Publications by authors named "Ji Wang"

822 Publications

Differential expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma.

Oncol Rep 2021 May 31;45(5). Epub 2021 Mar 31.

Cancer Research Center, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China.

Disruption in mucins (MUCs) is involved in cancer development and metastasis and is thus used as a biomarker. Non‑small cell lung carcinoma (NSCLC) is characterized by heterogeneous genetic and epigenetic alterations. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the two primary subtypes of NSCLC that require different therapeutic interventions. Here, we report distinct expression and epigenetic alterations in mucin 22 (), a new MUC family member, in LUSC vs. LUAD. In lung cancer cell lines and tissues, was downregulated in LUSC () but upregulated in LUAD () with co‑expression of . The aberrant expression of was inversely correlated with its promoter hypermethylation in LUSC and hypomethylation in LUAD cells and tissues, respectively. Decreased expression in NSCLC cell lines was restored upon treatment with epigenetic modifiers 5‑aza‑2'‑deoxycytidine (5‑Aza) or trichostatin A (TSA), accompanied by reduction in global protein level of histone deacetylase 1 (HDAC1) but increased enrichment of histone H3 lysine 9 acetylation (H3K9ac) specifically in the promoter in the SK‑MES‑1 cell line. knockdown increased the growth and motility of lung cancer cells and an immortalized human bronchial epithelial BEAS‑2B cell line via NF‑κB activation. Clinically, in LUSC and in LUAD were shown to be indicators of unfavorable overall survival for patients with early cancer stages. Our study reveals that changes in expression due to epigenetic alterations in NSCLC may have important biological significance and prognostic potential in LUSC when compared to LUAD. Thus, expression and epigenetic alterations may be used for molecular subtyping of NSCLC in precision medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2021.8029DOI Listing
May 2021

Decreased cellulose-degrading enzyme activity causes pod hardening of okra (Abelmoschus esculentus L. Moench).

Plant Physiol Biochem 2021 Mar 20;162:624-633. Epub 2021 Mar 20.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs, Northeast Agricultural University, Harbin, 150030, China; College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, 150030, China. Electronic address:

Okra (Abelmoschus esculentus L. Moench) is an important tropical and subtropical crop species, but okra pods age rapidly after they meet harvest standards. The underlying mechanisms by which okra pods harden are unclear. In this study, we determined the cellulose and lignin contents of 'Chaowuxing' okra pods from 4 to 14 days postanthesis (DPA). Based on the histochemical staining of okra fruit during the active period of cellulose accumulation, we found that the hardening of okra fruit is due to the rapid accumulation of cellulose in the cell walls of vascular cells in the pulp. We used RNA-sequencing (RNA-Seq) analyses to investigate the genes that regulate okra fruit aging. Transcriptome sequencing data showed that after 7 DPA, expression of the cellulose synthase gene (CesA) decreased with time. In addition, expression of the gene encoding the first functional enzyme involved in cellulose hydrolysis (endoglucanase) also decreased, but its rate of decrease was much faster than that of the CesA. The quantitative real-time PCR (qRT-PCR) results were consistent with the RNA-Seq data. Accordingly, we speculate that the accumulation of cellulose during okra pod hardening occurs via a reduction in cellulose hydrolysis activity. The above results suggest that thickening of the cell wall caused by a significant increase in cellulose content in the vascular bundles causes okra hardening. The accumulation of cellulose is not directly achieved via increased expression of CesA but rather indirectly via decreased hydrolysis of cellulose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plaphy.2021.03.035DOI Listing
March 2021

Cell Fragment Formation, Migration, and Force Exertion on Extracellular Mimicking Fiber Nanonets.

Adv Biol (Weinh) 2021 Mar 24:e2000592. Epub 2021 Mar 24.

Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA, 24061, USA.

Cell fragments devoid of the nucleus play an essential role in intercellular communication. Mostly studied on flat 2D substrates, their origins and behavior in native fibrous environments remain unknown. Here, cytoplasmic fragments' spontaneous formation and behavior in suspended extracellular matrices mimicking fiber architectures (parallel, crosshatch, and hexagonal) are described. After cleaving from the parent cell body, the fragments of diverse shapes on fibers migrate faster compared to 2D. Furthermore, while fragments in 2D are mostly circular, a higher number of rectangular and blob-like shapes are formed on fibers, and, interestingly, each shape is capable of forming protrusive structures. Absent in 2D, fibers' fragments display oscillatory migratory behavior with dramatic shape changes, sometimes remarkably sustained over long durations (>20 h). Immunostaining reveals paxillin distribution along fragment body-fiber length, while Forster Resonance Energy Transfer imaging of vinculin reveals mechanical loading of fragment adhesions comparable to whole cell adhesions. Using nanonet force microscopy, the forces exerted by fragments are estimated, and peculiarly small area fragments can exert forces similar to larger fragments in a Rho-associated kinase dependent manner. Overall, fragment dynamics on 2D substrates are insufficient to describe the mechanosensitivity of fragments to fibers, and the architecture of fiber networks can generate entirely new behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adbi.202000592DOI Listing
March 2021

Graphene-coated double D-type low loss optical fiber modulator.

Opt Express 2021 Jan;29(2):2025-2036

A graphene-coated double D-type low loss all-fiber modulator is proposed. The modulator is improved on the basis of standard fiber. Only the cladding is processed without grinding the original core structure. The upper and lower cladding are cut same distance. This can ensure that the mode field does not deviate in one direction, so that most of the mode field is still tied to the core, which greatly reduces the device loss. The existence of the double graphene layer can also ensure a very excellent modulation efficiency. The calculation results show that the mode loss of our proposed dual-D modulator under X polarization is 0.125 dB/mm, and the mode field mismatch loss is 0.25%. The mode loss in Y polarization is 0.033 dB/mm, and the mode field mismatch loss is 0.32%. When the modulation voltage is 5 V, the modulation depth is 78.4% under the condition of five-layer graphene, while the modulation speed can reach 15.38 GHz. Besides maintaining low modulation voltage and higher modulation efficiency, this structure makes full use of the advantages of good fiber coupling, and will be widely used in future fiber communications and all-fiber systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.413619DOI Listing
January 2021

Cancer stage-dependent alterations in cell-free DNA in patients with colorectal cancer.

J BUON 2021 Jan-Feb;26(1):109-115

Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China.

Purpose: Cell-free DNA (cfDNA) in plasma is a useful resource for liquid biopsy. The concentration and integrity of cfDNA may be clinical informative for detecting and predicting cancer progression.

Methods: Plasma from 40 healthy controls and 90 colorectal cancer patients was assessed. qPCR targeting the arithmetic-logic unit (Alu) repeats were performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated by the ratio of the long to the short fragments of amplified Alu repeats.

Results: cfDNA concentration was significantly higher in the patients than that in healthy controls. Patients with stage III colorectal cancer showed no significant difference in their cfDNA levels as compared with the healthy controls. In colorectal cancer, cfDNA level of stage IV patients was higher than that of stage 0-III (p=0.049). The DNA integrity was significantly lower in patients with stage I and II cancer than that in normal controls (p=0.007, 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with colorectal cancer from normal controls had an area under the curve of 0.672 (95%CI, 0.572 to 0.772) and cfDNA concentration increased within 21 days following surgery and dropped by 3 months after surgery.

Conclusion: Concentration of cfDNA is a promising molecular marker for assessing colorectal cancer progression. Both the cfDNA concentration and its integrity are highly variable. Some cancer stage dependent changes were observed, which warrants further investigation with more patients included.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

Molecular dynamics investigation on the interaction of human angiotensin-converting enzyme with tetrapeptide inhibitors.

Phys Chem Chem Phys 2021 Mar 12;23(11):6685-6694. Epub 2021 Mar 12.

College of Food Science and Engineering, National Engineering Laboratory of Wheat and Corn Deep Processing, Jilin Agricultural University, Changchun 130118, Jilin, People's Republic of China.

Angiotensin-converting enzyme (ACE) is a well-known zinc metalloenzyme whose physiological functions are vital to blood pressure regulation and management of hypertension. The development of more efficient peptide inhibitors is of great significance for the prevention and treatment of hypertension. In this research, molecular dynamics (MD) simulations were implemented to study the specific binding mechanism and interaction between human ACE (hACE) and tetrapeptides, YIHP, YKHP, YLVR, and YRHP. The calculation of relative binding free energy on the one hand verified that YLVR, an experimentally identified inhibitor, has a stronger inhibitory effect and, on the other hand, indicated that YRHP is the "best" inhibitor with the strongest binding affinity. Inspection of atomic interactions discriminated the specific binding mode of each tetrapeptide inhibitor with hACE and explained the difference of their affinity. Moreover, in-depth analysis of the MD production trajectories, including clustering, principal component analysis, and dynamic network analysis, determined the dynamic correlation between tetrapeptides and hACE and obtained the communities' distribution of a protein-ligand complex. The present study provides essential insights into the binding mode and interaction mechanism of the hACE-peptide complex, which paves a path for designing effective anti-hypertensive peptides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cp00172hDOI Listing
March 2021

Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism.

Front Genet 2020 16;11:623584. Epub 2021 Feb 16.

Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving "TGF-beta signaling pathway," "Notch signaling pathway," "MAPK signaling pathway," "long term depression," "thyroid hormone signaling pathway," etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.623584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928284PMC
February 2021

Numerical Simulation on Pulsed Laser Ablation of the Single-Crystal Superalloy Considering Material Moving Front and Effect of Comprehensive Heat Dissipation.

Micromachines (Basel) 2021 Feb 23;12(2). Epub 2021 Feb 23.

Labortary of Advanced Materials and Processing, PKU-HKUST ShenZhen-HongKong Institution, Shenzhen 518057, China.

In the present research, an iterative numerical model is proposed to investigate the nanosecond pulsed laser ablation (PLA) mechanism of the DD6 single-crystal superalloy. In the numerical model, two subroutines are introduced to trace the moving boundary and update the thermal load. The iteration between the main governing equation and the two subroutines enables the PLA numerical simulation to consider material moving front and effect of comprehensive heat dissipation including thermal convection and radiation. The basic experimental results exhibit a good agreement with simulation results which indicates the good accuracy of the simulation model. Therefore, the PLA mechanism of the DD6 single-crystal superalloy is studied base on the improved iterative model, which indicates the evolution of temperature field, ablation zone morphology, formation of recast layer and heat-affected zone are closely related with time. The temperature of the laser spot center increases sharply at the first stage, reaching a maximum value of 5252 K, and then decreases gradually. The thermal dissipation postpones the ablation rate but promotes the formation of a recast layer and heat-affected zone. Due to the evaporation and thermal dissipation, the depth of the molten layer exhibits two rapid increasing stages. The comprehensive analysis of the PLA processing by the improved simulation model helps the understanding of the intrinsic mechanism, which would contribute to the further optimizing parameters of PLA fabrication of the DD6 single-crystal superalloy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mi12020225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926763PMC
February 2021

Unveiling the strong dependence of the -relaxation dispersion on mixing thermodynamics in binary glass-forming liquids.

Phys Chem Chem Phys 2021 Mar;23(9):5644-5651

State Key Lab of Metastable Materials Science and Technology, and School of Materials Science and Engineering, Yanshan University, Qinhuangdao, Hebei 066004, China.

Structural α-relaxation dispersion in binary molecular glass forming mixtures with distinct mixing enthalpy ΔHmix was investigated using enthalpic and dielectric relaxation measurements across the entire composition range. This study focused on the dependence of the relaxation dispersion on the mixing thermodynamics by determining the non-exponential exponent β, and its composition dependence. The β values determined by the enthalpic and dielectric relaxations agree well. Remarkably, it is found that the systems with positive enthalpy of mixing (exothermic, ΔHmix >0) have positive deviations in the composition dependence of β from the linear averaging of the two β values of the pure components, while negative deviations are observed for the systems with negative enthalpy of mixing (endothermic, ΔHmix <0). Furthermore, the relation between the non-exponential behaviors and entropy of mixing is discussed, revealing that the positive or negative deviation of β in its composition dependence on mixing is accompanied by the same sign of the excess entropy of mixing relative to the ideal one.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp06358dDOI Listing
March 2021

Effect of vitamin E and alpha lipoic acid on intestinal development associated with wooden breast myopathy in broilers.

Poult Sci 2021 Mar 23;100(3):100952. Epub 2020 Dec 23.

Department of Animal Sciences, The Ohio State University, Wooster, OH 44691. Electronic address:

Intestinal development is closely associated with inflammatory wooden breast (WB) myopathy. Vitamin E (VE) and alpha lipoic acid (ALA) with antioxidant and anti-inflammatory effects were used independently and in combination to evaluate their effects on intestinal developmental changes in ileal morphology and expression of genes related with gut nutrient transport, structure, and inflammation in broilers during the first 3 wk posthatch. A total of 160 newly hatched Ross 708 broiler chicks were randomly assigned into a control and 3 dietary treatments with 10 replicates of 4 birds each. Supplementation of VE (160 mg/kg) and ALA (500 mg/kg) independently and in combination were fed during the first 3 wk. At 1, 2, and 3 wk of age, one chick from each pen was harvested. Plasma VE concentration and ileal morphology were determined. Gene expression was measured by real-time quantitative PCR. Broilers in VE and combination of ALA and VE group had higher plasma VE concentration than the control and ALA group at 1, 2, and 3 wk of age (P < 0.01). All dietary treatments increased ileal villus height at 1 wk of age (P < 0.01) and decreased intraepithelial lymphocytes at 3 wk of age compared to the control (P ≤ 0.05). Combination of VE and ALA increased collagen type IV alpha 1 chain expression (P ≤ 0.05) and improved basement membrane structure indicating increased gut basement membrane integrity at 2 and 3 wk of age compared to the control. Expression of lipopolysaccharide-induced tumor necrosis factor-alpha factor associated with inflammation was decreased in all dietary treatments at 3 wk of age compared to the control (P < 0.01). Ileal morphology and gene expression were closely correlated with breast muscle morphology and gene expression. These results suggest that VE and ALA especially when they were combined in the diet had positive effects on mitigating intestinal inflammation and improving nutrient transport beginning at 1 wk of age, which is likely critical in reducing the severity of WB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2020.12.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936179PMC
March 2021

Silica nanoparticles inducing the apoptosis via microRNA-450b-3p targeting MTCH2 in mice and spermatocyte cell.

Environ Pollut 2021 Feb 25;277:116771. Epub 2021 Feb 25.

Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. Electronic address:

Silica nanoparticles (SiNPs) could cause reproductive toxicity. The role of miRNAs in reproductive toxicity induced by SiNPs is still ambiguous. The present study was designed to investigate the role of miRNA-450 b-3p. In vivo, 40 male mice were randomly divided into control, and 20 mg/kg SiNPs groups. The mice were administrated by tracheal perfusion for 35 days. In vitro, spermatocyte cells (GC-2spd cells) were divided into 6 groups: 0 μg/mL SiNPs groups, 5 μg/mL SiNPs groups, 5 μg/mL SiNPs + miRNA-450 b-3p mimic transfection group, 5 μg/mL SiNPs + miRNA-450 b-3p mimic negative control group, 5 μg/mL SiNPs + miRNA-450 b-3p inhibitor transfection group, and 5 μg/mL SiNPs + miRNA-450 b-3p inhibitor negative control group. The results showed that SiNPs induced the apoptosis of spermatogenic cells, decreased the quantity and quality of the sperm, reduced the expressions of miR-450 b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, the mimic of miRNA-450 b-3p reversed the decrease of viability and the increase of apoptosis rate and significantly antagonized the expression enhancements of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3 induced by SiNPs, while inhibitor of miRNA-450 b-3p further promoted the effects induced by SiNPs. The result suggested that SiNPs could inhibit the miR-450 b-3p expression resulting in activation of the mitochondrial apoptosis signaling pathways by regulating the MTCH2 in the spermatocyte cells and, thus, induce the reproductive toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.116771DOI Listing
February 2021

Training model for the intraluminal continuous suturing technique for microvascular anastomosis.

Sci Rep 2021 Mar 1;11(1):4862. Epub 2021 Mar 1.

Department of Neurosurgery, Affiliated Hospital of Qinghai University, Xining, 810000, China.

Microvascular anastomosis is a critical procedure in cerebral bypass surgeries. In some rare cases, the extraluminal interrupted technique is not optimal because the vessels are immobile and cannot be rotated, and anastomosis can be performed effectively through the intraluminal continuous suturing technique. The authors reported the application of the intraluminal continuous suturing technique in microanastomosis training with silicone tube, rat's common iliac arteries and abdominal aorta. A silicone tube with a diameter of 1.5 mm was used to practice microanastomosis in intraluminal continuous suturing technique. Then the technique was applied in side-to-side, end-to-side anastomoses of common iliac arteries and the end-to-end abdominal aorta anastomoses of rat. The suturing time and patency rates were compared with an alternative intraluminal continuous suturing technique and one-way-up interrupted suturing technique in silicone tube and rat vessel anastomoses. The intraluminal continuous suturing technique could be gained through practicing with silicone tube, and the technique has also been demonstrated effective in side-to-side, end-to-side anastomoses of common iliac arteries of rat and the abdominal aorta end-to-end anastomoses. In all the animal experimental groups with different suturing techniques, there was no difference between the patency rates, all the immediate patency rate was 100%. There was no significant suturing time difference between the two intraluminal continuous suturing techniques, but the two intraluminal continuous suturing techniques were faster than the interrupted technique. The intraluminal continuous suturing technique described in the study could be used as an efficient method for side-to-side, end-to-side and end-to-end anastomosis, especially under the situation the posterior wall of the anastomosis could not be rotated. Proficiency of the technique could be achieved through practicing in laboratory with silicone tube and live animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84619-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921418PMC
March 2021

Long Non-coding RNAs and mRNAs Expression Profiles of Monocyte-Derived Dendritic Cells From PBMCs in AR.

Front Cell Dev Biol 2021 9;9:636477. Epub 2021 Feb 9.

National Institute of TCM Constitution and Preventive Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Objective: The objective of this study is to explore the long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles of monocyte-derived dendritic cells (DCs) obtained from peripheral blood mononuclear cells (PBMCs). DCs are known to play a major role in the regulating function of allergic rhinitis (AR).

Methods: PBMCs were separately isolated from the human peripheral blood of patients with AR and normal person (NP). The mixed lymphocyte reaction (MLR) assay was used to evaluate the function of DCs. Flow cytometry was used to determine the immune regulatory function of immature DCs (imDCs) and mature DCs (mDCs). lncRNAs and mRNAs in the NP group (DCs isolated from NP) and the test group (DCs isolated from patients with AR) were identified via chip technology and bioinformatic analyses. Moreover, bioinformatic analyses were employed to identify the related biological functions of monocyte-derived DCs and construct the functional networks of lncRNAs and mRNAs that are differentially expressed (DE) in imDCs and mDCs.

Results: MLR was significantly higher in the mDCs group than that in the imDCs group. CD14 was highly expressed in imDCs, whereas HLA-DR, CD80, and CD86 were highly expressed in mDCs ( < 0.001). We identified 962 DE lncRNAs and 308 DE mRNAs in the imDCs of NP and patients with AR. Additionally, there were 601 DE lncRNAs and 168 DE mRNAs in the mDCs in the NP and test groups. Quantitative RT-qPCR was used to study the significant fold changes of lncRNAs and mRNAs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found 16 significant regulated pathways in imDCs and 10 significant regulated pathways in mDCs, including the phagosome, cell adhesion signaling pathway, and inflammatory mediator regulation of TRP channels pathway.

Conclusion: Our research studied the lncRNA and mRNA expression profiles of monocyte-derived DCs and demonstrated the functional networks that are involved in monocyte-derived DCs-mediated regulation in AR. These results provided possible molecular mechanisms of monocyte-derived DCs in the immunoregulating function and laid the foundation for the molecular therapeutic targets of AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.636477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906227PMC
February 2021

Therapeutic targeting of DGKA-mediated macropinocytosis leads to phospholipid reprogramming in Tuberous Sclerosis Complex.

Cancer Res 2021 Feb 16. Epub 2021 Feb 16.

Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School

Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease affecting primarily women and is the primary lung manifestation of tuberous sclerosis complex (TSC). In LAM, biallelic loss of TSC1/2 leads to hyperactivation of mTORC1 and inhibition of autophagy. To determine how the metabolic vulnerabilities of TSC2-deficient cells can be targeted, we performed a high throughput screen utilizing the "Repurposing" library at the Broad Institute, with or without the autophagy inhibitor chloroquine. Ritanserin, an inhibitor of diacylglycerol kinase alpha (DGKA), was identified as a selective inhibitor of proliferation of Tsc2-/- MEFs, with no impact on Tsc2+/+ MEFs. DGKA is a lipid kinase that metabolizes diacylglycerol (DAG) to phosphatidic acid (PA), a key component of plasma membranes. PA levels were increased 5-fold in Tsc2-/- MEFs compared to Tsc2+/+ MEFs, and treatment of Tsc2-/- MEFs with ritanserin led to depletion of PA as well as rewiring of phospholipid metabolism. Macropinocytosis is known to be upregulated in TSC2-deficient cells. Ritanserin decreased macropinocytic uptake of albumin, limited the number of lysosomes, and reduced lysosomal activity in Tsc2-/- MEFs. In a mouse model of TSC, ritanserin treatment decreased cyst frequency and volume, and in a mouse model of LAM, genetic downregulation of DGKA prevented alveolar destruction and airspace enlargement. Collectively, these data indicate that DGKA supports macropinocytosis in TSC2-deficient cells to maintain phospholipid homeostasis and promote proliferation. Targeting macropinocytosis with ritanserin may represent a novel therapeutic approach for the treatment of TSC and LAM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-2218DOI Listing
February 2021

Walnut-Derived Peptide Activates PINK1 via the NRF2/KEAP1/HO-1 Pathway, Promotes Mitophagy, and Alleviates Learning and Memory Impairments in a Mice Model.

J Agric Food Chem 2021 Mar 16;69(9):2758-2772. Epub 2021 Feb 16.

College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, P. R. China.

Mitophagy has a pivotal protective function in the pathogenesis of neurological disorders. However, the mechanism of its modulation remains elusive, especially in PINK1-mediated mitophagy. Here, we investigated the neuroprotective effects of a walnut-derived peptide, YVLLPSPK, against scopolamine-induced cognitive deficits in mice and explored the underlying PINK1-mediated mitophagy mechanisms in HO-treated HT-22 cells. Using the Morris water maze, we showed that YVLLPSPK relieved the cognitive deficiency by alleviating oxidative stress. Mitochondrial morphology was observed in mice hippocampal tissues using transmission electron microscopy (TEM). Both Western blot and immunofluorescence analysis illustrated YVLLPSPK promoted the expression of mitophagy-related proteins and activated the NRF2/KEAP1/HO-1 pathway. Subsequently, an NRF2 inhibitor (ML385) was used to verify the contribution of the YVLLPSPK-regulated NRF2/KEAP1/HO-1 pathway in PINK1-mediated mitophagy in HO-treated HT-22 cells. These data suggested that YVLLPSPK improved learning and memory in scopolamine-induced cognitive-impaired mice through a mechanism associated with PINK1-mediated mitophagy via the NRF2/KEAP1/HO-1 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07546DOI Listing
March 2021

Species Identification in the - Species Complex (Ericaceae).

Front Plant Sci 2021 28;12:608964. Epub 2021 Jan 28.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education and State Key Lab of Hydraulics and Mountain River Engineering, College of Life Sciences, Sichuan University, Chengdu, China.

Delimitating species boundaries is the primary aim of biological classification and could be critical for evaluating the evolving process of species and conserving biodiversity. is an iconic group with an extraordinary diversity in southwest China. However, it remains unknown whether the recorded species therein comprise independently evolving lineages or artificially delimitated morphological entities. In this study, we carried out species delimitation of four species in the - species complex based on morphological analyses and population genetic data from nuclear simple sequence repeats (SSR) markers. We randomly selected a total of 105 specimens of different individuals identified as four species across their distributional ranges to examine the statistically distinct phenotypic clusters based on 19 morphological traits. Similarly, we genotyped 55 individuals of four species from 21 populations using 15 SSR markers. The morphological analyses sorted and the other three species into two different phenotypic clusters. The genetic clusters were consistent with the morphological clusters. However, we also recovered the third genetic cluster, comprising six populations and containing the admixed genetic compositions of the other two distinct genetic clusters. This hybrid group was morphologically similar to the typical (including the samples from its type specimen locality and both and ) but with more genetic ancestry from . Based on our findings, we identify two distinct species and one putative hybrid group due to introgression in the species complex. We propose to merge and into based on genetic compositions and our morphological analyses. The hybrid group inferred from our findings, however, needs further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.608964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876077PMC
January 2021

Cardiovascular disease-specific mortality in 270,618 patients with non-small cell lung cancer.

Int J Cardiol 2021 May 10;330:186-193. Epub 2021 Feb 10.

Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. Electronic address:

Background: This study aimed to investigate the trend of cardiovascular disease (CVD)-specific mortality in patients with non-small cell lung cancer (NSCLC) and identify prognostic factors for CVD-specific death in stage NSCLC patients.

Methods: In this study, 270,618 NSCLC patients were collected from the Surveillance, Epidemiology, and End Results database. CVD- and NSCLC-specific cumulative mortality and proportion of death were calculated and graphically displayed to describe the probability of specific endpoints. Prognostic factors for CVD-specific mortality were evaluated by cause-specific hazard ratios (HR) with 95% confidence intervals (CI) using the competing risk model with non-cardiovascular death as competing risks.

Results: Among all competing causes of death, lung cancer resulted in the highest cumulative mortality, followed by CVDs and other causes. In the proportion of cause-specific death, heart diseases accounted for approximately 5.3% of the total death, only secondary to primary cancer. In all three stages, higher age, squamous cell carcinoma, and no-or-unknown chemotherapy and/or radiotherapy were associated with a higher risk of CVD-specific death, while surgery treatment seemed to be a protective factor. Female gender was statistically related to CVD-specific death in stage I and III patients with HRs of 0.84 (0.78-0.91) and 0.84 (0.77-0.93), respectively. Interestingly, right-sided laterality was correlated with lower CVD-specific mortality with HR of 0.82 (0.74-0.90) in stage III.

Conclusions: This study illustrated the historical trend of CVD-specific death in NSCLC patients and assesses potential prognostic risk factors, highlighting the involvement of cardio-oncology teams in cancer treatment to provide optimal comprehensive care and long-term surveillance for cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.02.025DOI Listing
May 2021

The inactivated vaccine of reassortant H3N2 canine influenza virus based on internal gene cassette from PR8 is safe and effective.

Vet Microbiol 2021 Mar 27;254:108997. Epub 2021 Jan 27.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, 510642, China; Guangdong Technological Engineering Research Center for Pet, Guangzhou, 510642, China. Electronic address:

Canine influenza (CI) is a contagious respiratory disease in dogs, which poses a threat to canine health. A safe, high-yield vaccine seed virus is critical for CI vaccine development. We developed a PR8-based reassortant H3N2 canine influenza virus (RT CIV) using the reverse genetic method and evaluated its yield in canine kidney epithelial (MDCK) cells, Vero cells, and specific pathogen-free (SPF) chicken embryos. Mice and dogs were infected with RT CIV, and the pathogenicity was evaluated. The viral titers of RT CIV increased in MDCK cells, Vero cells, and SPF chicken embryos; the HA yield in SPF chicken embryos increased 4-fold. However, RT CIV was not lethal to mice, and it showed similar virulence as wild-type CIV. RT CIV also showed minimal pathogenicity in dogs, which manifested as mild fever and rhinorrhea for the first two days post-infection. Thus, RT CIV carrying the internal gene cassette from PR8 showed almost no pathogenicity in dogs. And the reassortant virus inactivated vaccine could provide complete protection against H3N2 CIV. To our knowledge, this is the first report on the pathogenicity of PR8-based reassortant H3N2 CIV in dogs. These studies are relevant for developing a high-yield and safe CI vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetmic.2021.108997DOI Listing
March 2021

Critical amino acids in the TM2 of EAAT2 are essential for membrane-bound localization, substrate binding, transporter function and anion currents.

J Cell Mol Med 2021 Mar 1;25(5):2530-2548. Epub 2021 Feb 1.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Excitatory amino acid transporter 2 (EAAT2), the gene of which is known as solute carrier family 1 member 2 (SLC1A2), is an important membrane-bound transporter that mediates approximately 90% of the transport and clearance of l-glutamate at synapses in the central nervous system (CNS). Transmembrane domain 2 (TM2) of EAAT2 is close to hairpin loop 2 (HP2) and far away from HP1 in the inward-facing conformation. In the present study, 14 crucial amino acid residues of TM2 were identified via alanine-scanning mutations. Further analysis in EAAT2-transfected HeLa cells in vitro showed that alanine substitutions of these residues resulted in a decrease in the efficiency of trafficking/targeting to the plasma membrane and/or reduced functionality of membrane-bound, which resulted in impaired transporter activity. After additional mutations, the transporter activities of some alanine-substitution mutants recovered. Specifically, the P95A mutant decreased EAAT2-associated anion currents. The Michaelis constant (K ) values of the mutant proteins L85A, L92A and L101A were increased significantly, whereas R87 and P95A were decreased significantly, indicating that the mutations L85A, L92A and L101A reduced the affinity of the transporter and the substrate, whereas R87A and P95A enhanced this affinity. The maximum velocity (Vmax) values of all 14 alanine mutant proteins were decreased significantly, indicating that all these mutations reduced the substrate transport rate. These results suggest that critical residues in TM2 affect not only the protein expression and membrane-bound localization of EAAT2, but also its interactions with substrates. Additionally, our findings elucidate that the P95A mutant decreased EAAT2-related anion currents. Our results indicate that the TM2 of EAAT2 plays a vital role in the transport process. The key residues in TM2 affect protein expression in the membrane, substrate transport and the anion currents of EAAT2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.16212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933967PMC
March 2021

Supplementation of vitamin E and omega-3 fatty acids during the early posthatch period on intestinal morphology and gene expression differentiation in broilers.

Poult Sci 2021 Mar 23;100(3):100954. Epub 2020 Dec 23.

Department of Animal Sciences, The Ohio State University, Wooster OH 44691, USA. Electronic address:

Early posthatch nutrition is important for gut health. Vitamin E (VE) and omega-3 (n-3) fatty acids can improve gut health through antioxidative and anti-inflammatory effects. The objective of this study was to identify the effects of VE, n-3 fatty acids, and combination of both during the starter phase (0-10 d) or grower phase (11-24 d) on intestinal morphology and expression of genes associated with gut health. A total of 210 Ross 708 broilers were randomly assigned into 7 treatments with 10 replicates of 3 birds each. The control group was fed a corn-soybean meal-basal diet during the entire study (0-58 d). Supplementation of VE (200 IU/kg), n-3 fatty acids (n-6/n-3 ratio of 3.2:1), and combination of both were fed during the starter phase (0-10 d) or grower phase (11-24 d). All of the broilers were harvested at 58 d of age. Villus height, crypt depth, villus width, distance between villi, and number of intraepithelial lymphocytes were obtained. Expression of 21 genes was measured using NanoString analysis. Expression of solute carrier family 15 member 1 (P = 0.01) associated with peptide transport and mucin 2 (P = 0.03) related with intestinal mucus barrier was increased in the broilers supplemented with n-3 fatty acids in the grower diet compared with the control. Expression of solute carrier family 7 member 1 associated with amino acid transport was decreased in the group supplemented with n-3 fatty acids during the starter phase compared with the group supplemented with n-3 fatty acids (P = 0.01) or VE and n-3 fatty acids during the grower phase (P = 0.03). These data suggest that VE and n-3 fatty acids supplemented during the grower phase have a positive effect on improving nutrient transport with n-3 fatty acids supplementation in the grower diet showing the most beneficial effect. These findings can be used in the development of nutritional management strategies to improve broiler growth performance and meat quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2020.12.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936210PMC
March 2021

Identification of TSC2 mosaic mutation limited to cortical tuber with TSC targeted sequencing: a case report and literature review.

Childs Nerv Syst 2021 Jan 30. Epub 2021 Jan 30.

The Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University, No.399, Wanyuan Road, Shanghai, 201102, China.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, mainly in childhood presents epilepsy due to cortical tubers. TSC1/TSC2 pathogenic variants cannot be detected in regular molecular genetic testing in around 10-15% of TSC patients.

Methods: We analyzed TSC genes in both cortical tuber, blood and skin samples from a pediatric patient with refractory epilepsy.

Results: We found no germline mutations by whole-exome sequencing. Well in targeted sequencing of TSC1/2 data, we identified de novo mutations only in cortical tuber: TSC2 NM_000548.5: exon34:c.4183C>T (p.Gln1395*) in 3% of the alleles. No other TSC mutations were found in patient's blood and skin samples and her parents' blood sample.

Conclusion: Our case report found TSC2 mosaic mutations can be only limited to cortical tuber in patients with TSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00381-021-05059-1DOI Listing
January 2021

Critique of the Chinese dietary guidelines on the consumption of cooking oils.

Food Sci Nutr 2021 Jan 5;9(1):583-585. Epub 2020 Nov 5.

Laboratory of Animal Clinical Toxicology Department of Clinical Veterinary Medicine College of Veterinary Medicine Hunan Agricultural University Changsha Hunan Province China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.1979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802536PMC
January 2021

miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways.

J Orthop Surg Res 2021 Jan 20;16(1):71. Epub 2021 Jan 20.

Department of Orthopedics, Chongqing General Hospital, University of the Chinese Academy of Sciences, No. 312 Zhongshanyi Road, Yuzhong District, Chongqing, 400013, China.

Background: Bone neoplasms present poor prognosis due to recurrence and metastasis. Although the role microRNAs (miRNAs) in inhibiting growth and metastasis of bone neoplasms has been investigated, the underlying potential molecular mechanisms mediated by miRNA-128 (miR-218) for the invasiveness of bone neoplasms cells are still not completely understood. The purpose of this study was to identify the regulatory mechanisms of miR-218 in bone neoplasms cells.

Methods: Western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Counting Kit-8 assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, luciferase activity assay immunofluorescence, and immunohistochemistry were used to analyze the regulatory effects of miR-218 on bone neoplasms cells.

Results: Here, the results showed that transfection of miR-128 suppressed bone neoplasms cells proliferation, migration, and invasion. Genetic knockdown of miR-128 in bone neoplasms cells suppressed the activation of the Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signaling pathways. Activation of Wnt or EMT blocked miR-128-inhibited cells proliferation and migration in bone neoplasms cells. Exogenously introduced miR-128 markedly inhibited tumor regeneration in bone neoplasms xenograft models.

Conclusions: These results define a tumor-regulated function for miR-128 in bone neoplasms by down-regulation of the Wnt/β-catenin and EMT signal pathways, which provided a potential target for bone neoplasms gene therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-020-02164-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816476PMC
January 2021

Requirement of CRAMP for mouse macrophages to eliminate phagocytosed through an autophagy pathway.

J Cell Sci 2021 Mar 8;134(5). Epub 2021 Mar 8.

Laboratory of Cancer ImmunoMetabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA

Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild-type, WT) mouse macrophages increased their expression of cathelin-related antimicrobial peptide (CRAMP, encoded by ) after infection by viable or stimulation with inactivated and its product lipopolysaccharide (LPS), a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages for elimination of phagocytosed , with participation of autophagy-related proteins ATG5, LC3-II and LAMP-1, as well as for aggregation of the bacteria with p62 (also known as SQSTM1). This process was impaired in macrophages, resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate that CRAMP is a critical component in autophagy-mediated clearance of intracellular by mouse macrophages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jcs.252148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970306PMC
March 2021

Postoperative outcomes of free myocutaneous flap and pedicled myocutaneous flap for reconstruction in locally invasive thyroid carcinoma.

Medicine (Baltimore) 2021 Jan;100(2):e24070

Department of Otorhinolaryngology Head and Neck surgery, West China Hospital, Sichuan University, 37 Guo Xue Lane, Chengdu, Sichuan, PR China.

Abstract: Locally invasive thyroid carcinoma (TC) often involves trachea. In such patients, the trachea needs to be reconstructed after surgery. We discuss the postoperative outcome and complications after trachea reconstruction by free myocutaneous flap (FMF) and pedicled myocutaneous flap (PMF).From January 2009 to September 2019, the clinical data of 38 patients with TC were retrospectively analyzed. Demographics, pathologic results, neoplasm staging, surgical protocol, decannulation, subjective speech function, and complications were documented.A total of 38 patients were analyzed (22 FMFs and 16 PMFs). Of the 38 patients, there is a similar rate of decannulation (81.8% in FMF and 75% in PMF), subjective speech function and complications.The FMF reconstruction and the PMF reconstruction have a similar result in terms of postoperative outcome and complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808483PMC
January 2021

Effects on the structure and properties of native corn starch modified by enzymatic debranching (ED), microwave assisted esterification with citric acid (MCAE) and by the dual ED/MCAE treatment.

Int J Biol Macromol 2021 Feb 5;171:123-129. Epub 2021 Jan 5.

State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, PR China; Key Laboratory of Food Nutrition and Safety, Ministry of Education, Tianjin, Tianjin University of Science & Technology, 300457, PR China; College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, PR China.

Native corn starch was modified by enzymatic debranching (ED), microwave assisted citric acid esterification (MCAE), and by dual ED/MCAE. The structure and properties of native starch (NS), and the resulting debranched starch (DS), microwave assisted citric acid esterified starch (MCS), and microwave assisted citric acid debranched starch (MCDS) were determined and compared. Both the morphology and crystalline regions of the modified starches were changed by ED and MCAE. ED increased significantly the amylose content and transparency, but decreased the in vitro enzymatic digestibility, freeze thaw stability and relative crystallinity of DS compared to those of NS. MCAE produced a decrease in amylose content, transparency, in vitro enzymatic digestibility, and relative crystallinity, but increased the freeze-thaw stability of MCS compared to NS, and of MCDS compared to DS. The A-type crystalline structure of NS and DS was changed to B-type crystalline structure after MCAE treatment, and a new FTIR characteristic band at 1735 cm was observed for MCS and MCDS. This work provides insights for producing esterified corn starches by a combined enzyme, microwave and organic acid novel technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.01.012DOI Listing
February 2021

Enlightenment about using TCM constitutions for individualized medicine and construction of Chinese-style precision medicine: research progress with TCM constitutions.

Sci China Life Sci 2020 Dec 30. Epub 2020 Dec 30.

Center for Studies in Constitution Research of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.

TCM constitution is a new branch of TCM. It provides enlightenment on individualized medicine, including the development of new models of individualized research based on nine constitutions, the acquisition of comprehensive health information for individuals, and establishment of a consistent individualized diagnosis and treatment system. Further, we propose a Chinese-style "precision medicine" based on individualization using the TCM constitutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1872-7DOI Listing
December 2020

Combination of Modified Free Anterolateral Thigh Skin-Fascia Flap and Pedicled Thoracoacromial Artery Perforator Flap for Entire Circumferential Pharyngoesophageal Defect and External Neck Skin Defect Reconstructions.

Dysphagia 2021 Jan 3. Epub 2021 Jan 3.

Department of Otorhinolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.

Simultaneous reconstructions of entire circumference pharyngoesophageal defect and external neck skin defect are challenges for head and neck surgeons. A 57-year old man, who underwent radical tumor resection, suffered with an advanced metachronous second primary esophageal squamous cell carcinoma (SPESCC). Our modified operative technique (mALT-TAAP), a combination of modified free anterolateral thigh (ALT) flap (a fasciocutaneous flap with an extension of fascia) and pedicled thoracoacromial artery perforator (TAAP) flap, was utilized to reconstruct the entire circumference of pharyngoesophageal and external neck skin defect reconstructions. The modified ALT flap, TAAP flap and donor wounds recovered well postoperatively. No morbidity of the donor site or operation-related complication was observed. The postoperative recovery of swallowing function was satisfactory. Our mALT-TAAP reconstruction method could be a decent option for simultaneous reconstructions of entire circumference of pharyngoesophageal defect and external neck skin defect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00455-020-10237-5DOI Listing
January 2021

Developing a multivariable risk prediction model to predict prolonged viral clearance in patients with COVID-19.

J Infect 2021 04 31;82(4):e20-e22. Epub 2020 Dec 31.

Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Laboratory of Pulmonary Immunology and inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu 610041, PR China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2020.12.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773527PMC
April 2021

Oxidative stress in retrotrapezoid nucleus/parafacial respiratory group and impairment of central chemoreception in rat offspring exposed to maternal cigarette smoke.

Reprod Toxicol 2021 Mar 28;100:35-41. Epub 2020 Dec 28.

Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address:

We have reported that smoking during pregnancy is associated with deficit in neonatal central chemoreception. However, the underlying mechanism is not well clarified. In this study, we developed a rat model of maternal cigarette smoke (CS) exposure. Pregnant rats were exposed to CS during gestational day 1-20. Offspring were studied on postnatal day 2. Reactive oxygen species (ROS) content and expressions of antioxidant proteins in retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) were examined by fluorogenic dye MitoSOX™ Red and Western blotting, respectively. The response of hypoglossal rootlets discharge to acidification was also detected with micro-injection of HO into RTN/pFRG of offspring brainstem slices in vitro. Results showed that maternal CS exposure led to an increase in ROS production, and brought about decreases in mitochondrial superoxide dismutase and Kelch-like ECH-associated protein-1, and an increase in NF-E2-related factor 2 in offspring RTN/pFRG. Catalase and glutathione reductase expressions were not significantly changed. Moreover, oxidative stress induced by micro-injection of HO into RTN/pFRG in vitro inhibited the discharge response of hypoglossal rootlets to acidification. These findings suggest that maternal CS exposure results in oxidative stress in RTN/pFRG of rat offspring, which might play a role in the impairment of central chemoreception.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reprotox.2020.12.017DOI Listing
March 2021