Publications by authors named "Yang Fu"

432 Publications

[Relationship between Reference Interval Establishment and Clinical Evaluation in Quantitative Diagnostic Reagents].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jun;45(3):326-329

Jiangsu Bioperfectus Technology Co. Ltd., Taizhou, 225300.

Reference interval study and clinical evaluation are crucial supportive researches to demonstrate the intended use of quantitative diagnostic reagents. The process of determining reference interval, as well as the problems found frequently in clinical evaluation, are discussed here, and the links between them are analyzed from the aspects of product's traceability, intended use and group design. Further, some suggestions are offered in this paper.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.03.020DOI Listing
June 2021

Structural Monoclinicity and Its Coupling to Layered Magnetism in Few-Layer CrI.

ACS Nano 2021 Jun 2. Epub 2021 Jun 2.

Department of Physics, University of Michigan, 450 Church Street, Ann Arbor, Michigan 48109, United States.

Using polarization-resolved Raman spectroscopy, we investigate layer number, temperature, and magnetic field dependence of Raman spectra in one- to four-layer CrI. Layer-number-dependent Raman spectra show that in the paramagnetic phase a doubly degenerated E mode of monolayer CrI splits into one A and one B mode in -layer ( > 1) CrI due to the monoclinic stacking. Their energy separation increases in thicker samples until an eventual saturation. Temperature-dependent measurements further show that the split modes tend to merge upon cooling but remain separated until 10 K, indicating a failed attempt of the monoclinic-to-rhombohedral structural phase transition that is present in the bulk crystal. Magnetic-field-dependent measurements reveal an additional monoclinic distortion across the magnetic-field-induced layered antiferromagnetism-to-ferromagnetism phase transition. We propose a structural change that consists of both a lateral sliding toward the rhombohedral stacking and a decrease in the interlayer distance to explain our experimental observations.
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http://dx.doi.org/10.1021/acsnano.1c02868DOI Listing
June 2021

Inferior outcome of bone metastasis in non-small-cell-lung-cancer patients treated with epidermal growth factor receptor inhibitors.

J Bone Oncol 2021 Aug 4;29:100369. Epub 2021 May 4.

Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Background: Targeted therapy has been established as the standard-of-care for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Among patients with advanced lung cancer, 30-40% have bone metastases (BoM) at first diagnosis. However, little is known on the clinical characteristics and prognostic factors of BoM in patients with NSCLC harboring EGFR mutations.

Methods: Treatment-naive patients with advanced NSCLC harboring EGFR mutations who were prescribed tyrosine kinase inhibitors (TKIs) were screened and enrolled between June 2009 and April 2019 from West China Hospital. Patients were dichotomized according to whether they had BoM. The demographic characteristics, gene mutation status and therapeutic efficacy, including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), were collected.

Results: A cohort of 604 patients were enrolled. The BoM group had worse PFS (11.7 vs. 14.0 months, HR = 0.73,  = 0.00013) and OS (32.8 vs. 46.1 months, HR = 0.54,  < 0.0001) compared with the non-BoM group. No significant differences were observed in disease control rate ( = 0.407) or ORR ( = 0.537) between the two groups. The metastatic sites in the two groups exhibited obvious differences. In multivariate analysis, BoM was found to be an independent factor of worse prognosis.

Conclusion: BoM was identified as an independent inferior prognostic factor for EGFR-TKI treatment, and may have complex biological implications.
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http://dx.doi.org/10.1016/j.jbo.2021.100369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138759PMC
August 2021

Biliteracy and acquisition of novel written words: the impact of phonological conflict between L1 and L2 scripts.

Psychol Res 2021 May 18. Epub 2021 May 18.

Centre for Cognition and Decision Making, Institute for Cognitive Neuroscience, HSE University, Moscow, Russian Federation.

The acquisition of new orthographic representations is a rapid and accurate process in proficient monolingual readers. The present study used biliterate and bialphabetic population to address the impact of phonological inconsistencies across the native (L1) and second (L2) alphabets. Naming latencies were collected from 50 Russian-English biliterates through a reading-aloud task with familiar and novel word forms repeated across 10 blocks. There were three Script conditions: (1) native Cyrillic, (2) non-native Roman, and (3) Ambiguous (with graphically identical, but phonologically inconsistent graphemes shared by both alphabets). Our analysis revealed the main effect of Script on both reading and orthographic learning: naming latencies during training were longer for the ambiguous stimuli, particularly for the novel ones. Nonetheless, novel word forms in the ambiguous condition approached the latencies for the familiar words along the exposures, although this effect was faster in the phonologically consistent trials. Post-training tests revealed similarly successful performance patterns for previously familiar and newly trained forms, indicating successful rapid acquisition of the latter. Furthermore, we found the highest free recall rates for the ambiguous stimuli. Overall, our results indicate that phonological inconsistency initially interferes with the efficiency of novel word encoding. Nevertheless, it does not prevent efficient attribution of orthographic representations; instead, the knowledge of two distinct alphabets supports a more efficient learning and a better memory for ambiguous stimuli via enhancing their encoding and retrieval.
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http://dx.doi.org/10.1007/s00426-021-01529-yDOI Listing
May 2021

Color mismatch and observer metamerism between conventional liquid crystal displays and organic light emitting diode displays.

Opt Express 2021 Apr;29(8):12292-12306

Organic light emitting diode (OLED) displays use red, green, and blue primaries with a higher saturation level to produce larger color gamuts than conventional liquid crystal displays (LCD). No past study, however, experimentally investigated how such a difference between these two display types causes color mismatch and observer metamerism using the most widely used color matching functions (CMFs)-the CIE 1931 2° CMFs-for color calibration and specification. In this study, 50 human observers performed color matching tasks for six color stimuli with a field-of-view of 4.77° between four test displays (i.e., one LCD and three OLED) and a reference OLED display. The color gamuts of the LCD and OLED displays were similar to the sRGB and P3 standard color gamuts. It was found the CIE 1931 2° CMFs cannot accurately characterize the color matches between the LCD and OLED displays, with different chromaticities required to produce matched color appearance. Particularly, when the stimuli had matched color appearance, the chromaticities of the stimuli produced by the LCD display were all shifted towards the -u'+v' direction in the CIE 1976 u'v' chromaticity diagram in comparison to those produced by the OLED display. This suggested that using the CIE 1931 2° CMFs for display calibration would cause the colors shown on OLED displays to have a yellow-green tint if those on LCD displays appear neutral. In addition, a larger degree of observer metamerism was found between the LCD and OLED displays, while little differences, in terms of color mismatch and observer metamerism, were found between the OLED displays. The CIE 2006 2° CMFs were found to have better performance than the CIE 1931 2°, 1964 10°, and 2006 10° CMFs, which could be partially due to the size of the stimulus used in the experiment.
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http://dx.doi.org/10.1364/OE.418675DOI Listing
April 2021

Early Passive Leg Movement Prevents Against the Development of Heart Failure With Preserved Ejection Fraction in Rats.

Front Cardiovasc Med 2021 21;8:655009. Epub 2021 Apr 21.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Exercising was reported by several studies to bring great benefits to heart failure with preserved ejection fraction (HFpEF), which reduced the hospitalization and the mortality of heart failure. However, the underlying mechanism of exercising on HFpEF remains unclear. In the present study, we designed and constructed a device that can perform early passive leg movement (ePLM) in rats and further observed whether treatment of ePLM exerts protective effects on HFpEF of rats. Rats were fed with high salt feed to establish an animal model of pre-clinical diastolic dysfunction (PDD), which would eventually develop into HFpEF, and then treated rats with ePLM. We conducted several experiments to evaluate the conditions of heart and blood vessel. The results show that diastolic functions of heart and blood vessel in rats were significantly improved by treatment of ePLM. We also found that pathological injuries of heart and blood vessel were ameliorated after treatment of ePLM. Moreover, treatment of ePLM decreased the protein levels of Collagen type I, Collagen type III, MMP2, and MMP9 in heart and blood vessel, indicating that cardiac and vascular fibrosis were reduced apparently by treatment of ePLM. Further investigation suggested that treatment of ePLM probably inhibit the activation of TGF-β1/Smad3 signaling pathway as well as promote the activation of Akt/eNOS signaling pathway in high salt diet induced HFpEF. In conclusion, treatment of ePLM alleviated high salt diet induced HFpEF by inhibiting fibrosis suppressing TGF-β1/Smad3 signaling pathway as well as activating Akt/eNOS signaling pathway, implicating treatment of ePLM as a promising novel non-pharmacological approach for HFpEF.
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http://dx.doi.org/10.3389/fcvm.2021.655009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096912PMC
April 2021

Factors Associated with the Expression of ACE2 in Human Lung Tissue: Pathological Evidence from Patients with Normal FEV and FEV/FVC.

J Inflamm Res 2021 28;14:1677-1687. Epub 2021 Apr 28.

Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: Whether COVID-19 comorbidities and risk factors such as old age, male gender, smoking, obesity, eosinophils and blood types have direct contact with expression of ACE2 and pro-inflammation cytokines in human lung tissues were still unclear.

Patients And Methods: Sixty-four patients with normal FEV and FEV/FVC underwent thoracotomy for pulmonary nodules were included. Blinded histological assessments were performed by two pathologists. Clinical features and results of the immunohistochemical staining of ACE2 were collected and analyzed.

Results: ACE2 expressed in alveolar macrophages (most obvious), alveolar epithelia and vascular endothelia, but not in small-airway epithelia. ACE2 expressions are positively related to age ( =0.26, =0.040), weight ( =0.43, <0.001), as well as BMI ( = 0.38, =0.002), and male patients show higher expressions of ACE2 in lungs ( <0.05). ACE2 expressions are negatively related to peripheral eosinophils ( = -0.30, =0.017). There was no correlation between ABO blood types and ACE2 expression in normal lung tissues ( > 0.05). IL-13 and IL-6R expression in lung tissue increased with age ( =0.26, <0.05, for both).

Conclusion: Our pathological evidences showed that the alveolar epithelia, vascular endothelia, and alveolar macrophages are susceptible in human lungs for SARS-CoV-2 infection. The risk factors such as high body weight/BMI, old age, male gender, and eosinopenia may be related to ACE2 expression in human lungs, and associated with more chance to develop the severe cases. IL-6R expression in lung tissue also increased with age. Therefore, weight control and smoking cessation are essential to reduce the susceptibility of SARS-CoV-2 infection, especially in obesity, old or male patients. Peripheral eosinophils monitor is also quite necessary to detect severe tendency in COVID-19 patients.
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http://dx.doi.org/10.2147/JIR.S300747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091594PMC
April 2021

LncRNA ENSG00000254615 Modulates Proliferation and 5-FU Resistance by Regulating p21 and Cyclin D1 in Colorectal Cancer.

Cancer Invest 2021 May 1:1-32. Epub 2021 May 1.

Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.

5-fluorouracil (5-FU) resistance is an urgent problem of colorectal cancer (CRC) chemotherapy that needs to be resolved. To investigate 5-FU-associated lncRNAs for CRC might be of great significant. LncRNA ENSG00000254615 was detected by RNA-sequencing. ENSG00000254615 were detected highly expressed in 5-FU-sensitive CRC cells and tissue specimens, and inhibited cell proliferation and attenuated 5-FU resistance in vitro and in vivo. Furthermore, ENSG00000254615 participated in the regulation of p21 and Cyclin D1. Taken together, we proposed that ENSG00000254615 inhibits proliferation and attenuates 5-FU resistance of CRC by regulating p21 and Cyclin D1 expression.
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http://dx.doi.org/10.1080/07357907.2021.1923727DOI Listing
May 2021

Ba with Unusual Oxidation States in Ba Chalcogenides under Pressure.

J Phys Chem Lett 2021 May 26;12(17):4203-4210. Epub 2021 Apr 26.

State Key Laboratory of Metastable Materials Science & Technology and Key Laboratory for Microstructural Material Physics of Hebei Province, School of Science, Yanshan University, Qinhuangdao 066004, China.

The preparation of compounds with novel atomic oxidation states and emergent properties is of fundamental interest in chemistry. As s-block elements, alkali-earth metals invariably show a +2 formal oxidation state at normal conditions, and among them, barium (Ba) presents the strongest chemical reactivity. Herein, we propose that novel valence states of Ba can be achieved in pressure-induced chalcogenides, where it also shows a feature of 5d-elements. First-principles swarm-intelligence structural search calculations identify three novel stoichiometric compounds: BaCh (Ch = O, S) containing Ba, BaCh (Ch = S, Se, Te) with Ba and Ba, and BaCh (Ch = Se, Te) with Ba cations. The pressure-induced drop of the Ba 5d level relative to Ba 6s is responsible for this unusual oxidation state. These compounds display captivating structural characters, such as Ba-centered polyhedra and chain-shaped Ch units. More interestingly still, the interaction between two Ba ions ensures their structural stability.
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http://dx.doi.org/10.1021/acs.jpclett.1c00994DOI Listing
May 2021

Visible-Light-Responsive Nanofibrous α-FeO Integrated FeOx Cluster-Templated Siliceous Microsheets for Rapid Catalytic Phenol Removal and Enhanced Antibacterial Activity.

ACS Appl Mater Interfaces 2021 May 22;13(17):19803-19815. Epub 2021 Apr 22.

Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, PR China.

Visible-light-driven environmental contaminants control using 2D photocatalytic nanomaterials with an unconfined reaction-diffusion path is advantageous for public health. Here, cost-effective siliceous composite microsheets (FeSiO-MS) combined with two distinct refined α-FeO nanospecies as photofunctional catalysts were constructed via a one-pot synthesis approach. Through precise control of Fe precursor addition, specially configured α-FeO nanofibers combined with FeOx cluster-functionalized siliceous microsheets of ∼15 nm gradually evolved from the iron oxide-bearing molecular sieve, endowing a superior light-response characteristic of the formed nanocomposite. The catalytic experiment along with the ESR study demonstrated that the produced FeSiO-MS showed reinforced photo-Fenton reactivity, which was effective for rapid phenol degradation under visible light radiation. Moreover, the phenol removal process was found to be regulated by the specially configured types and concentrations of iron oxides. Notably, the obtained composites exhibited a considerable visible-light-induced bactericidal effect against . The constructed FeSiO-MS nanocomposites as integrated and eco-friendly photocatalysts exhibit enormous potentials for environmental and hygienic application.
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http://dx.doi.org/10.1021/acsami.1c04123DOI Listing
May 2021

Situs inversus totalis patients with gastric cancer: Robotic surgery the standard of treatment?-A case report.

Int J Surg Case Rep 2021 Apr 26;81:105818. Epub 2021 Mar 26.

First Affiliated Hospital of Zhengzhou University, 450000 Jianshe Street, Erqi District, Zhengzhou, Henan, China; Gastrointestinal Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Introduction And Importance: Situs inversus totalis (SIT) is a very rare congenital condition. Situs inversus totalis (SIT) patients who present with gastric cancer have been reported in Japan, China, the United States, and other countries. China has a high incidence of gastric cancer, accounting for 40% of the global annual incidence. Surgical treatment options for situs inversus totalis (SIT) gastric cancer patients are of great concern due to the rare nature of the condition and the anatomical variations. This case aims to demonstrate the utility of robotic surgery in treating situs inversus totalis patients with gastric cancer.

Case Presentation: We report a 69-year-old male situs inversus totalis (SIT) gastric cancer patient who successfully underwent a DaVinci robotic-assisted distal gastrectomy with Roux-en-Y reconstruction. The patient had no complications after the operation and was discharged postoperative day 15.

Clinical Discussion: Gastric cancer is an aggressive disease that requires timely diagnosis and appropriate intervention. Unfortunately, many patients present late with gastric cancer and do not benefit from surgical or other appropriate interventions. Patients who are eligible for surgery however still need a clean marginal resection to maximize prognosis, which is not always possible due to complex anatomy or variations as seen in situs inversus totalis. DaVinci robotic surgery system is a new generation of minimally invasive operating systems after conventional laparoscopy, and its visual field clarity, operating flexibility, and instrument stability have obvious advantages over conventional laparoscopic surgery and traditional open surgery.

Conclusion: Robotic surgery for situs inversus totalis (SIT) patients is more advantageous than laparoscopic and traditional surgeries as it offers a broader view of the variant anatomy and allows optimum dexterity and clarity.
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http://dx.doi.org/10.1016/j.ijscr.2021.105818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050025PMC
April 2021

Porous SiO -coated ultrasmall selenium particles nanospheres attenuate cerulein-induce acute pancreatitis in mice by downregulating oxidative stress.

J Dig Dis 2021 Apr 12. Epub 2021 Apr 12.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

Objective: To investigate the potential therapeutic role of porous SiO -coated ultrasmall selenium particles nanospheres ([email protected] nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism.

Methods: C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with [email protected] nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg [email protected] ) groups, respectively. Serum levels of amylase and lipase, inflammatory cytokines (interleukin [IL]-6, IL-1β and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of reactive oxygen species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue.

Results: [email protected] nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, [email protected] nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1.

Conclusion: [email protected] nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/Myd88/p-p65 and NQO1/Nrf2/HO-1 pathways.
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http://dx.doi.org/10.1111/1751-2980.12989DOI Listing
April 2021

HBV-pgRNA increases the stemness and promotes the development of HBV-related HCC through reciprocal regulation with IGF2BP3.

Hepatology 2021 Apr 7. Epub 2021 Apr 7.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

HBV-pgRNA has been proposed for predicting the response of NAs treatment, guiding discontinuation of NAs therapy and monitoring the emergence of viral mutations. However, the contributions of HBV-pgRNA to HCC remain largely unknown. Double-center cohorts of serum samples with undetectable serum HBV-DNA (below the lower limit of detection) were obtained from long-term NAs-treated (at least 48 weeks) of HBV-related HCC patients. The correlation between serum pgRNA concentration and the prognosis of HCC were analyzed. The role pgRNA played in HCC development was assessed both in vitro and in vivo. Our findings revealed that for patients underwent long-term NAs therapy with undetectable serum HBV-DNA, patients with high serum pgRNA expression had poorer overall survival rate and higher cumulative recurrence rate after hepatectomy. Experiments demonstrated that pgRNA promotes proliferation, stemness and tumorigenicity of HCC cells. Mechanistically, we found that pgRNA could up-regulate the expression of IGF2BP3, a well-proved oncoprotein, at post-transcriptional level. Furthermore, IFN-α-2a could degrade the stability of pgRNA through increasing its m6A RNA modification. Collectively, our findings uncover that serum pgRNA could serve as a potential biomarker for predicting the prognosis and recurrence of HCC in patients who received long-term NAs therapy with undetectable serum HBV-DNA; And pgRNA-IGF2BP3 axis plays an important role in the development of HBV-related HCC. Moreover, IFN-α-2a could reduce the stability of pgRNA by increasing its m6A RNA modification level, thereby suppressing the development of HBV-related HCC. In conclusion: Our studies reveal a significance and mechanism of HBV-pgRNA in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HBV-related HCC.
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http://dx.doi.org/10.1002/hep.31850DOI Listing
April 2021

Single-Cell RNA-seq Reveals Characteristics of Malignant Cells and Immune Microenvironment in Subcutaneous Panniculitis-Like T-Cell Lymphoma.

Front Oncol 2021 18;11:611580. Epub 2021 Mar 18.

Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary T-cell lymphoma that is challenging to distinguish from autoimmune disorders and reactive panniculitides. Delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis.

Methods: We performed single-cell RNA sequencing of matched subcutaneous lesion tissue, peripheral blood, and bone marrow from a patient with SPTCL, as well as peripheral blood, bone marrow, lymph node, and lung tissue samples from healthy donors as normal controls. We conducted cell clustering, gene expression program identification, gene differential expression analysis, and cell-cell interaction analysis to investigate the ecosystem of SPTCL.

Results: Based on gene expression profiles in a single-cell resolution, we identified and characterized the malignant cells and immune subsets from a patient with SPTCL. Our analysis showed that SPTCL malignant cells expressed a distinct gene signature, including chemokines families, cytotoxic proteins, T cell immune checkpoint molecules, and the immunoglobulin family. By comparing with normal T cells, we identified potential novel markers for SPTCL (e.g., ) specifically differentially expressed in the malignant cells. We also found that macrophages and fibroblasts dominated the cell-cell communication landscape with the SPTCL malignant cells.

Conclusions: This work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.
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http://dx.doi.org/10.3389/fonc.2021.611580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013729PMC
March 2021

Correlation Between Promoter Hypomethylation and Increased Expression of Syncytin-1 in Non-Small Cell Lung Cancer.

Int J Gen Med 2021 19;14:957-965. Epub 2021 Mar 19.

Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People's Republic of China.

Introduction: Syncytin-1 is a human endogenous retroviral () envelope protein, which has been implicated in trophoblast and cancer cell fusions as well as in immunomodulatory functions. We investigated syncytin-1 expression and promoter methylation in non-small cell lung cancer (NSCLC) and the adjacent, para-carcinoma tissues. In addition, the correlation to patient survival differentiation of between 5-year survival and death group was analyzed.

Methods: Survival ratio was calculated by Kaplan-Meier survival curve. Death risk assessment was executed by Cox risk regression model. The 5'-LTR methylation level of promoter was detected by EpiTYPER method.

Results: Syncytin-1 expression in NSCLC tissue was found to be significantly higher than in para-carcinoma tissues. Moreover, the 5-year survival group has a lower syncytin-1 expression than the death group. Clinical stage and the percentage of syncytin-1 positive cells were top risk factors according to Cox ratio risk regression model analysis. While the methylation level of the 5'-LTR in gene promoter was relatively lower in NSCLC than para-carcinoma tissues, the methylation status of a CpG-2 site overlapping the Oct-1 binding site was found to be an important element potentially involved in the epigenetic regulation of gene expression.

Conclusion: These findings suggest that syncytin-1 could be a biomarker for the diagnosis/prognosis of NSCLC, and further studies are required to elucidate the exact role of syncytin-1 in the development of NSCLC as well as the underlying molecular mechanism for syncytin-1 function and regulation.
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http://dx.doi.org/10.2147/IJGM.S294392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989540PMC
March 2021

Expression patterns and prognostic value of m6A RNA methylation regulators in adrenocortical carcinoma.

Medicine (Baltimore) 2021 Mar;100(10):e25031

Department of Urology.

Abstract: Adrenocortical carcinoma (ACC) is considered a rare cancer with poor prognosis. We used public datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to assess the relationships between N6-methyladenosine (m6A)-related genes and ACC.We used the Wilcoxon signed-rank test to compare m6A-related gene expression in ACC tissues with that in normal tissues. Then, ACC patients were grouped based on a cluster analysis of m6A-related gene expression. m6A-related genes that were significantly associated with survival were incorporated into a risk signature, and 2 groups were divided according to median risk score. Fisher exact tests were utilized to analyze differences in clinical variables between groups. We compared the overall survival (OS) rates of the groups by means of Kaplan-Meier curves and Cox regression analyses.We found that RBM15, ZC3H3, YTDHF1, YTDHF2, and ALBH5 were overexpressed in ACC and that KIAA1429, YTHDC1, HNRNPC, WTAP, METTL3, and FTO were down regulated in ACC. In addition, membership in cluster 2 or the high-risk group was associated with advanced clinical factors and poor prognosis. The univariable and multivariable Cox regression analyses showed that risk score can be considered an independent prognostic factor for ACC.We found that the expression of m6A-related genes could be used as an independent prognostic factor in ACC. However, the current study has some limitations, and further studies of m6A-related genes in ACC are needed.
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http://dx.doi.org/10.1097/MD.0000000000025031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969304PMC
March 2021

Biology of interleukin-38 and its role in chronic inflammatory diseases.

Int Immunopharmacol 2021 Jun 13;95:107528. Epub 2021 Mar 13.

Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address:

Interleukin (IL)-38 is the tenth member of the IL-1 cytokine family. IL-38 shares high similarity with IL-36Ra and IL-1Ra and can bind to their receptors, thus exerting an anti-inflammatory effect. Despite the lack of a signal peptide, IL-38 can be released from several cell types, but its maturation process remains obscure. The role of IL-38 in numerous inflammatory diseases, especially in autoimmune diseases, has been extensively studied. In this review, we discuss the characteristics, biological functions and pathways of IL-38, as well as its role in several chronic inflammatory diseases. Better understanding the role of IL-38 will pave the way for clinical treatments in the near future.
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http://dx.doi.org/10.1016/j.intimp.2021.107528DOI Listing
June 2021

Geniposide from var. Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway.

Drug Des Devel Ther 2021 3;15:949-962. Epub 2021 Mar 3.

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.

Introduction: Hypertension is closely related to myocardial injury. Long-term hypertension can cause myocardial injury. Therefore, it is very important to find drugs to treat myocardial injury caused by hypertension. The aim of present study is to investigate the effects and mechanisms of geniposide on myocardial injuries in spontaneously hypertensive rats (SHR) and H9c2 cells induced by NaCl solution.

Materials And Methods: Male Wistar-Kyoto (WKY) and SHR rats were given different doses of geniposide (25 mg/kg/d or 50 mg/kg/d) or distilled water for three consecutive weeks. Meanwhile, an H9c2 cell line-injury model was established using a solution of 150 µmol/L NaCl for 8 h. The cardiac function and related indexes of rats were detected.

Results: The results showed that geniposide decreased the levels of COI and COIII, which promoted the phosphorylation of AMPK (p-AMPK) and enhanced the energy metabolism pathway. Geniposide improved myocardial apoptosis by regulating apoptotic proteins (p38, BAX and Bcl-2). Finally, heart function was regulated, and the markers of myocardial injury were decreased. Geniposide increased the viability of H9c2 cells treated with the NaCl solution and decreased the rate of apoptosis by regulating the levels of apoptotic proteins. Geniposide could activate energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and reduce H9c2 cell apoptosis.

Conclusion: Our results showed that the mechanisms by which geniposide improves myocardial injury in SHR may be through regulating the energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and improving myocardial apoptosis by regulating apoptotic proteins.
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http://dx.doi.org/10.2147/DDDT.S292107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937395PMC
March 2021

Characterization of Molecular Species and Anti-Inflammatory Activity of Purified Phospholipids from Antarctic Krill Oil.

Mar Drugs 2021 Feb 25;19(3). Epub 2021 Feb 25.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China.

The phospholipids (PLs) from Antarctic krill oil were purified (>97.2%) using adsorption column chromatography. Forty-nine PL molecular species were characterized by ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Most of molecular species contained eicosapentaenoic acid (EPA, 20:5), docosahexaenoic acid (DHA, 22:6), docosapentaenoic acid (DPA, 22:5), and arachidonic acid (AA, 20:4). Notably, a special species PC (20:5/22:6) (1298.17 nmol/g) and many ether PLs were detected. The Antarctic krill PL liposome (IC = 0.108 mg/mL) showed better anti-inflammatory activity than crude Antarctic krill oil (IC = 0.446 mg/mL). It could block NF-κB signaling pathway via suppression of IκB-α degradation and p65 activation and dose-dependently reduce the cellular content of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In addition, it can suppress carrageenan-induced mouse paw swelling. Results from the present study could provide a reference for better evaluation of nutritional and medicinal values of Antarctic krill oil.
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http://dx.doi.org/10.3390/md19030124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996531PMC
February 2021

Pulmonary Lymphoepithelioma-Like Carcinoma Treated with Immunotherapy or Chemotherapy: A Single Institute Experience.

Onco Targets Ther 2021 16;14:1073-1081. Epub 2021 Feb 16.

Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

Background: Lymphoepithelioma-like carcinoma (LELC) is a rare malignant tumor of the lung. It is related to EB virus infection. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are rarely found in this disease, while high level programmed cell death ligand 1 (PD-L1) expression is observed. Here a series of patients with advanced LELC treated with immunotherapy were summarized.

Methods: This retrospective, observational study was conducted in patients who were pathologically confirmed, metastatic or recurrent LELC patients. Patients were prescribed with either chemotherapy or immunotherapy, according to treating physicians' discretion.

Results: A total of 27 patients were included in our study, 10 with immunotherapy (ICI group) and 17 with chemotherapy (Chemo group). The objective response rates (ORR) of the two groups were 80.0% and 70.5% (p=0.678), and disease control rates (DCR) were 100% and 88.2% (p=0.516). However, the response depth was better in the ICI group. Although the cohort of patients in the ICI group was in a disadvantageous state (both up-front and salvage), the progression-free survival (PFS) was much longer (15.0 and 7.9 m, p=0.005). The 1-year PFS rate in the ICI group was also much higher (40% and 5.9%, p=0.047).

Conclusion: This study implicated the high efficiency of ICI therapy in this disease.
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http://dx.doi.org/10.2147/OTT.S290113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897714PMC
February 2021

Major pathological response after neoadjuvant immunotherapy in esophageal spindle cell carcinoma: A case report.

Thorac Cancer 2021 04 22;12(8):1234-1239. Epub 2021 Feb 22.

Department of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.

Esophageal spindle cell carcinoma (ESpCC) is a rare subtype of esophageal carcinoma, accounting for 1% of all esophageal malignancies. The clinical outcome is unknown due to the lack of treatment options. Here, we present the case of a 60-year-old male with initially unresectable ESpCC, in which platinum-based concurrent chemoradiotherapy was unsuccessful. He was subsequently treated with neoadjuvant immunotherapy and after surgery achieved a complete pathological response; therefore, neoadjuvant immunotherapy might be a novel option for ESpCC patients.
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http://dx.doi.org/10.1111/1759-7714.13905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046125PMC
April 2021

The Efficacy and Safety of the mTOR Signaling Pathway Activator, MHY1485, for Activation of Human Ovarian Tissue.

Front Genet 2020 4;11:603683. Epub 2021 Feb 4.

Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Premature ovarian insufficiency (POI) is characterized by abnormal ovarian function before the age of 40. POI showed that primordial follicles developed in disorder. mTOR signaling plays a vital role in the process of follicle development. It has been verified that the mTOR signaling pathway activator, MHY1485, can promote primordial follicle development in mice. We considered that MHY1485 would be a promising fertility preservation method for POI patients.

Methods: The fragmented ovarian tissues of normal woman was cultured with activator MHY1485 , and then the control and activated ovaries were transplanted into the kidney capsules of ovariectomized mice. We then used the Infinium Human Methylation EPIC BeadChip to verify the DNA methylation level of ovarian tissues, thus exploring the effectiveness of them.

Results: MHY1485 stimulated mTOR, S6K1, and rpS6 phosphorylation. Cultured with MHY1485, ovarian weights increased and endocrine function was restored. The number of growing follicles was increased. The activation process did not induce histological changes or abnormal DNA methylation occurrence.

Conclusion: MHY1485 for activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.
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http://dx.doi.org/10.3389/fgene.2020.603683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890121PMC
February 2021

Does Practice Enhance Adaptability? The Role of Personality Trait, Supervisor Behavior, and Career Development Training.

Front Psychol 2020 4;11:594791. Epub 2021 Feb 4.

School of Business Administration, Southwestern University of Finance and Economics, Chengdu, China.

Drawing upon career construction theory, we examined the mediating effect of deliberate practice (DP) on career adaptability (CA) and the effects of learning goal orientation (LGO) and supervisor incompetence accusations (SIA) as well as career development training (CDT) on DP. Using data collected from 204 Chinese PhD students in three waves over a period of 2 months, we found that individuals who were inclined to learn new skills and obtain new knowledge were more likely to deliberately practice professional activities in their fields. When a PhD student's professional competence was questioned by his or her supervisor, the student was more prone to negative emotions and would reduce his or her effort in the development of expertise. CDT - contrary to expectations - negatively predicted DP of professional activities. One possible reason is that the participants in this study have strong autonomy so that those who really struggling are participating in training and seeking help and those who with strong professional abilities are not accessing training programs. Moreover, results showed that DP of professional activities significantly promoted PhD students to adapt to their academic circumstances. Implications for career-related practice within the academic domain are provided.
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http://dx.doi.org/10.3389/fpsyg.2020.594791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890024PMC
February 2021

Investigation and improvement of the desulfurization performance of molten carbonates under the influence of typical pyrolysis gases.

Waste Manag 2021 Apr 15;124:46-53. Epub 2021 Feb 15.

State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Co-pyrolysis with oxygen-lean waste tires could improve the quality of pyrolytic oil from the bio-wastes while HS/COS generated during co-pyrolysis process has a negative impact on the utilization of oil/syngas as well as the flue gas pollution control. Compared to traditional wet desulfurization process, high-temperature desulfurization via molten carbonates could reduce heat loss and favor the recycling of captured sulfur. Notably, small-molecule pyrolytic gases might change the species of sulfur-containing gases and promote the re-emission of absorbed sulfur from the molten salts. To fully understand the effects of pyrolysis gases (H/CO/HO/CO) on molten salts desulfurization efficiency as well as mutual conversion mechanism of HS and COS, equilibrium compositions calculations and adsorption experiments were carried out in the present study. The results showed that H/CO had few effects on molten salts desulfurization performance and mutual conversion of HS/COS. In contrast, CO and HO had obvious adverse effects on desulfurization efficiency through the transferring of free S into emitted sulfur-containing gases. More specifically, only a small amount of CO reacted with S to produce COS while more S was converted to HS and released from the reactor outlet when HO was introduced. Fortunately, the impact of HO or CO on molten salts desulfurization could be weakened with the addition of CaCO by transferring the molten free S into precipitated CaS. Besides, multi-stage desulfurization units connected in series and parallel were proposed and estimated, which was confirmed to show good performance to maintain the high desulfurization efficiency from the complicated pyrolytic gases.
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http://dx.doi.org/10.1016/j.wasman.2021.01.029DOI Listing
April 2021

Revealing the changes of IgG subclass-specific N-glycosylation in colorectal cancer progression by high-throughput assay.

Proteomics Clin Appl 2021 May 15;15(2-3):e2000022. Epub 2021 Apr 15.

The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Purpose: The changes of glycosylation of different IgG subclass in colorectal cancer (CRC) were rarely investigated. The authors aimed to use a simple and high-throughput analytical method to explore the changes of subclass-specific IgG glycosylation in CRC, and to find the specific glyco-biomarkers for early detection of this disease.

Experimental Design: Serum samples from 71 cancer patients and 22 benign patients with 50 age- and sex-matched healthy controls were collected from two independent cohorts. Subclass-specific IgG glycosylation was profiled by MALDI-MS followed by the structural identification through MALDI-MS/MS. The exported MS data was automatically and rapidly processed by the self-developed MATLAB code.

Results: Statistical analysis suggested the significantly decreased galactosylation and remarkably increased agalactosylation of IgG1 or IgG2 in the malignant transformation of CRC, which enables the differentiation between cancer patients and healthy controls. The changes of glycan features were elucidated by the exploration of individual glycopeptides, showing the biantennary fucosylated glycan without galactose (H3N4F1) or with two galactose (H5N4F1) of IgG1 and IgG2 could distinguish cancer group from both benign and control groups.

Conclusions And Clinical Relevance: Through the simple and high-throughput procedures, this study revealed the important role of IgG glycopeptides in the premature pathology of CRC.
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http://dx.doi.org/10.1002/prca.202000022DOI Listing
May 2021

Cleavage of Carboxylic Esters by Aluminum and Iodine.

J Org Chem 2021 Mar 17;86(5):4254-4261. Epub 2021 Feb 17.

College of Chemical Engineering and Pharmacy, Jingchu University of Technology, 33 Xiangshan Road, Jingmen, Hubei 448000, P. R. China.

A one-pot procedure for deprotecting carboxylic esters under nonhydrolytic conditions is described. Typical alkyl carboxylates are readily deblocked to the carboxylic acids by the action of aluminum powder and iodine in anhydrous acetonitrile. Cleavage of lactones affords the corresponding ω-iodoalkylcarboxylic acids. Aryl acetylates undergo deacetylation with the participation of the neighboring group. This method enables the selective cleavage of alkyl carboxylic esters in the presence of aryl esters.
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http://dx.doi.org/10.1021/acs.joc.1c00034DOI Listing
March 2021

Melatonin alleviates Ochratoxin A-induced liver inflammation involved intestinal microbiota homeostasis and microbiota-independent manner.

J Hazard Mater 2021 07 26;413:125239. Epub 2021 Jan 26.

Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Melatonin (MEL) shows an anti-inflammatory effect and regulates intestinal microbiota communities in animals and humans; Ochratoxin A (OTA) induces liver inflammation through intestinal microbiota. However, it remains to know whether MEL alleviates the liver inflammation induced by OTA. In this study, MEL reversed various adverse effects induced by OTA. MEL recovered the swarming and motility of intestinal microbiota, decreased the accumulation of lipopolysaccharide (LPS), enhanced the tight junction proteins of jejunum and cecum segments; ultimately alleviated OTA-induced liver inflammation in ducks. However, it is worth noting that MEL still had positive effects on the OTA-exposed ducks after antibiotic treatment. These results suggest that both the maintenance of intestinal microbiota homeostasis and intestinal microbiota-independent manner involved the MEL anti-inflammatory function in OTA-induced liver inflammation. MEL represent a promising protective approach for OTA, even other mycotoxins.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125239DOI Listing
July 2021

Application of extracorporeal carbon dioxide removal combined with continuous blood purification therapy in ARDS with hypercapnia in patients with critical COVID-19.

Clin Hemorheol Microcirc 2021 Feb 3. Epub 2021 Feb 3.

National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.

Introduction: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI.

Case Report: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment.

Conclusion: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes.
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http://dx.doi.org/10.3233/CH-201080DOI Listing
February 2021

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats.

Front Pharmacol 2020 14;11:600953. Epub 2021 Jan 14.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.
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http://dx.doi.org/10.3389/fphar.2020.600953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841406PMC
January 2021

Low GSTM3 expression is associated with poor disease-free survival in resected esophageal squamous cell carcinoma.

Diagn Pathol 2021 Jan 22;16(1):10. Epub 2021 Jan 22.

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China.

Background: Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients.

Methods: In the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry.

Results: Downregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor.

Conclusions: The findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients.
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http://dx.doi.org/10.1186/s13000-021-01069-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821639PMC
January 2021