Publications by authors named "Wenjing Zhao"

212 Publications

Discovery of Small Molecule NSC290956 as a Therapeutic Agent for KRas Mutant Non-Small-Cell Lung Cancer.

Front Pharmacol 2021 5;12:797821. Epub 2022 Jan 5.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.

HRas-GTP has a transient intermediate state with a "non-signaling open conformation" in GTP hydrolysis and nucleotide exchange. Due to the same hydrolysis process and the structural homology, it can be speculated that the active KRas adopts the same characteristics with the "open conformation." This implies that agents locking this "open conformation" may theoretically block KRas-dependent signaling. Applying our specificity-affinity drug screening approach, NSC290956 was chosen by high affinity and specificity interaction with the "open conformation" structure HRasG60A-GppNp. In mutant KRas-driven non-small-cell lung cancer (NSCLC) model system, NSC290956 effectively suppresses the KRas-GTP state and gives pharmacological KRas inhibition with concomitant blockages of both the MAPK-ERK and AKT-mTOR pathways. The dual inhibitory effects lead to the metabolic phenotype switching from glycolysis to mitochondrial metabolism, which promotes the cancer cell death. In the xenograft model, NSC290956 significantly reduces H358 tumor growth in nude mice by mechanisms similar to those observed in the cells. Our work indicates that NSC290956 can be a promising agent for the mutant KRas-driven NSCLC therapy.
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http://dx.doi.org/10.3389/fphar.2021.797821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766838PMC
January 2022

Large-Scale Screening of Antifungal Peptides Based on Quantitative Structure-Activity Relationship.

ACS Med Chem Lett 2022 Jan 8;13(1):99-104. Epub 2021 Dec 8.

Translational Medicine Research Center, Guizhou Medical University, Guiyang 550025, China.

Antifungal peptides are effective, biocompatible, and biodegradable, and thus, they are promising to be the next generation of drugs for treating infections caused by fungi. The identification processes of highly active peptides, however, are still time-consuming and labor-intensive. Quantitative structure-activity relationships (QSARs) have dramatically facilitated the discovery of many bioactive drug molecules without knowledge. In this study, we have established an effective QSAR protocol for screening antifungal peptides. The screening protocol integrates an accurate antifungal peptide classification model and four activity prediction models against specified target fungi. A demonstrative application was performed on more than three million candidate peptides, and three outstanding peptides were identified. The whole screening took only a few days, which was much faster than our previous experimental screening works. In conclusion, the protocol is useful and effective for reducing repetitive laboratory efforts in antifungal peptide discovery. The prediction server () is freely available at www.chemoinfolab.com/antifungal.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762751PMC
January 2022

Plasma angiopoietin-like protein 2 levels and mortality risk among younger-old Japanese people: a population-based case-cohort study.

J Gerontol A Biol Sci Med Sci 2022 Jan 17. Epub 2022 Jan 17.

Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Aging is important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict risk of some aging-related diseases and subsequent death. However, there are as yet no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an on-going, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A sub-cohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. More robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in subjects with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.
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http://dx.doi.org/10.1093/gerona/glac017DOI Listing
January 2022

Identification and function analysis of chitinase 2 gene in housefly, Musca domestica.

Comp Biochem Physiol B Biochem Mol Biol 2022 Jan 10;259:110717. Epub 2022 Jan 10.

The Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, China; Translational Medicine Research Center, Guizhou Medical University, Guiyang 550025, China. Electronic address:

Chitinases are hydrolytic enzymes that play important roles in chitin degradation during the insect development process, and thus are considered as the potential targets for pest management. Here, we identified and characterized the group VII chitinase gene from health pest Musca domestica (MdCht2). We found that MdCht2 was 1932 bp in length with an open reading frame of 1530 bp, which encodes a polypeptide of 509 amino acid residues. Phylogenetic analysis showed that MdCht2 gene was homologs with other closed insects, and belong to the group VII chitinases. Moreover, Real-time PCR analysis indicated that MdCht2 mRNA was highly expressed in pupa stage, as well as in integument and trachea. However, RNAi-mediated knockdown of MdCht2 resulted in high mortality rates and abnormal eclosion. Therefore, we hypothesized that MdCht2 was a crucial gene required for housefly development, which was supported by the transcription level of MdCht2 could be induced by 20-hydroxyecdysone (20E), and the dsMdCht2 could resulted in decrease of the chitinase activity and increase of the chitin content. Taken together, our findings suggested that MdCht2 regulated the chitin content via chitinases, thereby leading to abnormal development. Our results provide a potential target for M. domestica management.
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http://dx.doi.org/10.1016/j.cbpb.2022.110717DOI Listing
January 2022

Association of healthy lifestyle with risk of obstructive sleep apnea: a cross-sectional study.

BMC Pulm Med 2022 Jan 11;22(1):33. Epub 2022 Jan 11.

School of Public Health, Guangdong Pharmaceutical University, No. 283 Jianghai Avenue, Haizhu District, Guangzhou, 510310, China.

Background: No studies investigated the whole effect of modifiable lifestyle factors on OSA risk. This study aimed to examine the individual and combined effects of lifestyle factors on OSA risk among Chinese adults.

Methods: This cross-sectional study included 9733 participants aged 35 to 74 years from the baseline survey of Guangzhou Heart Study. OSA was evaluated by Berlin Questionnaire. The healthy lifestyle score (HLS), representing the overall effect of lifestyles, was derived from seven lifestyle factors: active smoking, passive smoking, alcohol, diet, waist-hip ratio, leisure-time physical activity, and mental status. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model.

Results: 8107 participants were divided into the non-OSA group and 1626 participants into the OSA group. No passive smoking (OR 0.83, 95% CI 0.74-0.94), healthy waist-hip ratio (OR 0.67, 95% CI 0.58-0.77) and healthy mental status (OR 0.45, 95% CI 0. 29-0.73) were associated with a reduced risk of OSA after adjusting for confounders, while others not. Participants with higher HLS were negatively associated with OSA risk (P < 0.001). In comparison to the participants with 0-3 HLS, the OR for participants with 4, 5, 6, and 7 HLS was 0.68 (95% CI 0.56-0.84), 0.71 (95% CI 0.59-0.86), 0.62 (95% CI 0.51-0.76) and 0.49 (95% CI 0.37-0.65) after adjusting for confounders. Every 1-score increment of HLS was associated with a 13% lower risk of OSA.

Conclusions: The results suggest that HLS reflecting the combined effect of multiple-dimensional lifestyle factors was inversely associated with OSA risk. Preventive strategies integrating multiple lifestyle factors may provide a more feasible approach for OSA prevention.
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http://dx.doi.org/10.1186/s12890-021-01818-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751297PMC
January 2022

Prediction of long-term mortality by using machine learning models in Chinese patients with connective tissue disease-associated interstitial lung disease.

Respir Res 2022 Jan 7;23(1). Epub 2022 Jan 7.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, The People's Republic of China.

Background: The exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. In the present study, we develop a nomogram to predict 3‑ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients.

Methods: CTD-ILD patients who were diagnosed and treated at the First Affiliated Hospital of Zhengzhou University were enrolled based on a prior well-designed criterion between February 2011 and July 2018. Cox regression with the least absolute shrinkage and selection operator (LASSO) was used to screen out the predictors and generate a nomogram. Internal validation was performed using bootstrap resampling. Then, the nomogram and ILD-GAP model were assessed via likelihood ratio testing, Harrell's C index, integrated discrimination improvement (IDI), the net reclassification improvement (NRI) and decision curve analysis.

Results: A total of 675 consecutive CTD-ILD patients were enrolled in this study, during the median follow-up period of 50 (interquartile range, 38-65) months, 158 patients died (mortality rate 23.4%). After feature selection, 9 variables were identified: age, rheumatoid arthritis, lung diffusing capacity for carbon monoxide, right ventricular diameter, right atrial area, honeycombing, immunosuppressive agents, aspartate transaminase and albumin. A predictive nomogram was generated by integrating these variables, which provided better mortality estimates than ILD-GAP model based on the likelihood ratio testing, Harrell's C index (0.767 and 0.652 respectively) and calibration plots. Application of the nomogram resulted in an improved IDI (3- and 5-year, 0.137 and 0.136 respectively) and NRI (3- and 5-year, 0.294 and 0.325 respectively) compared with ILD-GAP model. In addition, the nomogram was more clinically useful revealed by decision curve analysis.

Conclusions: The results from our study prove that the ILD-GAP model may exhibit an inapplicable role in predicting mortality risk in Chinese CTD-ILD patients. The nomogram we developed performed well in predicting 3‑ and 5-year mortality risk of Chinese CTD-ILD patients, but further studies and external validation will be required to determine the clinical usefulness of the nomogram.
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http://dx.doi.org/10.1186/s12931-022-01925-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742429PMC
January 2022

AMPK-Mediated Metabolic Switching Is High Effective for Phytochemical Levo-Tetrahydropalmatine (l-THP) to Reduce Hepatocellular Carcinoma Tumor Growth.

Metabolites 2021 Nov 29;11(12). Epub 2021 Nov 29.

Department of Chemistry and Physics, Stony Brook University, Stony Brook, NY 11794-3400, USA.

Targeting cancer cell metabolism has been an attractive approach for cancer treatment. However, the role of metabolic alternation in cancer is still unknown whether it functions as a tumor promoter or suppressor. Applying the cancer gene-metabolism integrative network model, we predict adenosine monophosphate-activated protein kinase (AMPK) to function as a central hub of metabolic landscape switching in specific liver cancer subtypes. For the first time, we demonstrate that the phytochemical levo-tetrahydropalmatine (l-THP), a -derived clinical drug, as an AMPK activator via autophagy-mediated metabolic switching could kill the hepatocellular carcinoma HepG2 cells. Mechanistically, l-THP promotes the autophagic response by activating the AMPK-mTOR-ULK1 and the ROS-JNK-ATG cascades and impairing the ERK/AKT signaling. All these processes ultimately synergize to induce the decreased mitochondrial oxidative phosphorylation (OXPHOS) and mitochondrial damage. Notably, silencing AMPK significantly inhibits the autophagic flux and recovers the decreased OXPHOS metabolism, which results in HepG2 resistance to l-THP treatment. More importantly, l-THP potently reduces the growth of xenograft HepG2 tumor in nude mice without affecting other organs. From this perspective, our findings support the conclusion that metabolic change is an alternative approach to influence the development of HCC.
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http://dx.doi.org/10.3390/metabo11120811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703446PMC
November 2021

Glomerular C4d Deposition and Kidney Disease Progression in IgA Nephropathy: A Systematic Review and Meta-analysis.

Kidney Med 2021 Nov-Dec;3(6):1014-1021. Epub 2021 Aug 6.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Background: Glomerular deposition of C4d is a widely used biomarker for activation of the lectin pathway in the complement system and is reported to be associated with kidney progression in immunoglobulin A nephropathy (IgAN). The aim of this study was to evaluate whether glomerular C4d deposition, as a new biomarker, improves the prediction of kidney prognosis in IgAN.

Study Design: Systematic review and meta-analysis.

Setting & Population: Patients with biopsy-proven primary IgAN without age limitations.Selection Criteria for Studies: Cross-sectional or cohort studies reporting the prevalence of glomerular C4d deposition or evaluating its association with IgAN progression.

Predictor: Glomerular C4d deposition.

Outcome: Composite progression event of a >30% decline in estimated glomerular filtration rate or end-stage kidney disease.

Results: 12 studies with 1,251 patients were included. The prevalence of glomerular C4d deposition was 34% (95% CI, 27%-41%), with large heterogeneity (  = 86%;  < 0.001). Patients with C4d deposition had lower estimated glomerular filtration rates (mean difference [MD], -11.48; 95% CI, -18.27 to -4.70;  < 0.001) as well as higher urinary protein-creatinine ratios (MD, 0.87; 95% CI, 0.53-1.21;  < 0.001) or 24-hour urinary protein excretion (MD, 0.99; 95% CI, 0.50-1.47;  < 0.001) and higher risk for hypertension (relative risk [RR], 1.45; 95% CI, 1.06-1.99;  = 0.02) than patients without C4d deposition. Glomerular C4d deposition was associated with a high Oxford classification score, including M1, E1, S1, and T1/2 lesions (all  ≤ 0.006). Patients with C4d deposition had higher rates of use of renin-angiotensin system blockers and immunosuppressants. Glomerular C4d was found to be a risk factor for the composite kidney event (RR, 3.17; 95% CI, 2.29-4.40;  < 0.001; adjusted HR, 2.05; 95% CI, 1.53-2.76;  < 0.001) and end-stage kidney disease (RR, 4.37; 95% CI, 3.15-6.07;  < 0.001) without evidence of heterogeneity.

Limitations: The definition of positive C4d was not uniform and not all studies provided data about kidney outcomes.

Conclusions: Glomerular C4d deposition is associated with an adverse prognosis and may be a useful biomarker of disease prediction in IgAN.
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http://dx.doi.org/10.1016/j.xkme.2021.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664744PMC
August 2021

Host-guest type multiple site fluorescent probe for GSH detection in living organisms.

Chem Commun (Camb) 2021 Dec 16;57(100):13764-13767. Epub 2021 Dec 16.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China.

The host-guest type molecular size matching strategy, which embodied intramolecular hydrogen bond, aromatic nucleophilic substitution and nucleophilic addition, was utilized to develop a fluorescent probe for GSH specific detection and imaging in organisms.
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http://dx.doi.org/10.1039/d1cc05494eDOI Listing
December 2021

Unraveling Passivation Mechanism of Imidazolium-Based Ionic Liquids on Inorganic Perovskite to Achieve Near-Record-Efficiency CsPbIBr Solar Cells.

Nanomicro Lett 2021 Dec 2;14(1). Epub 2021 Dec 2.

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Key Laboratory for Advanced Energy Devices; Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

The application of ionic liquids in perovskite has attracted wide-spread attention for its astounding performance improvement of perovskite solar cells (PSCs). However, the detailed mechanisms behind the improvement remain mysterious. Herein, a series of imidazolium-based ionic liquids (IILs) with different cations and anions is systematically investigated to elucidate the passivation mechanism of IILs on inorganic perovskites. It is found that IILs display the following advantages: (1) They form ionic bonds with Cs and Pb cations on the surface and at the grain boundaries of perovskite films, which could effectively heal/reduce the Cs/I vacancies and Pb-related defects; (2) They serve as a bridge between the perovskite and the hole-transport-layer for effective charge extraction and transfer; and (3) They increase the hydrophobicity of the perovskite surface to further improve the stability of the CsPbIBr PSCs. The combination of the above effects results in suppressed non-radiative recombination loss in CsPbIBr PSCs and an impressive power conversion efficiency of 17.02%. Additionally, the CsPbIBr PSCs with IILs surface modification exhibited improved ambient and light illumination stability. Our results provide guidance for an in-depth understanding of the passivation mechanism of IILs in inorganic perovskites.
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http://dx.doi.org/10.1007/s40820-021-00763-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639893PMC
December 2021

Microbiota in mesenteric adipose tissue from Crohn's disease promote colitis in mice.

Microbiome 2021 Nov 23;9(1):228. Epub 2021 Nov 23.

Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.

Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn's disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown.

Methods: Mesenteric microbiome, metabolome, and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing, and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in the dextran sulfate sodium (DSS) model and in the Il10 gene-deficient (Il10) mouse colitis model to validate their pro-inflammatory roles.

Results: Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. The presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene-deficient (Il10) spontaneous colitis in mice. The levels of A. pulmonis in both mAT and mucous layer from CD patients were higher compared to those from the non-CD group.

Conclusions: This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01178-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609859PMC
November 2021

Calibration method of multi-projector display system with extra-large FOV and quantitative registration accuracy analysis.

Opt Express 2021 Oct;29(22):36704-36719

The calibration of multi-projector display with extra-large field of view (FOV) and quantitative registration analysis for realizing perfect visual splicing is crucial and difficult. In this paper, we present a novel calibration method to realize the seamless splicing for a multi-projector display system with extra-large FOV. The display consists of 24 projectors, covering the range of 360 degrees in the longitude direction and 210 degrees in the latitude direction. A wide-angle camera fixed on a rotating optical system is used to scan the entire display scene and establish point-to-point correspondence between projector pixels and spatial points using the longitude and latitude information. Local longitude table and latitude table are established on the target of the wide-angle camera. A deterministic method is proposed to locate the North Pole of the display. The local tables corresponding to different camera views can be unified based on the image of the North Pole to form global longitude and latitude tables of arbitrary free-form surface. The mapping between the projector pixels and the camera pixels is established by inverse projection technique, and then each pixel of each projector can be appointed a pair of unique longitude and latitude values. A quantitative registration accuracy analysis method is proposed for multi-projector display system, in which, three-frequency temporal unwrapping method based on coded longitude and latitude values is applied to calculate the registration accuracy. Experiments prove that the registration error of the multi-projector system is less than 0.4 pixels.
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http://dx.doi.org/10.1364/OE.443325DOI Listing
October 2021

DGUOK-AS1 acts as a tumorpromoter through regulatingmiR-204-5p/IL-11 axis in breast cancer.

Mol Ther Nucleic Acids 2021 Dec 19;26:1079-1091. Epub 2021 Oct 19.

Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China.

Breast cancer is one of the most lethal malignancies among women; however, the underlying molecular mechanism involved in the progression and metastasis of breast cancer remains unclear. Numerous studies have confirmed that long noncoding RNAs are abnormally expressed in breast cancer and play crucial roles in cell proliferation and metastasis. In the study, we evaluated the functional role and detailed mechanism of DGUOK-AS1 in breast cancer progression and metastasis. DGUOK-AS1 knockdown suppressed proliferation, migration, and invasion of breast cancer cells and . Mechanistically, miR-204-5p was identified as an inhibitory target of DGUOK-AS1, which served as a tumor suppressor in breast cancer. Significantly, we found that the ectopic expression of miR-204-5p could counteract DGUOK-AS1-mediated promotion of cell proliferation and metastasis in breast cancer. Moreover, IL-11 was found to be the downstream target of miR-204-5p, and DGUOK-AS1 could protect IL-11 from miR-204-5p-mediated degradation. DGUOK-AS1 overexpression promoted breast cancer cell migration, angiogenesis, and macrophage migration, mediating by the increased secretion of IL-11, which was extremely important for cancer progression. Collectively, our studies reveal that DGUOK-AS1/miR-204-5p/IL-11 axis plays a significant role in the progression and metastasis of breast cancer, and DGUOK-AS1 might be a novel biomarker and therapeutic target for breast cancer.
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http://dx.doi.org/10.1016/j.omtn.2021.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571540PMC
December 2021

Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development.

Acta Pharm Sin B 2021 Oct 9;11(10):2957-2972. Epub 2021 Mar 9.

State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193 China.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.
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http://dx.doi.org/10.1016/j.apsb.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546663PMC
October 2021

An Integrative Pan-Cancer Analysis of the Oncogenic Role of COPB2 in Human Tumors.

Biomed Res Int 2021 12;2021:7405322. Epub 2021 Oct 12.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Nantong University, China.

Several studies have suggested that coatomer protein complex subunit beta 2 (COPB2) may act as an oncogene in various cancer types. However, no systematic pan-cancer analysis has been performed to date. Therefore, the present study analyzed the potential oncogenic role of COPB2 using TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The majority of the cancer types overexpressed the COPB2 protein, and its expression significantly correlated with tumor prognosis. In certain tumors, such as those found in breast and ovarian tissues, phosphorylated S859 exhibited high expression. It was found that mutations of the COPB2 protein in kidney and endometrial cancers exhibited a significant impact on patient prognosis. It is interesting to note that COPB2 expression correlated with the number of cancer-associated fibroblasts in certain tumors, such as cervical and endocervical cancers and colon adenocarcinomas. In addition, COPB2 was involved in the transport of substances and correlated with chemotherapy sensitivity. This is considered the first pan-tumor study, which provided a relatively comprehensive understanding of the mechanism by which COPB2 promotes cancer growth.
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http://dx.doi.org/10.1155/2021/7405322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526247PMC
October 2021

Association Between Eating Habits and Risk of Obstructive Sleep Apnea: A Population-Based Study.

Nat Sci Sleep 2021 9;13:1783-1795. Epub 2021 Oct 9.

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, Guangzhou, People's Republic of China.

Objective: The effect of dietary factors on OSA remains unclear. This study was to investigate the association of obstructive sleep apnea (OSA) with individual and overall effects of eating habits among adult Chinese.

Methods: A total of 9733 participants were selected from the baseline survey of the Guangzhou Heart Study. OSA was ascertained by Berlin Questionnaire. Food consumption was collected using a food frequency questionnaire, and eating patterns were extracted by principal component analysis. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by the logistic regression model.

Results: After adjustment for confounders, fried food intake with ≥1/week was associated with an increased risk of OSA (OR: 1.77, 95% CI: 1.37-2.27), while fruit consumption of ≥1/day was associated with a 26% reduced risk of OSA (OR: 0.74, 95% CI: 0.62-0.88). Three eating patterns were defined and labeled as pattern I, II, and III. Eating pattern III which had higher factor loadings of animal innards, fried food, salted food, carbonate, and non-carbonated beverages was associated with an increased risk of OSA (OR: 1.30, 95% CI: 1.09-1.55) when comparing the highest with the lowest tertile of pattern score, after adjusting for confounders; every 1-unit increment of pattern III score was associated with an increased risk of OSA (OR: 1.09, 95% CI: 1.04-1.14). Neither pattern I nor pattern II was observed to be associated with OSA risk.

Conclusion: A higher frequency intake of fruits was associated with a reduced OSA risk and a diet with higher levels of consumption of animal innards, fried food, salted food, carbonated beverages, and non-carbonated beverages may increase the risk of OSA.
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http://dx.doi.org/10.2147/NSS.S325494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517635PMC
October 2021

Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer.

Dis Markers 2021 27;2021:5529106. Epub 2021 Sep 27.

Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Objectives: Molecular subtypes are employed as a guide for targeted treatment and important prognostic factors. This study focused on investigating the association of serum levels of CEA, CA15-3, and CA125 with clinicopathological characteristics of breast cancer to find prognostic markers for breast cancer and provide precise targeted therapy.

Materials And Methods: In this study, 961 breast cancer patients with preoperative serum levels of CEA, CA15-3, and CA125 and molecular subtypes were analyzed. Cut-off values of 5 ng/ml, 25 U/ml, and 35 U/ml were used for CEA, CA15-3, and CA125, respectively. The test and Fisher exact test along with logistic multivariate regression analysis were performed for investigating the correlation of CEA, CA15-3, and CA125 serum levels with molecular subtypes and associated factors.

Results: An increase in the serum concentrations of CEA, CA15-3, and CA125 was discovered in 48 (4.99%), 54 (5.62%), and 55 (5.72%) breast cancer patients, respectively. Univariate analysis demonstrated that the levels of CEA ( < 0.01) and CA15-3 ( < 0.05) were significantly linked with molecular types of breast cancer. Moreover, patients having larger tumor size ( < 0.01, < 0.0001, and < 0.05, respectively) along with nodal metastasis ( < 0.05, = 0.0001, and < 0.05, respectively) exhibited higher rates of elevated CEA, CA15-3, and CA125 levels. Status of Her-2 positive ( < 0.01) had a significant connection with elevated CEA levels. Multivariate analysis further indicated that molecular subtypes were independent factors associated with CEA and CA15-3 levels. Also, Her-2 status was significantly and independently related to CEA levels.

Conclusion: Preoperative serum levels of CEA and CA15-3 were independently associated with molecular subtypes of breast cancer. CEA and CA15-3 might improve the prognostic prediction for patients with breast cancer and inform the selection of specific therapies. A further biological analysis is needed for investigating the relationship between Her-2 expression and CEA levels.
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http://dx.doi.org/10.1155/2021/5529106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492280PMC
January 2022

Comprehensive Analysis of Glutamate-Rich WD Repeat-Containing Protein 1 and Its Potential Clinical Significance for Pancancer.

Biomed Res Int 2021 27;2021:8201377. Epub 2021 Sep 27.

Cancer Research Center Nantong, Affiliated Tumor Hospital of Nantong University, China.

Methods: The expression level of GRWD1 in human cancer tissues was analyzed using the Tumor Immune Evaluation Resource (ver. 2.0, TIMER2), Gene Expression Profiling Interactive Analysis (ver. 2, GEPIA2), and UALCAN databases. The Kaplan-Meier plotter was utilized to analyze the survival data. Spearman's correlation analysis was used to find out the correlation between the expression level of GRWD1 and predictive biomarkers, such as tumor mutation burden (TMB) and microsatellite instability (MSI). Furthermore, the MEXPRESS website was used to study the potential relationship between DNA methylation level of GRWD1 and pathological staging. We utilized the "immune" module provided on the TIMER2 website to explore the relationship between the expression level of GRWD1 and immune infiltration in all types of cancer in TCGA. Pearson's correlation analysis was used to investigate the correlation between the expression level of GRWD1 and the expression levels of immune checkpoint-related genes. For protein expression analysis, we used the CPTAC module provided by the UALCAN portal to compare the total protein and phosphorylated protein level of GRWD1 in adjacent normal and tumor tissues.

Results: GRWD1 was overexpressed in tissues of most types of cancer, in which the expression levels of GRWD1 in the kidney chromophobe (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC) tissues showed an opposite trend, and the expression level of GRWD1 was correlated to only the KIRC tumor stage. The results of survival analysis showed that the expression level of GRWD1 was significantly associated with overall survival in six types of cancer and disease-free survival (DFS) in three types of cancer. Importantly, the increased expression level of GRWD1 was strongly correlated with prognosis of KIRC patients. There was a positive relationship between the expression level of GRWD1 and immune cell infiltration in several types of cancer, and the expression level of GRWD1 was also positively correlated with TMB, MSI, and DNA methylation in some types of cancer. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that "ubiquitin mediated proteolysis," "spliceosome," and "nucleotide excision repair" were involved in the effect of GRWD1 expression on tumor pathogenesis.

Conclusion: This pancancer analysis provided a comprehensive overview of the carcinogenic effects of GRWD1 on a variety of human cancers. The results of bioinformatics analysis indicated GRWD1 as a promising biomarker for detection, prognosis, and therapeutic assessment of diverse types of cancer, and GRWD1 could act as a tumor suppressor in KIRC.
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http://dx.doi.org/10.1155/2021/8201377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490071PMC
January 2022

Association of gait with global cognitive function and cognitive domains detected by MoCA-J among community-dwelling older adults: a cross-sectional study.

BMC Geriatr 2021 10 2;21(1):523. Epub 2021 Oct 2.

Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

Background: Gait was proved to be strongly associated with global cognitive function and multiple cognitive domains; however, previous research usually concentrated on individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and cognitive domains.

Methods: The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70-81 years. Gait was measured by asking participants to walk a 6-m course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and cognitive domains adjusted for several confounding factors.

Results: Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β = - 0.487, [- 0.890, - 0.085]) and executive function (P = 0.049); initial contact was associated with executive function (P = 0.017).

Conclusion: General cycle of gait might be the better marker of global cognitive function and gait is most strongly associated with executive function. The longitudinal relationships should be examined in future cohort studies.
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http://dx.doi.org/10.1186/s12877-021-02467-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487567PMC
October 2021

Imaging Features for Predicting High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Systematic Review and Meta-Analysis.

Ann Surg Oncol 2022 Feb 23;29(2):1297-1312. Epub 2021 Sep 23.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to determine imaging features and their diagnostic accuracy for predicting high-grade dysplasia (HGD)/malignancy in BD-IPMN, including mixed type.

Methods: The PubMed, Embase, and Cochrane databases were searched, and data were extracted from relevant studies. As the main diagnostic accuracy index, diagnostic odds ratios (DORs) of imaging features for diagnosing HGD/malignancy in BD-IPMNs were pooled using the random-effects model. A bivariate random-effects approach was used to construct summary receiver operating characteristic curves for sensitivity and specificity estimation.

Results: The pooled DOR was the highest for the enhanced solid component/mural nodule (MN) (DOR, 12.21; 95 % confidence interval [CI], 6.14-24.27), followed by a main pancreatic duct (MPD) diameter of 10 mm or greater (DOR, 7.93; 95 % CI, 3.02-20.83), solid component (DOR, 4.85; 95 % CI, 2.49-9.42), lymphadenopathy (DOR, 4.84; 95 % CI, 1.11-21.06), MN (DOR, 4.48; 95 % CI, 3.15-6.39), an MPD diameter of 5 mm or greater (DOR, 3.69; 95 % CI, 2.62-5.19), abrupt change in MPD caliber with distal pancreatic atrophy (DOR, 2.65; 95 % CI, 1.66-4.24), thickened/enhancing walls (DOR, 2.38; 95 % CI, 1.57-3.60), and cyst size of 3 cm or larger (DOR, 1.98; 95 % CI, 1.48-2.64). The largest area under the curve (0.89 and 0.95, respectively) and high specificity (0.95 and 0.98, respectively) also were found for enhanced solid component/MN and an MPD diameter of 10 mm or greater, albeit with low sensitivity (0.38 and 0.14, respectively).

Conclusions: The aforementioned imaging features could aid in predicting HGD/malignancy of BD-IPMN. Furthermore, enhanced solid component/MN and an MPD diameter of 10 mm or greater were the most important predictors of HGD/malignancy in BD-IPMN and should be considered as indications for surgery.
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http://dx.doi.org/10.1245/s10434-021-10662-2DOI Listing
February 2022

ASO Author Reflections: Imaging Predictors of High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.

Ann Surg Oncol 2022 02 22;29(2):1313-1314. Epub 2021 Sep 22.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 1 Shuai Fu Yuan Hu Tong, Beijing, 100730, China.

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http://dx.doi.org/10.1245/s10434-021-10746-zDOI Listing
February 2022

circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway.

Mol Ther 2022 Jan 25;30(1):415-430. Epub 2021 Aug 25.

Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Ji'nan, Shandong, China; Pathology Tissue Bank, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; Research Institute of Breast Cancer, Shandong University, Ji'nan, Shandong, China. Electronic address:

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.
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http://dx.doi.org/10.1016/j.ymthe.2021.08.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753373PMC
January 2022

A DNA Nanoflower-Assisted Separation-Free Nucleic Acid Detection Platform with a Commercial Pregnancy Test Strip.

Angew Chem Int Ed Engl 2021 11 18;60(47):24823-24827. Epub 2021 Oct 18.

Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S4K1, Canada.

There is a constant drive for affordable point-of-care testing (POCT) technologies for the detection of infectious human diseases. Herein, we report a simple platform for DNA detection that takes advantage of four techniques: commercially available pregnancy test strips (PTS), amplicon generation via loop-mediated isothermal amplification (LAMP), toehold-mediated strand displacement, and noncovalent immobilization of DNA on paper surface with DNA nanoflowers. This simple, separation-free platform is highly specific, as demonstrated with the detection of rtL180M, a single-nucleotide polymorphism observed in hepatitis B virus (HBV) associated with antiviral drug resistance. It is very sensitive, capable of detecting the targeted mutation at 2 copies μL . It is able to correctly identify the unmutated and rtL180M genome types of HBV in clinical samples. Given its wide adaptability, we expect this platform can be easily modified for the detection of genetic variations associated with various pathogens and human diseases.
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http://dx.doi.org/10.1002/anie.202108827DOI Listing
November 2021

A Special Additive Enables All Cations and Anions Passivation for Stable Perovskite Solar Cells with Efficiency over 23.

Nanomicro Lett 2021 Aug 6;13(1):169. Epub 2021 Aug 6.

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Key Laboratory for Advanced Energy Devices, Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science & Engineering, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

Passivating undercoordinated ions is an effective way to reduce the defect densities at the surface and grain boundaries (GBs) of perovskite materials for enhanced photovoltaic performance and stability of perovskite solar cells (PSCs). Here, (BBF) complex is chosen as a multifunctional additive, which contains both CHN and BF groups working as Lewis base and Lewis acid, respectively, can bond with Pb/I and FA on the surface and in the GBs in the perovskite film, affording passivation of both cation and anion defects. The synergistic effect of the CHN and BF complex slows the crystallization during the perovskite film deposition to improve the crystalline quality, which reduces the trap density and the recombination in the perovskite film to suppress nonradiative recombination loss and minimizes moisture permeation to improve the stability of the perovskite material. Meanwhile, such an additive improves the energy-level alignment between the valence band of the perovskite and the highest occupied molecular orbital of the hole-transporting material, Spiro-OMeTAD. Consequently, our work achieves power conversion efficiency of 23.24%, accompanied by enhanced stability under ambient conditions and light illumination and opens a new avenue for improving the performance of PSCs through the use of a multifunctional complex.
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http://dx.doi.org/10.1007/s40820-021-00688-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346611PMC
August 2021

Association between frequency of snacking and all-cause mortality among community-dwelling young-old adults: An age-specific prospective cohort study.

Geriatr Gerontol Int 2021 Aug 25;21(8):697-704. Epub 2021 Jun 25.

Department of Public Health, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.

Aim: We aimed to clarify whether snacking habits decrease the risk of all-cause mortality in an older Japanese population.

Methods: The study participants were 64- or 65-year-old community-dwelling residents recruited each survey year from 1996 through 2005. Data on the frequency of snacking and other lifestyle factors were obtained during the baseline survey using self-administered questionnaires, and the participants were followed up annually until the end of 2017. In total, 2943 participants (1484 men and 1459 women) were eligible. All-cause mortality was compared among participants grouped by frequency of snacking (no snacking, one to four times/week, or every day).

Results: The number of deaths recorded over the study period of 43 204 person-years was 357 (24.1%) for men and 173 (11.9%) for women. The mean ± standard deviations for the follow-up period were 14.2 ± 4.9 years in men and 15.2 ± 4.5 years in women. Cox proportional hazard regression analyses showed that after adjusting for potential confounding factors, the hazard ratios for women were 0.64 (95% confidence interval [CI], 0.43-0.94) in the group that had a habit of snacking one to four times/week, and 0.93 (95% CI 0.63-1.36) in the group that had a habit of snacking every day compared with those in the no snacking group. These associations were not observed among men.

Conclusions: A moderate frequency of snacking slightly decreases the risk of all-cause mortality among women. Our findings might be useful for improving the nutrition statuses in older female adults. Geriatr Gerontol Int 2021; 21: 697-704.
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http://dx.doi.org/10.1111/ggi.14209DOI Listing
August 2021

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19.

Synth Syst Biotechnol 2021 Sep 14;6(3):135-143. Epub 2021 Jun 14.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China.

SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including , and were notably depleted in the pharynges of COVID-19 patients, while , , and were relatively increased. The abundance of and were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.
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http://dx.doi.org/10.1016/j.synbio.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200311PMC
September 2021

Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk.

Eur J Nutr 2021 Dec 27;60(8):4357-4366. Epub 2021 May 27.

Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 2F, Block 20, No.74, Zhongshan Second Road, Guangzhou, 510080, China.

Purpose: This study was to evaluate the associations of dietary intake of total and specific phytosterols and risk of esophageal squamous cell carcinoma (ESCC) and to explore their joint effects with PLCE1 rs2274223 polymorphisms.

Methods: A population-based case-control study was conducted in a Chinese rural population and 856 eligible incident ESCC cases and 856 controls were included. A validated food frequency questionnaire was used to collect dietary consumption and PLCE1 rs2274223 polymorphisms were genotyped. Unadjusted and adjusted odds ratios (ORs) with 95% confidence interval (CI) were assessed via logistic regression model.

Results: When comparing the highest with lowest intake quartiles, β-sitosterol, campesterol, stigmasterol, β-sitostanol, campestanol, and total phytosterols were all associated with a decreased risk of ESCC, with adjusted ORs being 0.32 (95% CI 0.20-0.48), 0.18 (95% CI 0.11-0.27), 0.45 (95% CI 0.29-0.70), 0.13 (95% CI 0.08-0.20), 0.14 (95% CI 0.09-0.22) and 0.28 (95% CI 0.18-0.43), respectively. An exposure-response relationship was also observed for both total and five specific phytosterols (all P for trend < 0.001). In comparison to rs2274223 AA genotype, both GA genotype (OR: 1.47, 95% CI 1.16-1.85) and GG genotype (OR: 2.13, 95% CI 1.20-3.84) were associated with an increased risk of ESCC. However, no interaction was observed between total/specific phytosterols intake and rs2274223 polymorphisms.

Conclusion: Higher dietary intake of total and five specific phytosterols was associated with a lower risk of ESCC, and the risk of ESCC increased with the increment of rs2274223 G allele. The negative association between phytosterols and ESCC risk was not modified by rs2274223 polymorphisms. Foods or supplements rich in phytosterols are a promising source for chemoprevention of ESCC, and still, clinical trials will be required in any specific case.
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http://dx.doi.org/10.1007/s00394-021-02561-9DOI Listing
December 2021
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