Publications by authors named "Yuping Chen"

143 Publications

Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial.

JAMA Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Importance: The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.

Objective: To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC.

Design, Setting, And Participants: The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.

Interventions: Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization.

Main Outcomes And Measures: The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.

Results: A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively.

Conclusions And Relevance: In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.

Trial Registration: ClinicalTrials.gov Identifier: NCT01216527.
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http://dx.doi.org/10.1001/jamasurg.2021.2373DOI Listing
June 2021

Smoking affects the patterns of metabolic disorders and metabolic syndrome in patients with first-episode drug-naive schizophrenia - a large sample study based on Chinese Han population.

Int J Neuropsychopharmacol 2021 Jun 21. Epub 2021 Jun 21.

Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: Although metabolic disorders and smoking are common in schizophrenia, few studies investigated the effects of smoking on metabolic disorders or metabolic syndrome (MetS) in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. To investigate the differences in metabolic disorders and MetS between smoking and non-smoking FEDN schizophrenia patients.

Methods: A total of 428 FEDN schizophrenia patients and 435 controls were recruited. Blood pressure, waist circumference, body mass index (BMI), lipid profiles and glucose metabolism were measured. The psychopathology was evaluated by Positive and Negative Syndrome Scale (PANSS).

Results: FEDN schizophrenia patients had higher smoking rate than controls (23.8% vs. 14.0%, p<0.001). After adjusting for confounding variables, the prevalence of MetS, overweight, hypertension, hypertriglyceridemia, elevated insulin and insulin resistance in smoking patients were higher than those in non-smoking patients, while overweight and hypertension in the smoking controls were higher than those in non-smoking controls (all p<0.05). In smoking patients, triglyceridemia, HDLC and fasting blood glucose were the main contributing components to MetS, while in non-smoking patients, waist circumference, systolic BP, triglyceridemia, HDLC and fasting blood glucose were the main contributing components to MetS. In smoking patients, BMI and HOMA-IR were associated factors of MetS (both p<0.05). In non-smoking patients, sex, BMI, insulin and HOMA-IR were associated factors of MetS (all p<0.05).

Conclusions: Our study indicates that smoking schizophrenia patients have a higher prevalence of MetS and metabolic disorders than non-smoking patients. Moreover, smoking and non-smoking patients have different contributing components and associated factors for MetS.
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http://dx.doi.org/10.1093/ijnp/pyab038DOI Listing
June 2021

Development and Validation of a Sensitive GC-MS/MS Method for the Determination of Five Potential Genotoxic Impurities in Abiraterone Acetate.

J Chromatogr Sci 2021 May 31. Epub 2021 May 31.

Jiangxi Institute for Drug Control, NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Province Engineering Research Center of Drug and Medical Device Quality, 1566 East Beijing Road, NanChang 330029, Jiangxi, China.

A sensitive and selective gas chromatography-tandem mass spectrometry method was developed for the identification and quantification of five potential genotoxic impurities (PGIs), i.e., chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate, in abiraterone acetate. The method was validated according to the International Council for Harmonisation (ICH) guidelines. The linearity was established for the concentration range of 30-480 ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90-1440 ng/mL (chloromethane). The correlation coefficient of each PGIs was >0.995. The extraction recoveries ranged from 90.49 to 106.79% for the five PGIs. The quantitation limit, detection limit, accuracy, precision, repeatability and stability of the method demonstrated that the method was an adequate quality control tool for quantitation and identification of chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate at trace levels in drug substances and drug products.
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http://dx.doi.org/10.1093/chromsci/bmab052DOI Listing
May 2021

Activation of Insulin-Like Growth Factor-2 Ameliorates Retinal Cell Damage and Exerts Protection in in vitro Model of Diabetic Retinopathy.

Neuroimmunomodulation 2021 May 5:1-10. Epub 2021 May 5.

Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Background: The major event in the development of diabetes-related blindness and vision impairment is the onset of retinal cell damage. Overall awareness of insulin-like growth factor-2 (IGF2) mechanisms emphasizes its protective behavior in retinal cells that help to provide new information about the development of treatment for retinal complications.

Objectives: This study analyzes the effect of in vitro changes associated with the cell survival and rescue mechanism in IGF2 inhibition and activation using chromeceptin and IGF2 peptides in ARPE-19 cells cultured in high glucose conditions.

Method: Cell death was induced using high glucose (15 mmol/L), IGF2 inhibition was done using chromeceptin (1 µM) (Sigma Aldrich, Saint Louis, MO, USA), and IGF2 activation was done using IGF2 peptide (10 ng/mL). The cells were analyzed for changes in cell proliferation, apoptosis markers, antioxidant molecules, and alteration of cytokines.

Results: The study demonstrated that cells lacking IGF2 exhibited a significant increase in reactive oxygen levels with apoptosis patterns. Also, gene expression analysis by qRT-PCR demonstrated a significant increase in Yes-associated protein 1, CDK2, TNF-α, and BIRC5 genes in cells under high glucose stress and IGF inhibition compared to control. Further, the cytokine analysis also revealed that cells devoid of IGF2 activated an increase in cytokines such as IL-8, CX43, ICAM-1, IL-17, CCL3, and MCP-1 and decreased paraoxonase compared to normal control cells. On the other hand, ARPE-19 cells grown in high glucose shows that IGF2 increases the survival genes with reduced levels of inflammatory cytokines.

Conclusion: The finding of the investigation, therefore, shows that the use of IGF2 activators may prevent the progression of ocular dysfunction in the control of diabetes-related complications.
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http://dx.doi.org/10.1159/000515662DOI Listing
May 2021

Advances in Injectable and Self-healing Polysaccharide Hydrogel Based on the Schiff Base Reaction.

Macromol Rapid Commun 2021 May 20;42(10):e2100025. Epub 2021 Apr 20.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan, 421001, China.

Injectable hydrogel possesses great application potential in disease treatment and tissue engineering, but damage to gel often occurs due to the squeezing pressure from injection devices and the mechanical forces from limb movement, and leads to the rapid degradation of gel matrix and the leakage of the load material. The self-healing injectable hydrogels can overcome these drawbacks via automatically repairing gel structural defects and restoring gel function. The polysaccharide hydrogels constructed through the Schiff base reaction own advantages including simple fabrication, injectability, and self-healing under physiological conditions, and therefore have drawn extensive attention and investigation recently. In this short review, the preparation and self-healing properties of the polysaccharide hydrogels that is established on the Schiff base reaction are focused on and their biological applications in drug delivery and cell therapy are discussed.
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http://dx.doi.org/10.1002/marc.202100025DOI Listing
May 2021

Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases.

J Drug Target 2021 Apr 9:1-14. Epub 2021 Apr 9.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, China.

The liver is a vital metabolic and detoxifying organ and suffers diverse endogenous or exogenous damage. Hepatocyte mitochondria experience various structural and functional defects from liver injury, bearing oxidative stress, metabolic dysregulation, and the disturbance of mitochondrial quality control (MQC) mechanisms. Mitochondrial malfunction initiates the mitochondria-mediated apoptotic pathways and the release of damage signals, aggravating liver damage and disease progression via inflammation and reparative fibrogenesis. Removal of mitochondrial impairment or the improvement of MQC mechanisms restore mitochondrial homeostasis and benefit liver health. This review discusses the association of mitochondrial disorders with hepatic pathophysiological processes and the resultant potential of mitochondrion-targeting therapeutics for hepatic disorders. The recent advances in the MQC mechanisms and the mitochondrial-derived damage-associated molecular patterns (DAMPs) in the pathology and treatment of liver disease are particularly focussed.
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http://dx.doi.org/10.1080/1061186X.2021.1909051DOI Listing
April 2021

Impact of Lymph Node Dissection on Survival after Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

Ann Surg 2021 Feb 10. Epub 2021 Feb 10.

Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China Sun Yat-sen University Cancer Center, Guangzhou, China Cancer Hospital of Shantou University Medical College, Shantou, China Taizhou Hospital, Wenzhou Medical University, Taizhou, China Tianjin Medical University Cancer Hospital, Tianjin, China Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China Zhejiang Cancer Hospital, Hangzhou, China Fudan University Shanghai Cancer Center, Shanghai, China The University of Hong Kong-Shenzhen Hospital, Hong Kong, China.

Objective: To clarify whether systemic lymph node dissection (LND) influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT).

Summary Background Data: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification.

Methods: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence and survival outcomes were analyzed in the nCRT group.

Results: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P=0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (HR, 0.358; P < 0.001) and disease-free survival (HR, 0.415; P=0.001), but without any negative impact on postoperative complications. Less LND (< 20 vs ≥ 20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P=0.004) and total recurrence rates (41.2% vs 25.8%, P=0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥ 20, but not in those with LND < 20.

Conclusions: Systemic lymph node dissection does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.
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http://dx.doi.org/10.1097/SLA.0000000000004798DOI Listing
February 2021

Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling.

Oncogene 2021 Mar 18;40(11):1974-1987. Epub 2021 Feb 18.

Department of General Surgery, The First Affiliated Hospital of Jinan University, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.

Smoking is one of the most impactful lifestyle-related risk factors in many cancer types including esophageal squamous cell carcinoma (ESCC). As the major component of tobacco and e-cigarettes, nicotine is not only responsible for addiction to smoking but also a carcinogen. Here we report that nicotine enhances ESCC cancer malignancy and tumor-initiating capacity by interacting with cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) and subsequently activating the JAK2/STAT3 signaling pathway. We found that aberrant CHRNA7 expression can serve as an independent prognostic factor for ESCC patients. In multiple ESCC mouse models, dextromethorphan and metformin synergistically repressed nicotine-enhanced cancer-initiating cells (CIC) properties and inhibited ESCC progression. Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7. Since dextromethorphan and metformin are two safe FDA-approved drugs with minimal undesirable side-effects, the combination of these drugs has a high potential as either a preventive and/or a therapeutic strategy against nicotine-promoted ESCC and perhaps other nicotine-sensitive cancer types as well.
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http://dx.doi.org/10.1038/s41388-021-01682-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979537PMC
March 2021

Identification of Potential Diagnostic and Prognostic Biomarkers for Colorectal Cancer Based on GEO and TCGA Databases.

Front Genet 2020 14;11:602922. Epub 2021 Jan 14.

Department of Gastroenterology, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, China.

Colorectal cancer (CRC) is one of the most common neoplastic diseases worldwide. With a high recurrence rate among all cancers, treatment of CRC only improved a little over the last two decades. The mortality and morbidity rates can be significantly lessened by earlier diagnosis and prompt treatment. Available biomarkers are not sensitive enough for the diagnosis of CRC, whereas the standard diagnostic method, endoscopy, is an invasive test and expensive. Hence, seeking the diagnostic and prognostic biomarkers of CRC is urgent and challenging. With that order, we screened the overlapped differentially expressed genes (DEGs) of GEO (GSE110223, GSE110224, GSE113513) and TCGA datasets. Subsequent protein-protein interaction network analysis recognized the hub genes among these DEGs. Further functional analyses including Gene Ontology and KEGG pathway analysis and gene set enrichment analysis were processed to investigate the role of these genes and potential underlying mechanisms in CRC. Kaplan-Meier analysis and Cox hazard ratio analysis were carried out to clarify the diagnostic and prognostic role of these genes. In conclusion, our present study demonstrated that CCNA2, MAD2L1, DLGAP5, AURKA, and RRM2 are all potential diagnostic biomarkers for CRC and may also be potential treatment targets for clinical implication in the future.
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http://dx.doi.org/10.3389/fgene.2020.602922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841465PMC
January 2021

Comparison of two-dimensional shear wave elastography, magnetic resonance elastography, and three serum markers for diagnosing fibrosis in patients with chronic hepatitis B: a meta-analysis.

Expert Rev Gastroenterol Hepatol 2021 Feb 4:1-13. Epub 2021 Feb 4.

Department of Ultrasound, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Background: Two-dimensional shear wave elastography (2D-SWE), magnetic resonance elastography (MRE), aspartate transaminase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and King's score have been proposed for diagnosing fibrosis.

Methods: Literature databases were searched until October 1st, 2020. The summary area under the receiver operating characteristic curve (AUROC), the summary diagnostic odds ratios, and the summary sensitivities and specificities were used to assess the performance of these noninvasive methods for staging fibrosis.

Results: Our final data contained 72 studies. The prevalence of significant fibrosis, advanced fibrosis, and cirrhosis was 58.3%, 36.2%, and 20.5%, respectively, in chronic hepatitis B (CHB). For 2D-SWE and MRE, the summary AUROCs were 0.89 and 0.97, 0.95 and 0.97, and 0.94 and 0.97 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. The summary AUROCs using APRI and FIB-4 for detecting significant fibrosis, advanced fibrosis, and cirrhosis were 0.76 and 0.75, 0.74 and 0.77, and 0.77 and 0.82, respectively. The summary AUROCs of King's score for detecting significant fibrosis and cirrhosis were 0.77 and 0.83, respectively.

Conclusion: MRE and 2D-SWE may show the best diagnostic accuracy for predicting fibrosis in CHB. Among the three serum markers, King's score may be more useful for diagnosing fibrosis.
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http://dx.doi.org/10.1080/17474124.2021.1880894DOI Listing
February 2021

Synthesis of SnO nanoparticles for formaldehyde detection with high sensitivity and good selectivity.

J Mater Res 2020 1;35(16):2208-2217. Epub 2020 Aug 1.

Department of Science and Technology, Shiyuan College of Nanning Normal University, Nanning, 530226 China.

During the detection of industrial hazardous gases, like formaldehyde (HCHO), the selectivity is still a challenging issue. Herein, an alternative HCHO chemosensor that based on the tin oxide nanoparticles is proposed, which was obtained through a facile hydrothermal method. Gas sensing performances showed that the optimal working temperature located at only 180 °C, the response value of 79 50 ppm HCHO was much higher than that of 35 at 230 °C. However, the compromised test temperature was selected as 230 °C, taking into account the faster response/recovery speeds than 180 °C, named 20/23versus 53/60 s, respectively. The response (35) of the SnO nanoparticles-based sensor to 50 ppm of HCHO is about 400% higher than that of bulk SnO sensor (9), especially when the gas concentration is 1 ppm, SnO nanoparticles also has a higher sensitivity which may possibly result from more exposed active sites and small size effect for nanoparticles than for bulk ones. The gas sensor based on SnO nanoparticles can be utilized as a promising candidate for practical low-temperature detectors of HCHO due to its higher gas response, excellent response-recovery properties, and perfect selectivity.
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http://dx.doi.org/10.1557/jmr.2020.181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770746PMC
August 2020

Chimeric RNA ASTN2-PAPPA aggravates tumor progression and metastasis in human esophageal cancer.

Cancer Lett 2021 Mar 31;501:1-11. Epub 2020 Dec 31.

Department of General Surgery, The First Affiliated Hospital of Jinan University, Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China. Electronic address:

Transcription-induced chimeric RNAs are an emerging area of research into molecular signatures for disease biomarker and therapeutic target development. Despite their importance, little is known for chimeric RNAs-relevant roles and the underlying mechanisms for cancer pathogenesis and progression. Here we describe a unique ASTN2-PAPPA chimeric RNA (A-PchiRNA) that could be the first reported chimeric RNA derived from the splicing of exons and intron antisense of two neighboring genes, respectively. Aberrant A-PchiRNA level in ESCC tissues was associated with tumor progression and patients' outcome. In vitro and in vivo studies demonstrated that A-PchiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-PchiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.
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http://dx.doi.org/10.1016/j.canlet.2020.10.052DOI Listing
March 2021

Radix Rehmanniae and Corni Fructus against Diabetic Nephropathy via AGE-RAGE Signaling Pathway.

J Diabetes Res 2020 2;2020:8358102. Epub 2020 Dec 2.

Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.

Background And Aims: Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet.

Methods: The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments.

Results: In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN.

Conclusions: The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function.
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http://dx.doi.org/10.1155/2020/8358102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725584PMC
December 2020

CircDUSP16 Contributes to Cell Development in Esophageal Squamous Cell Carcinoma by Regulating miR-497-5p/TKTL1 Axis.

J Surg Res 2021 Apr 14;260:64-75. Epub 2020 Dec 14.

Department of Thoracic Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.

Background: The vital roles of circular RNAs in human cancers have been demonstrated. In this study, we aimed to investigate the functions of circDUSP16 in esophageal squamous cell carcinoma (ESCC) development.

Methods: Quantitative real-time polymerase chain reaction was executed for the expression levels of circDUSP16, DUSP16, miR-497-5p, and transketolase-like-1 (TKTL1) messenger RNA. Actinomycin D assay and RNase R digestion assay were used to determine the characteristics of circDUSP16. Cell Counting Kit-8 assay and colony formation assay were applied for cell proliferation. Transwell assay was performed to assess cell migration and invasion. The glycolysis level was evaluated using specific kits. Protein levels were measured by Western blot assay. RNA pull-down assay and dual-luciferase reporter assay were adopted to explore the relationships among circDUSP16, miR-497-5p, and TKTL1. Murine xenograft model was used to determine the role of circDUSP16 in ESCC in vivo.

Results: CircDUSP16 level was elevated in ESCC tissues, cells, and hypoxia-stimulated ESCC cells. Knockdown of circDUSP16 suppressed hypoxia-induced ESCC cell viability, colony formation, migration, invasion, and glycolysis. For mechanism analysis, circDUSP16 could positively regulate TKTL1 expression by sponging miR-497-5p in ESCC cells. Moreover, miR-497-5p inhibition restored the effects of circDUSP16 knockdown on the malignant behaviors of ESCC cells under hypoxia condition. MiR-497-5p overexpression suppressed hypoxia-induced ESCC cell progression by targeting TKTL1. In addition, circDUSP16 knockdown repressed the tumorigenesis of ESCC in vivo.

Conclusions: CircDUSP16 knockdown suppressed hypoxia-induced ESCC cell growth, invasion, and glycolysis by regulating TKTL1 expression through sponging miR-497-5p.
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http://dx.doi.org/10.1016/j.jss.2020.11.052DOI Listing
April 2021

Catalpol ameliorates diabetes-induced testicular injury and modulates gut microbiota.

Life Sci 2021 Feb 10;267:118881. Epub 2020 Dec 10.

Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing 210023, Jiangsu, China. Electronic address:

Aims: To explore the mechanisms of diabetes mellitus (DM)-induced testicular injury caused by modulation of testicular glycolysis and gut microbiota (GM), and evaluation of the efficacy of catalpol in reversing testicular morbidity.

Main Methods: A model of DM-induced testicular injury was established using a high-fat diet in KK-Ay mice. Microbial communities in the feces of mice in normal, model and catalpol (Cat) groups were analyzed by 16S gene sequencing. Correlations between the GM and lactate metabolism levels, lactate dehydrogenase activity, and indicators of testicular injury were analyzed.

Key Findings: Cat significantly reduced general indicators of diabetes in mice with DM-induced reproductive injury, mitigated damage to the testicular tissue, and increased sperm count and motility. Additionally, the levels of products of glycolysis metabolism (e.g. lactate) increased following Cat treatment compared with the Model group. Disorders in the GM were also reversed in the Cat group.

Significance: Cat ameliorated DM-induced testicular injury in KK-Ay mice by increasing the energy available to germ cells through glycolysis, principally through modulation of the GM and a reduction in the quantities of associated pathogenic bacteria.
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http://dx.doi.org/10.1016/j.lfs.2020.118881DOI Listing
February 2021

Upregulation of Chemokines in the Paraventricular Nucleus of the Hypothalamus in Rats with Stress-Induced Hypertension.

Med Sci Monit 2020 Nov 17;26:e926807. Epub 2020 Nov 17.

Department of Science and Technology, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, China (mainland).

BACKGROUND The neuroinflammation of paraventricular nucleus (PVN) of the hypothalamus has been implicated in the development of hypertension. The promoted invasion of peripheral immune cells into PVN may be attributed to the upregulation of chemokines, then exacerbating neuroinflammation. We studied the expressions of chemokines, activation of microglial cells, and inflammatory mediators in PVN of rats with stress-induced hypertension (SIH). MATERIAL AND METHODS SIH was induced by electrical foot shock combined with noise for 2 h twice a day, at an interval of 4 h for 14 consecutive days. At the end of the 14th day, fresh PVN tissues were collected to measure the expressions of chemokines using the RayBiotech antibody array. RESULTS We are the first to report that the expression of CXCL7 was extremely high in PVN of control rats, and was significantly lower in SIH rats. The expressions of CCL2 and CX3CL1 in PVN of SIH rats significantly exceeded those of control rats. The numbers of CX3CR1 (receptor of CX3CL1)-immunostained cells and oxycocin-42 (OX-42, marker of microglia)-positive cells increased in PVN of the SIH rats. The stress enhanced the protein expressions of proinflammatory cytokines IL-6 and IL-17 and reduced those of anti-inflammatory cytokines TGF-ß and IL-10 in PVN. CONCLUSIONS In PVN of SIH rats, chronic stress induced neuroinflammation characterized by the activated microglia and upregulated proinflammatory cytokines. Expressions of chemokines CXCL7, CX3CL1, and CCL2 were altered. The causal link of chemokines to PVN neuroinflammation and hypertension remain to be determined.
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http://dx.doi.org/10.12659/MSM.926807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680658PMC
November 2020

Scaling gene expression for cell size control and senescence in Saccharomyces cerevisiae.

Curr Genet 2021 Feb 5;67(1):41-47. Epub 2020 Nov 5.

Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, 11794-5222, USA.

Cells divide with appropriate frequency by coupling division to growth-that is, cells divide only when they have grown sufficiently large. This process is poorly understood, but has been studied using cell size mutants. In principle, mutations affecting cell size could affect the mean size ("set-point" mutants), or they could affect the variability of sizes ("homeostasis" mutants). In practice, almost all known size mutants affect set-point, with little effect on size homeostasis. One model for size-dependent division depends on a size-dependent gene expression program: Activators of cell division are over-expressed at larger and larger sizes, while inhibitors are under-expressed. At sufficiently large size, activators overcome inhibitors, and the cell divides. Amounts of activators and inhibitors determine the set-point, but the gene expression program (the rate at which expression changes with cell size) determines the breadth of the size distribution (homeostasis). In this model, set-point mutants identify cell cycle activators and inhibitors, while homeostasis mutants identify regulators that couple expression of activators and inhibitors to size. We consider recent results suggesting that increased cell size causes senescence, and suggest that at very large sizes, an excess of DNA binding proteins leads to size induced senescence.
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http://dx.doi.org/10.1007/s00294-020-01098-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886820PMC
February 2021

Surface modification of black phosphorus-based nanomaterials in biomedical applications: Strategies and recent advances.

Acta Biomater 2020 12 7;118:1-17. Epub 2020 Oct 7.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research; Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang, Hunan, 421001, China. Electronic address:

Black phosphorus-based nanomaterials (BPNMs), an emerging member of two-dimensional (2D) nanomaterials, possess excellent physicochemical properties and hold great potential for application in advanced nanomedicines. However, the bare BPNMs easily decrease their biomedical activities due to their degradability and in vivo interactions with biological macromolecules such as plasma proteins, largely restricting their biomedical application. A variety of surface modifications, via chemical, physical or biological approaches, have been developed for BPNMs to avoid these limitations and achieve stable, long-lasting and safe therapeutic effects, thus enlighten the development of the multifunctional BPNMs for more practical application in the field of biomedicine. The present review summarizes the recent advances in the surface modification of BPNMs and the resultant expansion of their biomedical applications. Focus is put on the strategy and method of modification while the effects incurred on the behavior and potential toxicity of BPNMs are also included. The future and challenge of the surface modification of the therapeutic BPNMs are finally discussed.
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http://dx.doi.org/10.1016/j.actbio.2020.10.004DOI Listing
December 2020

Systematic Study of the Glutathione Reactivity of -Phenylacrylamides: 2. Effects of Acrylamide Substitution.

J Med Chem 2020 10 9;63(20):11602-11614. Epub 2020 Oct 9.

AMGEN Research, One Amgen Center Drive, Thousand Oaks, California 91320, United States.

A comprehensive understanding of structure-reactivity relationships is critical to the design and optimization of cysteine-targeted covalent inhibitors. Herein, we report glutathione (GSH) reaction rates for -phenyl acrylamides with varied substitutions at the α- and β-positions of the acrylamide moiety. We find that the GSH reaction rates can generally be understood in terms of the electron donating or withdrawing ability of the substituent. When installed at the β-position, aminomethyl substituents with amine p's > 7 accelerate, while those with p's < 7 slow the rate of GSH addition at pH 7.4, relative to a hydrogen substituent. Although a computational model was able to only approximately capture experimental reactivity trends, our calculations do not support a frequently invoked mechanism of concerted amine/thiol proton transfer and C-S bond formation and instead suggest that protonated aminomethyl functions as an electron-withdrawing group to reduce the barrier for thiolate addition to the acrylamide.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00749DOI Listing
October 2020

Chemical composition and sources of submicron aerosol in a coastal city of China: Results from the 2017 BRICS summit study.

Sci Total Environ 2020 Nov 24;741:140470. Epub 2020 Jun 24.

Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.

Chemical compositions of non-refractory submicron aerosol (NR-PM) were measured via an Aerodyne Aerosol Chemical Speciation Monitor at the coastal city Xiamen during the 2017 BRICS summit from August 10 to September 10. Mean hourly concentration of NR-PM was 13.55 ± 8.83 μg m during the study period, decreasing from 18.83 μg m before-BRICS to 13.02 μg m in BRCIS I and 8.42 μg m in BRICS II. Positive matrix factor analyses resolved four organic aerosols (OA): a hydrocarbon-like OA (HOA, 14.78%), a cooking-related OA (COA, 28.21%), a biomass burning OA (BBOA, 18.00%), and an oxygenated OA (OOA, 39.22%). The contributions of local pollutants like nitrate and HOA reduced, while the proportions of sulfate and OOA increased during the control episodes. The diurnal patterns of NR-PM species and OA components in each episode were characterized. The results showed that BC, nitrate, COA, and HOA had peaks in the morning and evening, which became less obvious under the emission control. Moreover, the diurnal variations of all species in Ep 3 with emission control were much flatter due to the effect of transport. Backward trajectories analysis confirmed the long-range transport of air masses from the continent, which resulted in the high proportions of sulfate (43.69%) and OOA (50.28%) in Ep 3. Our study implies the significant effect of emission control on reducing primary pollutants, but the formation of particles during the long-range transport need to be paid more attention when set the air quality control strategies in coastal cities.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140470DOI Listing
November 2020

Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010.

Eur J Cancer 2020 10 30;138:113-121. Epub 2020 Aug 30.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Background: The aim of this study was to compare recurrence patterns and prognostic factors for developing recurrences in patients with oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (CRT) followed by surgery or surgery alone from a multicenter phase III trial NEOCRTEC5010.

Patients And Methods: Patients with locally advanced ESCC were randomly assigned in a 1:1 ratio to receive neoadjuvant CRT plus surgery (CRT + S group) or surgery alone (S group). CRT consisted of two cycles of vinorelbine and cisplatin with concurrent radiotherapy of 40.0 Gy in 20 fractions. Recurrence patterns, sites, frequency, and timing and potential prognostic factors were compared.

Results: Of the 451 patients enrolled from 2007 to 2014, 411 patients who underwent resection were analysed. After a median follow-up of 51.9 months, 62 patients (33.7%) in the CRT + S group versus 104 patients (45.8%) in the S group experienced recurrences (P = 0.013). The CRT + S group demonstrated a significantly better locoregional failure-free survival (P = 0.012) and a more favourable distant metastasis-free survival (P = 0.028) than the S group. Recurrences occurred earlier in the S group (P = 0.053), and late relapses were much more frequent in the CRT + S group (P = 0.029). On multivariate analysis, R1 resection and surgery alone were adverse factors for developing locoregional recurrences, whereas R1 resection was the only independent factor associated with distant metastases.

Conclusions: The neoadjuvant CRT regimen was associated with significantly reduced locoregional and distant recurrences compared with surgery alone. Recurrence patterns, sites and frequency were different between groups. TRIAL REGISTRATION CLINICALTRIALS.

Gov Identifier: NCT01216527.
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http://dx.doi.org/10.1016/j.ejca.2020.08.002DOI Listing
October 2020

Orally Bioavailable Small-Molecule CD73 Inhibitor (OP-5244) Reverses Immunosuppression through Blockade of Adenosine Production.

J Med Chem 2020 09 9;63(18):10433-10459. Epub 2020 Sep 9.

ORIC Pharmaceuticals, 240 E. Grand Avenue, Floor 2, South San Francisco, California 94080, United States.

The adenosinergic pathway represents an attractive new therapeutic approach in cancer immunotherapy. In this pathway, ecto-5-nucleotidase CD73 has the unique function of regulating production of immunosuppressive adenosine (ADO) through the hydrolysis of AMP. CD73 is overexpressed in many cancers, resulting in elevated levels of ADO that correspond to poor patient prognosis. Therefore, reducing the level of ADO via inhibition of CD73 is a potential strategy for treating cancers. Based on the binding mode of adenosine 5'-(α,β-methylene)diphosphate (AOPCP) with human CD73, we designed a series of novel monophosphonate small-molecule CD73 inhibitors. Among them, OP-5244 () proved to be a highly potent and orally bioavailable CD73 inhibitor. In preclinical studies, completely inhibited ADO production in both human cancer cells and CD8 T cells. Furthermore, lowered the ratio of ADO/AMP significantly and reversed immunosuppression in mouse models, indicating its potential as an tool compound for further development.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01086DOI Listing
September 2020

An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy.

J Immunother Cancer 2020 08;8(2)

Department of Pathology and Pathophysiology, Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Shantou University Medical College, Shantou, China

Background: Recent impressive advances in cancer immunotherapy have been largely derived from cellular immunity. The role of humoral immunity in carcinogenesis has been less understood. Based on our previous observations we hypothesize that an immunoglobulin subtype IgG4 plays an essential role in cancer immune evasion.

Methods: The distribution, abundance, actions, properties and possible mechanisms of IgG4 were investigated with human cancer samples and animal tumor models with an extensive array of techniques both in vitro and in vivo.

Results: In a cohort of patients with esophageal cancer we found that IgG4-containing B lymphocytes and IgG4 concentration were significantly increased in cancer tissue and IgG4 concentrations increased in serum of patients with cancer. Both were positively related to increased cancer malignancy and poor prognoses, that is, more IgG4 appeared to associate with more aggressive cancer growth. We further found that IgG4, regardless of its antigen specificity, inhibited the classic immune reactions of antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity against cancer cells in vitro, and these effects were obtained through its Fc fragment reacting to the Fc fragments of cancer-specific IgG1 that has been bound to cancer antigens. We also found that IgG4 competed with IgG1 in reacting to Fc receptors of immune effector cells. Therefore, locally increased IgG4 in cancer microenvironment should inhibit antibody-mediated anticancer responses and help cancer to evade local immune attack and indirectly promote cancer growth. This hypothesis was verified in three different immune potent mouse models. We found that local application of IgG4 significantly accelerated growth of inoculated breast and colorectal cancers and carcinogen-induced skin papilloma. We also tested the antibody drug for cancer immunotherapy nivolumab, which was IgG4 in nature with a stabilizing S228P mutation, and found that it significantly promoted cancer growth in mice. This may provide an explanation to the newly appeared hyperprogressive disease sometimes associated with cancer immunotherapy.

Conclusion: There appears to be a previously unrecognized immune evasion mechanism with IgG4 playing an essential role in cancer microenvironment with implications in cancer diagnosis and immunotherapy.
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http://dx.doi.org/10.1136/jitc-2020-000661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443307PMC
August 2020

Second-harmonic computer-generated holographic imaging through monolithic lithium niobate crystal by femtosecond laser micromachining.

Opt Lett 2020 Aug;45(15):4132-4135

The computer-generated holography technique is a powerful tool for three-dimensional display, beam shaping, optical tweezers, ultrashort pulse laser parallel processing, and optical encryption. We have realized nonlinear holography in ferroelectric crystals by utilizing spatial light modulators in our previous works. Here, we demonstrate an improved method to realize second-harmonic (SH) holographic imaging through a monolithic lithium niobate crystal based on binary computer-generated holograms (CGHs). The CGH patterns were encoded with the detour phase method and fabricated by femtosecond laser micromachining. By the use of the birefringence phase-matching process in the longitudinal direction, bright nonlinear holograms can be obtained in the far-field. The realization of SH holography through monolithic crystal opens wide possibilities in the field of high power laser nonlinear holographic imaging.
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http://dx.doi.org/10.1364/OL.394162DOI Listing
August 2020

High optical damage threshold on-chip lithium tantalate microdisk resonator.

Opt Lett 2020 Aug;45(15):4100-4103

Lithium tantalate (LT) is one of the most attractive optical nonlinear materials, as it possesses a high optical damage threshold and great UV transparency (0.28-5.5 µm). Recently, optical grade LT nanoscale film was developed. Here a high-quality-factor (∼10) LT microdisk resonator based on LT-on-insulator (LTOI) film is fabricated by utilizing focused ion beam (FIB) milling. 2 µW output second-harmonic waves are achieved in the LTOI microdisk at about 500 mW input power. Cascaded third-harmonic generation is also observed in the fabricated device. This work may pave the way for LTOI in integrated photonic chips.
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http://dx.doi.org/10.1364/OL.394171DOI Listing
August 2020

Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks.

Int J Infect Dis 2020 Oct 25;99:171-178. Epub 2020 Jul 25.

Department of Hepatology, the First Hospital of Jilin University, Changchun, China. Electronic address:

Background: In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported.

Methods: A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion.

Results: The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r=0.094, P=0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC=0.821).

Conclusions: The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.
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http://dx.doi.org/10.1016/j.ijid.2020.07.031DOI Listing
October 2020

Study on the inhibitive effect of Catalpol on diabetic nephropathy.

Life Sci 2020 Sep 18;257:118120. Epub 2020 Jul 18.

Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Electronic address:

Aims: Catalpol (Cat) can ameliorate oxide stress and inflammation caused by diabetic nephropathy (DN), but the molecular mechanisms are unclear. This study was designed to investigate the anti-diabetic effects of Cat and its potential mechanism.

Main Methods: We constructed high-fat diet/streptozotocin (HFD/STZ)-induced DN mice and high glucose (HG)-induced podocyte model. The hypoglycemic effect of Cat was analyzed by general features of DN mice. Kidney function was detected via ELISA assay and Western blotting. Renal histopathology analysis was conducted via hematoxylin and eosin (H&E), Masson and periodic acid-silver metheramine (PASM) staining. Cellular viability was measured by TUNEL assay. In order to further study the potential mechanisms of Cat, various proteins in AMPK/SIRT1/NF-κB pathway were detected in DN mice and podocytes with siRNA-AMPK intervention using Western blotting, respectively.

Key Findings: We found hyperglycemia, renal structural and function abnormalities, and increased renal inflammation in DN mice. However, Cat effectively attenuated kidney damage caused by inflammation and increased AMPK, p-AMPK and SIRT1 levels. After AMPK-siRNA transfected into HG-induced podocyte model, AMPK, p-AMPK and SIRT1 levels were obviously decreased, while Cat reversed these chandes. The levels of p-NF-κB, ASC, Cleaved IL-1β, NLRP3, Cleaved caspase1 and GSDMD-N significantly decreased by Cat treatment both in DN mice and podocyte model, which indicated that Cat could activate AMPK/SIRT1/NF-κB pathway.

Significance: Cat could effectively inhibit oxide stress and inflammation accompanied with pyroptosis and its mechanism might be related to AMPK/SIRT1/NF-κB pathway, indicating that Cat possessed potential value in the treatment of DN.
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http://dx.doi.org/10.1016/j.lfs.2020.118120DOI Listing
September 2020

Low-Dose Metformin Reprograms the Tumor Immune Microenvironment in Human Esophageal Cancer: Results of a Phase II Clinical Trial.

Clin Cancer Res 2020 09 9;26(18):4921-4932. Epub 2020 Jul 9.

Department of General Surgery, The First Affiliated Hospital of Jinan University, and Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China.

Purpose: The tumor immune microenvironment (TIME) has an important impact on response to cancer immunotherapy using immune checkpoint inhibitors. Specifically, an "infiltrated-excluded"/"cold" TIME is predictive of poor response. The antidiabetic agent metformin may influence anticancer immunity in esophageal squamous cell carcinoma (ESCC).

Experimental Design: We analyzed matched pre- and posttreatment ESCC specimens in a phase II clinical trial of low-dose metformin treatment (250 mg/day) to evaluate direct anti-ESCC activity and TIME reprogramming. Follow-up correlative studies using a carcinogen-induced ESCC mouse model were performed with short-term (1 week) or long-term (12 weeks) low-dose metformin (50 mg/kg/day) treatment.

Results: In the clinical trial, low-dose metformin did not affect proliferation or apoptosis in ESCC tumors as assayed by Ki67 and cleaved caspase-3 immunostaining. However, metformin reprogrammed the TIME toward "infiltrated-inflamed" and increased the numbers of infiltrated CD8 cytotoxic T lymphocyte and CD20 B lymphocyte. Further, an increase in tumor-suppressive (CD11c) and a decrease in tumor-promoting (CD163) macrophages were observed. Metformin augmented macrophage-mediated phagocytosis of ESCC cells . In the ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME toward an active state (e.g., reduction in CD4 FoxP3 regulatory T cells) and inhibited ESCC growth. In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e., TNFα, IFNγ, and IL10) in the immune cells.

Conclusions: Low-dose metformin reprograms the TIME to an activated status and may be a suitable immune response modifier for further investigation in patients with ESCC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0113DOI Listing
September 2020

Relationships of ozone formation sensitivity with precursors emissions, meteorology and land use types, in Guangdong-Hong Kong-Macao Greater Bay Area, China.

J Environ Sci (China) 2020 Aug 21;94:1-13. Epub 2020 Apr 21.

School of Environment and Energy, South China University of Technology (SCUT), Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution Control, SCUT, Guangzhou 510006, China; National Engineering Laboratory for Volatile Organic Compounds Pollution Control Technology and Equipment, SCUT, Guangzhou 510006, China.

Due to the influences of precursors emissions, meteorology, geography and other factors, ozone formation sensitivity (OFS) is generally spatially and temporally heterogeneous. This study characterized detailed spatial and temporal variations of OFS in Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2012 to 2016 based on OMI satellite data, and analyzed the relationships of OFS with precursors emissions, meteorology and land use types (LUTs). From 2012 to 2016, the OFS tended to be NO-limited in GBA, with the value of FNR (HCHO/NO) increasing from 2.04 to 2.22. According to the total annual emission statistics of precursors, NO emissions decreased by 33.1% and VOCs emissions increased by 35.2% from 2012 to 2016, directly resulting in OFS tending to be NO-limited. The Grey Relation Analysis results show that total column water (TCW), surface net solar radiation (SSR), air temperature at 2 m (T2) and surface pressure (SP) are the top four meteorological factors with the greatest influences on OFS. There are significant positive correlations between FNR and T2, SSR, TCW, and significant negative correlations between FNR and SP. In GBA, the OFS tends to be NO-limited regime in wet season (higher T2, SSR, TCW and lower SP) and VOCs-limited regime in dry season (lower T2, SSR, TCW and higher SP). The FNR displays obvious gradient variations on different LUTs, with the highest in "Rural areas", second in "Suburban areas" and lowest in "Urban areas".
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http://dx.doi.org/10.1016/j.jes.2020.04.005DOI Listing
August 2020

Gut microbiota modulates stress-induced hypertension through the HPA axis.

Brain Res Bull 2020 09 12;162:49-58. Epub 2020 Jun 12.

Jiangsu Vocational College of Medicine, Yancheng 224005, China. Electronic address:

Stress is associated with an increased risk of hypertension, and the incidence of stress-related hypertension has risen rapidly in recent years; however, the underlying mechanisms remain elusive. Gut dysbiosis has been demonstrated to contribute to hypertension and hyperactivation of the hypothalamus-pituitary-adrenal (HPA) axis. Based on our previous findings showing the altered gut microbiota in the rats of stress-induced hypertension (SIH), the present study aims to investigate whether the stress-induced alteration in gut microbiota can lead to the dysfunction of the HPA axis which contributes to the development of SIH. SIH was developed in rats subjected to electric foot-shock combined with buzzer noise stressors. The gut microbiota of rats were deleted by administering an antibiotic cocktail containing ampicillin (1 g/L), vancomycin (500 mg/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water. The serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were tested using enzyme-linked immunosorbent assay (ELISA). The mRNA expression of glucocorticoid receptor (GR) and corticotropin-releasing factor (CRF), CRFR1 and CRFR2 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cellular protein expressions of corticotropin-releasing hormone (CRH), c-fos, and GR were examined by immunohistochemical staining. In the present study, SIH rats showed a hyperactive HPA axis as indicated by the increased CRH expression in the paraventricular nucleus (PVN) of the hypothalamus, the elevated serum ACTH or CORT concentrations, and increased adrenal gland index. The decreased GR expression and increased CRFR1 in the hypothalamus might underlie the hyperactivation of the HPA axis. The microbial deletion by antibiotics mitigated the hyperactivation of the HPA axis and attenuated the stress-induced elevation of blood pressure, indicating that the causal link of gut microbiota to SIH is mediated, at least in part, by the HPA axis activity. Our findings shed new light on the mechanisms underlying SIH.
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http://dx.doi.org/10.1016/j.brainresbull.2020.05.014DOI Listing
September 2020