Publications by authors named "Zhigang Wang"

1,048 Publications

  • Page 1 of 1

Sanghuang Tongxie Formula Ameliorates Insulin Resistance in Through Regulating PI3K/Akt Signaling.

Front Pharmacol 2022 6;13:874180. Epub 2022 Jun 6.

Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China.

Insulin resistance (IR) is a pivotal pathological characteristic that affects the occurrence and development of type 2 diabetes mellitus (T2DM). Thus, the effective control of IR is of great significance for diabetes prevention and treatment. Traditional Chinese medicine (TCM) represents a valuable tool handed down to the world by the Chinese nation and has a long history of use for diabetes clinical therapy. In this study, we focused on a self-drafted TCM-patented formula, Sanghuang Tongxie Formula (SHTXF), which exhibits clinical efficacy in the treatment of diabetes. To explore the effect and molecular mechanism of SHTXF on IR , was used and a () > InR diabetic IR fly model was established. SHTXF water extract was found to contribute toward carbohydrate clearance from the circulating system by converting it into triglycerides (TAG), not glycogen, for nutrient storage. In addition, SHTXF activated phosphatidylinositol-3-kinase (PI3K) activity and improved protein kinase B (PKB, also termed Akt) phosphorylation. Finally, SHTXF promoted Forkhead Box O (dFoxO) cytoplasmic localization and inhibited its transcriptional activity. Taken together, these findings not only highlight the positive role of SHTXF in ameliorating IR the PI3K/Akt pathway but also provide potential drug targets and key insights for use in T2DM clinical treatment strategies.
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http://dx.doi.org/10.3389/fphar.2022.874180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207506PMC
June 2022

E4BP4 Coordinates Circadian Control of Cognition in Delirium.

Adv Sci (Weinh) 2022 Jun 17:e2200559. Epub 2022 Jun 17.

Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Improved understanding of the etiologies of delirium, a common and severe neuropsychiatric syndrome, would facilitate the disease prevention and treatment. Here, the authors invesitgate the role of circadian rhythms in the pathogenesis of delirium. They observe perturbance of circadian rhythms in mouse models of delirium and disrupted clock gene expression in patients with delirium. In turn, physiological and genetic circadian disruptions sensitize mice to delirium with aggravated cognitive impairment. Likewise, global deletion of E4bp4 (E4 promoter-binding protein), a clock gene markedly altered in delirium conditions, results in exacerbated delirium-associated cognitive decline. Cognitive decline in delirium models is attributed to microglial activation and impaired long-term potentiation in the hippocampus. Single-cell RNA-sequencing reveals microglia as the regulatory target of E4bp4. E4bp4 restrains microglial activation via inhibiting the ERK1/2 signaling pathway. Supporting this, mice lacking in microglial E4bp4 are delirious prone, whereas mice with E4bp4 specifically deleted in hippocampal CA1 neurons have a normal phenotype. Mechanistically, E4bp4 inhibits ERK1/2 signaling by trans-repressing Mapk1/3 (genes encoding ERK1/2) via direct binding to a D-box element in the promoter region. These findings define a causal role of clock dysfunction in delirium development and indicate E4bp4 as a regulator of cognition at the crosstalk between circadian clock and delirium.
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http://dx.doi.org/10.1002/advs.202200559DOI Listing
June 2022

Correction to: Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms.

J Nanobiotechnology 2022 Jun 16;20(1):286. Epub 2022 Jun 16.

Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.

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http://dx.doi.org/10.1186/s12951-022-01492-9DOI Listing
June 2022

Multi-model averaging improves the performance of model-guided infliximab dosing in patients with inflammatory bowel diseases.

CPT Pharmacometrics Syst Pharmacol 2022 Jun 15. Epub 2022 Jun 15.

Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Leuven, Belgium.

Infliximab dosage de-escalation without prior knowledge of drug concentrations may put patients at risk for underexposure and trigger the loss of response. A single-model approach for model-informed precision dosing during infliximab maintenance therapy has proven its clinical benefit in patients with inflammatory bowel diseases. We evaluated the predictive performances of two multi-model approaches, a model selection algorithm and a model averaging algorithm, using 18 published population pharmacokinetic models of infliximab for guiding dosage de-escalation. Data of 54 patients with Crohn's disease and ulcerative colitis who underwent infliximab dosage de-escalation after an earlier escalation were used. A priori prediction (based solely on covariate data) and maximum a posteriori prediction (based on covariate data and trough concentrations) were compared using accuracy and precision metrics and the classification accuracy at the trough concentration target of 5.0 mg/L. A priori prediction was inaccurate and imprecise, with the lowest classification accuracies irrespective of the approach (median 59%, interquartile range 59%-63%). Using the maximum a posteriori prediction, the model averaging algorithm had systematically better predictive performance than the model selection algorithm or the single-model approach with any model, regardless of the number of concentration data. Only a single trough concentration (preferably at the point of care) sufficed for accurate and precise prediction. Predictive performance of both single- and multi-model approaches was robust to the lack of covariate data. Model averaging using four models demonstrated similar predictive performance with a five-fold shorter computation time. This model averaging algorithm was implemented in the TDMx software tool to guide infliximab dosage de-escalation in the forthcoming prospective MODIFI study (NCT04982172).
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http://dx.doi.org/10.1002/psp4.12813DOI Listing
June 2022

Chylomicron production is repressed by RPTOR knockdown, R-α-lipoic acid and 4-phenylbutyric acid in human enterocyte-like Caco-2 cells.

J Nutr Biochem 2022 Jun 9:109087. Epub 2022 Jun 9.

Department of Nutrition & Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. Electronic address:

Although the role of mechanistic target of rapamycin complex 1 (mTORC1) in lipid metabolism has been the subject of previous research, its function in chylomicron production is not known. In this study, we created three stable human colorectal adenocarcinoma Caco-2 cell lines exhibiting normal, low or high mTORC1 kinase activity, and used these cells to investigate the consequences of manipulating mTORC1 activity on enterocyte differentiation and chylomicron-like particle production. Constitutively active mTORC1 induced Caco-2 cell proliferation and differentiation (as judged by alkaline phosphatase activity) but weakened transepithelial electrical resistance (TEER). Repressed mTORC1 activity due to the knockdown of RPTOR significantly decreased the expression of lipogenic genes FASN, DGAT1 and DGAT2, lipoprotein assembly genes APOB and MTTP, reduced protein expression of APOB, MTTP and FASN, downregulated the gene expression of very long-chain fatty acyl-CoA ligase (FATP2), acyl-CoA binding protein (DBI), and prechylomicron transport vesicle-associated proteins VAMP7 (vesicle-associated membrane protein 7) and SAR1B (secretion associated Ras related GTPase 1B) resulting in the repression of apoB-containing triacylglycerol-rich lipoprotein secretion. Exposure of Caco-2 cells harboring a constitutively active mTORC1 to short-chain fatty acid derivatives, R-α-lipoic acid and 4-phenylbutyric acid, downregulated chylomicron-like particle secretion by interfering with the lipidation and assembly of the particles, and concomitantly repressed mTORC1 activity with no change to Raptor abundance or PRAS40 (Thr246) phosphorylation. R-α-lipoic acid and 4-phenylbutyric acid may be useful to mitigate intestinal lipoprotein overproduction and associated postprandial inflammation.
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http://dx.doi.org/10.1016/j.jnutbio.2022.109087DOI Listing
June 2022

Discovery of CC-99677, a Selective Targeted Covalent MAPKAPK2 (MK2) Inhibitor for Autoimmune Disorders.

Transl Res 2022 Jun 9. Epub 2022 Jun 9.

Bristol Myers Squibb, Princeton, NJ, USA.

As an anti-inflammatory strategy, MAPK-activated protein kinase-2 (MK2) inhibition can potentially avoid the clinical failures seen for direct p38 inhibitors, especially tachyphylaxis. CC-99677, a selective targeted covalent MK2 inhibitor, employs a rare chloropyrimidine that bonds to the sulfur of cysteine 140 in the ATP binding site via a nucleophilic aromatic substitutions (SAr) mechanism. This irreversible mechanism translates biochemical potency to cells shown by potent inhibition of heat shock protein 27 (HSP27) phosphorylation in LPS-activated monocytic THP-1 cells. The cytokine inhibitory profile of CC-99677 differentiates it from known p38 inhibitors, potentially suppressing a p38 pathway inflammatory response while avoiding tachyphylaxis. Dosed orally, CC-99677 is efficacious in a rat model of ankylosing spondylitis. Single doses, 3 to 400 mg, in healthy human volunteers show linear pharmacokinetics and apparent sustained tumor necrosis factor-α inhibition, with a favorable safety profile. These results support further development of CC-99677 for autoimmune diseases like ankylosing spondylitis.
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http://dx.doi.org/10.1016/j.trsl.2022.06.005DOI Listing
June 2022

Effect of Matching Between the Adopted Corporate Response Strategy and the Type of Hypocrisy Manifestation on Consumer Behavior: Mediating Role of Negative Emotions.

Front Psychol 2022 20;13:831197. Epub 2022 May 20.

China Baowu Iron and Steel Group Co., Ltd., Wuhan, China.

Consumers may sense hypocrisy in corporate social responsibility (CSR) if they note inconsistency in enterprises' words and deeds related to CSR. This inconsistency originates from the intentional selfish actions and unintentional actions of enterprises. Studies have revealed that consumers' perception of hypocrisy has a negative influence on enterprise operation. However, studies have not examined how corporate responses to consumers' hypocrisy perception affect consumers' attitude and behavior. Therefore, the present study attempted to determine the measures that should be undertaken by enterprises to reduce consumers' negative response to them when consumers perceive them to be hypocritical. We conducted a situational simulation experiment to explore the effect of the match between corporate hypocrisy manifestation (moral hypocrisy vs. behavioral hypocrisy) and the corporate response strategy (reactive CSR communication vs. proactive CSR communication) on consumers' negative behaviors toward an enterprise and to test the mechanism influencing this effect. The results indicated that the interaction between the type of corporate hypocrisy and the corporate response strategy has a significant effect on consumers' negative behaviors toward an enterprise. Consumers' negative emotions have a mediating influence on the aforementioned effect. This study explored the response strategies of enterprises during a corporate hypocrisy crisis, classified corporate hypocrisy crises into two types (moral hypocrisy vs. behavioral hypocrisy) according to the different manifestations of corporate hypocrisy, and introduced situational crisis communication theory (SCCT) into research on corporate hypocrisy. The present results help expand knowledge on corporate hypocrisy.
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http://dx.doi.org/10.3389/fpsyg.2022.831197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164134PMC
May 2022

A Novel Fault Diagnosis Method of Rolling Bearing Based on Integrated Vision Transformer Model.

Sensors (Basel) 2022 May 20;22(10). Epub 2022 May 20.

Key Laboratory of Metallurgical Equipment and Control Technology, Wuhan University of Science and Technology, Ministry of Education, Wuhan 430081, China.

In order to improve the diagnosis accuracy and generalization of bearing faults, an integrated vision transformer (ViT) model based on wavelet transform and the soft voting method is proposed in this paper. Firstly, the discrete wavelet transform (DWT) was utilized to decompose the vibration signal into the subsignals in the different frequency bands, and then these different subsignals were transformed into a time-frequency representation (TFR) map by the continuous wavelet transform (CWT) method. Secondly, the TFR maps were input with respective to the multiple individual ViT models for preliminary diagnosis analysis. Finally, the final diagnosis decision was obtained by using the soft voting method to fuse all the preliminary diagnosis results. Through multifaceted diagnosis tests of rolling bearings on different datasets, the diagnosis results demonstrate that the proposed integrated ViT model based on the soft voting method can diagnose the different fault categories and fault severities of bearings accurately, and has a higher diagnostic accuracy and generalization ability by comparison analysis with integrated CNN and individual ViT.
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http://dx.doi.org/10.3390/s22103878DOI Listing
May 2022

A new technology for rapid determination of isomers of hydroxybenzoic acid by terahertz spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Oct 30;279:121313. Epub 2022 Apr 30.

The 34th Research Institute of CETC, Guilin 541004, China.

This study investigated the feasibility of using terahertz (THz) technology for the rapid identification of isomers. The time-domain spectra of 2-hydroxybenzoic acid (2-HA), 3-hydroxybenzoic acid (3-HA), and 4-hydroxybenzoic acid (4-HA) were measured by a THz time-domain spectroscopy system (THz-TDS) in the range of 0.3-1.8 THz. Aiming at the isomer classification problem, a THz spectral data classification model based on a variational mode decomposition-particle swarm optimization-support vector machine (VMD-PSO-SVM) method was proposed. Empirical mode decomposition (EMD) and variational mode decomposition (VMD) were used to extract the first eight intrinsic mode functions (IMFs) of the time-domain signal. Principal component analysis (PCA) was used to extract the first 80 principal components of each modal component as the classification feature vector. The particle swarm optimization (PSO) and support vector machine (SVM) algorithms were used to construct 2-, 3-, and 4-HA classification models. We found that the prediction accuracy of the VMD-PSO-SVM model was significantly higher than that of EMD-PSO-SVM model regardless of the modal components. For both EMD and VMD, with the increase in the IMF number, the corresponding classification recognition accuracy tended to decrease. The results showed that the rapid identification model of hydroxybenzoic acid isomers based on THz spectroscopy and SVM was effective and feasible, providing an accurate and rapid method for the chemical synthesis and quality monitoring of biomedicine.
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http://dx.doi.org/10.1016/j.saa.2022.121313DOI Listing
October 2022

Research on the Pollutant Migration Law Based on Large-Scale Three-Dimensional Similar Simulation Experiments of Underground Coal Gasification.

ACS Omega 2022 May 26;7(18):15982-15995. Epub 2022 Apr 26.

College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong 266590, China.

The potential pollution risk of underground coal gasification (UCG) has become a key factor restricting the development of UCG industrialization. Therefore, studying the migration and diffusion behavior of harmful pollutants is of great significance for preventing UCG pollution. In this paper, a large-scale three-dimensional similar simulation experimental device for UCG is used to simulate the gasification of Tianjin fat coal under actual working conditions. The rock layer around the simulated coal seam was sampled after the gasification was completed, the contaminants in the samples were examined by XRD, and the changes in the relative content of the contaminants at different sampling points were studied by FTIR. The results showed that benzene, phenols, aldehydes, aromatic hydrocarbons, and aromatic heterocyclic compounds remained after the gasification of No. 7 sampling point in Qianjiang, Tianjin, and that the main pollutants were aromatic hydrocarbons. The migration and enrichment of phenol and aldehyde pollutants were about the same on the east and west sides of the gasification center, while benzene pollutants were more easily migrated and enriched than aromatic heterocyclic compounds. The migration distance of phenolic pollutants on the south side of the gasification area is smaller than that of other pollutants and their maximum vertical distance from the gasification reaction area to the south is about 0.7 m. The results can provide a scientific basis for pollutant risk identification and prevention and control in the later UCG field test.
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http://dx.doi.org/10.1021/acsomega.2c01135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097200PMC
May 2022

Maize (Zea mays L.) genotypes induce the changes of rhizosphere microbial communities.

Arch Microbiol 2022 May 14;204(6):321. Epub 2022 May 14.

School of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, 161006, Heilongjiang, China.

Plant-microbe interactions affect ecosystem function, and plant species influence relevant microorganisms. However, the different genotypes of maize that shape the structure and function of the rhizosphere microbial community remain poorly investigated. During this study, the structures of the rhizosphere microbial community among three genotypes of maize were analyzed at the seedling and maturity stages using high-throughput sequencing and bioinformatics analysis. The results demonstrated that Tiannuozao 60 (N) showed higher bacterial and fungal diversity in both periods, while Junlong1217 (QZ) and Fujitai519 (ZL) had lower diversity. The bacterial community structure among the three varieties was significantly different; however, fewer differences were found in the fungal community. The bacterial community composition of N and QZ was similar yet different from ZL at the seedling stage. The bacterial networks of the three cultivars were more complex than the fungal networks, and the networks of the mature stages were more complex than those of the seedling stages, while the opposite was true for the fungi. FAPROTAX functional and FUNGuild functional predictions revealed that different varieties of maize were different in functional abundance at the genus level, and these differences were related to breeding characteristics. This study suggested that different maize genotypes regulated the rhizosphere bacterial and fungal communities, which would help guide practices.
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http://dx.doi.org/10.1007/s00203-022-02934-6DOI Listing
May 2022

SIRT2 Is Critical for Sheep Oocyte Maturation through Regulating Function of Surrounding Granulosa Cells.

Int J Mol Sci 2022 Apr 30;23(9). Epub 2022 Apr 30.

College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, China.

Oocyte in vitro maturation is crucial for in vitro embryo production technology, which provides oocytes resources for in vitro fertilization and somatic cell nuclear transfer. Previous studies proved that SIRT2, a member of the sirtuin family, plays a role in oocyte meiosis, but its role in sheep oocyte maturation and its regulating mechanism remains unknown. Firstly, we confirmed the role of Sirt2 in sheep oocytes maturation by supplementation of SIRT2 inhibitor and activator. To further explore the specific mechanism, we performed knockdown of Sirt2 in granulosa cells and then cocultured them with oocytes. Moreover, we determined the effects of Sirt2 on granulosa cell oxidative apoptosis, cell migration, and diffusion, and examined its effects on granulosa cell mitochondrial function, mitophagy, and steroid hormone levels. The results showed that supplementation of SIRT2 inhibitor decreased the oocytes maturation rate (69.28% ± 1.28 vs. 45.74% ± 4.74, < 0.05), while resveratrol, a SIRT2 activator, increased its maturation rate (67.44% ± 1.68 vs. 78.52 ± 1.28, < 0.05). Knockdown of Sirt2 in sheep granulosa cells also reduced the oocytes maturation rate (47.98% ± 1.43 vs. 33.60% ± 1.77, < 0.05), and led to decreased cell migration and expansion ability, oxidative apoptosis, abnormal mitochondrial gene expression, decreased mitochondrial membrane potential and ATP level, and increased mitophagy level. Overexpression of Sirt2 improved mitochondrial membrane potential and ATP level and improved mitochondrial function. Furthermore, we found that Sirt2 knockdown in granulosa cells promotes the secretion of P through regulating p-ERK1/2. In conclusion the present study showed that SIRT2 is critical for sheep oocyte maturation through regulating the function of ovarian granulosa cells, especially affecting its mitochondrial function.
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http://dx.doi.org/10.3390/ijms23095013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104768PMC
April 2022

Three OsMYB36 members redundantly regulate Casparian strip formation at the root endodermis.

Plant Cell 2022 May 11. Epub 2022 May 11.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.

Plants have evolved a lignin-based Casparian strip (CS) in roots that restricts passive diffusion of mineral elements from the soil to the stele. However, the molecular mechanisms underlying CS formation in rice (Oryza sativa), which contains a CS at both the exodermis and endodermis, are poorly understood. Here, we demonstrate that CS formation at the rice endodermis is redundantly regulated by three MYELOBLASTOSIS (MYB) transcription factors, OsMYB36a, OsMYB36b, and OsMYB36c, that are highly expressed in root tips. Knockout of all three genes resulted in a complete absence of CS at the endodermis and retarded plant growth in hydroponic conditions and in soil. Compared to the wild type, the triple mutants showed higher Ca levels and lower Mn, Fe, Zn, Cu, and Cd levels in shoots. High Ca supply further inhibited mutant growth and increased Ca levels in shoots. Transcriptome analysis identified 1093 downstream genes regulated by OsMYB36a/b/c, including the key CS formation gene OsCASP1 and other genes that function in CS formation at the endodermis. Three OsMYB36s regulate OsCASP1 and OsESB1 expression by directly binding to MYB-binding motifs in their promoters. Our findings thus provide important insights into the mechanism of CS formation at the endodermis and the selective uptake of mineral elements in roots.
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http://dx.doi.org/10.1093/plcell/koac140DOI Listing
May 2022

ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling.

J Nanobiotechnology 2022 May 6;20(1):213. Epub 2022 May 6.

Department of Ultrasound, Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-β (TGF-β), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-β expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation.

Results: We synthesized DMF-loaded ROS-responsive [email protected] liposomes ([email protected] NPs). [email protected] NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while [email protected] NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that [email protected] NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-β and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, [email protected] NPs treatment presented enhanced antifibrotic effect. [email protected] NPs also had a prolonged residence time in the lung as well as excellent biocompatibility.

Conclusions: [email protected] NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.
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http://dx.doi.org/10.1186/s12951-022-01435-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074278PMC
May 2022

Two-Dimensional Ultra-Thin Nanosheets with Extraordinarily High Drug Loading and Long Blood Circulation for Cancer Therapy.

Small 2022 Jun 6;18(22):e2200299. Epub 2022 May 6.

School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.

Nanoparticle drug delivery is largely restricted by the low drug loading capacity of nanoparticle carriers. To address this critical challenge and maximize the potential of nanoparticle drug delivery, a 2D ultra-thin layered double hydroxide (LDH) nanosheet with exceptionally high drug loading, excellent colloidal stability, and prolonged blood circulation for cancer treatment is constructed. The nanosheet is synthesized via a biocompatible polymer-assisted bottom-up method and exhibits an ultra-thin 2D sheet-like structure that enables a considerable amount of cargo anchoring sites available for drug loading, leading to an extraordinary 734% (doxorubicin/nanoparticle mass ratio) drug loading capacity. Doxorubicin delivered by the nanosheet remains stable on the nanosheet carrier under the physiological pH condition, while showing sustained release in the tumor microenvironment and the intracellular environment, thus demonstrating on-demand drug release as a result of pH-responsive biodegradation of nanosheets. Using in vitro and in vivo 4T1 breast cancer models, the nanosheet-based ultra-high drug-loading system demonstrates even enhanced therapeutic performance compared to the multilayered LDH-based high drug-loading system, in terms of increased cellular uptake efficiency, prolonged blood circulation, superior therapeutic effect, and reduced systemic toxicity.
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http://dx.doi.org/10.1002/smll.202200299DOI Listing
June 2022

SP1-mediated up-regulation of lncRNA TUG1 underlines an oncogenic property in colorectal cancer.

Cell Death Dis 2022 May 4;13(5):433. Epub 2022 May 4.

Department of General Surgery, Yan'an People's Hospital, Yan'an, 716000, P.R. China.

The long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) acts as tumor-promoting factor in colorectal cancer (CRC). We aimed to elucidate the mechanism by which the transcription factor specificity protein 1 (SP1) regulates TUG1 and microRNAs (miRs)/mRNAs in the context of CRC, which has not been fully studied before. Expression patterns of TUG1 and SP1 were determined in clinical CRC samples and cells, followed by identification of their interaction. Next, the functional significance of TUG1 in CRC was investigated. An in vivo CRC model was established to validate the effect of TUG1. The results demonstrated that TUG1 and SP1 were highly-expressed in CRC, wherein SP1 bound to the TUG1 promoter and consequently, positively regulated its expression. Silencing of TUG1 caused suppression of CRC cell growth and promotion of cell apoptosis. TUG1 could bind to miR-421 to increase KDM2A expression, a target gene of miR-421. TUG1 could activate the ERK pathway by impairing miR-421-targeted inhibition of KDM2A. Additionally, SP1 could facilitate the tumorigenesis of CRC cells in vivo by regulating the TUG1/miR-421/KDM2A/ERK axis. Altogether, the current study emphasizes the oncogenic role of TUG1 in CRC, and illustrates its interactions with the upstream transcription factor SP1 and the downstream modulatory axis miR-421/KDM2A/ERK, thus offering novel insights into the cancerogenic mechanism in CRC.
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http://dx.doi.org/10.1038/s41419-022-04805-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068916PMC
May 2022

Concurrent Improvement in Maize Grain Yield and Nitrogen Use Efficiency by Enhancing Inherent Soil Productivity.

Front Plant Sci 2022 14;13:790188. Epub 2022 Apr 14.

College of Agronomy, Inner Mongolia Agricultural University, Hohhot, China.

Quantifying the relationships of maize yield and nitrogen use efficiency (NUE) to inherent soil productivity (ISP) could provide a theoretical basis for implementing strategies that concurrently narrow the yield gap, increase NUE, and improve soil quality. A field study under irrigation conditions was conducted at five locations with large differences in ISP (estimated by maize grain yield without using fertilizers) across various ecological regions in Inner Mongolia, China. Our results showed that the changes in maize yield and nitrogen partial factor productivity (PFP) to ISP followed a linear-plateau model, with a common inflection point. When ISP was below 8.0 t ha, maize yield and PFP were stagnating at a low level, due to a trade-off between the contribution of soil and chemical fertilizers to yield. When ISP exceeded 8.0 t ha, the contribution rate of soil to yield stabilized at 80%, resulting in a simultaneous increase in maize yield by 1.2 t ha and PFP by 4.6 kg kg, for increasing ISP at each t ha. Our results indicated that while keeping other management strategies unchanged, to increase maize yield and PFP by 15% or further 30%, it is necessary to increase ISP to 9.3 and 10.4 t ha, respectively. In this scenario, N input will be reduced by 33.5 and 47.5%, and apparent N losses will be reduced by 11.7 and 21.5%, respectively. Therefore, enhancing ISP could lead to a simultaneous improvement in yield and NUE as well as strongly support the green development of maize production.
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http://dx.doi.org/10.3389/fpls.2022.790188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047177PMC
April 2022

Alterations in Fetal Doppler Parameters Before and Twenty-Four Hours After Radiofrequency Ablation for Twin Reversed Arterial Perfusion Sequence.

Front Med (Lausanne) 2022 14;9:802666. Epub 2022 Apr 14.

Institute of Metabolism and System Research, University of Birmingham, Birmingham, United Kingdom.

Objective: To evaluate alterations in the fetal Doppler parameters of pump fetuses before and 24 h after radiofrequency ablation surgery for twin reversed arterial perfusion sequence (TRAPs).

Methods: This is a retrospective study of 28 pump fetuses in TRAPs and 28 normal control twins between 2016 and 2021. The fetal Doppler parameters, including the umbilical artery pulsatility index (UA-PI), middle cerebral artery peak systolic velocity (MCA-PSV), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR), of the controls, and pump fetuses before and 24 h after surgery were compared.

Results: An increasing trend and a further increase in the MCA-PSV, MCA-PI, MCA-PSV Z score, and MCA-PI Z score after surgery were observed in pump fetuses with gestational age (GA) ≥20 weeks; however, such changes were not observed in those with a GA of <20 weeks. The UA-PI and CPR before and after surgery were not different between control and pump fetuses, whether the GA was ≥20 or <20 weeks.

Conclusion: In the middle second trimester, the pump fetus might suffer from high cardiac output rather than hypoxemia before surgery and congestive heart failure, or hemodilutional anemia after surgery. This may provide some theoretical evidence in favor of early intervention, rather than waiting for a more advanced GA, to avoid unnecessary hemodynamic alterations.
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http://dx.doi.org/10.3389/fmed.2022.802666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046669PMC
April 2022

Analysis of glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels.

Ren Fail 2022 Dec;44(1):731-740

Department of Nephrology, Kidney Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Objective: To verify glomerular PLA2R antigen and serum PLA2R antibody expression in membranous nephropathy as well as to explore glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy (IMN) in the background of different serum anti-PLA2R levels.

Methods: We retrospectively analyzed 155 patients who were diagnosed with IMN by kidney biopsy. Patients were divided into six groups according to their serum PLA2R antibody or glomerular PLA2R antigen positiveness and the level of serum anti-PLA2R titer. Both clinical features and pathological characteristics were recorded, and the remission time was compared among groups. Correlation between clinical figures and the anti-PLA2R titer or semi-quantity of glomerular PLA2R antigen was detected.

Results: A positive correlation between time to partial remission and serum anti-PLA2R titer was found. Among patients with serum anti-PLA2R titer <150 RU/ml, there were shorter remission time in negative glomerular PLA2R antigen group compared with positive glomerular PLA2R antigen, and a positive correlation between time to complete remission and semi-quantity of glomerular PLA2R antigen was found.

Conclusion: Both glomerular PLA2R antigen and serum anti-PLA2R play a role in disease presentation and prognosis in primary membranous nephropathy. Glomerular PLA2R antigen has a major role on disease prognosis when serum anti-PLA2R titer is less than 150RU/ml, while serum anti-PLA2R has predominant role in IMN prognosis when serum anti-PLA2R titer is above 150RU/ml.
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http://dx.doi.org/10.1080/0886022X.2022.2068442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067982PMC
December 2022

Nondestructive Testing of Pear Based on Fourier Near-Infrared Spectroscopy.

Foods 2022 Apr 8;11(8). Epub 2022 Apr 8.

College of Horticulture, Northwest A&F University, Taicheng Road No. 3, Yangling, Xianyang 712100, China.

Fourier transform near-infrared (FT-NIR) spectroscopy is a nondestructive, rapid, real-time analysis of technical detection methods with an important reference value for producers and consumers. In this study, the feasibility of using FT-NIR spectroscopy for the rapid quantitative analysis and qualitative analysis of 'Zaosu' and 'Dangshansuli' pears is explored. The quantitative model was established by partial least squares (PLS) regression combined with cross-validation based on the spectral data of 340 pear fresh fruits and synchronized with the reference values determined by conventional assays. Furthermore, NIR spectroscopy combined with cluster analysis was used to identify varieties of 'Zaosu' and 'Dangshansuli'. As a result, the model developed using FT-NIR spectroscopy gave the best results for the prediction models of soluble solid content (SSC) and titratable acidity (TA) of 'Dangshansuli' (residual prediction deviation, RPD: 3.272 and 2.239), which were better than those developed for 'Zaosu' SSC and TA modeling (RPD: 1.407 and 1.471). The results also showed that the variety identification of 'Zaosu' and 'Dangshansuli' could be carried out based on FT-NIR spectroscopy, and the discrimination accuracy was 100%. Overall, FT-NIR spectroscopy is a good tool for rapid and nondestructive analysis of the internal quality and variety identification of fresh pears.
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http://dx.doi.org/10.3390/foods11081076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026391PMC
April 2022

Diagnosis of Acute Leukemia by Multiparameter Flow Cytometry with the Assistance of Artificial Intelligence.

Diagnostics (Basel) 2022 Mar 28;12(4). Epub 2022 Mar 28.

Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

We developed an artificial intelligence (AI) model that evaluates the feasibility of AI-assisted multiparameter flow cytometry (MFC) diagnosis of acute leukemia. Two hundred acute leukemia patients and 94 patients with cytopenia(s) or hematocytosis were selected to study the AI application in MFC diagnosis of acute leukemia. The kappa test analyzed the consistency of the diagnostic results and the immunophenotype of acute leukemia. Bland-Altman and Pearson analyses evaluated the consistency and correlation of the abnormal cell proportion between the AI and manual methods. The AI analysis time for each case (83.72 ± 23.90 s, mean ± SD) was significantly shorter than the average time for manual analysis (15.64 ± 7.16 min, mean ± SD). The total consistency of diagnostic results was 0.976 (kappa (κ) = 0.963). The Bland-Altman evaluation of the abnormal cell proportion between the AI analysis and manual analysis showed that the bias ± SD was 0.752 ± 6.646, and the 95% limit of agreement was from -12.775 to 13.779 ( = 0.1225). The total consistency of the AI immunophenotypic diagnosis and the manual results was 0.889 (kappa, 0.775). The consistency and speedup of the AI-assisted workflow indicate its promising clinical application.
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http://dx.doi.org/10.3390/diagnostics12040827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029950PMC
March 2022

Complete Genome Sequence Data of LZP02, a Bacterium from the Rice Rhizosphere, for Studying the Promotion of Plant Growth.

Mol Plant Microbe Interact 2022 05 13;35(5):428-431. Epub 2022 Apr 13.

School of Life Science and Agriculture Forestry, Qiqihar University, Qiqihar, Heilongjiang 161006, China.

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http://dx.doi.org/10.1094/MPMI-01-22-0012-ADOI Listing
May 2022

An Improved Chemotaxis Assay for the Rapid Identification of Rhizobacterial Chemoattractants in Root Exudates.

J Vis Exp 2022 03 25(181). Epub 2022 Mar 25.

School of Life Science and Agriculture Forestry, Qiqihar University; Heilongjiang Provincial Technology Innovation Center of Agromicrobial Preparation Industrialization;

Chemotaxis identification is very important for the research and application of rhizosphere growth-promoting bacteria. We established a straightforward method to quickly identify the chemoattractants that could induce the chemotactic movement of rhizosphere growth-promoting bacteria on sterile glass slides via simple steps. Bacteria solution (OD600 = 0.5) and sterile chemoattractant aqueous solution were added dropwise on the glass slide at an interval of 1 cm. An inoculating loop was used to connect the chemoattractant aqueous solution to the bacterial solution. The slide was kept at room temperature for 20 min on the clean bench. Finally, the chemoattractant aqueous solution was collected for bacterial counting and microscopic observation. In this study, through multiple comparisons of experimental results, the method overcame multiple shortcomings of traditional bacterial chemotaxis methods. The method reduced the error of plate counting and shortened the experimental cycle. For the identification of chemoattractant substances, this new method can save 2-3 days compared to the traditional method. Additionally, this method allows any researcher to systematically complete a bacterial chemotaxis experiment within 1-2 days. The protocol can be considered a valuable resource for understanding plant-microbe interactions.
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http://dx.doi.org/10.3791/63249DOI Listing
March 2022

Dual-imaging magnetic nanocatalysis based on Fenton-like reaction for tumor therapy.

J Mater Chem B 2022 May 11;10(18):3462-3473. Epub 2022 May 11.

Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P. R. China.

Sequential nano-catalytic therapy has emerged as a novel therapeutic modality for cancer treatment as it utilizes the unique tumor microenvironment for selective tumor treatment. This study reports a magnetic nanoparticle to achieve Fenton-like reaction and dual-imaging guidance/monitoring. Natural glucose oxidase (GOx) and superparamagnetic FeO nanoparticles have been integrated into poly(lactic--glycolic acid) (PLGA) to fabricate a sequential nanocatalyst (designated as [email protected]). This nanocatalyst can functionally deplete glucose in tumor tissues, producing a considerable amount of highly cytotoxic hydroxyl radicals the sequential Fenton-like reaction, and meanwhile maximizing the potential imaging capability as a contrast agent for magnetic resonance imaging and photoacoustic imaging. By ribonucleic acid sequencing (RNA-seq) technology, [email protected] nanoparticles are demonstrated to induce tumor cell death by inhibiting multiple gene regulation pathways involving tumor growth and recurrence. Therefore, this finding provides a novel strategy to achieve promising therapeutic efficacy by the rational design of multifunctional nanoparticles with various features, including magnetic targeting, sequential nano-catalytic therapy, and dual-imaging guidance/monitoring.
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http://dx.doi.org/10.1039/d1tb02308jDOI Listing
May 2022

Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer.

Front Oncol 2022 24;12:848783. Epub 2022 Mar 24.

Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Patients with stage I-III gastric cancer (GC) undergoing R0 radical resection display extremely different prognoses. How to discriminate high-risk patients with poor survival conveniently is a clinical conundrum to be solved urgently.

Methods: Patients with stage I-III GC from 2010 to 2016 were included in our study. The associations of clinicopathological features with disease-free survival (DFS) and overall survival (OS) were examined Cox proportional hazard model. Nomograms were developed which systematically integrated prognosis-related features. Kaplan-Meier survival analysis was performed to compare DFS and OS among groups. The results were then externally validated by The Sixth Affiliated Hospital, Sun Yat-sen University.

Results: A total of 585 and 410 patients were included in the discovery cohort and the validation cohort, respectively. T stage, N stage, lymphatic/vascular/nerve infiltration, preoperative CEA, and CA19-9 were independent prognostic factors (P < 0.05). Two prognostic signatures with a concordance index (C-index) of 0.7502 for DFS and 0.7341 for OS were developed based on the nomograms. The 3-year and 5-year calibration curves showed a perfect correlation between predicted and observed outcomes. Patients were divided into three risk groups (low, intermediate, high), and distinct differences were noticed (p < 0.001). Similar results were achieved in the validation cohort. Notably, a free website was constructed based on our signatures to predict the recurrence risk and survival time of patients with stage I-III GC.

Conclusions: The signatures demonstrate the powerful ability to conveniently identify distinct subpopulations, which may provide significant suggestions for individual follow-up and adjuvant therapy.
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http://dx.doi.org/10.3389/fonc.2022.848783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987912PMC
March 2022

Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy.

Theranostics 2022 21;12(6):2987-3006. Epub 2022 Mar 21.

Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China.

Multidrug resistance (MDR) and metastasis of breast cancer remain major hurdles in clinical anticancer therapy. The unsatisfactory outcome is largely due to insufficient cytotoxicity of chemotherapeutic agents and limited immunogenic cell death (ICD). On the other hand, efflux proteins, especially P-glycoprotein (P-gp), can recognize and promote the efflux of drugs from tumor cells. In this study, silver nanoparticles (Ag NPs) and peptide- functionalized doxorubicin (DOX) were used to prepare a theranostic nanocomposite ([email protected]), which induced organelle-mediated immunochemotherapy and drug efflux protein inhibition in drug-resistant breast cancer cells (MCF-7/ADR) via a strategy based on endoplasmic reticulum (ER) stress and cell-nucleus penetration. The silver nanoparticle-triggered persistent activation of ER stress synergizes with chemotherapy to enhance cytotoxicity and stimulate the ICD effect. It has the potential to enhance chemosensitivity by downregulating of P-gp expression due to the increased production of ATP-consuming chaperones. In addition, the novel peptide (CB5005), which not only penetrates the cell membrane but also has a nuclear localization sequence, is conjugated to DOX to improve both cellular internalization and intranuclear accumulation. Moreover, surface TA-Fe engineering endows the nanocomposite with ATP-responsive disassembly and ATP depletion properties to improve biocompatibility and decrease ATP-dependent drug efflux. [email protected] has potential as a dual-mode (PAI/MRI) contrast-enhanced agent for realizing theranostic guidance. This theranostic nanocomposite greatly restricts the growth of drug-resistant breast tumors and activates a strong immune response as well, providing an opportunity for the development of therapeutics that reverse tumor MDR and metastasis at the subcellular level.
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http://dx.doi.org/10.7150/thno.71693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965496PMC
March 2022

LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques.

Bioact Mater 2022 Oct 3;16:120-133. Epub 2022 Mar 3.

Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.

Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive [email protected] nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and FeO endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered [email protected] nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on and evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.
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http://dx.doi.org/10.1016/j.bioactmat.2022.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958425PMC
October 2022

Surgical outcomes of acute type A aortic dissection in dialysis patients: lessons learned from a single-center's experience.

Sci Rep 2022 03 30;12(1):5372. Epub 2022 Mar 30.

Department of Cardio-Thoracic Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, China.

There is a paucity of data describing the safety and efficacy of acute type A aortic dissection (ATAAD) repair surgeries in dialysis patients. Our study aimed to investigated the influence of dialysis on early and late outcomes in end-stage renal disease (ESRD) patients who received repair surgery for ATAAD. A total of 882 ATAAD patients who received emergency aortic dissection repair at our center from January 2015 to December 2019 were retrospectively screened in this study and divided into the dialysis group (n = 16) and the non-dialysis group (n = 866), depending on whether they required dialysis for preoperative ESRD. No significant difference of age, preoperative hemodynamics, organ ischemia conditions, operative variables as well as the 30-Day mortality and in-hospital complications was discovered between two groups. However, the survival rates and the proportion of late aortic event (sudden death and reoperation) free population at 1 and 3 years after surgery were significantly decreased in dialysis patients compared to non-dialysis patients. Our study indicated that the short-term surgical outcomes of ATAAD in dialysis patients were comparable to non-dialysis patient. However, the dialysis patients were associated with a worse long-term prognosis.
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http://dx.doi.org/10.1038/s41598-022-09448-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967816PMC
March 2022

Enhancing Circulation and Tumor Accumulation of Carboplatin via an Erythrocyte-Anchored Prodrug Strategy.

Angew Chem Int Ed Engl 2022 Jun 21;61(25):e202203838. Epub 2022 Apr 21.

Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, SAR 999077, P. R. China.

The short circulatory half-lives and low tumor accumulation of carboplatin greatly limit the drug's efficacy in vivo. Herein, we address these challenges by using a prodrug strategy and present the rational design of a novel platinum(IV) anticancer prodrug that can hitchhike on erythrocytes. This prodrug, designated as ERY1-Pt , can bind to erythrocytes efficiently and stably, possessing a circulatory half-life 18.5 times longer than that of carboplatin in mice. This elongated circulatory half-life enables platinum to accumulate at levels 7.7 times higher than with carboplatin, with steady levels in the tumors. As a consequence, the ERY1-Pt prodrug is proved to exhibit significantly enhanced antitumor activity and reduced side effects compared with carboplatin. Collectively, our novel approach highlights an efficient strategy to utilize intrinsic erythrocytes as auto-binding carriers to enhance the tumor accumulation and subsequent antitumor efficacy of platinum drugs.
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http://dx.doi.org/10.1002/anie.202203838DOI Listing
June 2022

Epigallocatechin-3-gallate suppresses the growth of human osteosarcoma by inhibiting the Wnt/β-catenin signalling pathway.

Bioengineered 2022 04;13(4):8490-8502

Department of General Surgery, Chongqing Traditional Chinese Medicine Hospital, Chongqing, P.R. China.

Osteosarcoma (OS) is one of the most common malignant tumors in adolescents. Due to local invasion, distant metastasis and drug resistance, the clinical treatment efficacy and prognosis of OS have remained almost unchanged for decades. Epigallocatechin-3-gallate (EGCG) is a unique catechin from tea leaves, and some studies have confirmed its antitumour effects on various tumors. Here, cellular experiments showed that EGCG significantly promoted OS cell apoptosis and inhibited proliferation, migration and invasion, and cell and animal experiments demonstrated that the Wnt/β-catenin pathway played an indispensable role in the antitumour effects of EGCG. Moreover, EGCG inhibited the growth of OS cells in vitro while suppressing tumor cell damage to the bone in situ and distant lung metastasis. The results indicate that the antitumour effect of EGCG on human OS may be mediated by regulating the Wnt/β-catenin pathway and that EGCG can be used alone or in combination with other regimens as a potentially effective anticancer treatment.
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http://dx.doi.org/10.1080/21655979.2022.2051805DOI Listing
April 2022
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