Publications by authors named "Lei Lei"

915 Publications

Exploring the concepts and practices of advanced breast cancer treatment: a narrative review.

Ann Transl Med 2021 Apr;9(8):721

Department of Medical Oncology (Breast Cancer), Cancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Hangzhou, China.

Objective: To explore the concepts and practices of advanced breast cancer treatment.

Background: Metastatic breast cancer (MBC) has become a chronic disease, with a median overall survival (OS) of around 3 years and a 5-year survival rate of about 25%. OS are strongly associated with the best available care, which consists of not only application of guidelines, but also multidisciplinary specialized care, the most efficacious medicines, and so on. Advanced breast cancer (ABC) Guidelines are the most important and authoritative guidelines for MBC.

Methods: In this review, we demonstrate the history and evolution of the global ABC Guidelines. Since 2015, Chinese multidisciplinary experts have drafted guidelines for clinical diagnosis and treatment of MBC. All of these ABC guidelines describe specialized therapeutic principles for different subtypes MBC in detail. Encouragingly, we have found that some special subtypes are hopeful of being cured, such as HER-2 positive patients with low tumor burden or HR-positive (HR+) MBC with non-visceral metastasis. In our opinion, the definition of cure of MBC is that MBC patients achieve CR and remain for more than five years after systemic treatment, including those with local therapy. Consequently, we also have conducted some researches and meaningful explorations in different subtypes of MBC. In HER2 positive MBC, our study revealed that regular HER2 circulating extracellular domain (ECD) assay can provide the real-time monitoring of tumor burden and prediction of poor outcome, and may present an important opportunity to reassess HER2 status. In HR+ MBC, we suggested that hormone therapy (HT) maintenance is the priority choice for HR+/HER2- MBC after first-line combined chemotherapy. Besides, our real-world study revealed that fulvestrant combined with ovarian suppression was an active option for premenopausal HR+/HER2- MBC. And also, we observed that everolimus (low-dose) combined with hormone therapy was still effective for HR+/HER2- MBC. For mTNBC patients, we found that THA and endostatin exhibited potential efficacy and was well tolerated in pretreated patients.

Conclusions: Our concepts and practices will contribute to the design of relevant clinical research and accumulation of evidence, and cure of MBC is promising.
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http://dx.doi.org/10.21037/atm-21-1458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106003PMC
April 2021

Ki67 and progesterone receptor status predicts sensitivity to palbociclib: a real-world study.

Ann Transl Med 2021 Apr;9(8):707

Department of Medical Oncology (Breast Cancer), Cancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Hangzhou, China.

Background: Palbociclib combined with endocrine therapy has been approved as a front-line treatment for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment.

Methods: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR) as detected by immunohistochemistry in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS).

Results: In the total population, women with Ki67 ≥14% had marginally significantly shorter PFS than those with Ki67 <14% (P=0.062). Patients with Ki67 ≥30% had significantly shorter PFS than those with Ki67 <30% (P=0.048). Meanwhile, PR ≥20% was associated with longer PFS. Moreover, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. As for the hormone therapy subgroup, there were significant associations between Ki67 and PR levels and PFS in the aromatase inhibitors (AIs) subgroup. Patients with Ki67 ≥14% or Ki67 ≥30% had shorter PFS than those with Ki67 <14% or Ki67 <30%, respectively (P=0.024, P<0.001). Additionally, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. When both Ki67 and PR were considered, there were significant differences between the different cohorts. Compared with patients with Ki67 ≥14% and PR <20%, those with Ki67 <14% and PR ≥20% had significantly longer PFS. In addition, patients with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%. Furthermore, in the AI cohort, patients with Ki67 <14% and PR ≥20% had significantly longer PFS than those with Ki67 ≥14% and PR <20%. Women with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%.

Conclusions: The present study indicates that both Ki67 and PR have great impacts on palbociclib and hormone therapy and may contribute to selecting more effective partners for palbociclib.
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http://dx.doi.org/10.21037/atm-21-1340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106007PMC
April 2021

Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma.

Bosn J Basic Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of Epidemiology and Statistics, School of Public Health, Guangxi Medical University, Nanning, China; Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, China.

Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the "Metabolic pathways" pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (p = 0.008) and significantly improved the prediction value of the T stage (p = 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.
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http://dx.doi.org/10.17305/bjbms.2021.5690DOI Listing
April 2021

Integrating Positive and Negative Thermal Quenching Effect for Ultrasensitive Ratiometric Temperature Sensing and Anti-counterfeiting.

ACS Appl Mater Interfaces 2021 May 11. Epub 2021 May 11.

College of Materials and Chemistry, China Jiliang University, Hangzhou 310018, China.

Fluorescence intensity ratio-based temperature sensing with a self-referencing characteristic is highly demanded for reliable and accurate sensing. Although enormous efforts have been devoted to explore high-performance luminescent temperature probes, it remains a daunting challenge to achieve highly relative sensitivity which determines temperature resolution. Herein, we employ a novel strategy to achieve temperature probes with ultrahigh relative sensitivity through integrating both positive and negative thermal quenching effect into a hydrogel. Specifically, Er ions show evidently a positive thermal quenching effect in Yb/Er:NaYF@NaYF nanocrystals while Nd and Tm ions in a YbWO bulk exhibit prominently a negative thermal quenching effect. With elevating temperature from 313 to 553 K, the fluorescence intensity ratio of Er (540 nm) to Nd (799 nm) and Tm (796 nm) to Er (540 nm) is significantly decreased about 1654 times and increased about 14,422 times, respectively. The maximum relative sensitivity of 15.3% K at 553 K and 23.84% K at 380 K are achieved. The strategy developed in this work sheds light on highly sensitive probes using lanthanide ion-doped materials.
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http://dx.doi.org/10.1021/acsami.1c05611DOI Listing
May 2021

Establishment of an Agrobacterium-mediated genetic transformation and CRISPR/Cas9-mediated targeted mutagenesis in Hemp (Cannabis Sativa L.).

Plant Biotechnol J 2021 May 7. Epub 2021 May 7.

Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, Hunan, China.

Hemp (Cannabis sativa L.) is an annual and typically dioecious crop. Due to the therapeutic potential for human diseases, phytocannabinoids as a medical therapy is getting more attention recently. Several candidate genes involved in cannabinoid biosynthesis have been elucidated using omics analysis. However, the gene function was not fully validated due to few reports of stable transformation for Cannabis tissues. In this study, we firstly report the successful generation of gene-edited plants using an Agrobacterium-mediated transformation method in C. sativa. DMG278 achieved the highest shoot induction rate, which was selected as the model strain for transformation. By overexpressing the cannabis developmental regulator chimera in the embryo hypocotyls of immature grains, the shoot regeneration efficiency was substantially increased. We used CRISPR/Cas9 technology to edit the phytoene desaturase gene and finally generated four edited cannabis seedlings with albino phenotype. Moreover, we propagated the transgenic plants and validated the stable integration of T-DNA in cannabis genome.
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http://dx.doi.org/10.1111/pbi.13611DOI Listing
May 2021

Nonalcoholic Fatty Liver Disease Development in Zebrafish upon Exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, a Novel Brominated Flame Retardant.

Environ Sci Technol 2021 May 2. Epub 2021 May 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, can potentially cause lipid metabolism disorder; however, its biological effects on lipid homeostasis remain unknown. We investigated its ability to cause nonalcoholic fatty liver disease (NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0.02, 2.0 μM) for 2 weeks. Consequently, HFD-fed fish showed a higher measured concentration of TBPH than ND-fed fish. Further, TBPH-treated fish in the HFD group showed higher hepatic triglyceride levels and steatosis. In comparison to ND-fed fish, treating HFD-fed fish with TBPH led to an increase in the concentration of several proinflammatory markers (e.g., TNF-α, IL-6); TBPH exposure also caused oxidative stress. In addition, the mRNA levels of genes encoding peroxisome proliferator-activated receptors were increased, and the transcription of genes involved in lipid synthesis, transport, and oxidation was upregulated in both ND- and HFD-fed fish. Both the ND and HFD groups also showed demethylation of the peroxisome proliferator-activated receptor-γ coactivator 1-α gene promoter, accompanied by the upregulation of and transcription. To summarize, we found that TBPH amplified the disruption of lipid homeostasis in zebrafish, leading to the enhancement of diet-induced NAFLD progression.
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http://dx.doi.org/10.1021/acs.est.1c01476DOI Listing
May 2021

Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Glucose Metabolism Accompanied by the Modulation of Gut Microbiota and Ileal Inflammatory Damage in Type 2 Diabetic KKAy Mice.

Front Pharmacol 2021 15;12:642400. Epub 2021 Apr 15.

Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of and , reduced the levels of and and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.
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http://dx.doi.org/10.3389/fphar.2021.642400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082153PMC
April 2021

DEK is highly expressed in breast cancer and is associated with malignant phenotype and progression.

Oncol Lett 2021 Jun 1;21(6):440. Epub 2021 Apr 1.

Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning 110001, P.R. China.

DEK proto-oncogene (DEK) has been demonstrated as an oncogene and is associated with the development of many types of tumor; however, the expression and role of DEK in breast cancer remain unknown. The present study aimed to determine the role of DEK in the progression of breast cancer. The expression of DEK in 110 breast cancer tissues and 50 adjacent normal breast tissues was examined using immunohistochemistry. Furthermore, DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in MCF7 cells. Proliferative and invasive abilities were examined in MCF7 cells using MTT assay, colony-formation assay and transwell invasion assays. The results demonstrated that DEK expression level was significantly increased in breast cancer tissues compared with normal breast tissues. Furthermore, high DEK expression was associated with high histological grade, lymph node metastasis, advanced Tumor-Node-Metastasis stage and high Ki-67 index; however, DEK expression was not associated with the expression level of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. High DEK expression indicated poor prognosis in patients with breast cancer. DEK overexpression upregulated the protein expression of β-catenin and Wnt and increased the proliferative and invasive abilities of breast cancer cells. DEK downregulation had the opposite effect. Taken together, the results from the present study demonstrated that high expression of DEK was common in patients with breast cancer and was associated with progression of the disease and poor prognosis, and that DEK overexpression promoted the proliferative and invasive abilities of breast cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045159PMC
June 2021

Computational Fluid Dynamics Analysis of Nasal Airway Changes after Treatment with C-Expander.

Appl Bionics Biomech 2021 31;2021:8874833. Epub 2021 Mar 31.

Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, 410008 Hunan, China.

The use of the C-expander is an effective treatment modality for maxillary skeletal deficiencies which can cause ailments and significantly reduce life expectancy in late adolescents and young adults. However, the morphological and dynamic effects on the nasal airway have not been reported. The main goal of this study was to evaluate the nasal airway changes after the implementation of a C-expander. A sample of nine patients (8 females, 1 male, age range from 15 to 29 years) was included. The morphology parameters and nasal airway ventilation parameters of pretreatment and posttreatment were measured. All study data were normally distributed. A paired -test was used to evaluate the changes before and after treatment. After expansion, the mean and standard deviation values of intercanine maxillary width (CMW) and intermolar maxillary width (MMW) increased from 35.75 ± 2.48 mm and 54.20 ± 3.17 mm to 37.87 ± 2.26 mm ( < 0.05) and 56.65 ± 3.10 mm ( < 0.05), respectively. The nasal cavity volume increased from 20320.00 ± 3468.25 mm to 23134.70 ± 3918.84 mm ( < 0.05). The nasal pressure drop decreased from 36.34 ± 3.99 Pa to 30.70 ± 3.17 Pa ( < 0.05), while the value of the maximum velocity decreased from 6.50 ± 0.31 m/s to 5.85 ± 0.37 m/s ( < 0.05). Nasal resistance dropped remarkably from 0.16 ± 0.14 Pa/ml/s to 0.08 ± 0.06 Pa/ml/s ( < 0.05). The use of C-expander can effectively broaden the area and volume of the nasal airway, having a positive effect in the reduction of nasal resistance and improvement of nasal airway ventilation. For patients suffering from maxillary width deficiency and respiratory disorders, a C-expander may be an alternative method to treat the disease.
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http://dx.doi.org/10.1155/2021/8874833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032540PMC
March 2021

Microfluidic synthesis of chitosan-coated magnetic alginate microparticles for controlled and sustained drug delivery.

Int J Biol Macromol 2021 Apr 15;182:639-647. Epub 2021 Apr 15.

College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an 710021, China. Electronic address:

The present work aimed to assemble a simple, portable and economical L-junction microfluidic device to realize the adjustment and tunability of homogeneous round-shaped particles synthesis. In this study, we synthesize two kind of microparticles, including magnetic alginate microparticles (MAM) and chitosan-coated magnetic alginate (CMAM) used for controlling the drug release under a mild condition. Comparing to the traditional method, the MAM synthesized via this microfluidic approach has uniform size distribution, adjustable diameter as well as tunable magnetism. By exploring the amoxicillin as model drug, the MAM displays excellent pH-sensitive release, the effect of particle size on the drug release rate was investigated as well. The results show the smaller particles (220 μm) show a faster release rate than the bigger materials (1000 μm) due to their larger specific area, providing more frequency to interact with the reaction solution. The positive polyelectrolyte, chitosan, coated on the magnetic alginate surface endows CMAM time extension in drug release by two times, successfully achieving drug controlled and sustained release via the kinetics analysis. In summary, this microfluidic approach provides a convenient and efficient fluidic design for the well-controlled synthesis of micro-and nanoscale particles, which is a potential choice used for controlled and sustained drug release.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.057DOI Listing
April 2021

The Perceptions of Patients, Families, Doctors, and Nurses Regarding Malignant Bone Tumor Disclosure in China: A Qualitative Study.

J Transcult Nurs 2021 Apr 15:10436596211005532. Epub 2021 Apr 15.

School of Nursing, Army Medical University, Chongqing, Peoples Republic of China.

Introduction: Withholding the malignant bone tumors disclosure from patients is common in China. The purpose of the study was to explore the perceptions of patients, families, doctors, and nurses regarding the disclosure of malignant bone tumors in China.

Method: Semistructured interviews were conducted with 25 cases, consisting of 69 participants (14 patients, 25 family members, 17 doctors, and 13 nurses), and the transcripts were analysed using Colaizzi's (1978) descriptive phenomenological analysis process.

Results: Five themes were identified: (1) doctors preferred to inform the family members first, (2) family members' decisions depended on different situations, (3) the patients agreed that disclosure should be different for each person/personally, (4) care from nurses reduced the overreaction of patients, and (5) key points improve the informing quality.

Discussion: Family participatory cancer disclosure and multidisciplinary teams could improve the quality of cancer disclosure. Culturally congruent health care and culturally sensitive interventions in cancer disclosure are suggested.
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http://dx.doi.org/10.1177/10436596211005532DOI Listing
April 2021

Jointed Synchronous Photocatalytic Oxidation and Chromate Reduction Enabled by the Defect Distribution upon BiVO: Mechanism Insight and Toxicity Assessment.

ACS Appl Mater Interfaces 2021 Apr 13;13(15):17586-17598. Epub 2021 Apr 13.

College of Environmental Science and Engineering and Key Laboratory of Environmental Biology and Pollution Control, Ministry of Education, Hunan University, Changsha 410082, China.

Exploring active and ecological materials for the restoration of complex pollution system is highly desired. This study presents a facile defect-tailoring strategy for combined pollutants purification with BiVO photocatalysis in which the jointed synchronous reaction of oxidation and reduction is integrated instead of the sequential reaction in two individual systems. XPS and EPR reveal that BiVO with a suitable oxygen vacancies (OVs) concentration and distribution exhibits superior photocatalytic activity under the coexistence of TC-HCl and Cr(VI) with Cr(VI) reduction efficiency increased by 71 times compared with the individual Cr(VI) system along with TC-HCl removal efficiency comparable to a single TC-HCl system. The mechanism of synchronous redox reactions mediated by surface OVs is revealed by comprehensive characterization together with reaction kinetic analysis, and the electronic band structure adjustment induced by the OVs variation is confirmed. Active species identification tests and intermediate product analysis confirm that singlet oxygen (O) accounts for the selective oxidation of TC-HCl, while electrons dominate the reduction of Cr(VI), under a coexistent environment. The influence of water quality parameters (e.g., pH, cations, anions, and organic substances) on the photocatalytic activity is investigated considering the complexity of the real aquatic environment. Importantly, toxicity assessment with Gram-negative strain as a model bacterium validates that the toxicity of the intermediates can be reduced to low or even ultralow levels. This work is dedicated to the mechanistic study of defect photocatalysis over BiVO and provides a jointed synchronous reaction system for combined pollutant purification.
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http://dx.doi.org/10.1021/acsami.1c01998DOI Listing
April 2021

The effects of maternal SSRI exposure on the serotonin system, prefrontal protein expression and behavioral development in male and female offspring rats.

Neurochem Int 2021 Jun 6;146:105041. Epub 2021 Apr 6.

School of Rehabilitation, Kunming Medical University, Kunming, China. Electronic address:

Fluoxetine (FLX), a commonly used selective serotonin reuptake inhibitor, is often used to treat depression during pregnancy. However, prenatal exposure to FLX has been associated with a series of neuropsychiatric illnesses. The use of a rodent model can provide a clear indication as to whether prenatal exposure to SSRIs, independent of maternal psychiatric disorders or genetic syndromes, can cause long-term behavioral abnormalities in offspring. Thus, the present study aimed to explore whether prenatal FLX exposure causes long-term neurobehavioral effects, and identify the underlying mechanism between FLX and abnormal behaviors. In our study, 12/mg/kg/day of FLX or equal normal saline (NS) was administered to pregnant Sprague-Dawley (SD) rats (FLX = 30, NS = 27) on gestation day 11 till birth. We assessed the physical development and behavior of offspring, and in vivo magnetic resonance spectroscopy (MRS) was conducted to quantify biochemical alterations in the prefrontal cortex (PFC). Ex vivo measurements of brain serotonin level and a proteomic analysis were also undertaken. Our results showed that the offspring (male offspring in particular) of fluoxetine exposed mothers showed delayed physical development, increased anxiety-like behavior, and impaired social interaction. Moreover, down-regulation of 5-HT and SERT expression were identified in the PFC. We also found that prenatal FLX exposure significantly decreased NAA/tCr with 1H-MRS in the PFC of offspring. Finally, a proteomic study revealed sex-dependent differential protein expression. These findings may have translational importance suggesting that using SSRI medication alone in pregnant mothers may result in developmental delay in their offspring. Our results also help guide the choice of outcome measures in identifying of molecular and developmental mechanisms.
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http://dx.doi.org/10.1016/j.neuint.2021.105041DOI Listing
June 2021

CircRNA_OTUD7A upregulates FOXP1 expression to facilitate the progression of diffuse large B-cell lymphoma via acting as a sponge of miR-431-5p.

Genes Genomics 2021 Apr 8. Epub 2021 Apr 8.

Clinical Laboratory, The First Hospital of Yulin, No. 59 Yuxi Avenue, Yulin, 719000, Shaanxi, China.

Background: A growing number of studies have shown that circular RNA (circRNA) is an important regulator molecule in cancer progression, but it has been poorly studied in diffuse large b-cell lymphoma (DLBCL).

Objective: This study aimed to explore the role of circ_OTUD7A in DLBCL.

Methods: Relative expression levels of circ_OTUD7A, microRNA (miR)-431-5p and forkhead box P1 (FOXP1) were determined by quantitative real-time PCR (qRT-PCR). The proliferation of cells was elevated by colony formation assay and MTT assay. Western blot (WB) analysis was employed to measure the protein levels of proliferation marker, epithelial-mesenchymal transition (EMT) markers, cyclin marker, apoptosis markers and FOXP1. Moreover, the apoptosis, cell cycle process, migration and invasion of cells were detected using flow cytometry and transwell assay, respectively. In addition, the interaction between miR-431-5p and circ_OTUD7A or FOXP1 was confirmed by dual-luciferase reporter assay.

Results: Circ_OTUD7A was highly expressed in DLBCL, and its knockdown could inhibit DLBCL cell proliferation and metastasis, while promote cell cycle arrest and apoptosis. Similarly, FOXP1 also was upregulated in DLBCL, and its silencing could restrain the progression of DLBCL cells. Further experiments revealed that circ_OTUD7A could sponge miR-431-5p and miR-431-5p could target FOXP1. MiR-431-5p inhibitor could reverse the suppressive effect of circ_OTUD7A silencing on DLBCL progression, and FOXP1 overexpression also could reverse the inhibitory effect of miR-431-5p mimic on DLBCL progression.

Conclusion: Circ_OTUD7A promoted the progression of DLBCL by regulating the miR-431-5p/FOXP1 axis, which suggested that circ_OTUD7A might function as an oncogene in DLBCL.
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http://dx.doi.org/10.1007/s13258-021-01094-zDOI Listing
April 2021

Construction and immunological evaluation of hepatitis B virus core virus-like particles containing multiple antigenic peptides of respiratory syncytial virus.

Virus Res 2021 Jun 2;298:198410. Epub 2021 Apr 2.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

Respiratory syncytial virus (RSV) infection causes severe disease in the lower respiratory tract of infants and young children. Currently, no licensed vaccine is available. In this study, we generated the chimeric virus-like particles (tHBc/F, tHBc/F/M2 and tHBc/F/M2/tG VLPs) containing multiple antigenic peptides of RSV proteins based on a truncated hepatitis B virus core carrier (tHBc). We investigated the immune protection against RSV infection induced by these VLPs in a mouse model. Immunization with the VLPs elicited RSV-specific IgG and neutralizing antibody production and conferred protection against RSV infection in vivo. Compared with UV-RSV or tHBc/F/M2/tG VLPs, the tHBc/F and tHBc/F/M2 VLPs induced significantly decreased Th2 cytokines (IL-4, IL-5) and increased Th1 cytokines (IFN-γ, TNF-α, IL-2) as well as increased IgG2a/IgG1 ratios. tHBc/F and tHBc/F/M2 VLPs also elicited an increased regulatory T (Treg) cell frequency and IL-10 secretion in the lungs of vaccinated mice, thereby relieving pulmonary pathology upon subsequent RSV infection. Our results demonstrate that the VLPs containing antigenic peptides of F protein combined with a CTL epitope of M2 may represent a promising RSV subunit vaccine candidate.
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http://dx.doi.org/10.1016/j.virusres.2021.198410DOI Listing
June 2021

Displacement Identification by Computer Vision for Condition Monitoring of Rail Vehicle Bearings.

Sensors (Basel) 2021 Mar 17;21(6). Epub 2021 Mar 17.

State Key Laboratory of Traction Power, Southwest Jiaotong University, Chengdu 610036, China.

Bearings of rail vehicles bear various dynamic forces. Any fault of the bearing seriously threatens running safety. For fault diagnosis, vibration and temperature measured from the bogie and acoustic signals measured from trackside are often used. However, installing additional sensing devices on the bogie increases manufacturing cost while trackside monitoring is susceptible to ambient noise. For other application, structural displacement based on computer vision is widely applied for deflection measurement and damage identification of bridges. This article proposes to monitor the health condition of the rail vehicle bearings by detecting the displacement of bolts on the end cap of the bearing box. This study is performed based on an experimental platform of bearing systems. The displacement is monitored by computer vision, which can image real-time displacement of the bolts. The health condition of bearings is reflected by the amplitude of the detected displacement by phase correlation method which is separately studied by simulation. To improve the calculation rate, the computer vision only locally focuses on three bolts rather than the whole image. The displacement amplitudes of the bearing system in the vertical direction are derived by comparing the correlations of the image's gray-level co-occurrence matrix (GLCM). For verification, the measured displacement is checked against the measurement from laser displacement sensors, which shows that the displacement accuracy is 0.05 mm while improving calculation rate by 68%. This study also found that the displacement of the bearing system increases with the increase in rotational speed while decreasing with static load.
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http://dx.doi.org/10.3390/s21062100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002472PMC
March 2021

Identification of Candidate Genes Conferring Cold Tolerance to Rice ( L.) at the Bud-Bursting Stage Using Bulk Segregant Analysis Sequencing and Linkage Mapping.

Front Plant Sci 2021 11;12:647239. Epub 2021 Mar 11.

Key Laboratory of Germplasm Enhancement, Physiology and Ecology of Food Crops in Cold Region, Ministry of Education, Northeast Agricultural University, Harbin, China.

Low-temperature tolerance during the bud-bursting stage is an important characteristic of direct-seeded rice. The identification of cold-tolerance quantitative trait loci (QTL) in species that can stably tolerate cold environments is crucial for the molecular breeding of rice with such traits. In our study, high-throughput QTL-sequencing analyses were performed in a 460-individual F mapping population to identify the major QTL genomic regions governing cold tolerance at the bud-bursting (CTBB) stage in rice. A novel major QTL, , which controls seed survival rate (SR) under low-temperature conditions of 5°C/9 days, was mapped on the 5.40-Mb interval on chromosome 9. Twenty-six non-synonymous single-nucleotide polymorphism (nSNP) markers were designed for the region based on re-sequencing data and local QTL mapping conducted using traditional linkage analysis. We mapped to a 483.87-kb region containing 58 annotated genes, among which six predicted genes contained nine nSNP loci. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that only Os09g0444200 was strongly induced by cold stress. Haplotype analysis further confirmed that the SNP 1,654,225 bp in the Os09g0444200 coding region plays a key role in regulating the cold tolerance of rice. These results suggest that Os09g0444200 is a potential candidate for . Our results are of great significance to explore the genetic mechanism of rice CTBB and to improve the cold tolerance of rice varieties by marker-assisted selection.
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http://dx.doi.org/10.3389/fpls.2021.647239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006307PMC
March 2021

A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice.

Front Cell Dev Biol 2021 11;9:659744. Epub 2021 Mar 11.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

CD4 T cells are essential for regulating effective immune response to pathogens and immune balance. Recent studies have demonstrated the unique features of T cells in neonate mice, such as more sensitive to antigen response and preference toward T helper 2 (Th2) response and regulatory T cells (Tregs) differentiation. However, the biological characteristics of neonatal age-derived CD4 T cells following homeostasis remain unclear. Here we utilized a lineage tracing model of δ to mark neonatal- and adult-derived CD4 T cells followed by a combination analysis of activation, proliferation, survival, and differentiation. Our results showed that neonatal CD4 T cells had higher capacity of activation, proliferation, apoptosis, and differentiation toward Th2 and T helper 17 (Th17) lineages, accompanied by a reduced potential for T helper 1 (Th1), T helper 9 (Th9), and Treg lineages. In contrast, tracked neonatal CD4 T cells exhibited similar characters of above-mentioned of tracked adult cells in adult mice. Therefore, our data support a natural requirement for CD4 T cells to acquire fully-equipped functional potentials of adult cells.
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http://dx.doi.org/10.3389/fcell.2021.659744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991801PMC
March 2021

The effect of physiotherapy in rotator cuff injury patients with platelet-rich plasma: study protocol of a non-randomized controlled trial.

BMC Musculoskelet Disord 2021 Mar 20;22(1):292. Epub 2021 Mar 20.

Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, 25 Tai Ping Road, Luzhou, Sichuan, 646000, People's Republic of China.

Background: The study aims to identify whether Platelet-rich plasma (PRP) combined with early physiotherapy has an advantage over PRP alone for rotator cuff injury patients, regarding pain release, function score, tear size, and quality of life improvement.

Methods: This is a single-center prospective non-randomized study implemented in July 2019 at the Affiliated Hospital of Southwest Medical University in Sichuan. Three hundred-forteen patients with rotator cuff injury aged over 18 years were recruited. Participants were assigned to the experiment group (PRP plus physiotherapy) or control group (PRP) by their desire. We used the Constant-Murley score to assess the shoulder function, the Visual Analogue Scale to evaluate shoulder pain, and the MOS Item Short-form Health Survey (SF-12) to measure the quality of life. MRI was applied to measure tear size, and the follow-up duration is 12 months.

Discussion: Our findings will give information on the effects of PRP and physiotherapy on rotator cuff injuries. Physiotherapy might be added to improve the effects of PRP in patients with rotator cuff injuries.

Trial Registration: This study was registered in the Chinese clinical trial registry on September 1st, 2019 ( ChiCTR1900025563 ).
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http://dx.doi.org/10.1186/s12891-021-04171-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981950PMC
March 2021

Correlation of pathogenic effects of laryngopharyngeal reflux and bacterial infection in COME of children.

Acta Otolaryngol 2021 May 18;141(5):454-458. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Head & Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Sichuan, PR China.

Background: Bacteria infection and laryngopharyngeal reflux (LPR) were believed the important pathogenesis of chronic otitis media with effusion (COME). But no study researched the relationship between them on COME.

Aims: To confirm bacterial could arrive middle ear through LPR and produced acid metabolites to activate the pepsinogen of LPR causing COME.

Material And Methods: Children (65) diagnosed COME with 122 middle ear effusions were included in COME group. Children (22) with congenital/acquired profound deafness with 22 middle ear lavage were included in CI group. Pepsin A concentration in the effusion and lavage fluid were measured. The DNA of the bacteria, IL-8 and TNF-α in the effusion were detected.

Results: The average concentration of pepsin A in the effusions and lavage were 176.65 ± 242.09 and 19 ng/ml. Bacterial infection rates were 75.76% and 24.24% in the pepsin A(+) and pepsin A(-) patients. In the bacterial (+), the patients of pepsin A(+) was 4.33 times higher than those of pepsin A(-). TNF-α in pepsin A(+) was higher than that in pepsin A(-). TNF-α and IL-8 were higher in bacteria(+) than those of bacteria(-).

Conclusions: Bacterial infection and LPR might act in synergy in the pathogenesis of COME.

Significance: First time to propose LPR and bacterial infection might work synergistically to cause COME.
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http://dx.doi.org/10.1080/00016489.2021.1883732DOI Listing
May 2021

Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling.

J Cell Mol Med 2021 05 17;25(10):4870-4876. Epub 2021 Mar 17.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

Under steady-state conditions, the pool size of peripheral CD8 T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8 T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild-type (WT) and Med1-deficient CD8 T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1-deficient CD8 T cells compared with WT counterparts. Finally, Med1-deficient CD8 T cells exhibited a decreased expression of interleukin-7 receptor α (IL-7Rα), down-regulation of phosphorylated-STAT5 (pSTAT5) and Bim up-regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8 T cells through IL-7Rα/STAT5 pathway-mediated cell survival.
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http://dx.doi.org/10.1111/jcmm.16465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107092PMC
May 2021

Stabilization of lead in polluted sediment based on an eco-friendly amendment strategy: Microenvironment response mechanism.

J Hazard Mater 2021 Feb 25;415:125534. Epub 2021 Feb 25.

College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082, China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha, Hunan 410082, China.

Stabilization is the most important remediation mechanisms for sediment polluted heavy metals. However, little research has been done on the identification of microenvironmental response and internal correlation, as well as synergistic mechanisms during heavy metal remediation. This study aims to investigate the inner response mechanisms of microenvironment after the lead (Pb) are gradually stabilized in sediment. An eco-friendly amendment strategy which firstly used 100% biodegradable sophorolipids (SOP) to modify chlorapatite (ClAP) for the fabrication of SOP@nClAP was applied in this study. The stabilization efficiency of Pb was significantly improved by SOP@nClAP compared with ClAP. Most importantly, the high-throughput sequencing showed that the dominant species in the sediment changed with the stabilization of Pb. The decrease of Proteobacteria and increase of Firmicutes, especially the Sedimentibacter within the phylum Firmicute directly suggested that large amounts of Pb were stabilized. This research is not only devoted to stabilize Pb in sediment by eco-friendly amendment strategy, but also keep a watchful eye on microenvironment response mechanisms during the Pb stabilization in sediment. Therefore, this study lays a foundation for the future application of more heavy metal amendment strategies in the sediment environment and improves the possibility of large-scale site amendment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125534DOI Listing
February 2021

Corrigendum to "Hypoxia Impairs NK Cell Cytotoxicity through SHP-1-Mediated Attenuation of STAT3 and ERK Signaling Pathways".

J Immunol Res 2021 25;2021:3625084. Epub 2021 Feb 25.

Biomedical Sciences, National University of Ireland Galway, Galway, Ireland.

[This corrects the article DOI: 10.1155/2020/4598476.].
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http://dx.doi.org/10.1155/2021/3625084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936882PMC
February 2021

Remarkable Response of Toripalimab Combined with Chemotherapy in Sarcomatoid Carcinoma of Palatine Tonsil: A Case Report.

J Multidiscip Healthc 2021 9;14:599-604. Epub 2021 Mar 9.

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, People's Republic of China.

Background: Sarcomatoid carcinoma (SaCa) of the palatine tonsil is a rare and aggressive subset of head and neck (H&N) cancer which is characterized by insensitivity to surgery and radiotherapy and a poor prognosis. Immunotherapy has led advances in the treatment of melanoma and H&N cancer, but the combined effects of immunotherapy and chemotherapy have not been sufficiently investigated.

Case Presentation: Herein, we report the case of 29-year-old Chinese women with local advanced non-resectable SaCa of the palatine tonsil who exhibited a substantial partial response to toripalimab and chemotherapy followed by radiation therapy. To the best of our knowledge, this is the first report of its successful application in this context.

Conclusion: Toripalimab combined with chemotherapy may be an effective approach for locally advanced H&N cancer in rare categories of patients, which was the first application as far as we know.
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http://dx.doi.org/10.2147/JMDH.S296584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955754PMC
March 2021

The effects of oral health education regarding periodontal health on non-dental undergraduates in southwestern China-exploring the feasibility of an e-learning course for oral health promotion.

BMC Oral Health 2021 03 16;21(1):119. Epub 2021 Mar 16.

Department of Preventive Dentistry, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Background: The high prevalence of periodontal diseases is an important oral health problem worldwide. It is necessary to increase public knowledge on and influence attitudes towards periodontal diseases in order to prevent them. However, the effect of oral health education (OHE) as a primary preventive method in China is unsatisfactory. The aim of this study is to investigate the feasibility of extending an e-learning course regarding periodontal health by comparing the effects of oral health education regarding periodontal health (OHE-PH) on dental and non-dental students and the effects between a traditional course and an e-learning course among non-dental students at Sichuan University.

Methods: A quasi-experimental study with a pre-test and a post-test was performed. A total of 217 dental students and 134 non-dental students attended a traditional course; 69 non-dental students attended an e-learning course. Before- and after-course questionnaires about periodontal health knowledge, attitudes and behaviours were administered.

Results: After the traditional/e-learning course, the knowledge of both dental and non-dental students about periodontal diseases and self-reported behaviours for gingival bleeding and oral care improved. The non-dental students reached or surpassed the level of dental students before the course. The non-dental students taking the e-learning course performed better in some areas than those taking the traditional course.

Conclusions: OHE-PH was effective for dental and non-dental students. The e-learning course on OHE-PH was sufficient for improving knowledge and self-reported behaviours among non-dental undergraduates and was even better than the traditional course in some areas. The e-learning course may be an effective method for periodontal health education and oral health promotion among undergraduates.
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http://dx.doi.org/10.1186/s12903-021-01476-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962077PMC
March 2021

[Short-term effectiveness of derotational distal femoral osteotomy combined with medial patellofemoral ligament reconstruction for recurrent patellar dislocation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Mar;35(3):343-348

Department of Orthopaedics, the Affiliated Hospital of Southwest Medical University & Sichuan Provincial Laboratory of Orthopaedic Engineering, Luzhou Sichuan, 646000, P.R.China.

Objective: To investigate the short-term effectiveness of derotational distal femoral osteotomy (DDFO) combined with medial patellofemoral ligament (MPFL) reconstruction in treatment of recurrent patellar dislocation with excessive femoral anteversion angle (FAA≥30°).

Methods: Between June 2017 and August 2019, 17 patients with recurrent patellar dislocation with FAA≥30° were treated with DDFO and MPFL reconstruction. There were 5 males and 12 females, aged 14-22 years, with an average of 17.7 years. The patella dislocated for 2 to 8 times (mean, 3.6 times). The disease duration was 2-7 years (mean, 4.6 years). The patellar apprehension tests were positive. Preoperative pain visual analogue scale (VAS) score, Lysholm score, Tegner score, and Kujala score were 4.2±1.1, 47.8±8.1, 3.6±1.1, and 56.8±5.7, respectively. FAA, mechanical lateral distal femoral angle (mLDFA), lateral patella displacement (LPD), tibial tuberosity-trochlear groove distance (TT-TG) were (34.9±3.4)°, (85.8±3.0)°, (13.7±3.8) mm, and (23.1±2.1) mm, respectively.

Results: All incisions healed by first intention, and there was no complications such as knee stiffness, infection, and re-dislocation of the patella. All patients were followed up 13-25 months, with an average of 17.7 months. The imaging review showed that 1 case of osteotomy did not union, and achieved satisfactory results after the secondary revision and strengthening fixation; the osteotomies of other patients healed completely after 3 to 4 months of operation. The patellar apprehension tests were negative. At last follow-up, the FAA, mLDFA, LPD, and TT-TG were (15.6±2.7)°, (83.0±2.1)°, (5.0±2.6) mm, and (20.5±2.5) mm, respectively; the VAS score, Lysholm score, Tegner score, and Kujala score were 2.4±1.4, 93.4±7.8, 6.8±1.5, and 89.0±8.0, respectively. There were significant differences in the above indicators between pre- and post-operation ( <0.05).

Conclusion: DDFO combined with MPFL reconstruction for the recurrent patellar dislocation with excessive FAA (≥30°) can achieve good short-term effectiveness, significantly reduce knee pain, and improve function.
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http://dx.doi.org/10.7507/1002-1892.202009111DOI Listing
March 2021

Molecular Investigation of from Clinical Companion Animals in Beijing, China, 2017-2019.

Pathogens 2021 Feb 27;10(3). Epub 2021 Feb 27.

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

This work is aimed to elucidate the prevalence and characteristics of antimicrobial resistance, virulence, and molecular typing in from clinical companion animals in Beijing, China. In total, 105 (2.0%) isolates were recovered from 5359 samples (dogs, n = 3356; cats, n = 2003). All tested isolates exhibited high resistance to amoxicillin-clavulanate (74.3%). Moreover, resistance rates in dog isolates (2.1%) were significantly higher than in cat isolates (0.9%); however, the rate of multidrug-resistance (MDR) was 57.1% and the MDR prevalence in cats was significantly higher than dogs. Whole-genome sequencing demonstrated plasmids IncX4 and IncFIA (HI1)/FII(K) carried (n = 1) and (n = 1), but (n = 1) and (n = 4) were harbored in IncX3-type plasmids, and the above genes were in different isolates. The most prevalent sequence types (STs) in companion animals were ST1 (n = 9) and ST37 (n = 9). Compared to National Center for Biotechnology Information (NCBI) data on human , resistance genes and were more prevalent in human isolates; however, and showed a higher prevalence in companion animals. Hypermucoviscosity was reported in 9 (8.6%) isolates, whereas 64 isolates (61.0%) were hypervirulent (hvKP) via the . These findings validate the high risk of and necessitate its relevant control in pet clinics.
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http://dx.doi.org/10.3390/pathogens10030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997213PMC
February 2021

T cell immune regulator 1 is a prognostic marker associated with immune infiltration in glioblastoma multiforme.

Oncol Lett 2021 Apr 3;21(4):252. Epub 2021 Feb 3.

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Glioma is the most common primary brain tumor and glioblastoma multiforme (GBM) is the most malignant brain glioma with the worst prognosis. T cell immune regulator 1 (TCIRG1) constitutes the Va subunit of vacuolar ATPase (V-ATPase), and the function of V-ATPase in malignant tumors, such as breast cancer, melanoma and hepatocellular carcinoma, has been reported. However, the effect of the TCIRG1 subunit on GBM remains to be fully elucidated. mRNA levels of TCIRG1 in different cancer types and the corresponding normal tissues were extracted from the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The Gene Expression Omnibus (access number: GSE16011), the Chinese Glioma Genome Atlas and The Cancer Genome Atlas were used to investigate the mRNA level of TCIRG1 in glioma. Protein level validation in glioma was performed using western blotting. The Database for Annotation, Visualization and Integrated Discovery was used to analyze Gene Ontology (GO) categories for genes correlated with TCIRG1 in GBM. Protein-protein interaction (PPI) networks and module analyses were performed using Cytoscape software and the MCODE plugin. The correlation between tumor immune cell infiltration and TCIRG1 expression was explored using the TIMER database. Additionally, the correlation between TCIRG1 and the gene signature of immune infiltration was explored through TIMER and Gene Expression Profiling Interactive Analysis. External validation of TCIRG1 expression according to immune signatures in GBM was performed using the GSE16011 dataset with the GlioVis online tool. It was found that TCIRG1 expression was increased in GBM and numerous malignant tumors and may serve as a biomarker of the mesenchymal subtype of GBM. GO category analysis of positively correlated genes revealed that TCIRG1 was correlated with the immune response in GBM. PPI network and module analyses also supported the potential function of TCIRG1 in the local immune response. The expression of TCIRG1 was associated with various immune markers. It was therefore speculated that TCIRG1 is associated with glioma malignancy and may be a marker of unfavorable prognosis in patients with GBM, and it could be regarded as a prognostic biomarker and an indicator of immune infiltration in GBM.
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http://dx.doi.org/10.3892/ol.2021.12514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882896PMC
April 2021

Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model.

Front Cell Dev Biol 2020 11;8:624380. Epub 2021 Feb 11.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.

In aged individuals, age-related changes in immune cells, especially T cell deficiency, are associated with an increased incidence of infection, tumor, and autoimmune disease, as well as an impaired response to vaccination. However, the features of gene expression levels in aged T cells are still unknown. Our previous study successfully tracked aged T cells generated from one wave of developing thymocytes of young age by a lineage-specific and inducible Cre-controlled reporter (δ mouse strain). In this study, we utilized this model and genome-wide transcriptomic analysis to examine changes in gene expression in aged naïve and memory T cell populations during the aging process. We identified profound gene alterations in aged CD4 and CD8 T cells. Both aged CD4 and CD8 naïve T cells showed significantly decreased organelle function. Importantly, genes associated with lymphocyte activation and function demonstrated a significant increase in aged memory T cells, accompanied by upregulation of immunosuppressive markers and immune checkpoints, revealing an abnormal T cell function in aged cells. Furthermore, aging significantly affects T cell survival and death signaling. While aged CD4 memory T cells exhibited pro-apoptotic gene signatures, aged CD8 memory T cells expressed anti-apoptotic genes. Thus, the transcriptional analysis of gene expression and signaling pathways in aged T cell subsets shed light on our understanding of altered immune function with aging, which will have great potential for clinical interventions for older adults.
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http://dx.doi.org/10.3389/fcell.2020.624380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905051PMC
February 2021

Diphenyl diselenide ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats via suppressing oxidative stress and inflammation.

Chem Biol Interact 2021 Apr 24;338:109427. Epub 2021 Feb 24.

Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen 518057, China. Electronic address:

Oxidative stress and inflammation are implicated in the occurrence and progression of diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple diaryl diselenide with anti-hyperglycemic, anti-inflammatory, and antioxidant activities. However, the effects of DPDS on DN are still unclear to date. Herein, we aimed to explore whether DPDS could improve renal dysfunction in streptozotocin (STZ)-induced diabetic rats and its underlying mechanisms. STZ-induced DN rats were administered with DPDS (5 or 15 mg/kg) or metformin (200 mg/kg) once daily by intragastric gavage for 12 weeks. DPDS supplementation significantly improved hyperglycemia, glucose intolerance, dyslipidemia, and the renal pathological abnormalities, concurrent with significantly reduced serum levels of creatinine, urea nitrogen, urine volume, and urinary levels of micro-albumin, β2-microglobulin and N-acetyl-glucosaminidase activities. Moreover, DPDS effectively promoted the activities of antioxidant enzymes, and reduced the levels of MDA and pro-inflammatory factors in serum and the kidney. Furthermore, DPDS supplementation activated the renal Nrf2/Keap1 signaling pathway, but attenuated the high phosphorylation levels of NFκB, JNK, p38 and ERK1/2. Altogether, the current study indicated for the first time that DPDS ameliorated STZ-induced renal dysfunction in rats, and its mechanism of action may be attributable to suppressing oxidative stress via activating the renal Nrf2/Keap1 signaling pathway and mitigating inflammation by suppressing the renal NFκB/MAPK signaling pathways, suggesting a potential therapeutic approach for DN.
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http://dx.doi.org/10.1016/j.cbi.2021.109427DOI Listing
April 2021