Publications by authors named "Jianping Liu"

538 Publications

Safety of Complementary and Alternative Medicine (CAM) treatment among children and young adults who suffer from adverse effects of conventional cancer treatment: A systematic review.

Integr Cancer Ther 2022 Jan-Dec;21:15347354221105563

UiT The Arctic University of Norway, Tromsø, Norway.

Background: Complementary and Alternative Medicine (CAM) is widely used around the world to treat adverse effects derived from cancer treatment among children and young adults. Parents often seek CAM to restore and maintain the child's physical and emotional condition during and after cancer treatment.

Objectives: The objectives of this review were (i) to identify literature that investigates CAM use for treating adverse effects of conventional cancer treatment, (ii) to investigate the safety of the included CAM modalities, and (iii) to evaluate the quality of included studies.

Methods: Five scientific research databases were used to identify observational, quasi-experimental, and qualitative studies from January 1990 to May 2021. Included studies investigated the use of CAM to treat adverse effects of cancer treatment in childhood cancer.

Results: Fifteen studies were included in this review. Ten quasi-experimental, 3 observational studies (longitudinal/prospective), 2 qualitative studies, and 1 study with a quasi-experimental and qualitative arm were identified. Less than half (n = 6; 40%) of the studies included reported adverse effects for the CAM modality being studied. Among the studies that reported adverse effects, they were mostly considered as direct risk, as 13% reported mainly bleeding and bruising upon acupuncture treatment, and dizziness with yoga treatment. All adverse effects were assessed as minor and transient. CAM modalities identified for treating adverse effects of cancer treatment were alternative medical systems, manipulative and body-based therapies, biologically-based therapies, and mind-body therapies. CAM modalities were used to alleviate anxiety, pain, toxicity, prevent trauma, and improve health-related quality of life, functional mobility, and physical activity levels. All studies assessed scored 70% or above according to the Joanna Briggs Institute critical appraisal for study quality checklists.

Conclusion: Most of the studies (58.3%) included in this review did not report adverse effects from CAM modalities used to treat adverse effects of cancer treatment in children and young adults. This lack of safety information is of concern because parents need to know whether the modality represents an extra burden or harm to the child. To improve awareness about safety in the field, a universal and uniform reporting system for adverse effects in CAM research is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15347354221105563DOI Listing
June 2022

Cyclodextrin boostered-high density lipoprotein for antiatherosclerosis by regulating cholesterol efflux and efferocytosis.

Carbohydr Polym 2022 Sep 20;292:119632. Epub 2022 May 20.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address:

A promising therapy for atherosclerosis treatment was designed by targeting LXR receptor (LXR) on atherosclerotic macrophage, where LXR activation could regulate cholesterol efflux and efferocytosis. Herein, a sequential-targeting nanoplatform (HT-rHDL) was constructed to deliver LXR agonist into macrophage, which was composed of discoidal reconstituted high-density lipoprotein (d-rHDL) core for agonist encapsulation and external modifications: (i) the outermost hyaluronan, targeting injured endothelium; (ii) modified β-cyclodextrin of d-rHDL, accelerating cholesterol efflux of foam cells; (iii) conjugated apolipoprotein A-I of d-rHDL, targeting macrophage. This design underlines that the nanoplatform could increase its plaque accumulation, accomplish cholesterol efflux-remodeling-drug delivery behavior and specifically activate LXR in macrophage. After a 3-month treatment with HT-rHDL, 31.47% plaque area reduction, 56.0% lipid accumulation decrease, obvious inflammation resolution and enhanced plaque stability were observed. Furthermore, the atherosclerosis intervention was demonstrated to benefit from the upregulations of ABC transporters and Mer tyrosine kinase. Collectively, HT-rHDL provides new strategies to regress atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2022.119632DOI Listing
September 2022

Comparative Analyses of Antibiotic Resistance Genes in Jejunum Microbiota of Pigs in Different Areas.

Front Cell Infect Microbiol 2022 26;12:887428. Epub 2022 May 26.

Yunnan Provincial Key Laboratory of Animal Nutrition and Feed Science, Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China.

Antibiotic resistance genes (ARGs) are emerging environmental contaminants that threaten human and animal health. Intestinal microbiota may be an important ARGs repository, and intensive animal farming is a likely contributor to the environmental burden of ARGs. Using metagenomic sequencing, we investigated the structure, function, and drug resistance of the jejunal microbial community in Landrace (LA, Kunming), Saba (SB, Kunming), Dahe (DH, Qujing), and Diannan small-ear piglets (DS, Xishuangbanna) from different areas in Yunnan Province, China. Remarkable differences in jejunal microbial diversity among the different pig breeds, while the microbial composition of pig breeds in close areas tends to be similar. Functional analysis showed that there were abundant metabolic pathways and carbohydrate enzymes in all samples. In total, 32,487 ARGs were detected in all samples, which showed resistance to 38 categories of drugs. The abundance of ARGs in jejunum was not significantly different between LA and SB from the same area, but significantly different between DS, DH and LA or SB from different areas. Therefore, the abundance of ARGs was little affected by pig breeds and microorganism community structure, but it was closely related to geographical location. In addition, as a probiotic, is also an important ARGs producing bacterium. Our results revealed the antibiotic exposure and intestinal microbial resistance of farms in the study areas, which could provide basic knowledge and potential strategies for rational use of antibiotics and reducing the risk of ARGs transmission in animal husbandry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2022.887428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204423PMC
June 2022

A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and Its Disruptive Application.

Front Immunol 2022 27;13:889596. Epub 2022 May 27.

Laboratory Animal Center, Chongqing Medical University, Chongqing, China.

Background: Previous studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the fovea centralis in the human retina. This study aimed to develop and explore the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea.

Methods: Tree shrews were clinically and pathologically evaluated for the development and characteristics of EAU immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs). IRBP-specific T-cell proliferation and serum cytokine of tree shrews were evaluated to determine the immune responses. Differentially expressed genes (DEGs) were identified in the eyes of tree shrews with EAU by RNA-sequencing. The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU.

Results: IRBP and R14 successfully induced chronic EAU with subretinal deposits and retinal damage in the tree shrews. The immunological characteristics presented the predominant infiltration of microglia/macrophages, dendritic cells, and CD4-T-cells into the uvea and retina and pathogenic T helper (Th) 1 and Th17 responses. The subretinal deposits positively expressed amyloid β-protein (Aβ), CD8, and P2Y purinoceptor 12 (P2RY12). The crucial DEGs in R14-induced EAU, such as and , were enriched for several pathways, including inflammatory mediator regulation of transient receptor potential (TRP) channels. The upregulated in IRBP-induced EAU was associated with mitogen-activated protein kinase (MAPK) activity. RGS4 inhibition and dihydroartemisinin could significantly alleviate the retinal pathological injuries of IRBP-induced EAU by decreasing the expression of CD4 T-cells.

Conclusion: Our study provides a novel chronic EAU in tree shrews elicited by bovine R14 and tree shrew IRBP characterized by retinal degeneration, retinal damage with subretinal Aβ deposits and microglia/macrophage infiltration, and T-cell response, probably by altering important pathways and genes related to bacterial invasion, inflammatory pain, microglial phagocytosis, and lipid and glucose metabolism. The findings advance the knowledge of the pathogenesis and therapeutics of the fovea-involved visual disturbance in human uveitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.889596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196886PMC
June 2022

Design and Development of a New Glucagon-Like Peptide-1 Receptor Agonist to Obtain High Oral Bioavailability.

Pharm Res 2022 Jun 13. Epub 2022 Jun 13.

School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.

Purpose: Semaglutide is the only oral GLP-1 RA in the market, but oral bioavailability is generally limited in range of 0.4-1%. In this study, a new GLP-1RA named SHR-2042 was developed to gain higher oral bioavailability than semaglutide.

Method: Self-association of SHR-2042, semaglutide and liraglutide were assessed using SEC-MALS. The intestinal perfusion test in SD rats was used to select permeation enhancers (PEs) including SNAC, C10 and LCC. ITC, CD and DLS were used to explore the interaction between SHR-2042 and SNAC. Gastric administrated test in SD rats was used to screen SHR-2042 granules with different SHR-2042/SNAC ratios. The oral bioavailability of SHR-2042 was studied in rats and monkeys.

Result: The designed GLP-1RA, SHR-2042, gives a better solubility and lipophilicity than semaglutide. While it forms a similar oligomer with that of semaglutide. During the selection of PEs, SNAC shows better exposure than the other competing PEs including C10 and LCC. SHR-2042 and SNAC bind quickly and exhibit hydrophobic interaction. SNAC could promote monomerization of SHR-2042 and form micelles to trap the monomerized SHR-2042. The oral bioavailability of SHR-2042 paired with SNAC is 0.041% (1:0, w/w), 0.083% (1:10, w/w), 0.32% (1:30, w/w) and 2.83% (1:60, w/w) in rats. And the oral bioavailability of SHR-2042 matched with SNAC is 3.39% (1:30, w/w) in monkeys, which is over 10 times higher than that of semaglutide.

Conclusion: We believe that the design and development of oral SHR-2042 will provide a new way to design more and more GLP-1RAs with high oral bioavailability in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-022-03265-3DOI Listing
June 2022

Association Between Serum Homocysteine Levels and Severity of Diabetic Kidney Disease in 489 Patients with Type 2 Diabetes Mellitus: A Single-Center Study.

Med Sci Monit 2022 Jun 10;28:e936323. Epub 2022 Jun 10.

Department of Endocrinology, The The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).

BACKGROUND This study from a single center aimed to investigate the association between serum homocysteine (Hcy) levels and severity of diabetic kidney disease (DKD) in 489 patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS A total of 1163 patients with T2DM, including 674 T2DM without kidney disease (T2DM group) and 489 T2DM with DKD (DKD group), were evaluated. The DKD group was subdivided according to the chronic kidney disease (CKD) and albuminuria staging criteria in "Kidney Disease: Improving Global Outcomes 2012 clinical practice guideline" to quantify the severity of DKD: CKD stage 1 (n=164), CKD stage 2 (n=103), CKD stage 3 (n=95), CKD stage 4 (n=71), and CKD stage 5 (n=56) and stage A1 (n=57), stage A2 (n=250), and stage A3 (n=182), respectively. Peripheral blood was collected after 8 hours of fasting to test Hcy levels. RESULTS In CKD stages, Hcy levels gradually increased with increasing DKD severity (CKD stage 1 to 5); while in albuminuria stages, Hcy levels did not gradually increase with increasing DKD severity (stage A1 to A3). Hcy was an independent risk factor for CKD stages 2-5 (P<0.05), and had no effect on the albuminuria stages (P>0.05), while it may indirectly affect the occurrence of albuminuria stages through its impact on estimated glomerular filtration rate. CONCLUSIONS The relationship between Hcy level and DKD severity was related to the different staging methods used. Hcy was an independent risk factor for CKD stages but not albuminuria stages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.936323DOI Listing
June 2022

Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses.

Cell Metab 2022 Jun 1. Epub 2022 Jun 1.

Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China. Electronic address:

The ovarian-tumor-domain-containing deubiquitinases (OTUDs) block ubiquitin-dependent protein degradation and are involved in diverse signaling pathways. We discovered a rare OTUD3 c.863G>A mutation in a family with an early age of onset of diabetes. This mutation reduces the stability and catalytic activity of OTUD3. We next constructed an experiment with Otud3 mice and found that they developed worse obesity, dyslipidemia, and insulin resistance than wild-type mice when challenged with a high-fat diet (HFD). We further found that glucose and fatty acids stimulate CREB-binding-protein-dependent OTUD3 acetylation, promoting its nuclear translocation, where OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARδ). Moreover, targeting PPARδ using a specific agonist can partially rescue the phenotype of HFD-fed Otud3 mice. We propose that OTUD3 is an important regulator of energy metabolism and that the OTUD3 c.863G>A is associated with obesity and a higher risk of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2022.05.005DOI Listing
June 2022

SOX12 Promotes Thyroid Cancer Cell Proliferation and Invasion by Regulating the Expression of POU2F1 and POU3F1.

Yonsei Med J 2022 Jun;63(6):591-600

Department of General Surgery, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Purpose: SOX12 is overexpressed in many cancers, and we aimed to explore the biological function and mechanism of SOX12 in thyroid cancer.

Materials And Methods: We first analyzed the expression of SOX12 in thyroid cancer using data in The Cancer Genome Atlas. Immunohistochemistry and qRT-PCR were performed to identify SOX12 expression in thyroid cancer tissue and cells. Thyroid cancer cells were transfected with small interfering RNA targeting SOX12, and cellular functional experiments, including CCK8, wound healing, and Transwell assays, were performed. Protein expression was examined by Western blot analysis. A xenograft model was developed to evaluate the effect of SOX12 on tumor growth in vivo.

Results: SOX12 expression was increased in thyroid cancer tissue and cells. SOX12 promoted cell proliferation, migration, and invasion and accelerated tumor growth in vivo. The expression of PCNA, Cyclin D1, E-cadherin, Snail, MMP-2, and MMP-9 was affected by SOX12 knockdown. Bioinformatic analysis showed that SOX12 could interact with the POU family. SOX12 knockdown inhibited the expression of POU2F1, POU2F2, POU3F1 and POU3F2, and SOX12 expression showed a positive correlation with POU2F1, POU3F1, and POU3F2 expression in clinical data. POU2F1 and POU3F1 were able to reverse the effect of SOX12 knockdown on thyroid cancer cells.

Conclusion: SOX12 affects the progression of thyroid cancer by regulating epithelial-mesenchymal transition and interacting with POU2F1 and POU3F1, which may be novel targets for thyroid cancer molecular therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2022.63.6.591DOI Listing
June 2022

Rapid Multilateral and Integrated Public Health Response to a Cross-City Outbreak of Enteritidis Infections Combining Analytical, Molecular, and Genomic Epidemiological Analysis.

Front Microbiol 2022 4;13:772489. Epub 2022 May 4.

Shenzhen Major Infectious Disease Control Key Laboratory, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.

On September 21, 2019, the Shenzhen and Dongguan Centers for Disease Control and Prevention received notification of a large cluster of suspected gastroenteritis involving primarily children who sought medical care at hospitals throughout two adjacent cities in China, Shenzhen, and Dongguan. A joint outbreak response was promptly initiated across jurisdictions in a concerted effort between clinical microbiologists, epidemiologists, and public health scientists. Concurrently, multiplex PCRs were used for rapid laboratory diagnosis of suspected cases; epidemiological investigations were conducted to identify the outbreak source, complemented by near real-time multicenter whole-genome analyses completed within 34 h. Epidemiological evidence indicated that all patients had consumed egg sandwiches served on September 20 as snacks to children and staff at a nursery in Dongguan, located near Shenzhen. Enteritidis was isolated from case-patients, food handlers, kitchenware, and sandwiches with kitchen-made mayonnaise. Whole-genome single-nucleotide polymorphism (SNP)-based phylogenetic analysis demonstrated a well-supported cluster with pairwise distances of ≤1 SNP between genomes for outbreak-associated isolates, providing the definitive link between all samples. In comparison with historical isolates from the same geographical region, the minimum pairwise distance was >14 SNPs, suggesting a non-local outbreak source. Genomic source tracing revealed the possible transmission dynamics of a . Enteritidis clone throughout a multi-provincial egg distribution network. The efficiency and scale with which multidisciplinary and integrated approaches were coordinated in this foodborne disease outbreak response was unprecedented in China, leading to the timely intervention of a large cross-jurisdiction outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.772489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117964PMC
May 2022

KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling.

Dev Cell 2022 Jun 18;57(11):1383-1399.e7. Epub 2022 May 18.

Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden; Department of Medicine Huddinge (MedH), Karolinska Institute, Campus Flemingsburg, Neo, Blickagången 16, 141 57 Huddinge, Sweden. Electronic address:

Loss- or gain-of-function mutations in ATP-sensitive potassium channel (K-ATP)-encoding genes, KCNJ8 and ABCC9, cause human central nervous system disorders with unknown pathogenesis. Here, using mice, zebrafish, and cell culture models, we investigated cellular and molecular causes of brain dysfunctions derived from altered K-ATP channel function. We show that genetic/chemical inhibition or activation of KCNJ8/ABCC9-containing K-ATP channel function leads to brain-selective suppression or promotion of arterial/arteriolar vascular smooth muscle cell (VSMC) differentiation, respectively. We further show that brain VSMCs develop from KCNJ8/ABCC9-containing K-ATP channel-expressing mural cell progenitor and that K-ATP channel cell autonomously regulates VSMC differentiation through modulation of intracellular Ca oscillation via voltage-dependent calcium channels. Consistent with defective VSMC development, Kcnj8 knockout mice showed deficiency in vasoconstrictive capacity and neuronal-evoked vasodilation leading to local hyperemia. Our results demonstrate a role for KCNJ8/ABCC9-containing K-ATP channels in the differentiation of brain VSMC, which in turn is necessary for fine-tuning of cerebral blood flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2022.04.019DOI Listing
June 2022

Tailoring therapeutic effect for chronotherapy of variant angina based on pharmacodynamic/deconvolution integrated model method.

Eur J Pharm Sci 2022 Aug 14;175:106208. Epub 2022 May 14.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, PR China. Electronic address:

The onset of variant angina (VA) shows circadian rhythmicity that its attacks occur most often from midnight to early morning. Thus, chronotherapeutic treatments should be tailored accordingly to its occurrence frequency. Tanshinol (TS), the bioactive component of Salvia miltiorrhiza was used as the model drug. The pharmacokinetics, pharmacodynamics and PK-PD relationship of TS was investigated in angina model rabbits. The therapeutic effect of TS was evaluated from different aspects including cardiac injury, oxidative stress and vascular endothelium by measuring the serum levels of cTn-I, CK-MB, SOD and NO. In addition, the change of cTn-I levels from baseline as the pharmacodynamic endpoint was used for establishing the pharmacodynamic model. To synchronize the therapeutic effect profile of TS to the occurrence frequency of VA, ideal time courses of therapeutic effect, plasma concentration and drug release were simulated and calculated based on pharmacodynamic/deconvolution integrated model method. Then, sustained release pellets of TS (TS-SRPs) were developed according to the above calculated results and evaluated in vitro-in vivo. The established pharmacodynamic model of TS could precisely quantify the relationship between its effect and concentration. Then, ideal time courses of therapeutic effect, plasma concentration and release of TS were simulated and calculated successfully. After formulation optimization, the prepared TS-SRPs exhibited similar in vitro and in vivo behaviors to the corresponding ideal ones. Meanwhile, the effect curves of TS were synchronous with the occurrence frequency of VA, implying that appropriate therapeutic effect could be provided according to the needs of patients. In conclusion, the tailor of therapeutic effect based on integrated model method is efficient, feasible and reliable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2022.106208DOI Listing
August 2022

A Deep Learning Model for Classification of Parotid Neoplasms Based on Multimodal Magnetic Resonance Image Sequences.

Laryngoscope 2022 May 16. Epub 2022 May 16.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Objective: To design a deep learning model based on multimodal magnetic resonance image (MRI) sequences for automatic parotid neoplasm classification, and to improve the diagnostic decision-making in clinical settings.

Methods: First, multimodal MRI sequences were collected from 266 patients with parotid neoplasms, and an artificial intelligence (AI)-based deep learning model was designed from scratch, combining the image classification network of Resnet and the Transformer network of Natural language processing. Second, the effectiveness of the deep learning model was improved through the multi-modality fusion of MRI sequences, and the fusion strategy of various MRI sequences was optimized. In addition, we compared the effectiveness of the model in the parotid neoplasm classification with experienced radiologists.

Results: The deep learning model delivered reliable outcomes in differentiating benign and malignant parotid neoplasms. The model, which was trained by the fusion of T2-weighted, postcontrast T1-weighted, and diffusion-weighted imaging (b = 1000 s/mm ), produced the best result, with an accuracy score of 0.85, an area under the receiver operator characteristic (ROC) curve of 0.96, a sensitivity score of 0.90, and a specificity score of 0.84. In addition, the multi-modal paradigm exhibited reliable outcomes in diagnosing the pleomorphic adenoma and the Warthin tumor, but not in the identification of the basal cell adenoma.

Conclusion: An accurate and efficient AI based classification model was produced to classify parotid neoplasms, resulting from the fusion of multimodal MRI sequences. The effectiveness certainly outperformed the model with single MRI images or single MRI sequences as input, and potentially, experienced radiologists.

Level Of Evidence: 3 Laryngoscope, 2022.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.30154DOI Listing
May 2022

The Mobile Phone Addiction and Depression Among High School Students: The Roles of Cyberbullying Victimization, Perpetration, and Gender.

Front Psychol 2022 27;13:845355. Epub 2022 Apr 27.

The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Objective: To examine the relation between mobile phone addiction and high school students' depression, and its inner mechanism-the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship.

Methods: 1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale.

Results: (1) Mobile phone addiction was positively correlated with and high school students' depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students' depression, which contained tow mediating paths-the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls.

Conclusion: The results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2022.845355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095501PMC
April 2022

High Expression of TGF-β1 Contributes to Hepatocellular Carcinoma Prognosis Regulating Tumor Immunity.

Front Oncol 2022 25;12:861601. Epub 2022 Apr 25.

Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Transforming growth factor-beta (TGF-β) signaling is essential in initialization and progression of hepatocellular carcinoma (HCC). Therefore, a treatment targeting TGF-β pathway may be a promising option for HCC control.

Methods: First, publicly available RNA-seq datasets and clinical characteristics of 374 HCC patients in The Cancer Genome Atlas (TCGA) database were downloaded. Then, Cox regression analysis and LASSO analysis were used to construct a prognostic model for TGF-β family genes. The area under the curve (AUC) of the risk signature was calculated to evaluate the predictive power of the model. Cox regression analysis was applied to predict whether TGF-β1 can be an independent prognosis factor for HCC. Next, hazard ratio and survival analyses were performed to investigate the correlation between TGF-β1 expression and survival time. Furthermore, differential expression level of TGF-β1 in HCC tissues and cells was determined. In addition, Gene Set Enrichment Analysis (GSEA) identified the top significantly activated and inhibited signal pathways related to high expression of TGF-β1. Finally, the CIBERSORT tool was adopted to correlate the tumor-infiltrating immune cells (TICs) with TGF-β1 expression in HCC cohorts.

Results: Cox regression analysis and LASSO analysis revealed that seven TGF-β family members (including TGF-β1) could be used as prognostic factors for HCC. Interestingly, TGF-β1 was demonstrated to be an independent prognostic factor of HCC. RT-qPCR and immunofluorescence staining confirmed the high expression of TGF-β1 in HCC cell lines and tissues, which is significantly related to pathological classifications, poor prognosis, and short survival time. Finally, GSEA and CIBERSORT analyses suggested that TGF-β1 may interact with various immune cells and influence the prognosis of HCC patients through Tregs and γδ T cells.

Conclusion: We established a novel prognostic prediction method to predict the risk scores of TGF-β genes in HCC prognosis. TGF-β1 is highly expressed in HCC cell lines and tissues, correlates to poor prognosis, and thus can be used as a potential biomarker to predict HCC prognosis. We showed that TGF-β1 may play its roles in HCC prognosis by modulating the immune microenvironment of tumor cells. Our data may shed more light on better understanding the role of TGF-β1 in HCC prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.861601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082360PMC
April 2022

Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery.

Bioact Mater 2023 Jan 7;19:115-126. Epub 2022 Apr 7.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu, 210009, PR China.

Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP ) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP , allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2022.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010555PMC
January 2023

Upregulation of ribosome biogenesis via canonical E-boxes is required for Myc-driven proliferation.

Dev Cell 2022 04;57(8):1024-1036.e5

Applied Tumor Genomics Research Program, University of Helsinki, Helsinki, Finland; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Biochemistry, University of Cambridge, Cambridge, UK. Electronic address:

The transcription factor Myc drives cell growth across animal phyla and is activated in most forms of human cancer. However, it is unclear which Myc target genes need to be regulated to induce growth and whether multiple targets act additively or if induction of each target is individually necessary. Here, we identified Myc target genes whose regulation is conserved between humans and flies and deleted Myc-binding sites (E-boxes) in the promoters of fourteen of these genes in Drosophila. E-box mutants of essential genes were homozygous viable, indicating that the E-boxes are not required for basal expression. Eight E-box mutations led to Myc-like phenotypes; the strongest mutant, ppan, also made the flies resistant to Myc-induced cell growth without affecting Myc-induced apoptosis. The ppan flies are healthy and display only a minor developmental delay, suggesting that it may be possible to treat or prevent tumorigenesis by targeting individual downstream targets of Myc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2022.03.018DOI Listing
April 2022

The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research.

Stem Cell Reports 2022 05 21;17(5):1089-1104. Epub 2022 Apr 21.

Department of Medicine, Huddinge, Karolinska Institutet, Solna, Sweden; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Electronic address:

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.stemcr.2022.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022216PMC
May 2022

Anchoring β-CD on simvastatin-loaded rHDL for selective cholesterol crystals dissolution and enhanced anti-inflammatory effects in macrophage/foam cells.

Eur J Pharm Biopharm 2022 May 18;174:144-154. Epub 2022 Apr 18.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address:

Macrophage/foam cells and cholesterol crystals (CCs) have been regarded as the central triggers of maladaptive inflammation in atherosclerotic plaque. Despite the tremendous progress of recombinant high-density lipoprotein (rHDL) serving for targeted drug delivery to alleviate inflammation in macrophage/foam cells, the active attempt to modulate/improve its CCs dissolution capacity remains poorly explored. The untreated CCs can seriously aggravate inflammation and threaten plaque stability. Based on the superb ability of β-cyclodextrin (β-CD) to bind CCs and promote cholesterol efflux, simvastatin-loaded discoidal-rHDL (ST-d-rHDL) anchored with β-CD (βCD-ST-d-rHDL) was constructed. We verified that βCD-ST-d-rHDL specifically bound and dissolved CCs extracellularly and intracellularly. Furthermore, anchoring β-CD onto the surface of ST-d-rHDL enhanced its cholesterol removal ability in RAW 264.7 cell-derived foam cells characterized by accelerated cholesterol efflux, reduced intracellular lipid deposition, and improved cell membrane fluidity/permeability. Finally, βCD-ST-d-rHDL exerted efficient drug delivery and effective anti-inflammatory effects in macrophage/foam cells. Collectively, anchoring β-CD onto the surface of ST-d-rHDL for selective CCs dissolution, accelerated cholesterol efflux, and improved drug delivery represents an effective strategy to enhance anti-inflammatory effects for the therapy of atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpb.2022.04.005DOI Listing
May 2022

Regulating the Size of Simvastatin-loaded Discoidal Reconstituted High-density Lipoprotein: Preparation, Characterization and Investigation of Cellular Cholesterol Efflux.

Curr Drug Deliv 2022 Apr 14. Epub 2022 Apr 14.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.

Background: Reverse cholesterol transportation is an essential way for high-density lipoprotein (HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that the particle size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs (rHDLs) possess similar function to natural ones.

Objective: The study aimed to investigate the effect of particle size on the cholesterol efflux capacity of discoidal rHDLs and whether drug loadings may have an influence on this effect.

Methods: Different-sized simvastatin-loaded discoidal rHDLs (ST-d-rHDLs) resembling nascent HDL were prepared by optimizing key factors related to the sodium cholate of film dispersion-sodium cholate dialysis method with a controlled single factor. We characterized their physicochemical properties such as particle size, zeta potential, and morphology in vitro, and evaluated their capacity of cellular cholesterol efflux in foam cells.

Results: We successfully constructed discoidal ST-d-rHDLs with different sizes (13.4 ± 1.4 nm, 36.6 ± 2.6 nm, and 68.6 ± 3.8 nm) with over 80% of encapsulation efficiency and sustained drug release. Among them, the small-sized ST-d-rHDL showed the strongest cholesterol efflux capacity and inhibitory effect on intracellular lipid deposition in foam cells. In addition, the results showed that the loaded drug didn't compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL.

Conclusion: Compared with the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced cellular cholesterol efflux capacity similar to drug-free one, the effect of particle size on cholesterol efflux wasn't influenced by the drug loading.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1567201819666220414120901DOI Listing
April 2022

Excitation of Surface Plasmon Polariton Modes with Double-Layer Gratings of Graphene.

Nanomaterials (Basel) 2022 Mar 30;12(7). Epub 2022 Mar 30.

Laboratory for Micro-Nano Physics and Technology of Hunan Province, School of Physics and Electronics, Hunan University, Changsha 410082, China.

A long-range surface plasmon polariton (SPP) waveguide, composed of double-layer graphene, can be pivotal in transferring and handling mid-infrared electromagnetic waves. However, one of the key challenges for this type of waveguide is how to excite the SPP modes through an incident light beam. In this study, our proposed design of a novel grating, consisting of a graphene-based cylindrical long-range SPP waveguide array, successfully addresses this issue using finite-difference time-domain simulations. The results show that two types of symmetric coupling modes (SCMs) are excited through a normal incident light. The transmission characteristics of the two SCMs can be manipulated by changing the interaction of the double-layer gratings of graphene as well as by varying various parameters of the device. Similarly, four SCMs can be excited and controlled by an oblique incident light because this light source is equivalent to two orthogonal beams of light. Furthermore, this grating can be utilized in the fabrication of mid-infrared optical devices, such as filters and refractive index sensors. This grating, with double-layer graphene arrays, has the potential to excite and manipulate the mid-infrared electromagnetic waves in future photonic integrated circuits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano12071144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000374PMC
March 2022

Fluorescence detection and imaging of intracellular sulphite using a remote light activatable photochromic nanoprobe.

J Mater Chem B 2022 May 4;10(17):3366-3374. Epub 2022 May 4.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.

The development of a responsive fluorescent probe for the detection of a particular biomolecule in a specific site at the desired moment is important in the fields of bioanalysis and imaging, molecular biology and biomedical research. In this work, we report the development of a remote-light activatable nanoprobe for the fluorescence detection of sulphite in pure aqueous solution and its imaging applications in living cells. The nanoprobe, Poly-Cm-SP, is fabricated simply by wrapping photochromic molecules (Cm-SP) into a polymer nanoparticle. Upon alternate UV/Vis light irradiation for several seconds, the Poly-Cm-SP nanoprobe exhibits red/blue fluorescence switch due to the inactive/active FRET processes from coumarins to the SP/MR isomers of the photochromic molecule. In the presence of sulphite, the specific reaction of sulphite with the electron deficit "CC" bond of the MR isomer occurs, resulting in an inefficient FRET process and thus exhibiting a constant "ON" blue channel fluorescence signal. After UV-light irradiation, the formation of activated Poly-Cm-MR thus enables the detection of sulphite through recording the ratiometric changes of fluorescence signals at both blue and red channels. The Poly-Cm-SP nanoprobe possesses excellent biocompatibility and lysosome distribution capability, allowing it to be used for photochromic imaging and sulphite detection in the lysosomes of living macrophage cells. This work thus offers a new remote-light activatable nanoprobe for the detection and imaging of sulphite in biological systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2tb00021kDOI Listing
May 2022

Parental uveitis causes elevated hair loss in offspring of C57BL/6J mice.

Exp Eye Res 2022 Jun 30;219:109056. Epub 2022 Mar 30.

Laboratory Animal Center, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Rodent Laboratory Animals, Chongqing, PR China. Electronic address:

Our previous study demonstrated that parental uveitis in a susceptible population can cause hair loss and increase the susceptibility to experimental autoimmune uveitis (EAU) in offspring. However, it is unclear whether parental uveitis affects the development of offspring in an EAU-moderate-susceptible population. Herein, moderate-susceptible C57BL/6J mice were immunized with inter-photoreceptor retinoid binding protein (IRBP) 651-670 to develop EAU and were kept together for mating. Gross examination and histopathological changes of the offspring gestated with parental uveitis were observed to evaluate the impact of parental uveitis on the development of the offspring. Differentially expressed genes (DEGs) were screened by RNA sequencing in the affected skin and eyeball of the offspring on postnatal day 27. Adult offspring were injected 75 μg IRBP to evaluate their susceptibility to EAU. Gross examination in the offspring revealed hair loss on postnatal days 11-31. Histopathological observation showed increased melanin granules and hair follicles of skin in the affected offspring with hair loss. Gene Ontology (GO) analysis in the skin revealed differential expression of genes involved in the mitotic cell cycle, response to endogenous stimulus, hair follicle development, and hair cycle. The DEGs in the skin were predominately associated with the cell cycle and peroxisome proliferator-activated receptor (PPAR) signaling pathway. The GO enrichment analysis in the eyeball showed differential expression of genes involved in the nervous system development, camera-type eye photoreceptor cell differentiation, neuron projection morphogenesis, axon development, and calcium-induced calcium release activity; enriched pathways included the circadian entrainment and glutamatergic synapses. No increased susceptibility to EAU in offspring gestated from parental remitting EAU was observed at a low-dose 75 μg IRBP induction. These results suggested that parental uveitis in a moderate-susceptible population could affect the skin development and DEG profiles of skin and eyeball related to the response to endogenous stimulus, the PPAR signaling pathway, and glutamatergic synapse, which provides the molecular evidence to explain the influence of parental uveitis on offspring development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exer.2022.109056DOI Listing
June 2022

Complementary and alternative medicine modalities used to treat adverse effects of anti-cancer treatment among children and young adults: a systematic review and meta-analysis of randomized controlled trials.

BMC Complement Med Ther 2022 Apr 2;22(1):97. Epub 2022 Apr 2.

Department of Community Medicine, Faculty of Health Science, National Research Center in Complementary and Alternative Medicine, NAFKAM, UiT The Arctic University of Norway, 9037, Tromsø, Norway.

Background: Dealing with the symptom burden of cancer diagnosis and treatment has led parents to seek different self-management strategies including Alternative and Complementary Medicine (CAM). The aim of this study was to perform a systematic review and meta-analysis about the use and effect of CAM modalities to treat adverse effects of conventional cancer treatment among children and young adults.

Methods: Six scientific research databases were used to identify randomized controlled trials (RCTs) from 1990 to September 2020. Included studies investigated the use of CAM to treat cancer treatment related adverse effects in children and young adults compared to controls.

Results: Twenty RCTs comprising 1,069 participants were included in this review. The included studies investigated acupuncture, mind-body therapies, supplements, and vitamins for chemotherapy-induced nausea and vomiting (CINV), oral mucositis, and anxiety among children and young adults who underwent conventional cancer treatment. Seven studies (315 participants) were included in the meta-analysis. The overall effect of CAM (including acupuncture and hypnosis only) on chemotherapy-induced nausea and/or vomiting and controls was statistically significant with a standard mean difference of -0.54, 95% CI [-0.77, -0.31] I = 0% (p < 0.00001). There was a significant difference between acupuncture and controls (n = 5) for intensity and/or episodes of CINV with an SMD -0.59, 95% CI [-0.85, -0.33] (p < 0.00001). No significant difference was found between hypnosis and controls (n = 2) for severity or episodes of CINV with an SMD -0.41, 95% CI [-1.09, 0.27] I = 41% (p = 0.19).

Conclusion: Current evidence from this meta-analysis of randomized controlled trials shows that CAM, including acupuncture and hypnosis only, is effective in reducing chemotherapy-induced nausea and vomiting in children and young adults. More rigorous trials and long-term effects should be investigated if acupuncture and hypnosis are to be recommended for clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-022-03537-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976304PMC
April 2022

Mechanistic insights into the subversion of the linear ubiquitin chain assembly complex by the E3 ligase IpaH1.4 of .

Proc Natl Acad Sci U S A 2022 03 16;119(12):e2116776119. Epub 2022 Mar 16.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.

Shigella flexneri, a gram-negative bacterium, is the major culprit of bacterial shigellosis and causes a large number of human infection cases and deaths worldwide annually. For evading the host immune response during infection, S. flexneri secrets two highly similar E3 ligases, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC) of host cells, which is composed of HOIP, HOIL-1L, and SHARPIN. However, the detailed molecular mechanism underpinning the subversion of the LUBAC by IpaH1.4/2.5 remains elusive. Here, we demonstrated that IpaH1.4 can specifically recognize HOIP and HOIL-1L through its leucine-rich repeat (LRR) domain by binding to the HOIP RING1 domain and HOIL-1L ubiquitin-like (UBL) domain, respectively. The determined crystal structures of IpaH1.4 LRR/HOIP RING1, IpaH1.4 LRR/HOIL-1L UBL, and HOIP RING1/UBE2L3 complexes not only elucidate the binding mechanisms of IpaH1.4 with HOIP and HOIL-1L but also unveil that the recognition of HOIP by IpaH1.4 can inhibit the E2 binding of HOIP. Furthermore, we demonstrated that the interaction of IpaH1.4 LRR with HOIP RING1 or HOIL-1L UBL is essential for the ubiquitination of HOIP or HOIL-1L in vitro as well as the suppression of NF-κB activation by IpaH1.4 in cells. In summary, our work elucidated that in addition to inducing the proteasomal degradation of LUBAC, IpaH1.4 can also inhibit the E3 activity of LUBAC by blocking its E2 loading and/or disturbing its stability, thereby providing a paradigm showing how a bacterial E3 ligase adopts multiple tactics to subvert the key LUBAC of host cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2116776119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944867PMC
March 2022

Solution Annealing Induces Surface Chemical Reconstruction for High-Efficiency PbS Quantum Dot Solar Cells.

ACS Appl Mater Interfaces 2022 Mar 15;14(12):14274-14283. Epub 2022 Mar 15.

Center for Advanced Optoelectronic Functional Materials Research, and Key Laboratory of UV Light-Emitting Materials and Technology of Ministry of Education, Northeast Normal University, Changchun 130024, Jilin, P. R. China.

Colloidal quantum dots (CQDs) have a large specific surface area and a complex surface structure. Their properties in diverse optoelectronic applications are largely determined by their surface chemistry. Therefore, it is essential to investigate the surface chemistry of CQDs for improving device performance. Herein, we realized an efficient surface chemistry optimization of lead sulfide (PbS) CQDs for photovoltaics by annealing the CQD solution with concentrated lead halide ligands after the conventional solution-phase ligand exchange. During the annealing process, the colloidal solution was used to transfer heat and create a secondary reaction environment, promoting the desorption of electrically insulating oleate ligands as well as the trap-related surface groups (Pb-hydroxyl and oxidized Pb species). This was accompanied by the binding of more conductive lead halide ligands on the CQD surface, eventually achieving a more complete ligand exchange. Furthermore, this strategy also minimized CQD polydispersity and decreased aggregation caused by conventional solution-phase ligand exchange, thereby contributing to yielding CQD films with twofold enhanced carrier mobility and twofold reduced trap-state density compared with those of the control. Based on these merits, the fabricated PbS CQD solar cells showed high efficiency of 11% under ambient conditions. Our strategy opens a novel and effective avenue to obtain high-efficiency CQD solar cells with diverse band gaps, providing meaningful guidance for controlling ligand reactivity and realizing subtly purified CQDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.2c01196DOI Listing
March 2022

USF1/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion.

Neuro Oncol 2022 Mar 14. Epub 2022 Mar 14.

Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.

Background: Glioblastoma stem cells (GSCs) and their interplay with tumor-associated macrophages (TAMs) are responsible for malignant growth and tumor recurrence of Glioblastoma (GBM), but the underlying mechanisms are largely unknown.

Methods: Cell viability, stemness, migration and invasion was measured in GSCs after knockdown of upstream stimulating factor 1 (USF1). Luciferase assay and chromatin immunoprecipitation qPCR were performed to determine the regulation of CD90 by USF1. Immunohistochemistry and immunofluorescent staining were used to examine the expression of USF1 and GSC markers, as well as the crosstalk between GSCs and TAMs. In addition, the interaction between GSCs and TAMs was confirmed using in vivo GBM models.

Results: We show that USF1 promotes malignant glioblastoma phenotypes and GSCs-TAMs physical interaction by inducing CD90 expression. USF1 predicts a poor prognosis for glioma patients, and is upregulated in patient-derived GSCs and glioblastoma cell lines. USF1 overexpression increases the proliferation, invasion and neurosphere formation of GSCs and glioblastoma cell lines, while USF1 knockdown exerts an opposite effect. Further mechanistic studies reveal that USF1 promotes GSC's stemness by directly regulating CD90 expression. Importantly, CD90 of GSCs functions as an anchor for physical interaction with macrophage. Additionally, the USF1/CD90 signaling axis supports the GSCs and TAMs adhesion and immunosuppressive feature of TAMs, which in turn enhance the stemness of GSCs. Moreover, the overexpression of CD90 restores the stemness property in USF1 knockdown GSCs and its immunosuppressive microenvironment.

Conclusions: Our findings indicate that the USF1/CD90 axis might be a potential therapeutic target for the treatment of glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noac063DOI Listing
March 2022

The Small RNA AmiL Regulates Quorum Sensing-Mediated Virulence in Pseudomonas aeruginosa PAO1.

Microbiol Spectr 2022 04 9;10(2):e0221121. Epub 2022 Mar 9.

Department of Laboratory Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Pseudomonas aeruginosa is an opportunistic and nosocomial pathogen of humans with hundreds of its virulence factors regulated by quorum sensing (QS) system. Small noncoding RNAs (sRNAs) are also key regulators of bacterial virulence. However, the QS regulatory sRNAs (Qrrs) that have been characterized in P. aeruginosa are still largely unknown. Here, sRNA AmiL (PA3366.1) in the operon of PAO1 was identified as a novel Qrr by transcriptome sequencing (RNA-Seq). The expression of AmiL was negatively regulated by the or system, of which RhlR probably inhibited its transcription. AmiL deletion mutant and overexpressing strains were constructed in PAO1. Broad phenotypic changes were found, including reduced pyocyanin synthesis, elastase activity, biofilm formation, hemolytic activity, and cytotoxicity, as well as increased rhamnolipid production and swarming motility. AmiL appears to be a new regulator that influences diverse QS-mediated virulence. Furthermore, AmiL directly targeted PhzC, a key member of pyocyanin synthesis. AmiL also negatively regulated expression in the early growth of PAO1, but predominantly increased expression and C4-HSL production in the middle and late stages. Therefore, a novel QS-sRNA signaling cascade of / (RhlR)-AmiL-PhzC// was demonstrated, and it will help to shed new light on the virulence regulatory network of P. aeruginosa PAO1. P. aeruginosa is a common nosocomial pathogen that causes diverse opportunistic infections in humans. The virulence crucial for infection is mainly regulated by QS. Small noncoding RNAs (sRNAs) involved in virulence regulation have also been identified in many bacteria. Recently, there is a growing interest in the new sRNA species, QS regulatory sRNAs (Qrrs). Understanding Qrrs-mediated regulation in P. aeruginosa virulence is therefore important to combat infection. In this study, a previously uncharacterized sRNA AmiL in PAO1 has been identified as a novel Qrr. It has been found to influence diverse QS-mediated virulence factors including pyocyanin, elastase, rhamnolipid, and hemolysin, as well as biofilm formation, swarming motility, and cytotoxicity. Furthermore, PhzC essential for pyocyanin synthesis was a direct target of AmiL. QS gene expression and C4-HSL production were also regulated by AmiL. This study provides insights into the roles of Qrr AmiL in modulating P. aeruginosa virulence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/spectrum.02211-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045362PMC
April 2022

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.

Nat Cancer 2022 02 28;3(2):156-172. Epub 2022 Feb 28.

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s43018-022-00331-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885417PMC
February 2022

Correction: Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization.

Biomater Sci 2022 Mar 15;10(6):1594-1595. Epub 2022 Mar 15.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, P. R. China.

Correction for 'Supramolecular copolymer modified statin-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization' by Qiqi Zhang , , 2021, , 6153-6168, DOI: 10.1039/D1BM00610J.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2bm90014aDOI Listing
March 2022
-->