cell Differentiation , Cell Lineage , Hematopoiesis , Hematopoietic Stem Cells/pathology , Histone-Lysine N-Methyltransferase/genetics , Inflammation/pathology , Zebrafish/genetics , Zebrafish/metabolism
2.
Cell Mol Life Sci ; 81(1): 158, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38556571

ABSTRACT

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases.


Subject(s)
Cardiomyopathy, Hypertrophic , LIM Domain Proteins , Zebrafish , Animals , Humans , Zebrafish/genetics , Zebrafish/metabolism , Cysteine/genetics , Cysteine/metabolism , Muscle Proteins/genetics , Muscle Proteins/metabolism , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/metabolism , Myocytes, Cardiac/metabolism
3.
Opt Express ; 32(2): 1843-1850, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297727

ABSTRACT

A distributed feedback (DFB) laser array of twenty wavelengths with highly reflective and anti-reflective (HR-AR) coated facets is both theoretically analyzed and experimentally validated. While the HR facet coating enhances high wall-plug efficiency, it inadvertently introduces a random facet grating phase, thereby compromising the lasing wavelength's predictability and the stability of the single-longitudinal-mode (SLM). In this study, two key advancements are introduced: first, the precisely spaced wavelength is achieved with an error of within ±0.2 nm using the reconstruction-equivalent-chirp (REC) technique; second, the random grating phase on the HR-coated facet is compensated by a controllable distributed phase shift through a two-section laser structure. The SLM stability can be improved while the wavelength can be continuously tuned to the standard wavelength grid. The overall chip size is compact with an area of 4000 × 500 µm2. The proposed laser array has a light power intensity above 13 dBm per wavelength, a high side mode suppression ratio above 50 dB, and low relative intensity noise under -160 dB/Hz. These attributes make it apt for deployment in DWDM-based optical communication systems and as a light source for optical I/O.

4.
Acta Pharmacol Sin ; 45(6): 1287-1304, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38360930

ABSTRACT

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Humans , Female , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/antagonists & inhibitors , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Immunoconjugates/therapeutic use , Immunoconjugates/pharmacology , Network Pharmacology , Models, Biological , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Mice , Cell Line, Tumor , Neoplasm Metastasis
5.
Development ; 147(18)2020 09 28.
Article in English | MEDLINE | ID: mdl-32988975

ABSTRACT

Teleost zebrafish and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through dedifferentiation and proliferation of pre-existing cardiomyocytes (CMs). Although many mitogenic signals that stimulate zebrafish heart regeneration have been identified, transcriptional programs that restrain injury-induced CM renewal are incompletely understood. Here, we report that mutations in gridlock (grl; also known as hey2), encoding a Hairy-related basic helix-loop-helix transcriptional repressor, enhance CM proliferation and reduce fibrosis following damage. In contrast, myocardial grl induction blunts CM dedifferentiation and regenerative responses to heart injury. RNA sequencing analyses uncover Smyd2 lysine methyltransferase (KMT) as a key transcriptional target repressed by Grl. Reduction in Grl protein levels triggered by injury induces smyd2 expression at the wound myocardium, enhancing CM proliferation. We show that Smyd2 functions as a methyltransferase and modulates the Stat3 methylation and phosphorylation activity. Inhibition of the KMT activity of Smyd2 reduces phosphorylated Stat3 at cardiac wounds, suppressing the elevated CM proliferation in injured grl mutant hearts. Our findings establish an injury-specific transcriptional repression program in governing CM renewal during heart regeneration, providing a potential strategy whereby silencing Grl repression at local regions might empower regeneration capacity to the injured mammalian heart.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Heart/physiology , Lysine/genetics , Methyltransferases/genetics , Regeneration/genetics , Transcription, Genetic/genetics , Vertebrates/genetics , Zebrafish Proteins/genetics , Animals , Animals, Newborn , Cell Differentiation/genetics , Cell Proliferation/genetics , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Phosphorylation/genetics , STAT3 Transcription Factor/genetics , Signal Transduction/genetics , Zebrafish/genetics
6.
Drug Chem Toxicol ; 46(3): 451-461, 2023 May.
Article in English | MEDLINE | ID: mdl-35287533

ABSTRACT

Epimedium sagittatum (Sieb. et Zucc.) Maxim., a traditional medicinal plant in Asia, is widely used in clinical settings but its safety in vivo is unclear. This study investigated the sub-chronic toxicity of E. sagittatum aqueous extract to rats with a 13-week daily intragastric administration of 7.5, 15, or 30 g/kg. Nine constituents of the aqueous extract were identified by ultra-performance liquid chromatography (UPLC). Organ weights, organ coefficients, serum biochemistry parameters, histopathology, and metabolomic analysis were performed. In female rats, treatment increased the liver, thymus, and adrenal gland coefficients (p < 0.05). Liver, pancreas, and adrenal gland injury were observed. The levels of six metabolites were altered by the treatment (p < 0.05). In male rats, treatment altered liver, heart, and thymus coefficients (p < 0.05) and liver, adrenal gland, and heart injury were observed. The levels of 11 metabolites were altered (p < 0.05). The no-observed-adverse-effect level was not determined but would be below 7.5 g/kg in rats treated for 13 weeks. In female rats, E. sagittatum may injure the liver and pancreas and dysregulate the biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine and the metabolism of phenylalanine. In male rats, the extract may injure the liver and adrenal gland and dysregulate the biosynthesis of valine, leucine, and isoleucine and the metabolism of pyruvate.


Subject(s)
Epimedium , Plants, Medicinal , Rats , Animals , Epimedium/chemistry , Isoleucine , Leucine
7.
Nurs Ethics ; : 9697330231215948, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38116631

ABSTRACT

BACKGROUND: Emergency nurses who thrive at work experience positive emotions that help reduce burnout and thus enhance career calling. However, few studies have focused on the relationships among thriving at work, career calling, and moral distress among emergency nurses. OBJECTIVES: To investigate the relationships among thriving at work, career calling, and moral distress and to explore the mediating role of career calling in the relationship between thriving at work and moral distress among emergency nurses. DESIGN: A quantitative, cross-sectional study. METHODS: A cross-sectional study was conducted by reference to 390 emergency nurses in China using an online survey that include the Thriving at Work Scale, the Career Calling Scale, and the Moral Distress Scale-Revised. The data were analyzed using SmartPLS software. ETHICAL CONSIDERATION: The study was approved by the Ethics Committee of Hunan Normal University (No. 2023-388). FINDINGS: Among emergency nurses, thriving at work is positively associated with career calling, while career calling is negatively associated with moral distress. Career calling negatively and completely mediates the relationship between thriving at work and moral distress (ß = -0.087, p < 0.01). DISCUSSION: Theoretically, the findings enhance our understanding of the relationships among thriving at work, career calling, and moral distress among emergency nurses. CONCLUSION: By emphasizing the benefits of thriving at work, nursing managers can improve nurses' level of thriving at work by providing a favorable environment, a flexible scheduling system, and appropriate authorization as well as by ensuring organizational fairness and providing training opportunities in a hierarchical manner.

8.
BMC Psychiatry ; 22(1): 416, 2022 06 21.
Article in English | MEDLINE | ID: mdl-35729548

ABSTRACT

BACKGROUND: Pediatric nurses experience a wide rang of stressful events at work every day, which can trigger a lot of emotional responses. The objectives of this study were mainly to explore the potential interrelationships of occupational stress, coping styles and mental health among pediatric nurse. METHODS: A total of 381 pediatric nurses from Chongqing, China were recruited in this cross-sectional study. We performed this study based on a questionnaire survey that contained the Chinese Perceived Stress Scale (CPSS), Simplified Coping Style Questionnaire and Symptom-Checklist 90(SCL-90). RESULTS: The pediatric nurses reported having health risk stress(HRS) was 54.3%, and nurses with different medical professional titles, style of coping and profiles of mental health had significantly different occupational stress levels (P < 0.01). And with the application of the Spearman correlation analysis and Structural Equation Modelling were revealed a significant relationship among occupational stress, coping style and mental health. The positive coping style had a negative direct predictive effect on occupational stress (ß = -0.499, P < 0.01) and mental health symptoms (ß = -0.115, P < 0.01), negative coping styles had positive predictive effect on occupational stress (ß = 0.185, P < 0.01) and mental health symptoms (ß = 0.205, P < 0.01). Occupational stress had significant impact on mental health symptoms (ß = 0.416, P < 0.01), and it was played a part of mediating effect between coping style and mental health. CONCLUSION: These findings demonstrated significant associations between occupational stress, coping style and mental health in pediatric nurses, and this SEM model highlighted that the potential prediction effects of occupational stress and coping styles for mental health and the mediated effect of occupational stress between coping style and mental health, which we believe facilitates the understanding of these associations. This model should be useful in the formulation of strategies to improve mental health level for this population.


Subject(s)
Nurses, Pediatric , Occupational Stress , Adaptation, Psychological , Child , China , Cross-Sectional Studies , Humans , Mental Health , Occupational Stress/psychology , Surveys and Questionnaires
9.
Microsc Microanal ; : 1-13, 2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35748406

ABSTRACT

The selection of high-quality sperms is critical to intracytoplasmic sperm injection, which accounts for 70­80% of in vitro fertilization (IVF) treatments. So far, sperm screening is usually performed manually by clinicians. However, the performance of manual screening is limited in its objectivity, consistency, and efficiency. To overcome these limitations, we have developed a fast and noninvasive three-stage method to characterize morphology of freely swimming human sperms in bright-field microscopy images using deep learning models. Specifically, we use an object detection model to identify sperm heads, a classification model to select in-focus images, and a segmentation model to extract geometry of sperm heads and vacuoles. The models achieve an F1-score of 0.951 in sperm head detection, a z-position estimation error within ±1.5 µm in in-focus image selection, and a Dice score of 0.948 in sperm head segmentation, respectively. Customized lightweight architectures are used for the models to achieve real-time analysis of 200 frames per second. Comprehensive morphological parameters are calculated from sperm head geometry extracted by image segmentation. Overall, our method provides a reliable and efficient tool to assist clinicians in selecting high-quality sperms for successful IVF. It also demonstrates the effectiveness of deep learning in real-time analysis of live bright-field microscopy images.

10.
Arch Psychiatr Nurs ; 33(1): 17-22, 2019 02.
Article in English | MEDLINE | ID: mdl-30663619

ABSTRACT

The purpose of this pilot study was to design, implement, and evaluate the family-focused psychoeducational therapy (FFPT) for autism spectrum disorder (ASD) family. In Phase I, 64 parents of ASD children (ASD-group) and 63 parents of typically development children (TD-group) were invited to investigate parenting self-efficacy and emotion at baseline. In Phase II, the 4-week of FFPT was offered for the ASD-group. Date was collected at baseline, post-intervention and one-month follow-up, using the parental self-efficacy, Self-Rating Anxiety Scale and Self-Rating Depression Scale. The results showed that ASD-group significantly lower levels of parenting self-efficacy and worse emotion than TD-group (p < 0.05); And after attending the program, ASD-group had significant improvements for all outcome measures and these changes maintained over a period of time (p < 0.05). This preliminary study suggests that the FFPT may effectively improve parenting self-efficacy, reduce anxiety and depression for parents of children with ASD.


Subject(s)
Autism Spectrum Disorder/psychology , Emotions , Family Therapy/education , Parenting/psychology , Self Efficacy , Adult , Child , Cross-Sectional Studies , Female , Humans , Male , Pilot Projects , Stress, Psychological/psychology , Surveys and Questionnaires
11.
Opt Express ; 25(21): 24960-24973, 2017 Oct 16.
Article in English | MEDLINE | ID: mdl-29041169

ABSTRACT

We propose a new kind of planar waveguide Bragg grating structure, i.e., planar waveguide moiré grating (MG), which is formed by two transverse adjacent gratings with slightly different Bragg wavelengths. It is found that this kind of structure shows the same light properties as the conventional MG that is realized by superimposing two Bragg gratings. Because the proposed MG structure is a planar pattern, the fabrication becomes much easier if applying a semiconductor microfabrication process, which is very beneficial for its applications in photonic integrated devices. Similar to the well-known Vernier effect, the coupling coefficient distribution can be easily adjusted by the alignment of the two adjacent gratings. Consequently, some special grating profiles can be achieved, such as perfect apodization with two sides of the coupling coefficient approaching zero. One important potential application of these specific features is the distributed feedback (DFB) semiconductor laser for improved properties, such as reduced spatial-hole burning and more power extraction. Some design examples are also given in this paper.

12.
Opt Express ; 25(22): 27595-27608, 2017 Oct 30.
Article in English | MEDLINE | ID: mdl-29092230

ABSTRACT

A monolithic optical injection-locked (MOIL) DFB laser with large stable injection locking range is experimentally demonstrated using the side-mode injection locking technique. The low-frequency roll-off in the MOIL DFB laser is suppressed significantly. The relaxation oscillation frequency is measured to be 26.84 GHz and the intrinsic 3-dB response bandwidth is more than 30 GHz, which is about 20 GHz higher than that of the free running DFB laser. The nonlinear distortions, including the 1-dB compression point, second harmonic distortion (2HD) and third-order intermodulation distortion (IMD3), are also suppressed significantly. A simple radio-over-fiber system transmitting 40 Msymbol/s 32-QAM signal with 6 GHz carrier is achieved using the MOIL DFB laser. After 50 km transmission, the average error vector magnitude (EVM) of the whole link is 2.94% in injection locked state, while the EVM in free running DFB laser is 5.25% as a comparison. To our knowledge, this is the first time that the MOIL DFB laser is realized utilizing the side-mode injection locking method.

13.
Eukaryot Cell ; 14(3): 241-51, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25576483

ABSTRACT

The anillin-related protein Bud4 of Saccharomyces cerevisiae is required for axial bud site selection by linking the axial landmark to the septins, which localize at the mother bud neck. Recent studies indicate that Bud4 plays a role in septin organization during cytokinesis. Here we show that Bud4 is also involved in septin organization during bud growth prior to cytokinesis, as bud4Δ shs1Δ cells displayed an elongated bud morphology and defective septin organization at 18°C. Bud4 overexpression also affected septin organization during bud growth in shs1Δ cells at 30°C. Bud4 was previously thought to associate with the septins via its central region, while the C-terminal anillin-related region was not involved in septin association. Surprisingly, we found that the central region of Bud4 alone targets to the bud neck throughout the cell cycle, unlike full-length Bud4, which localizes to the bud neck only during G2/M phase. We identified the anillin-related region to be a second targeting domain that cooperates with the central region for proper septin association. In addition, the anillin-related region could largely mediate Bud4's function in septin organization during bud growth and bud site selection. We show that this region interacts with the C terminus of Bud3 and the two segments depend on each other for association with the septins. Moreover, like the bud4Δ mutant, the bud3Δ mutant genetically interacts with shs1Δ and cdc12-6 mutants in septin organization, suggesting that Bud4 and Bud3 may cooperate in septin organization during bud growth. These observations provide new insights into the interaction of Bud4 with the septins and Bud3.


Subject(s)
Cell Cycle Proteins/metabolism , Cell Division , GTP-Binding Proteins/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Septins/metabolism , Amino Acid Sequence , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/genetics , Contractile Proteins/metabolism , GTP-Binding Proteins/chemistry , GTP-Binding Proteins/genetics , Molecular Sequence Data , Protein Binding , Protein Structure, Tertiary , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/genetics
14.
J Neurosci ; 33(44): 17413-21, 2013 Oct 30.
Article in English | MEDLINE | ID: mdl-24174674

ABSTRACT

Establishment of synaptic connections in the neuropils of the developing nervous system requires the coordination of specific neurite-neurite interactions (i.e., axon-axon, dendrite-dendrite and axon-dendrite interactions). The molecular mechanisms underlying coordination of neurite-neurite interactions for circuit assembly are incompletely understood. In this report, we identify a novel Ig superfamily transmembrane protein that we named Borderless (Bdl), as a novel regulator of neurite-neurite interactions in Drosophila. Bdl induces homotypic cell-cell adhesion in vitro and mediates neurite-neurite interactions in the developing visual system. Bdl interacts physically and genetically with the Ig transmembrane protein Turtle, a key regulator of axonal tiling. Our results also show that the receptor tyrosine phosphatase leukocyte common antigen-related protein (LAR) negatively regulates Bdl to control synaptic-layer selection. We propose that precise regulation of Bdl action coordinates neurite-neurite interactions for circuit formation in Drosophila.


Subject(s)
Cell Communication/genetics , Drosophila Proteins/physiology , Membrane Proteins/physiology , Nerve Net/physiology , Visual Pathways/physiology , Animals , Down-Regulation/genetics , Drosophila Proteins/genetics , Drosophila melanogaster/enzymology , Drosophila melanogaster/genetics , Female , Immunoglobulin Subunits/genetics , Immunoglobulins/genetics , Immunoglobulins/physiology , Male , Membrane Proteins/genetics , Mutation/genetics , Nerve Net/enzymology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Neurites/physiology , Receptor-Like Protein Tyrosine Phosphatases/genetics , Receptor-Like Protein Tyrosine Phosphatases/physiology , Visual Pathways/enzymology
15.
Opt Express ; 21(13): 16022-8, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23842388

ABSTRACT

A novel concavely apodized (CA) distributed feedback (DFB) semiconductor laser was theoretically analyzed and experimentally demonstrated. The CA grating profile is equivalently realized by changing the duty cycle of the sampling structure along the cavity in the middle of which an equivalent phase shift is also inserted. Because the basic grating (seed grating) is uniform, only a common holographic exposure and a µm-level photolithography are required. Therefore, the fabrication cost is highly reduced compared with the true CA grating whose index modulation continuously changes along the cavity. The experimental results show that the laser has good single longitudinal mode operation.

16.
Int J Biol Macromol ; 244: 125393, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37331543

ABSTRACT

Pickering emulsions are attracting increased attention owing to their therapeutic applications. However, the slow-release property of Pickering emulsions and the in vivo solid particle accumulation caused by the solid particle stabilizer film limit their applications in therapeutic delivery. In this study, drug-loaded, acid-sensitive Pickering emulsions were prepared using acetal-modified starch-based nanoparticles as stabilizers. The acetalized starch-based nanoparticles (Ace-SNPs) not only act as a solid-particle emulsifier to stabilize Pickering emulsions but also exhibit acid sensitivity and degradability, conducive to the destabilization of Pickering emulsions to release the drug and reduce the effect of particle accumulation in an acidic therapeutic environment. In vitro drug release profiles show that 50 % of curcumin was released in 12 h in an acidic medium (pH 5.4), whereas only 14 % of curcumin was released in 12 h at higher pH (7.4), indicating that the Ace-SNP stabilized Pickering emulsion possess good acid-responsive release characteristics in acidic environments. Moreover, acetalized starch-based nanoparticles and their degradation products showed good biocompatibility, and the resulting curcumin-loaded Pickering emulsions exhibited significant anticancer activity. These features suggest that the acetalized starch-based nanoparticle-stabilized Pickering emulsion has the potential for application as an antitumor drug carrier to enhance therapeutic effects.


Subject(s)
Antineoplastic Agents , Curcumin , Nanoparticles , Emulsions/chemistry , Starch/chemistry , Drug Carriers , Curcumin/chemistry , Antineoplastic Agents/pharmacology , Excipients , Nanoparticles/chemistry , Particle Size
17.
Article in English | MEDLINE | ID: mdl-37957850

ABSTRACT

BACKGROUND: Herba Epimedii, a commonly used traditional herb, has been proven effective in ameliorating osteoporosis. However, the active ingredients and potential mechanism need further exploration. OBJECTIVE: To screen active ingredients of Herba Epimedii with the effect of ameliorating osteoporosis and to explore their potential mechanisms. METHODS: TCMSP and Swiss Target Prediction were applied to collect the ingredients of Herba Epimedii and their targets. UniProt, GeneCards, TTD, DisGeNET, and OMIM were adopted to search osteoporosis-related genes. STRING and DAVID were used to perform enrichment analysis. Effects of screened ingredients were evaluated on MC3T3-E1 cells and RAW264.7 cells, respectively. RESULTS: Eleven ingredients were screened by Network Pharmacology. They exerted a promoting effect on MC3T3-E1 cells (10-9-10-5 M). The ingredients didn't significantly affect ALP activity and osteoblastogenesis-related genes. Baohuoside 1, Sagittatoside B, Chlorogenic acid, Cryptochlorogenic acid, and Neochlorogenic acid significantly increased calcium depositions. The ingredients didn't exhibit a dose-dependent inhibition or promotion on RAW264.7 cells. Baohuoside 1, Sagittatoside B, Neochlorogenic acid, Cryptochlorogenic acid, Icariin, Epimedin A, Chlorogenic acid, Sagittatoside A, and Epimedin C suppressed the level of TRACP. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, Sagittatoside A, and Icariin decreased the number of multinucleated osteoclastic cells. Baohuoside 1, Sagittatoside B, and Cryptochlorogenic acid could significantly inhibit MMP-9 expression. CONCLUSION: Neochlorogenic acid, Sagittatoside B, Chlorogenic acid, and Cryptochlorogenic acid promoted MC3T3-E1 differentiation, among which Neochlorogenic acid showed significant promotion in viability, mineralization, and OPN expression. Baohuoside 1, Sagittatoside B, Cryptochlorogenic acid, Neochlorogenic acid, Chlorogenic acid, and Icariin inhibited RAW264.7 differentiation, among which Baohuoside 1 showed significant inhibition on TRACP, multinucleated osteoclastic cells number and MPP-9 expression. The mechanism might relate to the FoxO signaling pathway, MAPK signaling pathway, and TNF signaling pathway.

18.
Mol Biomed ; 4(1): 21, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37442861

ABSTRACT

Atherosclerosis (AS) is a major contributor to morbidity and mortality worldwide. However, the molecular mechanisms and mediator molecules involved remain largely unknown. Copper, which plays an essential role in cardiovascular disease, has been suggested as a potential risk factor. Copper homeostasis is closely related to the occurrence and development of AS. Recently, a new cell death pathway called cuproptosis has been discovered, which is driven by intracellular copper excess. However, no previous studies have reported a relationship between cuproptosis and AS. In this study, we integrated bulk and single-cell sequencing data to screen and identify key cuproptosis-related genes in AS. We used correlation analysis, enrichment analysis, random forest, and other bioinformatics methods to reveal their relationships. Our findings report, for the first time, the involvement of cuproptosis-related genes FDX1, SLC31A1, and GLS in atherogenesis. FDX1 and SLC31A1 were upregulated, while GLS was downregulated in atherosclerotic plaque. Receiver operating characteristic curves demonstrate their potential diagnostic value for AS. Additionally, we confirm that GLS is mainly expressed in vascular smooth muscle cells, and SLC31A1 is mainly localized in macrophages of atherosclerotic lesions in experiments. These findings shed light on the cuproptosis landscape and potential diagnostic biomarkers for AS, providing further evidence about the vital role of cuproptosis in atherosclerosis progression.

19.
Opt Express ; 20(16): 17374-9, 2012 Jul 30.
Article in English | MEDLINE | ID: mdl-23038289

ABSTRACT

A three phase shifted (3PS) distributed feedback (DFB) semiconductor laser based on Reconstruction-Equivalent-Chirp (REC) technique is experimentally demonstrated for the first time. The simulation results show that the performances of the equivalent 3PS DFB semiconductor laser are nearly the same as that of the true 3PS laser. However, it only changes the µm-level sampling structures but the seed grating is uniform. So, its cost of fabrication is low. The measurement results exhibit its good single longitudinal mode (SLM) operation even at high bias current and surrounding temperature.

20.
Opt Lett ; 37(16): 3315-7, 2012 Aug 15.
Article in English | MEDLINE | ID: mdl-23381242

ABSTRACT

An eight-wavelength distributed feedback semiconductor laser array with λ/4 equivalent phase shift based on reconstruction-equivalent-chirp technique was demonstrated. It shows very good linearity in lasing wavelengths with its deviation from -0.22 to 0.20 nm. The threshold currents are between 19 and 24 mA. The side-mode suppression ratios are all larger than 40 dB under the bias currents of 70 mA. The slope efficiencies at room temperature are all about 0.4 W/A. The grating was fabricated only by common holographic exposure and an additional micrometer-level conventional photolithography, which results in a low cost.

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