Publications by authors named "Yujie Huang"

112 Publications

Evaluation of heterogeneity of osteosarcoma and efficacy of neoadjuvant chemotherapy by MRI multimodal imaging combined with texture analysis.

Minerva Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Pathology, Xinjiang Medical University First Affiliated Hospital, Urumqi, China.

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http://dx.doi.org/10.23736/S2724-5691.21.08926-7DOI Listing
June 2021

Development and Validation of a Nomogram Based on Nutritional Indicators and Tumor Markers for Prognosis Prediction of Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 31;11:682969. Epub 2021 May 31.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Purpose: This study aimed to develop and validate a nomogram with preoperative nutritional indicators and tumor markers for predicting prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: We performed a bicentric, retrospective study including 155 eligible patients with PDAC. Patients were divided into a training group (n = 95), an internal validation group (n = 34), an external validation group (n = 26), and an entire validation group (n = 60). Cox regression analysis was conducted in the training group to identify independent prognostic factors to construct a nomogram for overall survival (OS) prediction. The performance of the nomogram was assessed in validation groups and through comparison with controlling nutritional status (CONUT) and prognostic nutrition index (PNI).

Results: The least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate Cox regression analysis revealed that serum albumin and lymphocyte count were independent protective factors while CA19-9 and diabetes were independent risk factors. The concordance index (C-index) of the nomogram in the training, internal validation, external validation and entire validation groups were 0.777, 0.769, 0.759 and 0.774 respectively. The areas under curve (AUC) of the nomogram in each group were 0.861, 0.845, 0.773, and 0.814. C-index and AUC of the nomogram were better than those of CONUT and PNI in the training and validation groups. The net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis showed improvement of accuracy of the nomogram in predicting OS and better net benefit in guiding clinical decisions in comparison with CONUT and PNI.

Conclusions: The nomogram incorporating four preoperative nutritional and tumor markers including serum albumin concentration, lymphocyte count, CA19-9 and diabetes mellitus could predict the prognosis more accurately than CONUT and PNI and may serve as a clinical decision support tool to determine what treatment options to choose.
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http://dx.doi.org/10.3389/fonc.2021.682969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200845PMC
May 2021

The Severity of CVB3-Induced Myocarditis Can Be Improved by Blocking the Orchestration of NLRP3 and Th17 in Balb/c Mice.

Mediators Inflamm 2021 12;2021:5551578. Epub 2021 May 12.

Internal Medicine-Cardiovascular Department, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, China.

Background: The functional characteristics of NLRP3 in the pathogenesis of coxsackievirus B3- (CVB3-) induced viral myocarditis (VMC) have not been fully elucidated, and the targeted therapeutic effect of NLRP3 or its related pathway in VMC has not been reported.

Method: In this work, the change patterns of NLRP3- and Th17-related factors were detected during the pathological process of CVB3-induced VMC in Balb/c mice. The correlation between NLRP3 and Th17 cells during the VMC process was analyzed by Spearman test. The coculture system of spleen CD4 T and bone marrow CD11c DC cells was set to explore the orchestration of NLRP3 and Th17 in the pathological development of VMC in vitro. Anti-IL-1 antibody or NLRP3 Balb/c were used to block the NLRP3 pathway indirectly and directly to analyze the NLRP3-targeting therapeutic value.

Results: The change patterns of NLRP3- and Th17-related molecules in the whole pathological process of mouse CVB3-induced VMC were described. Through Spearman correlation analysis, it was confirmed that there was a close correlation between NLRP3 and Th17 cells in the whole pathological process of VMC. And the interaction mode between NLRP3 and Th17 was preliminarily explored in the cell experiment in vitro. Under the intervention of an anti-IL-1 antibody or NLRP3 knockout, the survival rate of the intervention group was significantly improved, the degree of myocardial inflammation and fibrosis was significantly alleviated, and the content of myocardial IL-17 and spleen Th17 was also significantly decreased.

Conclusion: Our findings demonstrated a key role of the NLRP3 inflammasome and its close relationship with Th17 in the pathological progression of CVB3-induced VMC and suggested a possible positive feedback-like mutual regulation mechanism between the NLRP3 inflammasome and Th17 in vitro and in the early stage of CVB3 infection. Taking NLRP3 as a new starting point, it provides a new target and idea for the prevention and treatment of CVB3-induced VMC.
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http://dx.doi.org/10.1155/2021/5551578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139334PMC
May 2021

Involvement of nitrosative stress cytotoxicity induced by CdTe quantum dots in human vascular endothelial cells.

J Toxicol Sci 2021 ;46(6):273-282

Center Laboratory, The First Affiliated Hospital, Zhejiang University School of Medicine, China.

Quantum dots (QDs) are new types of fluorescent nanomaterials which can be utilized as ideal agents for intracellular tracking, drug delivery, biomedical imaging and diagnosis. It is urgent to understand their potential toxicity and the interactions with the toxin-susceptible vascular system, especially vascular endothelial cells. In this study, we intended to explore whether the cytotoxicity of CdTe (cadmium telluride) QDs was partly induced by nitrosative stress in vascular endothelial cells. Our results showed that the intracellular amount of CdTe QDs was gradually increased in a dose- and time-dependent manner, and a concentration-dependent decrease in viability were observed when incubated with CdTe QDs of 20-80 nM. The peroxynitrite level was significantly up-regulated by QDs treatment, which indicated the nitrosative stress was activated. Furthermore, nitrotyrosine level was increased after 24 hr CdTe QDs exposure in a dose-dependent manner, which suggested that CdTe QDs-induced nitrosative stress was associated with tyrosine nitration in EA.hy926. In addition, CdTe QDs induced EA.hy926 apoptosis, and the percentage of cells with low Δψm was increased after CdTe QDs treatment, indicating the mitochondrion depolarization was induced. The increased ROS fluorescence was observed in a QDs dose-dependent manner, which suggested that the oxidative stress was also involved in the CdTe QDs-induced endothelial cytotoxicity. Our work provided experimental evidence into QDs toxicity and potential vascular risks induced by nitrosative stress for the future applications of QDs.
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http://dx.doi.org/10.2131/jts.46.273DOI Listing
January 2021

A study on the effects of regional differences on agricultural water resource utilization efficiency using super-efficiency SBM model.

Sci Rep 2021 May 11;11(1):9953. Epub 2021 May 11.

College of Economics and Trade, Xinjiang Agricultural University, Urumqi, 830052, Xinjiang, China.

This study evaluated the water resource utilization efficiency and resource consumption for planting, forestry, animal husbandry, and fishery in various regions of China. Using the super-efficiency Slacks-Based Measure (SBM) analysis method, the main agricultural pollution emissions (Chemical Oxygen Demand, ammonia nitrogen, and agricultural carbon emissions) were proposed as environmental constraints for the first time. The threshold regression model was used to measure the impact of agricultural water use efficiency on agricultural water consumption by constructing seven different explanatory variables. The results show that the overall utilization efficiency of agricultural water resources in China presents a fluctuating downward trend, and the regional differences are significant. A single threshold effect on agricultural water consumption was found in five variables: per capita water resources, disposable income, dependence on foreign trade, industrial structure, and Gross Domestic Product. The increase in each parameter will have a positive effect on agricultural water consumption. The relationship between agricultural water use efficiency and agricultural water use was non-linear when the government's attention and the rural labor force were used as threshold variables.
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http://dx.doi.org/10.1038/s41598-021-89293-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113275PMC
May 2021

Influence of electrical fields enhanced phytoremediation of multi-metal contaminated soil on soil parameters and plants uptake in different soil sections.

Environ Res 2021 07 7;198:111290. Epub 2021 May 7.

Shandong Provincial Key Laboratory of Applied Microbiology, Ecology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China.

The influence of electrical fields on phytoremediation of multi-metal (Cd, Cu, and Zn) naturally contaminated soils has been investigated based on different soil sections. After ryegrass and hybrid penisetum were sowed for 30 d, electrical fields were applied during 30 days with the switching polarity every 30 min and continuing for 16 h d. After electrokinetic (EK) assisted phytoremediation process, soil electrical conductivity (EC) in anode section and available soil potassium (K) in cathode section were obviously elevated. Plants biomass in middle and cathode sections were increased in both plants, especially in middle section the overall biomass of hybrid penisetum increased by 68.8%. The influence of electrical field on the contents of heavy metals in plants was different depending on the species of plants, kind of heavy metals and soil section. For Cd, Cu, and Zn co-contaminated soils, shoot metals accumulation in middle section in both plants were improved at least about 20% (with the exception of Zn in ryegrass). Electrical fields had the most significant effect on copper absorption by ryegrass and shoot Cu accumulation were elevated 32.5% in all the section. The soil EC maybe an important factor that affected electrical fields enhanced plants growth, plant metals concentrations and remediation efficiency.
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http://dx.doi.org/10.1016/j.envres.2021.111290DOI Listing
July 2021

Genetic analysis of 32 InDels in four ethnic minorities from Chinese Xinjiang.

PLoS One 2021 22;16(4):e0250206. Epub 2021 Apr 22.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

The present study used the previously constructed 32-plex InDels panel to investigated the genetic diversity of four ethnic minorities (Hui, Mongol, Uygur and Kazakh) from Xinjiang, and analyzed the genetic relationships between the four populations and 27 reference populations. No significant deviations were observed from the Hardy-Weinberg equilibrium (HWE) at the 32 InDels for each population. The average observed heterozygosity (Hexp), average polymorphic information content (PIC), combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) for the 32 InDels were all higher than the Qiagen Investigator DIPplex kit in the four populations from Xinjiang. The CPD ranged from 0.999999999999903 (Kazakh) to 0.999999999999952 (Hui) and CPE ranged from 0.9971 (Uygur) to 0.9985 (Hui), which indicated that the 32 InDels were capable for individual identification and could be a supplementary tool in paternity test for these populations. Population genetic analysis by the method of analysis of molecular variance (AMOVA), FST, phylogenetic tree, TreeMix-based topology, multi-dimensional scale analysis (MDS), principal components analysis (PCA) and STRUCTURE analysis showed that Xinjiang Hui population has a close relationship with East Asians (EAS), especially Chinese Han, and the populations of Xinjiang Mongol, Uygur and Kazakh showed mixed ancestral components related to EAS and Europeans (EUR).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250206PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061914PMC
April 2021

Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T-cell acute lymphoblastic leukaemia.

Br J Haematol 2021 Jun 25;193(6):1096-1104. Epub 2021 Mar 25.

Department of Hematology, School of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.
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http://dx.doi.org/10.1111/bjh.17424DOI Listing
June 2021

Rab12 Promotes Radioresistance of HPV-Positive Cervical Cancer Cells by Increasing G2/M Arrest.

Front Oncol 2021 25;11:586771. Epub 2021 Feb 25.

Department of Microbiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: HPV-positive (HPV+) cervical cancer cells are more radioresistant compared with HPV-negative (HPV-) cervical cancer cells, but the underlying mechanism is not fully illuminated. Our previous mass spectrometry data showed that Ras-associated binding protein Rab12 was up-regulated by HPV, and this study is to investigate the role of Rab12 in the radioresistance of HPV-positive cervical cancer cells.

Methods: CCK-8 assay, colony formation assay, flow cytometry, and Western blot were performed to determine cell proliferation, apoptosis, cell cycle distribution, and protein expressions. DNA damage and repair levels were measured by comet assays and detection of γ-H2AX, XRCC4, and pBRCA1 protein expressions.

Results: Rab12 mRNA and protein expressions were up-regulated in cervical cancer tissues and HPV+ cervical cancer cells. Knockdown of Rab12 enhanced radiosensitivity while overexpression of Rab12 promotes radioresistance. Knockdown of Rab12 alleviated G2/M arrest by decreasing p-Cdc2(Tyr15) after radiation, which was a result of the reduction of p-Cdc25C(Ser216). Rab12 knockdown caused more DNA double-strand breaks (DSBs) and inhibited DNA homologous recombination repair (HRR) after radiation. Instead, overexpression of Rab12 enhanced radioresistance by increasing G2/M arrest, which provided more time for DNA HRR.

Conclusions: Rab12 may serve as a potential therapeutic target to improve clinical treatment outcome of cervical cancer.
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http://dx.doi.org/10.3389/fonc.2021.586771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947205PMC
February 2021

Using Immunofluorescence to Detect PM2.5-induced DNA Damage in Zebrafish Embryo Hearts.

J Vis Exp 2021 02 15(168). Epub 2021 Feb 15.

School of Public Health, Soochow University;

Ambient fine particulate matter (PM2.5) exposure can lead to cardiac developmental toxicity but the underlying molecular mechanisms are still unclear. 8-hydroxy-2'deoxygenase (8-OHdG) is a marker of oxidative DNA damage and γH2AX is a sensitive marker for DNA double strand breaks. In this study, we aimed to detect PM2.5-induced 8-OHdG and γH2AX changes in the heart of zebrafish embryos using an immunofluorescence assay. Zebrafish embryos were treated with extractable organic matters (EOM) from PM2.5 at 5 μg/mL in the presence or absence of antioxidant N-acetyl-L-cysteine (NAC, 0.25 μM) at 2 h post fertilization (hpf). DMSO was used as a vehicle control. At 72 hpf, hearts were dissected from embryos using a syringe needle and fixed and permeabilized. After being blocked, samples were probed with primary antibodies against 8-OHdG and γH2AX. Samples were then washed and incubated with secondary antibodies. The resulting images were observed under fluorescence microscopy and quantified using ImageJ. The results show that EOM from PM2.5 significantly enhanced 8-OHdG and γH2AX signals in the heart of zebrafish embryos. However, NAC, acting as a reactive oxygen species (ROS) scavenger, partially counteracted the EOM-induced DNA damage. Here, we present an immunofluorescence protocol for investigating the role of DNA damage in PM2.5-induced heart defects that can be applied to the detection of environmental chemical-induced protein expression changes in the hearts of zebrafish embryos.
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http://dx.doi.org/10.3791/62021DOI Listing
February 2021

Central Neural Circuits Orchestrating Thermogenesis, Sleep-Wakefulness States and General Anesthesia States.

Curr Neuropharmacol 2021 Feb 25. Epub 2021 Feb 25.

Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Ave 1095, Wuhan 430030. China.

Great progress has been made in specifically identifying the central neural circuits (CNCs) of the core body temperature (Tcore), sleep-wakefulness states (SWs), and general anesthesia states (GAs), mainly utilizing optogenetic or chemogenetic manipulations. We summarize the neuronal populations and neural pathways of these three CNCs, which gives evidence for the orchestration within these three CNCs, and the integrative regulation of these three CNCs by different environmental light signals. We also outline some transient receptor potential (TRP) channels that function in the CNCs-Tcore and are modulated by some general anesthetics, which makes TRP channels possible targets for addressing the general-anesthetics-induced-hypothermia (GAIH). We suggest this review will provide new orientations for further consummating these CNCs and elucidating the central mechanisms of GAIH.
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http://dx.doi.org/10.2174/1570159X19666210225152728DOI Listing
February 2021

Myricetin inhibits TNF-α-induced inflammation in A549 cells via the SIRT1/NF-κB pathway.

Pulm Pharmacol Ther 2020 12 16;65:102000. Epub 2021 Feb 16.

Institute of Respiratory Diseases, Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. Electronic address:

Background: Although myricetin exerts anti-inflammation, anti-cancer, and anti-oxidation effects, the relationship between myricetin and tumor necrosis factor alpha (TNF-α) -stimulated inflammation in A549 cells remains unclear. This study sought to assess whether myricetin has an anti-inflammatory effect on TNF-α-induced A549 cells and clarify the potential mechanisms.

Methods: Cell viability was examined with a Cell Counting Kit-8, and cytokine levels were determined by enzyme-linked immunosorbent assay and reverse transcription-quantitative PCR. Potential mechanisms were further explored by western blotting, immunofluorescence, and SIRT1 activity assays.

Results: In A549 cells, TNF-α stimulation upregulated the production of interleukin-6 (IL-6) and interleukin-8 (IL-8). Moreover, TNF-α activated the nuclear factor-κB (NF-κB) pathway, as confirmed by IκB-α degradation, and phosphorylation and nuclear migration of NF-κB p65. However, pretreatment with myricetin significantly attenuated the observed responses triggered by TNF-α. Mechanistically, myricetin strongly increased the deacetylase activity through decreasing phosphorylation, but not expression, of sirtuin-1 (SIRT1) in TNF-α-stimulated A549 cells. Myricetin-mediated SIRT1 activation was further evidenced by the decreased acetylation of NF-κB p65 and p53. Subsequently, all of these concurrent changes were reversed by the addition of salermide (SIRT1 inhibitor), illustrating the critical role of SIRT1 in mediation of anti-inflammatory processes by myricetin.

Conclusions: Myricetin, an enhancer of SIRT1, inhibited TNF-α-induced NF-κB activation in A549 cells, therefore, reducing their inflammatory response. Our findings provide insight for novel therapies for inflammation-related diseases, such as asthma and chronic obstructive pulmonary disease.
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http://dx.doi.org/10.1016/j.pupt.2021.102000DOI Listing
December 2020

Protective effects of resveratrol against the cardiac developmental toxicity of trichloroethylene in zebrafish embryos.

Toxicology 2021 03 29;452:152697. Epub 2021 Jan 29.

School of Biology and Basic Medical Sciences, Medical College of Soochow University, Suzhou, China. Electronic address:

Trichloroethylene (TCE), a prevalent environmental contaminant, has been shown to induce cardiac malformations. Resveratrol (RSV) is a natural polyphenolic compound exhibiting protective effects on heart development. To investigate if RSV could protect against TCE-induced heart defects, we exposed zebrafish embryos to TCE (10 ppb) in the presence or absence of RSV (1 μg/mL). Our results showed that RSV significantly attenuated TCE-induced heart defects in zebrafish embryos. The TCE-induced ROS (reactive oxygen species) generation, 8-OHdG (8-hydroxy-2`-deoxyguanosine) formation and cell proliferation were significantly counteracted by RSV. Moreover, RSV attenuated the TCE-induced changes in mRNA expression or activity of genes involved in AHR and Nrf2 signal pathways. We further showed that RSV might inhibit TCE-enhanced cell proliferation by rescuing the downregulation of the p53/p21 axis. In conclusion, our data demonstrates that RSV protects against the cardiac developmental toxicity of TCE by inhibiting AHR activity, oxidative stress and cell proliferation.
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http://dx.doi.org/10.1016/j.tox.2021.152697DOI Listing
March 2021

The protective role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under inflammatory environment.

Exp Cell Res 2021 Mar 29;400(2):112505. Epub 2021 Jan 29.

Department of Prosthodontics, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Shanghai, 200011, China; National Clinical Research Center for Oral Diseases, No.639 Zhizaoju Road, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, No.639 Zhizaoju Road, Shanghai, 200011, China. Electronic address:

Inflammation and alveolar bone destruction constitute the main pathological process of periodontitis. However, the molecular mechanisms of bone destruction under the inflammation environment remain unclear. This study aims to explore the role of Ephrin-B2/EphB4 signaling in osteogenic differentiation under the inflammation environment. Mouse pre-osteoblasts MC3T3-E1 were pretreated with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS). The Ephrin-B2/EphB4 signaling was activated, and the osteogenic differentiation of cells was examined. The results showed that activation of Ephrin-B2/EphB4 signaling promoted the expression levels of osteogenic differentiation-related genes, and also relieved the inhibitory effect of Pg-LPS on osteogenesis. Noticeably, the effect of Ephrin-B2/EphB4 signaling might be related to the mitogen-activated protein kinase (MAPK) pathway. While applying Ephrin-B2-Fc and EphB4-Fc to periodontitis mice, we observed the reduction of alveolar crest destruction. The current study revealed the possible role of Ephrin-B2/EphB4 signaling in reducing bone destruction in periodontitis and suggested its potential values for further research.
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http://dx.doi.org/10.1016/j.yexcr.2021.112505DOI Listing
March 2021

Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy.

Nat Commun 2021 01 4;12(1):107. Epub 2021 Jan 4.

School of Optical and Electronic Information- Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, 430074, Wuhan, China.

Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm), entire gastrocnemius and tibialis muscles (~200 mm) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.
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http://dx.doi.org/10.1038/s41467-020-20329-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782498PMC
January 2021

High-Dose Vitamin C Tends to Kill Colorectal Cancer with High MALAT1 Expression.

J Oncol 2020 23;2020:2621308. Epub 2020 Nov 23.

Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, China.

Background: Vitamin C (Vc) deficiency is frequently observed in cancer sites and has been proposed to have an antitumor effect. However, the mechanism of Vc's killing effect is not clear. Besides, epigenetic alterations exhibit significant effects on colorectal cancer (CRC). This study aimed to explore the mechanism of Vc's killing effect and its association to epigenetic alterations in CRC.

Methods: Cell morphology, apoptosis, proliferation, and cycle were assayed to test Vc's suppressive function in CRC cell lines. Xenograft and peritoneal implantation metastasis models were performed to evaluate the high-dose Vc's inhibitory effect on tumor growth and metastasis. Immunohistochemistry was used to measure CD31 expression in solid tumors. A literature summary was applied for screening differently expressed long noncoding RNAs (lncRNAs) in CRC tissues and was closely associated with CRC progression. The qPCR was used to detect the expression of these lncRNAs. The association between Vc and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was evaluated in MALAT1-transfected CRC cells and a xenograft model.

Results: Vc was confirmed to function in proliferation suppression, apoptosis induction, and S phase arresting in CRC cell lines. High-dose Vc, but not physiologically low-dose Vc, was identified as a suppressive function on tumor growth in xenograft models and an inhibitory effect on implantation metastasis in peritoneal implantation metastasis mice. Furthermore, a consistent downregulation of MALAT1 induced by Vc was verified among CRC cell lines and tumor tissues from both mouse models. Finally, experiments on MALAT1-knockdown CRC cells and its xenograft model suggested that Vc had a tendency in killing CRC with high MALAT1 expression.

Conclusions: Our findings demonstrate that high-dose Vc has more efficiency in suppressing CRC with higher MALAT1 expression. It gives high-dose Vc the possibility of a better curative effect on CRC with overexpressed MALAT1. Further clinical studies are still needed.
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http://dx.doi.org/10.1155/2020/2621308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714606PMC
November 2020

Systems pharmacology approach uncovers Ligustilide attenuates experimental colitis in mice by inhibiting PPARγ-mediated inflammation pathways.

Cell Biol Toxicol 2021 Feb 31;37(1):113-128. Epub 2020 Oct 31.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.

Inflammatory bowel disease (IBD) is a chronic idiopathic disorder causing inflammation in the gastro-intestinal tract, which is lack of effective drug targets and medications. To identify novel therapeutic agents against consistent targets, we exploited a systems pharmacology-driven framework that incorporates drug-target networks of natural product and IBD disease genes. Our in silico approach found that Ligustilide (LIG), one of the major active components of Angelica acutiloba and Cnidium Officinale, potently attenuated IBD. The following in vivo and in vitro results demonstrated that LIG prevented experimental mice colitis induced by dextran sulfate sodium (DSS) via suppressing inflammatory cell infiltration, the activity of MPO and iNOS, and the expression and production of IL-1β, IL-6, and TNF-α. Subsequently, the network analysis helped to validate that LIG alleviated colitis by inhibiting NF-κB and MAPK/AP-1 pathway through activating PPARγ, which were further confirmed in RAW 264.7 cells and bone marrow-derived macrophages in vitro. In summary, this study reveals that LIG activated PPARγ to inhibit the activation of NF-κB and AP-1 signaling thus eventually alleviated DSS-induced colitis, which has promising activities and may serve as a candidate for the treatment of IBD.Graphical abstract This study suggested novel computational and experimental pharmacology approaches to identify potential IBD therapeutic agents by exploiting polypharmacology of natural products. We demonstrated that LIG could attenuate inflammation in IBD by inhibiting NF-κB and AP-1 pathways via PPARγ activation to reduce the expression of pro-inflammatory cytokines in macrophages. These findings offer comprehensive pre-clinical evidence that LIG may serve as a promising candidate for IBD therapy in the future. Graphical headlights: 1. Systems pharmacology uncovered Ligustilide attenuates experimental colitis in mice. 2. Network-based analysis predicted the mechanism of Ligustilide against IBD, which was validated by inhibiting PPARγ-mediated inflammation pathways. 3. Ligustilide activated PPARγ to inhibit NF-κB and AP-1 activation thus eventually alleviated DSS-induced colitis.4. Ligustilide has promising activities and may serve as a candidate for the treatment of IBD.
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http://dx.doi.org/10.1007/s10565-020-09563-zDOI Listing
February 2021

Monochromatic Blue Light Activates Suprachiasmatic Nucleus Neuronal Activity and Promotes Arousal in Mice Under Sevoflurane Anesthesia.

Front Neural Circuits 2020 18;14:55. Epub 2020 Aug 18.

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

: Monochromatic blue light (MBL), with a wavelength between 400-490 nm, can regulate non-image-forming (NIF) functions of light in the central nervous system. The suprachiasmatic nucleus (SCN) in the brain is involved in the arousal-promoting response to blue light in mice. Animal and human studies showed that the responsiveness of the brain to visual stimuli is partly preserved under general anesthesia. Therefore, this study aimed to investigate whether MBL promotes arousal from sevoflurane anesthesia activation of the SCN in mice. : The induction and emergence time of sevoflurane anesthesia under MBL (460 nm and 800 lux) exposure was measured. Cortical electroencephalograms (EEGs) were recorded and the burst-suppression ratio (BSR) was calculated under MBL during sevoflurane anesthesia. The EEGs and local field potential (LFP) recordings with or without locally electrolytic ablated bilateral SCN were used to further explore the role of SCN in the arousal-promoting effect of MBL under sevoflurane anesthesia. Immunofluorescent staining of c-Fos was conducted to reveal the possible downstream mechanism of SCN activation. : Unlike the lack of effect on the induction time, MBL shortened the emergence time and the EEG recordings showed cortical arousal during the recovery period. MBL resulted in a significant decrease in BSR and a marked increase in EEG power at all frequency bands except for the spindle band during 2.5% sevoflurane anesthesia. MBL exposure under sevoflurane anesthesia enhances the neuronal activity of the SCN. These responses to MBL were abolished in SCN lesioned (SCNx) mice. MBL evoked a high level of c-Fos expression in the prefrontal cortex (PFC) and lateral hypothalamus (LH) compared to polychromatic white light (PWL) under sevoflurane anesthesia, while it exerted no effect on c-Fos expression in the ventrolateral preoptic area (VLPO) and locus coeruleus (LC) c-Fos expression. : MBL promotes behavioral and electroencephalographic arousal from sevoflurane anesthesia the activation of the SCN and its associated downstream wake-related nuclei. The clinical implications of this study warrant further study.
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http://dx.doi.org/10.3389/fncir.2020.00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461971PMC
August 2020

Establishment and characterization of a docetaxel-resistant human prostate cancer cell line.

Oncol Lett 2020 Nov 11;20(5):230. Epub 2020 Sep 11.

Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.

The aim of the present study was to establish a novel docetaxel-resistant prostate cancer cell line and investigate its biological characteristics. The human prostate cell line, PC-3, was exposed to docetaxel, the concentrations of which were increased in a stepwise manner in the medium to select the drug-resistant cell line, PC-3/DTX. The morphological features were observed using inverted microscopy. The growth curves of PC-3 and PC-3/DTX cells were drawn to calculate the doubling time. Flow cytometry was performed to determine cell-cycle distribution. A 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide assay was performed to test the drug resistance of PC-3 and PC-3/DTX cells. Western blot analysis was conducted to determine the protein expression levels of the mammalian target of rapamycin (mTOR) signaling pathway, which may serve a role in regulating drug resistance in the two cell lines. PC-3/DTX cells exhibited changes in morphology, proliferation rate, doubling time and cell-cycle distributions, compared with PC-3 cells. PC-3/DTX cells were 10.9-fold resistant to docetaxel in comparison with PC-3 cells. The results showed that PC-3/DTX cells overexpressed Rictor and p-AKT(S473) proteins, which are specific subunits or downstream substrates of mTORC2. The new findings suggested that the mTORC2 signaling pathway may serve an important role in the regulation of docetaxel drug resistance of PC-3 cells. In conclusion, PC-3/DTX cells may be applied to study the resistance of anticancer drugs and to identify methods to overcome resistance.
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http://dx.doi.org/10.3892/ol.2020.12093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499980PMC
November 2020

Uncovering the Mechanisms of Cryptotanshinone as a Therapeutic Agent Against Hepatocellular Carcinoma.

Front Pharmacol 2020 13;11:1264. Epub 2020 Aug 13.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Hepatocellular carcinoma (HCC) is a fatal and dominant form of liver cancer that currently has no effective treatment or positive prognosis. In this study, we explored the antitumor effects of cryptotanshinone (CPT) against HCC and the molecular mechanisms underlying these effects using a systems pharmacology and experimental validation approach. First, we identified a total of 296 CPT targets, 239 of which were also HCC-related targets. We elucidated the mechanisms by which CPT affects HCC through multiple network analysis, including CPT-target network analysis, protein-protein interaction network analysis, target-function network analysis, and pathway enrichment analysis. In addition, we found that CPT induced apoptosis in Huh7 and MHCC97-H ells due to increased levels of cleaved PARP, Bax, and cleaved caspase-3 and decreased Bcl-2 expression. CPT also induced autophagy in HCC cells by increasing LC3-II conversion and the expression of Beclin1 and ATG5, while decreasing the expression of p62/SQSTM1. Autophagy inhibitors (3-methyladenine and chloroquine) enhanced CPT-induced proliferation and apoptosis, suggesting that CPT-induced autophagy may protect HCC cells against cell death. Furthermore, CPT was found to inhibit the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Interestingly, activation of PI3K by insulin-like growth factor-I inhibited CPT-induced apoptosis and autophagy, suggesting that the PI3K/AKT/mTOR signaling pathway is involved in both CPT-induced apoptosis and autophagy. Finally, CPT was found to inhibit the growth of Huh7 xenograft tumors. In conclusion, we first demonstrated the antitumor effects of CPT in Huh7 and MHCC97-H cells, both and . We elucidated the potential antitumor mechanism of CPT, which involved inducing apoptosis and autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway. Our findings may provide valuable insights into the clinical application of CPT, serving as a potential candidate therapeutic agent for HCC treatment.
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http://dx.doi.org/10.3389/fphar.2020.01264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438559PMC
August 2020

Circadian differences in emergence from volatile anaesthesia in mice: involvement of the locus coeruleus noradrenergic system.

Br J Anaesth 2020 10 15;125(4):548-559. Epub 2020 Aug 15.

Department of Anaesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background: Circadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied.

Methods: The minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MAC), and MAC for recovery of righting reflex (MAC) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (Time) and recovery of righting reflex (Time) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements.

Results: MAC, Time, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MAC was higher and Time was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice.

Conclusion: Our data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.
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http://dx.doi.org/10.1016/j.bja.2020.07.012DOI Listing
October 2020

Bioequivalence Study of Amitriptyline Hydrochloride Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Drug Des Devel Ther 2020 4;14:3131-3142. Epub 2020 Aug 4.

Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Purpose: This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug.

Materials And Methods: A randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC, AUC), the peak plasma concentration (C), the time to achieve C (T), and the elimination half-life (t). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs).

Results: The values of t and T for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of C, AUC, and AUC between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events.

Conclusion: This study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.
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http://dx.doi.org/10.2147/DDDT.S258173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414938PMC
August 2020

Acute continuous nocturnal light exposure decreases BSR under sevoflurane anesthesia in C57BL/6J mice: possible role of differentially spared light-sensitive pathways under anesthesia.

Am J Transl Res 2020 15;12(6):2843-2859. Epub 2020 Jun 15.

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei Province, China.

Brain responses to external stimuli such as light are preserved under general anesthesia. In nocturnal animals, acute light exposure can induce sleep, and acute dark can increase wakefulness. This study aims to investigate the effect of acute continuous nocturnal light exposure (ACNLE) on burst-suppression patterns under sevoflurane anesthesia using electroencephalogram (EEG) monitoring in mice. We set the initial sevoflurane dose to 2.0% and increased it by 0.5% every 20 min until it reached 4.0%. Burst-suppression ratio (BSR), EEG power and quantitative burst analysis were used to assess the effects of ACNLE on burst suppression patterns under sevoflurane anesthesia. Blood serum corticosterone measurement and c-Fos immunofluorescent staining of the suprachiasmatic nucleus (SCN) and ventrolateral preoptic nucleus (VLPO) were used to demonstrate the biological consequence induced by ACNLE. Compared to darkness, ACNLE caused significant changes in EEG power and decrease of BSR at 2.5%, 3.0% and 3.5% sevoflurane. ACNLE was also associated with an increase in burst duration and burst frequency as well as a decrease in burst maximum peak-to-peak amplitude and burst power in the beta (15-25 Hz) and gamma (25-80 Hz) bands. ACNLE increased the concentration of serum corticosterone and the expression of c-Fos in the SCN, while not changed c-Fos expression in the VLPO. These results demonstrated that ACNLE influences the BSR under sevoflurane anesthesia, possibly by activating light-sensitive nonvisual pathways including SCN and increasing of peripheral serum corticosterone levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344097PMC
June 2020

Downregulation of miR-133a contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish.

Chemosphere 2020 Jul 1;251:126610. Epub 2020 Apr 1.

Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China. Electronic address:

Trichloroethylene (TCE), a widely used organic solvent, is a common environmental pollutant. Increasing evidence indicates that maternal TCE exposure is associated with congenital cardiac defects, but the underlining mechanisms remain largely unknown. In this study, we revealed that TCE exposure significantly induced heart defects and dysfunctions in zebrafish embryos. Heart tissues were dissected and subjected to high throughput sequencing and qPCR to identify differentially expressed miRNAs and mRNAs. The effects of miRNA were further verified by microinjection of antagomir or agomir. Reactive Oxygen Species (ROS) and cell proliferation were measured by using dichlorodihydrofluorescein diacetate (DCFH-DA) and EdU staining, respectively. Our results showed that 19 miRNAs were downregulated whereas 48 miRNAs were upregulated in the heart of zebrafish embryos. The downregulation of miR-133a and the upregulation of miR-182 were further validated. Moreover, we found that miR-133a agomir significantly alleviated the TCE-induced heart defects while miR-133a antagomir mimicked the toxic effect of TCE on heart development. Furthermore, miR-133a agomir significantly counteracted TCE-induced ROS production and excessive cell proliferation in the heart of zebrafish embryos. In conclusion, our results indicate that miR-133a mediates TCE-induced ROS generation, leading to excessive cell proliferation and heart defects.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126610DOI Listing
July 2020

Resveratrol protects against PM2.5-induced heart defects in zebrafish embryos as an antioxidant rather than as an AHR antagonist.

Toxicol Appl Pharmacol 2020 07 5;398:115029. Epub 2020 May 5.

Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China. Electronic address:

Resveratrol (RSV), a natural polyphenolic compound commonly found in food, has antioxidant and aryl hydrocarbon receptor (AHR) antagonist effects. We have recently demonstrated that AHR mediated reactive oxygen species (ROS) generation contributes to the cardiac developmental toxicity of ambient fine particle matter (PM2.5). Thus, we hypothesized that RSV protects against the cardiac developmental toxicity of PM2.5 by inhibiting ROS generation and AHR activity. To test this concept, we exposed zebrafish embryos to extractable organic matter (EOM) from PM2.5 in the presence or absence of RSV. We found that RSV significantly counteracted EOM-induced cardiac malformations in zebrafish embryos. The EOM-induced ROS production, DNA damage and apoptosis in the heart of zebrafish embryos were also counteracted by RSV supplementation. Furthermore, RSV attenuated EOM-induced changes in the expression of genes involved in cardiac development (nkx2.5, sox9b, axin2), oxidative stress (nrf2a, nrf2b, gstp1, gstp2, sod1, sod2, cat) and apoptosis (p53, bax). However, RSV did not suppress EOM-induced AHR activity. In conclusion, our data indicates that RSV protects against the PM2.5-induced heart malformations by inhibiting oxidative stress rather than through AHR antagonism.
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http://dx.doi.org/10.1016/j.taap.2020.115029DOI Listing
July 2020

Anti-TGF-β attenuates tumor growth via polarization of tumor associated neutrophils towards an anti-tumor phenotype in colorectal cancer.

J Cancer 2020 14;11(9):2580-2592. Epub 2020 Feb 14.

Medical Science Laboratory, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P. R. China 545005.

Tumor associated neutrophils (TANs) play important roles in the progress of CRC. Since tumor microenvironments could influence the phenotypes of TANs, altering the tumor microenvironment to polarize the phenotype of TANs may be a new strategy for tumor treatment. This study aims to investigate the effect of anti-TGF-β on the polarization of TANs from a pro-tumor phenotype towards an anti-tumor phenotype in CRC. In this work, CRC patients had more infiltration of TANs and higher expression of TGF-β in CRC tissue when compared with the controls. , SW480 cells were co-cultured with primed neutrophils, which simulated the TANs in the tumor microenvironment, and TGF-β was blocked by anti-TGF-β (1D11) in order to polarize TANs. Anti-TGF-β treatment increased the cytotoxicity of TANs and decreased the metastatic chemoattractants secreted by TANs, and ultimately increased the apoptosis of CRC cells significantly while remarkably suppressing the migration of tumor cells. The changes of signaling pathways in the TANs and tumor cells were explored. The results showed that anti-TGF-β attenuated CRC may be partly mediated by suppression of PI3K/AKT signaling pathways in TANs and partly mediated by suppression of TGF-β/Smad signaling pathways in tumor cells. Furthermore, the tumor in the mice treated with 1D11 was obviously smaller and had reverse tumorigenesis compared with the controls, while neutrophil depletion reduced the anti-tumor effect of 1D11. Our data suggest that anti-TGF-β attenuates tumor growth via the polarization of TANs to an anti-tumor phenotype in CRC, which provides new strategies for CRC treatment.
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http://dx.doi.org/10.7150/jca.38179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066015PMC
February 2020

Corrigendum to "Wogonin inhibits LPS-induced vascular permeability via suppressing MLCK/MLC pathway" [Vascular pharmacology 72 (2015) 43-52].

Vascul Pharmacol 2020 May - Jun;128-129:106612. Epub 2020 Mar 11.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.

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http://dx.doi.org/10.1016/j.vph.2019.106612DOI Listing
March 2020

Exhaustive Exercise Induces Gastrointestinal Syndrome through Reduced ILC3 and IL-22 in Mouse Model.

Med Sci Sports Exerc 2020 08;52(8):1710-1718

Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, PR CHINA.

Purpose: This study was to investigate the mechanism of intestinal physical and immune barriers in the occurrence of high-intensive exercise-induced gastrointestinal symptoms.

Methods: An overtraining model of male C57BL/6 mice was established by running-to-exhaustive exercise. Then, the mice were sacrificed, and a series of evaluation indicators, including the routine blood analysis as well as histological examinations, inflammatory factors, ultrastructure observation, and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors tumor necrosis factor α, interferon-γ, and interleukin (IL)-6 as well as the tight junction and adherence junction proteins ZO-1, Occludin, Claudin-1, and E-cadherin were measured, respectively. Furthermore, the mRNA level of IL-22 and the proportion of ILC3 and IL-22 produced in CD4 T cells in lamina propria lymphocytes (LPL) were analyzed by flow cytometry. Besides, the liver glycogen and the expressions of sirtuins-3 and hypoxia-inducible factor-1a, which were associated with the intestinal metabolism phenotype, were analyzed by Western blotting.

Results: Exhaustive exercise induced a disrupted intestinal barrier integrity, an aggravated intestinal inflammation, increased gut permeability, and the reduced IL-22 mRNA level. Compared with the nonexercise mice, the IL-22 produced in LPL was reduced followed by exhaustive exercise, whereas the proportion of IL-22 produced in CD4 T cells was still unchanged. Significantly, the proportion of ILC3 in the LPL was decreased obviously, including the NCR ILC3. Furthermore, the intestinal metabolism phenotype assessment showed lower liver glycogen and blood glucose as well as higher blood lactic acid and hypoxia-inducible factor-1a, respectively.

Conclusions: The data indicated that the acute high-intensity running-induced gastrointestinal symptom is closely associated with a reduced percentage of ILC3 and IL-22 level in the LPL, possibly due to the glycogen exhaustion and intestinal mucosa hypoperfusion.
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http://dx.doi.org/10.1249/MSS.0000000000002298DOI Listing
August 2020

Fast, 3D Isotropic Imaging of Whole Mouse Brain Using Multiangle-Resolved Subvoxel SPIM.

Adv Sci (Weinh) 2020 Feb 3;7(3):1901891. Epub 2019 Dec 3.

School of Optical and Electronic Information-Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074 China.

The recent integration of light-sheet microscopy and tissue-clearing has facilitated an important alternative to conventional histological imaging approaches. However, the in toto cellular mapping of neural circuits throughout an intact mouse brain remains highly challenging, requiring complicated mechanical stitching, and suffering from anisotropic resolution insufficient for high-quality reconstruction in 3D. Here, the use of a multiangle-resolved subvoxel selective plane illumination microscope (Mars-SPIM) is proposed to achieve high-throughput imaging of whole mouse brain at isotropic cellular resolution. This light-sheet imaging technique can computationally improve the spatial resolution over six times under a large field of view, eliminating the use of slow tile stitching. Furthermore, it can recover complete structural information of the sample from images subject to thick-tissue scattering/attenuation. With Mars-SPIM, a digital atlas of a cleared whole mouse brain (≈7 mm × 9.5 mm × 5 mm) can readily be obtained with an isotropic resolution of ≈2 µm (1 µm voxel) and a short acquisition time of 30 min. It provides an efficient way to implement system-level cellular analysis, such as the mapping of different neuron populations and tracing of long-distance neural projections over the entire brain. Mars-SPIM is thus well suited for high-throughput cell-profiling phenotyping of brain and other mammalian organs.
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http://dx.doi.org/10.1002/advs.201901891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001627PMC
February 2020

The evaluation of seven age-related CpGs for forensic purpose in blood from Chinese Han population.

Forensic Sci Int Genet 2020 05 24;46:102251. Epub 2020 Jan 24.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. Electronic address:

Age prediction of biological samples is one of the important tasks in forensic DNA phenotyping, and DNA methylation is regarded as the most promising biomarker for forensic age prediction. To date, numerous CpG sites have been reported to be age-related based on the changes in methylation. In this study, seven age-related CpG (AR-CpG) sites, cg02228185 (ASPA), cg09809672 (EDARADD), cg19283806 (CCDC102B), cg04208403 (ZNF423), chr17: 44,390,358 of GRCh38/hg38 (ITGA2B), cg14361627 (KLF14), and cg06639320 (FHL2), were selected and analyzed in 310 blood samples using a multiplex methylation SNaPshot assay to evaluate the value of selected AR-CpGs in age prediction in blood from Chinese Han population. The study confirmed the correlation of all the investigated markers with human age, and the correlation of cg19283806 with age is the highest while cg04208403 is the lowest in the Chinese Han population. Two different age prediction models, stepwise regression and support vector regression (SVR), were established based on the methylation SNaPshot data using 230 blood samples from donors aged 2-86 years old. The stepwise regression model included six AR-CpGs (except cg09809672) and enabled age prediction with R = 0.85, mean absolute deviation (MAD) = 4.22, while the SVR model enabled age prediction with R = 0.86, MAD = 4.01. An independent set of 80 samples was used to test the two models' performance and the prediction MAD for the validation set was 4.71 and 4.56 for the stepwise regression and SVR models, respectively. The number of correct predictions for ±5 years achieved a high level of 67.50 % and 73.75 %, respectively for the stepwise regression and SVR models. In general, the SVR model was superior to the linear regression model in age prediction. These results suggest that these seven CpG sites would be useful for age prediction in blood samples from the Chinese Han population.
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http://dx.doi.org/10.1016/j.fsigen.2020.102251DOI Listing
May 2020