Publications by authors named "Yuan Yuan"

1,919 Publications

  • Page 1 of 1

Assessment of MRI-Based Radiomics in Preoperative T Staging of Rectal Cancer: Comparison between Minimum and Maximum Delineation Methods.

Biomed Res Int 2021 10;2021:5566885. Epub 2021 Jul 10.

Department of Radiology, Changhai Hospital, No. 168 Changhai Road, Shanghai, China.

The manual delineation of the lesion is mainly used as a conventional segmentation method, but it is subjective and has poor stability and repeatability. The purpose of this study is to validate the effect of a radiomics model based on MRI derived from two delineation methods in the preoperative T staging of patients with rectal cancer (RC). A total of 454 consecutive patients with pathologically confirmed RC who underwent preoperative MRI between January 2018 and December 2019 were retrospectively analyzed. RC patients were grouped according to whether the muscularis propria was penetrated. Two radiologists segmented lesions, respectively, by minimum delineation (Method 1) and maximum delineation (Method 2), after which radiomics features were extracted. Inter- and intraclass correlation coefficient (ICC) of all features was evaluated. After feature reduction, the support vector machine (SVM) was trained to build a prediction model. The diagnostic performances of models were determined by receiver operating characteristic (ROC) curves. Then, the areas under the curve (AUCs) were compared by the DeLong test. Decision curve analysis (DCA) was performed to evaluate clinical benefit. Finally, 317 patients were assessed, including 152 cases in the training set and 165 cases in the validation set. Moreover, 1288/1409 (91.4%) features of Method 1 and 1273/1409 (90.3%) features of Method 2 had good robustness ( < 0.05). The AUCs of Model 1 and Model 2 were 0.808 and 0.903 in the validation set, respectively ( = 0.035). DCA showed that the maximum delineation yielded more net benefit. MRI-based radiomics models derived from two segmentation methods demonstrated good performance in the preoperative T staging of RC. The minimum delineation had better stability in feature selection, while the maximum delineation method was more clinically beneficial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5566885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289571PMC
July 2021

Organ preserving strategies is an alternative for the management of pediatric patients with solid pseudopapillary neoplasm.

Pancreatology 2021 Jul 24. Epub 2021 Jul 24.

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pan.2021.07.007DOI Listing
July 2021

CircSCAP aggravates oxidized low-density lipoprotein-induced macrophage injury by upregulating PDE3B via miR-221-5p in atherosclerosis.

J Cardiovasc Pharmacol 2021 Jul 22. Epub 2021 Jul 22.

General Practice, The Affliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China. Health Management Center, The Second People's Hospital of Guiyang, Guiyang 550081, Guizhou, China. Emergency department, The Affliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.

Abstract: Atherosclerosis (AS) is a major risk factor for cardiovascular disease, in which circular RNAs (circRNAs) play important regulatory roles. This research aimed to explore the biological role of circSCAP (hsa_circ_0001292) in AS development. Real-time PCR or western blot assay was conducted to analyze RNA or protein expression. Cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The levels of lipid accumulation-associated indicators and oxidative stress factors were detected using commercial kits. The levels of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). Intermolecular interaction was verified via dual-luciferase reporter analysis or RNA pull-down analysis. CircSCAP and phosphodiesterase 3B (PDE3B) levels were elevated, whereas miR-221-5p level was decreased in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced THP-1 cells. CircSCAP absence suppressed lipid deposition, inflammation, and oxidative stress in ox-LDL-induced THP-1 cells. MiR-221-5p was a target of circSCAP, and anti-miR-221-5p largely reversed si-circSCAP-induced effects in ox-LDL-induced THP-1 cells. PDE3B was a target of miR-221-5p, and PDE3B overexpression largely counteracted miR-221-5p accumulation-mediated effects in ox-LDL-induced THP-1 cells. NF-κB signaling pathway was regulated by circSCAP/miR-221-5p/PDE3B axis in ox-LDL-induced THP-1 cells. In conclusion, circSCAP facilitated lipid accumulation, inflammation, and oxidative stress in ox-LDL-induced THP-1 macrophages by regulating miR-221-5p/PDE3B axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0000000000001118DOI Listing
July 2021

Associations of individual and joint expressions of ERCC6 and ERCC8 with clinicopathological parameters and prognosis of gastric cancer.

PeerJ 2021 15;9:e11791. Epub 2021 Jul 15.

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, China.

Background: Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic diseases and cancers. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear.

Methods: In this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) in 109 paired GC and para-cancerous normal tissue samples. The mRNA expression was detected in 36 pairs of tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis to explore the function and regulation networks of ERCC6 and ERCC8 in GC.

Results: Individual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. ERCC6 mRNA expression showed no difference in GC and paired tissues, while ERCC8 mRNA was significantly decreased in GC tissues. Protein expression of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated that the OS was longer when ERCC6 protein expression and ERCC8 mRNA expression increased, and double negative ERCC6-ERCC8 expression was associated with a short OS. Bioinformatics analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. KEGG pathway showed that ERCC6/ERCC8 related gene sets were mainly involved in the regulation of PI3K/AKT/mTOR pathway. Direct physical interactions were found between ERCC6 and ERCC8.

Conclusions: Individual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Protein expression of ERCC6, ERCC6-ERCC8, and mRNA expression of ERCC8 were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and may regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286707PMC
July 2021

Microfluidic Transport of Hybrid Optoplasmonic Particles for Repeatable SERS Detection.

Anal Chem 2021 Aug 26;93(30):10672-10678. Epub 2021 Jul 26.

Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China.

For its ultrahigh sensitivity, the microfluidic system combined with surface-enhanced Raman spectroscopy (SERS) becomes one of the most interesting topics in integrated online monitoring related fields. In previous reports, the commonest surface plasmon-enhanced substrates in microfluidics consist of immobilized metal nanostructures on the channel surface to overcome the disturbance of Brownian motion. In this work, a hybrid optoplasmonic microfluidic conveyer is developed, in which the movable, highly ordered optoplasmonic particles are delivered to the detection spot for SERS detection. Here, the optoplasmonic particle is the SiO microsphere with in situ photochemical reduced Ag nanoparticles on the surface. Because of the converged light at the SiO microsphere surface, the SERS spectra collected at this optoplasmonic particle in the channel exhibit excellent performance, which is confirmed by the simulated electric field distribution. In addition, the experimental data also demonstrate that the quantitative analysis is achieved at 1 nM in this optoplasmonic microfluidic conveyer. Furthermore, the used optoplasmonic particle can be ejected from the microfluidic channel by modulating the velocity of injected fluid such that the new optoplasmonic particle will be delivered to the detection spot for repeatable SERS detection in the same channel. The dynamic process of optoplasmonic particle transport is investigated in this microconveyer, and the built theoretical model to predict the particle release is highly identical with the experimental data. These data point out that our hybrid optoplasmonic microfluidic conveyer has repeatable enhanced substrates with the high SERS sensitivity to overcome the cross-contamination of different target molecules in repeatable detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.1c02139DOI Listing
August 2021

A comparative study of epidural labor analgesia and natural delivery without analgesia.

Am J Transl Res 2021 15;13(6):7015-7021. Epub 2021 Jun 15.

Department of General Surgery, Fourth Hospital of Xinyu Xinyu, Jiangxi Province, China.

Objective: To investigate the effects of epidural labor analgesia and natural delivery without analgesia on labor duration, pain, uterine continuous contraction time, abnormal labor process and complications.

Methods: A total of 220 primiparas in our hospital were selected and divided into two groups according to whether they accepted epidural labor analgesia, including 146 cases in the study group and 74 cases in the blank group. Primiparas in the study group received epidural block analgesia, and those in the blank group received routine labor without analgesia. Duration of the first, second and third stages of labor was observed and recorded. The NRS pain score and uterine continuous contraction time were detected before and after the analgesia. The abnormal situation and complications of primiparas in the two groups were recorded.

Results: Compared with those in the blank group, the duration of the first stage of labor and the amount of postpartum hemorrhage in the study group were decreased (all P<0.001). The primiparas' NRS score in the study group was lower than that in the blank group at 10 min, 15 min, 30 min, 60 min and 120 min after analgesia (all P<0.001). The duration of uterine contractions in the study group was lower than that in the blank group at 15 min, 30 min and 60 min after analgesia (all P<0.01). Compared with those in the blank group, primiparas in the study group had a higher probability of active phase arrest in the process of labor (P<0.05). Compared with the blank group, the probability of urinary retention in the study group increased (P<0.05).

Conclusion: The effect of epidural labor analgesia is better, which is conducive to shorten the time of the first stage of labor, good analgesic effect, shorter duration of the uterine contraction and higher safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290643PMC
June 2021

Perceived Stress and Life Satisfaction Among Chinese Clinical Nursing Teachers: A Moderated Mediation Model of Burnout and Emotion Regulation.

Front Psychiatry 2021 8;12:548339. Epub 2021 Jul 8.

Department of Field Nursing, School of Nursing, Army Medical University, Chongqing, China.

Our previous study indicated that clinical teaching nurses in China suffered high levels of perceived stress and burnout, mainly because they were taking double responsibilities of nursing and teaching at the same time. The study aimed to investigate the underlying mechanisms of how and when perceived stress increased the risk of burnout and decreased life satisfaction among clinical teaching nurses. Questionnaires about perceived stress, burnout, emotion regulation, and life satisfaction were self-administered to 1,372 teaching nurses from eight tertiary military hospitals in China. Correlation and hierarchical multiple regressions were employed for data analysis. The results revealed that perceived stress had direct and indirect impacts on life satisfaction, with the principal element of burnout-emotional exhaustion-acting as a mediator. Moreover, the association between perceived stress and emotional exhaustion was moderated by emotion suppression-a key emotion regulation strategy. The negative impact of perceived stress on burnout was stronger among teaching nurses with high emotion suppression than among those with low emotion suppression. The present study contributed to a deeper understanding of the relationship between perceived stress and life satisfaction and also suggested further research into emotion regulation interventions to alleviate or eliminate the impact of perceived stress on burnout and eventually improve the life satisfaction for Chinese clinical nursing teachers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.548339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295563PMC
July 2021

Experimental research on sintering construction spoil bricks based on microwave heating technology.

Environ Sci Pollut Res Int 2021 Jul 23. Epub 2021 Jul 23.

School of Civil Engineering, Xi'an University of Architecture & Technology, 710055, Xi'an, China.

The accumulation of construction spoil has brought great challenges to urban construction and environmental protection. It is an effective way to solve the problem of construction spoil accumulation by using construction spoil to sinter brick. At the same time, it can also reduce the waste of clay resources and farmland destruction caused by the production of sintered brick. Microwave sintering technology can greatly improve the sintering efficiency of materials. Sintering brick by microwave sintering technology can avoid a series of environmental problems in the traditional production process of sintered brick and can lead to an eco-friendly production of bricks. In this study, construction spoil was used as the raw material, and AlO, FeO, and TiO powders were studied as MASM for improving the temperature rise rate and sintering efficiency of the brick in microwave sintering process. The characteristics of construction spoil brick sintered by microwave were studied by series experiments including unit weight, compressive strength, and meso-analysis. Results proven that microwave sintering technology is an efficient technology for brick making. The MASM can effectively increase the temperature rise rate of the sample and simultaneously improve the impermeability of the sample and sintering efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-15331-1DOI Listing
July 2021

By restoring autophagic flux and improving mitochondrial function, corosolic acid protects against Dox-induced cardiotoxicity.

Cell Biol Toxicol 2021 Jul 22. Epub 2021 Jul 22.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Despite effective anticancer effects, the use of doxorubicin (Dox) is limited due to its side effects as cardiotoxicity. Corosolic acid (CRA) is a pentacyclic triterpene acid isolated from Lagerstroemia speciosa L. (Banaba) leaves, and it has also been shown to improve myocardial hypertrophy and myocardial infarction which expected to be used in clinical pharmaceuticals. The purpose of this study was to explore whether CRA can improve myocardial injury caused by Dox and to clarify potential mechanisms. C57 BL/6J mice and AMPKα2 knockout mice were given a single intraperitoneal (i.p.) injection of Dox (5 mg/kg) every week for 4 weeks, while normal saline (NS) was used as control. Mice were given CRA (10 mg/kg or 20 mg/kg) or equal volumes of normal saline daily after the first time i.p. injection of Dox. After 4 weeks, echocardiography, gravimetric, hemodynamic, histological, and biochemical analyses were conducted. After Dox injury, compared with the control group, CRA increased the survival rate of mice, improved the cardiac function, decreased the oxidative stress, and reduced the apoptosis. CRA may function by promoting transcription factor EB (TFEB) nuclear translocation and thus restoring autophagic flux. We also observed that CRA protected mitochondrial structure and function, which may benefit from oxidative stress reduction or TFEB activation. In vitro, the protective effect of CRA is reversed by TFEB deletion. Then, we evaluated the expression of AMPKα2/mTOR C1 signaling pathway, the main pathway of TFEB activation. In vivo and in vitro, CRA promoted TFEB nuclear translocation by activating AMPKα2/mTOR C1 signaling, while ablating AMPKα2 reversed these results and accompanied with a decrease in the ability of CRA to resist Dox-induced cardiotoxicity. Thus, we suggested that CRA activated TFEB in an AMPKα2-dependent manner to protect against Dox cardiotoxicity. This study confirms the role and mechanism of CRA in the treatment of Dox-induced cardiac injury. Dox-induced damage to autophagy includes autophagosomes maturation disorders and autophagolysosomes acidification defects, CRA restored autophagic flux, and promoted lysosomal degradation by activating TFEB in an AMPKα2-depended manner, stabilized mitochondrial function, ultimately protected against Dox-induced cardiotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10565-021-09619-8DOI Listing
July 2021

miR-671-5p repressed progression of papillary thyroid carcinoma via TRIM14.

Kaohsiung J Med Sci 2021 Jul 22. Epub 2021 Jul 22.

Department of General Surgery, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan City, China.

The pivotal role of dysregulated miRNAs in development of papillary thyroid carcinoma has been emphasized in recent research. miR-671-5p was previously documented to function as a tumor suppressor. However, the role and mechanism of miR-671-5p in progression of papillary thyroid carcinoma remain to be further studied. Data from functional assays indicated that forced expression of miR-671-5p decreased cell viability, repressed cell proliferation, migration, and invasion in papillary thyroid carcinoma cells. In vivo study showed that miR-671-5p overexpression inhibited tumor growth, downregulated Ki67, and decreased tumor volume and weight. Tripartite motif containing 14 (TRIM14) was verified as downstream target of miR-671-5p. The expression of TRIM14 was suppressed by miR-671-5p in papillary thyroid carcinoma. Overexpression of TRIM14 increased cell viability, and promoted the proliferation, migration, and invasion of papillary thyroid carcinoma. Moreover, TRIM14 counteracted the suppressive effect of miR-671-5p overexpression on papillary thyroid carcinoma cell growth. In conclusion, miR-671-5p repressed progression of papillary thyroid carcinoma through downregulation of TRIM14, providing a promising target for therapy of papillary thyroid carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/kjm2.12424DOI Listing
July 2021

NDUFA4L2 promotes trastuzumab resistance in HER2-positive breast cancer.

Ther Adv Med Oncol 2021 30;13:17588359211027836. Epub 2021 Jun 30.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

Background: Trastuzumab (Herceptin) is the key systemic therapy for HER2-positive breast cancer. However, the initial response rate is limited to approximately 50% in patients. Moreover, most patients, especially at an advanced stage, eventually develop acquired resistance. Understanding the mechanisms of trastuzumab resistance is crucial for achieving better treatment outcome in this group of patients.

Methods: A trastuzumab-resistant (TR) cell line was developed using the BT474 HER2-positive breast cancer cell line. Whole-transcriptome expression array was performed and the TR-related gene NDUFA4L2 was identified by differential expression analysis between BT474 and BT474-TR. Mitochondrial localization of NDUFA4L2 was confirmed by immunofluorescence and western blotting using mitochondrial fractionation. Mitochondrial function and energy metabolism were evaluated using Seahorse, ATP production, and lactate production assays, and cellular reactive oxygen species (ROS) levels were determined using DCFDA. NDUFA4L2 expression in patients was evaluated by immunohistochemistry, and relapse-free survival was analyzed using the Kaplan-Meier method.

Results: NDUFA4L2 was highly expressed in the TR HER2-positive breast cancer cell line. High expression level of NDUFA4L2 was associated with shorter relapse-free intervals in trastuzumab-treated HER2-positive breast cancer patients. Overexpression of NDUFA4L2 enhanced Warburg effects, enhanced aerobic glycolysis, reduced oxygen consumption, and lowered ROS production. Mechanistically, overexpression of NDUFA4L2 facilitated mitochondrial relocalization of HER2 and suppressed ROS production, thus rendering cancer cells more resistant to trastuzumab treatment.

Conclusions: We identified NDUFA4L2 as a new biomarker and potential therapeutic target for TR HER2-positive breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17588359211027836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256255PMC
June 2021

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response.

J Zhejiang Univ Sci B 2021 Jul;22(7):590-598

Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou 310016, China.

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 () and transforming growth factor-β-activated kinase 1-binding protein 2 (), two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage. Meanwhile, overexpression of 3' untranslated region (UTR) in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155, which resulted in an elevated expression level of SOCS1 protein. These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1631/jzus.B2000826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284089PMC
July 2021

Impairment of Cardiac Autonomic Nerve Function in Pre-school Children With Intractable Epilepsy.

Front Neurol 2021 25;12:632370. Epub 2021 Jun 25.

National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing, China.

Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE). Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3-6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths-Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed. Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean_RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1_5 in awake state was lower, and areas 6_15 and 6_20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1_5 and sleep: area6_20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures. Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.632370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267887PMC
June 2021

Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis.

Cancer Cell Int 2021 Jul 12;21(1):368. Epub 2021 Jul 12.

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, No.155 NanjingBei Street, Heping District, Shenyang, 110001, Liaoning Province, China.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed.

Methods: Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue.

Results: The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC.

Conclusions: The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-02077-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274036PMC
July 2021

Long non-coding RNA Pvt1 modulates the pathological cardiac hypertrophy via miR-196b-mediated OSMR regulation.

Cell Signal 2021 Jul 8;86:110077. Epub 2021 Jul 8.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China; The Fifth Affiliated Hospital of Xin Jiang medical University, Department of Cardiology, Urumchi 830001, China. Electronic address:

Cardiac hypertrophy is the uppermost risk factor for the development of heart failure, leading to irreversible cardiac structural remodeling and sudden death. As a major mediator of cardiac remodeling, oncostatin M (OSM) and its receptor, OSMR, attract plenty of interest. Recent studies have demonstrated key effects of noncoding RNAs on myocardial remodeling. However, whether noncoding RNAs that regulate the expression of OSMR would regulate the process of remodeling remain unclear. Herein, we observed that long noncoding RNA (lncRNA) Pvt1 expression showed to be significantly elicited by aortic banding (AB) operation in vivo and by angiotensin (Ang II) treatment in vitro. Pvt1 knockdown significantly attenuated the myocardial hypertrophy caused by pressure overload within rats and the cardiac myocyte hypertrophy caused by Ang II in vitro. Moreover, Pvt1 knockdown also decreased cellular myomesin and B-raf, which was involved in OSM function in cardiac remodeling. Based on online tools prediction, miR-196b may simultaneously target Pvt1 and OSMR 3' untranslated region (UTR). In rat H9c2 cells and primary cardiac myocyte, Pvt1 and miR-196b exerted negative regulatory effects on each other and miR-196b negatively regulated OSMR expression. Pvt1 directly targeted miR-196b to relieve miR-196b-induced OSMR suppression via acting as a competing endogenous RNA (ceRNA). Moreover, the effect of miR-196b suppression upon the B-raf was opposite to Pvt1 knockdown, and miR-196b suppression might significantly attenuate the effect of Pvt1 knockdown. In summary, Pvt1/miR-196b axis modulating cardiomyocyte hypertrophy and remodeling via OSMR. Our findings provide a rationale for further studies on the potential therapeutic benefits of Pvt1 function and mechanism in cardiac and cardiomyocyte hypertrophy by a lncRNA-miRNA-mRNA network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2021.110077DOI Listing
July 2021

DWI and IVIM Imaging in a Murine Model of Rhabdomyosarcoma: Correlations with Quantitative Histopathologic Features.

J Magn Reson Imaging 2021 Jul 8. Epub 2021 Jul 8.

Department of Radiology, The Second Hospital, Dalian Medical University, Dalian, China.

Background: High cellularity and abnormal interstitial structures are some of the unfavorable factors that affect the treatment outcomes and survival of rhabdomyosarcoma (RMS) patients.

Purpose: To explore the correlation between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with quantitative histopathologic features in a murine model of RMS.

Study Type: Prospective.

Animal Model: Murine model of RMS (31 female BALB/c nude mice).

Field Strength/sequence: 3.0 T; fast spin-echo (FSE) T1-weighted imaging, fast relaxation fast spin-echo (FRFSE) T2-weighted imaging, DWI PROPELLER FSE imaging sequence, and IVIM echo planar imaging sequence; 10 different b-values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 1200 s/mm ).

Assessment: Magnetic resonance imaging (MRI) was performed after 30-45 days of implantation. The following MRI parameters were calculated: apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Histopathologic features, which contained nuclear, cytoplasmic, and stromal fractions, and the nuclear-to-cytoplasmic ratio within the tumor were measured using image-based segmentation.

Statistical Tests: Pearson's correlation, multiple linear regression analysis, and receiver operating characteristic curve analysis were performed. A P < 0.05 was considered statistically significant.

Results: The ADC value showed moderate negative correlation with nuclear fraction (r = -0.540), and moderate positive correlation with stroma fraction (r = 0.474). The D value showed moderate negative correlation with nuclear fraction (r = -0.491), and moderate positive correlation with stroma fraction (r = 0.421). The f value showed a moderate negative correlation with stroma fraction (r = -0.423). The D value showed the best diagnostic ability. The optimal cut-off D value of 0.460 was associated with 77.8% sensitivity and 68.2% specificity (area under the curve, 0.747).

Data Conclusion: The ADC, D, and f values obtained from DWI and IVIM images showed moderate correlation with the quantitative histopathologic features in a murine model of RMS.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27828DOI Listing
July 2021

The successful application of pyrotinib in the treatment of primary trastuzumab-resistant HER-2-positive breast cancer with bilateral axillary lymph node metastasis: a case report.

Ann Palliat Med 2021 Jun;10(6):7138-7145

Department of Chemotherapy, Jiangsu Cancer Hospital &Jiangsu Institute of Cancer Research &The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing China.

Breast cancer patients with synchronous contralateral axillary lymph node metastasis (CAM) are very rare, and there is a lack of published treatment guidelines for this kind of patients. We presented a human epidermal growth factor receptor 2 (HER-2)-positive breast cancer case, who was diagnosed as CAM with primary trastuzumab resistance. In this case report, we describes a 47-year-old woman diagnosed with HER-2 positive breast cancer with regional lymph nodes metastasis. However, physical examination identified contralateral axillary lymph nodes, the auxiliary inspection did not assist in determining the nature of the right axillary lymph nodes, and there was no obvious mass in the right breast. Hence, we performed the core needle biopsy on the right axillary lymph node, which revealed the presence of metastatic breast adenocarcinoma. The patient received trastuzumab-based treatment, but this only afforded a progression-free survival of 5 months, owing to primary trastuzumab resistance. She was then successfully treated with pyrotinib, and the outcome was close to clinical complete response (CCR) with a progression-free survival of over 27 months thus far. This case report may help inform clinicians in the diagnosis of breast cancer with CAM and offer the treatment options in HER-2-positive metastasis breast cancer with primary trastuzumab resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-1364DOI Listing
June 2021

Application of bone turnover markers and DXA and QCT in an elderly Chinese male population.

Ann Palliat Med 2021 Jun;10(6):6351-6358

Department of Geriatrics, Beijing Jishuitan Hospital, Beijing, China.

Background: To investigate the clinical values and relationships of bone turnover markers (BTMs), dual-energy X-ray absorptiometry (DXA), and quantitative computed tomodensitometry (QCT) in the screening of osteoporosis (OP) in elderly Chinese males.

Methods: General data, including age, height, and weight, the results of BTM measurements, and the findings of DXA and QCT in 357 male patients aged ≥50 years who visited the outpatient or inpatient Department of Geriatrics, Beijing Jishuitan Hospital from June 2017 to May 2019 were retrospectively analyzed.

Results: The OP detection rates based on T-scores of DXA L1-4, DXA total hip, and spine QCT were 3.4% (12/357), 13.2% (47/357), and 40.3% (144/357), respectively. QCT had a significantly higher OP detection rate than did DXA (P<0.001). There were 24 cases of fragility fractures, which were significantly correlated with the DXA total hip BMD and its T-score, with risk cut-off values of 0.607 g/cm2 and -2.950, respectively. The measured levels of the 5 BTMs were as follows: total procollagen type I amino-terminal propeptide (tPINP), 39.23±20.82 ng/mL; β-isomerized C-terminal telopeptides (β-CTX), 0.38±0.21 ng/mL; osteocalcin (OC), 13.50±8.80 ng/mL; 25-hydroxycholecalciferol (25(OH)D3), 12.90±7.46 ng/mL; and parathormone (PTH), 54.50±25.35 pg/mL. The elevation of tPINP, β-CTX, and OC were negatively correlated with aging and positively correlated with decreased BMD (all P<0.05). OC and 25(OH)D3 values were significantly lower than their normal range. Among the 43 patients with normal bone mass on both DXA and QCT examinations, 34 presented with abnormal BTMs, including elevated tPINP in 2 cases, elevated β-CTX in 2 cases, and OC decreased in 31 cases.

Conclusions: In the Chinese elderly male population, spine QCT has a higher detection rate of OP than DXA, whereas hip DXA is more advantageous in predicting the risk of fragility fracture. tPINP, β-CTX, and OC can be used as reliable indicators for the dynamic observation of bone content changes and may screen for early bone metabolism abnormalities when BMD examinations still show negative results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-21-612DOI Listing
June 2021

Functional characteristics of a novel odorant binding protein in the legume pod borer, Maruca vitrata.

Sci Rep 2021 Jul 7;11(1):14027. Epub 2021 Jul 7.

Wuhan Donghu University, Wuhan, 430212, China.

Insect olfaction system plays a key role in the foraging food, pollination, mating, oviposition, reproduction and other insect physiological behavior. Odorant binding protein are widely found in the various olfactory sensilla of different insect antennae and involved in chemical signals discrimination from natural environment. In this study, a novel OBP gene, MvitOBP3 is identified from the legume pod borer, Maruca vitrata, which it mainly harms important legume vegetables including cowpea, soybean and lablab bean. Real-time PCR results demonstrated that MvitOBP3 gene was abundantly expressed in the antennal tissue of M. vitrata, while low levels were distributed in the head, thorax, abdomen, leg and wing of adult moths. The recombinant OBP3 protein was purified using the prokaryotic expression and affinity chromatography system. Fluorescence competitive binding experiments indicated that that MvitOBP3 protein exhibited greater binding affinities with host-plant flower volatiles including Butanoic acid butyl ester, Limonene, 1H-indol-4-ol and 2-methyl-3-phenylpropanal, highlighting they may have attractant activities for the oviposition of female moths on the legume vegetables. Moreover, protein homology modeling and molecular docking analysis revealed that there are six amino acid sites of MvitOBP3 involved in the binding of the host-plant volatiles. These findings will further promote to understand the key role of odorant binding protein during host perception and oviposition of M. vitrata moths, which improve the efficiency of semiochemical-based prevention and monitoring for this pest in the legume vegetables field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-93382-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263619PMC
July 2021

Long-term effects of weather condition and air pollution on acute hemorrhagic conjunctivitis in China: A nationalwide surveillance study in China.

Environ Res 2021 Jul 4;201:111616. Epub 2021 Jul 4.

Department of Infectious Diseases, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, 310051, China. Electronic address:

Background: Global climate change could have potential impact on enterovirus (EV)-induced infectious diseases. However, the environmental factors promoting acute hemorrhagic conjunctivitis (AHC) circulation remain inconclusive. This study aimed to quantify the relationship between the environment and AHC.

Methods: We retrieved the monthly counts and incidence of AHC, meteorological variables and air quality in mainland China between 2013 and 2018. Exposure risks were evaluated by multivariate distributed lag nonlinear models.

Results: A total of 219,599 AHC cases were reported in 31 provinces of China, predominantly in southern and central China, seasonally increased in summer. AHC incidence increased by 7% between 2013 and 2018, from 2.6873 to 2.7570 per 100,000 people. A moderate positive correlation was seen between AHC and monthly mean temperature, relative humidity (RH) and precipitation. Each unit increment was associated with a relative risk for AHC of 1.058 at 17°-32 °C at lag 0 months, 1.017 at 65-71% RH at lag 1.4 months, and 1.039 at 400-569 mm at lag 2.4 months. By contrast, a negative correlation was seen between monthly ambient NO and AHC.

Conclusion: Long-term exposure to higher mean temperature, RH and precipitation were associated with an increased risk of AHC. The general public, especially susceptible populations, should pay close attention to weather changes and take protective measures in advance to any AHC outbreak as the above situations occur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2021.111616DOI Listing
July 2021

DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury.

Cell Death Discov 2021 Jun 17;7(1):167. Epub 2021 Jun 17.

Department of Nephrology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Jinhua, 322000, China.

Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers' expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41420-021-00528-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257623PMC
June 2021

Prediction of Remnant Liver Regeneration after Right Hepatectomy in Patients with Hepatocellular Carcinoma Using Preoperative CT Texture Analysis and Clinical Features.

Contrast Media Mol Imaging 2021 10;2021:5572470. Epub 2021 Jun 10.

Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China.

Objectives: To predict the regenerative rate of liver in patients with HCCs after right hepatectomy using texture analysis on preoperative CT combined with clinical features.

Materials And Methods: 88 patients with 90 HCCs who underwent right hepatectomy were retrospectively included. The future remnant liver was semiautomatically segmented, and the volume of future remnant liver on preoperative CT (LV) and the volume of remnant liver on following-up CT (LV) were measured. We calculated the regeneration index (RI) by the following equation: (LV - LV)/LV) × 100 (%). The support vector machine recursive method was used for the feature selection. The Naive Bayes classifier was used to predict liver RI, and 5-fold cross-validation was performed to adjust the parameters. Sensitivity, specificity, and accuracy were calculated to evaluate the diagnostic efficiency of the model.

Results: The mean RI was 142.99 ± 92.17%. Of all clinical parameters and texture features, the AST, ALB, PT-INR, Perc.10%, and S(5, -5)Correlat were found to be statistically significant with RI. The diagnostic sensitivity, specificity, and accuracy of the model in the training group were 0.902, 0.634, and 0.768, and the AUC value of the obtained model was 0.841. In the test group, the sensitivity, specificity, and accuracy of the model were 1.0, 0.429, and 0.778, respectively, and the AUC value was 0.844.

Conclusion: The use of texture analysis on preoperative CT combined with clinical features can be helpful in predicting the liver regeneration rate in patients with HCCs after right hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5572470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213498PMC
June 2021

Impact of Arterial Remodeling of Intermediate Coronary Lesions on Long-Term Clinical Outcomes in Patients with Stable Coronary Artery Disease: An Intravascular Ultrasound Study.

J Interv Cardiol 2021 11;2021:9915759. Epub 2021 Jun 11.

Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

Background: Treatment of coronary intermediate lesions remains a controversy, and the role of arterial remodeling patterns determined by intravascular ultrasound in intermediate lesion is still not well known. The aim of this study was to investigate the impact of arterial remodeling of intermediate coronary lesions on long-term clinical outcomes.

Methods: Arterial remodeling patterns were assessed in 212 deferred intermediate lesions from 162 patients after IVUS examination. Negative, intermediate, and positive remodeling was defined as a remodeling index of <0.88, 0.88∼1.0, and >1.0, respectively. The primary endpoint was the composite vessel-oriented clinical events, defined as the composition of target vessel-related cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Quantitative flow ratio was assessed for evaluating the functional significance of intermediate lesions.

Results: 72 intermediate remodeling lesions were present in 66 patients, whereas 77 negative remodeling lesions were present in 71 patients, and 63 positive remodeling lesions were present in 55 patients. Negative remodeling lesions had the smallest minimum lumen area (4.16 ± 1.03 mm vs. 5.05 ± 1.39 mm vs. 4.85 ± 1.76 mm; < 0.01), smallest plaque burden (63.45 ± 6.13% vs. 66.12 ± 6.82% vs. 71.17 ± 6.45%; < 0.01), and highest area stenosis rate (59.32% ± 10.15% vs. 54.61% ± 9.09% vs. 51.67% ± 12.96%; < 0.01). No significant difference was found in terms of quantitative flow ratio among three groups. At 5 years follow-up, negative remodeling lesions had a higher rate of composite vessel-oriented clinical event (14.3%), compared to intermediate (1.4%, =0.004) or positive remodeling lesions (4.8%, =0.06). After adjusting for multiple covariates, negative remodeling remained an independent determinant for vessel-oriented clinical event (HR: 4.849, 95% CI 1.542-15.251, =0.007).

Conclusion: IVUS-derived negative remodeling is associated with adverse long-term clinical outcome in stable patients with intermediate coronary artery stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9915759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213497PMC
July 2021

Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer.

Eur J Cancer 2021 Jul 1;154:11-20. Epub 2021 Jul 1.

Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Beckman Research Institute, Duarte, CA, USA.

Background: CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR) human epidermal growth factor receptor 2 negative (HER2) metastatic breast cancer (MBC).

Patients And Methods: Women with stage IV HR HER2 MBC were enrolled and treated with palbociclib, pembrolizumab and letrozole. Primary end-points were safety, tolerability and efficacy.

Results: Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately.

Conclusion: The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.05.035DOI Listing
July 2021

Adsorption and catalytic performance of pipe growth rings from water distribution networks using 5-BSA as the target pollutant.

Chemosphere 2021 Jun 28;284:131343. Epub 2021 Jun 28.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, 150090, China.

In this study, we investigated the use of pipe growth rings from water distribution networks as a catalyst in heterogeneous Fenton-like oxidation processes. The major constituents of real pipe growth rings (α- and γ-FeOOH) were prepared and considered as a simulated growth ring (SGR). Its performance in removing 5-bromosalicylic acid (5-BSA), a novel phenolic halogenated disinfection byproduct, was examined. SGR exhibited strong catalytic ability and a certain degree of adsorption capacity. Under acidic conditions, the adsorption and oxidation efficiencies were 32.65% and 87.67%, respectively. Furthermore, 72.19% of 5-BSA could be oxidized even at pH of 7. Kinetic characterizations at various temperatures revealed that both the adsorption and catalytic oxidation processes followed pseudo-second-order kinetic models and were surface-controlled with high activation energies (31.26 and 23.58 kJ mol, respectively). Ecotoxicity analyses of the transformation products (TPs) showed that the SGR/HO system could effectively reduce the toxicity of 5-BSA. Moreover, the number of iron ions leaching from SGR was below 0.1 mg L in all experiments. The results of this study support further investigation of using real pipe growth rings in off-line water treatment, as well water network contamination remediation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.131343DOI Listing
June 2021

Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome.

NPJ Breast Cancer 2021 Jul 1;7(1):84. Epub 2021 Jul 1.

Department of Physics and Astronomy, University of California, Irvine, Irvine, CA, USA.

While tumor infiltration by CD8 T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method 'occupancy') to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00291-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249408PMC
July 2021

Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis.

Biomolecules 2021 Jun 22;11(7). Epub 2021 Jun 22.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11070923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301948PMC
June 2021

Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients.

Cancers (Basel) 2021 Jun 3;13(11). Epub 2021 Jun 3.

Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA 91010, USA.

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx panel. The most prevalent genes with somatic mutations were , , , and . In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations in the mutually exclusive gene pair and showed an opposite effect on the overall survival. However, patients with mutations showed significantly shorter OS (HR: 1.72, 95% CI: 1.34-2.21, < 0.001) after adjusting for cancer type, age at diagnosis, and sex. Five-year post metastatic diagnosis survival analysis showed a significant improvement in OS (median survival 28 and 43 months in pre-2015 and post-2015 metastatic diagnosis, respectively, = 0.00021) based on the year of metastatic diagnosis. Although the use of targeted therapies after metastatic diagnosis prolonged OS, the benefit was not statistically significant. However, longer five-year progression-free survival (PFS) was significantly associated with targeted therapy use (median 10.9 months (CI: 9.7-11.9 months) compared to 9.1 months (CI: 8.1-10.1 months) for non-targeted therapy, respectively, = 0.0029). Our results provide a clinically relevant overview of the complex molecular landscape and survival mechanisms in metastatic solid cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13112776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199748PMC
June 2021

Pleural Fluid GSDMD Is a Novel Biomarker for the Early Differential Diagnosis of Pleural Effusion.

Front Microbiol 2021 7;12:620322. Epub 2021 Jun 7.

Department of Laboratory Medicine, The Second Hospital of Chongqing Medical University, Chongqing, China.

Objective: Gasdermin D (GSDMD), controlling pyroptosis in cells, has multiple physiological functions. The diagnostic role of GSDMD in pleural effusion (PE) remains unknown.

Methods: Sandwich ELISA kits that we developed were applied to measure the level of GSDMD for 335 patients with a definite cause of PE, including transudative PE, tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). The diagnostic accuracy of Light's criteria vs. the new marker GSDMD was performed. Clinical follow-up of 40 cases of PPE was conducted and divided into efficacy and non-efficacy groups according to the therapeutic outcome. Nucleated cells (NCs) in PE were isolated and further infected with bacteria to verify the cell source of GSDMD.

Results: The diagnostic accuracy of GSDMD for the diagnosis of PE were 96% (sensitivity) and 94% (specificity). The receiver operating characteristic (ROC) curve indicated that GSDMD can be an efficient biomarker for the differential diagnosis of transudative PE and other groups (all AUC > 0.973). Noteworthily, the highest AUC belonged to tuberculosis diagnosis of 0.990, and the cut-off value was 18.40 ng/mL. Moreover, the same cut-off value of PPE and MPE was 9.35 ng/mL. The combination of GSDMD, adenosine deaminase (ADA), and lactate dehydrogenase (LDH) will further improve the diagnostic efficiency especially between TPE and PPE (AUC = 0.968). The AUC of GSDMD change at day 4, which could predict the therapeutic effect at an early stage, was 0.945 ( < 0.0001). Interestingly, bacterial infection experiments further confirm that the pleural fluid GSDMD was expressed and secreted mainly by the NCs.

Conclusion: GSDMD and its combination are candidates as a potentially novel biomarker not only to separate PEs early and effectively, but also monitor disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.620322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215111PMC
June 2021

Application of Capillary Electrophoresis in Monoclonal Gammopathies and the Cutoff Value of Monoclonal Protein in Differential Diagnosis of Multiple Myeloma and Other Monoclonal Gammopathies.

Ann Clin Lab Sci 2021 May;51(3):400-407

Department of Clinical Laboratory, the Affiliated Hospital of Qingdao University, Qingdao, China

Objective: Monoclonal protein (MP) exists in various diseases, and capillary electrophoresis (CE) has been widely used to detect MP. However, there is not much research on the application value of MP in the differential diagnosis of monoclonal gammopathies. This study aimed to explore MP's cutoff value for the differential diagnosis of multiple myeloma (MM) and other monoclonal gammopathies (MGs).

Methods: A retrospective analysis of 8167 cases was conducted. Serum MP was detected by CE, and the patients' clinical information was collected from the clinical database of our hospital.

Results: 985 cases had MP with high peaks, and 91.1% were diagnosed with malignant diseases. The MP showed small peaks in 471 cases, and only 24.4% were diagnosed with malignant diseases. Among the MPs, the IgG-κ type was the most common type, followed by the IgG-λ, IgA-κ, IgA-λ, free λ light chain, IgM-κ, free κ light chain, double clone, and IgM-λ types. Differences in the MP of the IgG, IgA, IgM, and FLC types between the MM group and MGUS group were statistically different (<0.01). The MP of the IgG, IgA, and FLC types showed clear specificity and sensitivity in discriminating MM from other monoclonal gammopathies in ROC curve analysis. Serum IgM had statistical significance in the differential diagnosis between WM and other MGs (<0.01). However, there was no statistical significance in the differential diagnosis between MM and other MGs (=0.140). The cutoff values of the MP of the IgG, IgA, and FLC types were >18.67g/L, >13.86g/L, and >10.15g/L, respectively, for the differential diagnosis of MM and other MGs. The cutoff value of the MP of IgM for the WM diagnosis was >37.75 g/L.

Conclusion: CE has good clinical application value in the diagnosis of monoclonal gammopathies, and MP can be used in the differential diagnosis of MM and other monoclonal gammopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2021
-->