Publications by authors named "Hong Lu"

1,102 Publications

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CircATP5SL promotes infantile haemangiomas progression via IGF1R regulation by targeting miR-873-5p.

Am J Transl Res 2021 15;13(3):1322-1336. Epub 2021 Mar 15.

The Department of Pediatric Surgery, The Ningbo Women and Children's Hospital Ningbo 315211, China.

Infantile haemangiomas (IH) are the most common soft-tissue tumours in infants. Several studies have demonstrated the importance of circular RNA (circRNA) for the regulation of various cancer cells. The present study aims to evaluate the functions and molecular mechanisms of circATP5SL in IH progression. In this study, we found that circATP5SL is significantly dysregulated in IH. We conducted Transwell, MTT, and flow cytometry analysis to evaluate the role of circATP5SL in IH cell proliferation, invasion, migration, and apoptosis. Meanwhile, by using subcellular distribution detection, as well as dual-luciferase reporter test and RIP analysis, it has been confirmed that miR-873-5p directly binds to the 3'UTR of IGF1R mRNA, thereby inhibiting the expression of IGF1R. Besides, circATP5SL promoted IGF1R expression by directly adsorbing miR-873-5p, an IGF1R inhibitor, thereby promoting cellular invasion, proliferation, and migration as well as inhibition of apoptosis. In summary, our study suggests that circATP5SL promotes IH progression by regulating IGF1R expression through adsorption of miR-873-5p, elucidating circATP5SL as a promising therapeutic target for the prognostication and treatment of IH.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014409PMC
March 2021

Chinese midwives' perceptions on upright positions during the second stage of labour: A qualitative study.

Midwifery 2021 Mar 19;98:102993. Epub 2021 Mar 19.

School of Nursing, Peking University, Beijing, China.

Objective: Upright positions are recommended by many international organizations due to their positive effects on improving birth outcomes. The effects can only be achieved when upright positions are properly adopted by women under the guidance of midwives. However, whether midwives in China have a clear understanding of upright positions during the second stage of labour is an issue that has not been explored. The aim of this study was to explore midwives' perceptions on assisting women in upright positions during the second stage of labour in the context of China.

Design: A qualitative descriptive design was adopted. We analysed the data using the conventional content analysis and reported the study in line with the COREQ checklist.

Setting: The study was conducted at the labour wards of two maternity hospitals and two general hospitals in China where the adoption of upright positions was encouraged during the second stage of labour.

Participants: Semi-structured individual interviews with 17 midwives were conducted between May and July 2020.

Findings: Three main themes were identified: (1) safety and availability; (2) unclear method of implementation; (3) lack of knowledge of the potential risks and precautions. Midwives' perceptions were based primarily on clinical experience rather than evidence-based practice. Their perceptions on the indications and contraindications of upright positions were divergent and ambiguous. Midwives' suggested that the indications and contraindications should be adjusted in the context of China. Time limit for keeping an upright position and maternal pushing during uterine contractions were two questions that still confused midwives. Midwives lacked knowledge of the potential risks of upright positions and rarely systematically summarized the precautions.

Key Conclusions: This study shows that assisting women to give birth in upright positions during the second stage of labour can be a challenge for midwives in China, and also highlights the need for clarifying the detailed implementation methods of upright positions in the context of China by evidence-based approaches.

Implications For Practice: An evidence-based protocol for implementing upright positions during the second stage of labour should be developed to guide midwives' practice and facilitate the successful use of upright positions in China.
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http://dx.doi.org/10.1016/j.midw.2021.102993DOI Listing
March 2021

Authentication of In Situ Measurements for Thoracic Aortic Aneurysms in Mice.

Arterioscler Thromb Vasc Biol 2021 Apr 1:ATVBAHA121315983. Epub 2021 Apr 1.

Saha Cardiovascular Research Center, University of Kentucky, Lexington. (S.O.-U., M.K., M.K.F., W.S., M.C.G., H.S.L., A.D., H.S.).

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http://dx.doi.org/10.1161/ATVBAHA.121.315983DOI Listing
April 2021

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

J Exp Med 2021 Jun;218(6)

Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
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http://dx.doi.org/10.1084/jem.20201839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008365PMC
June 2021

Lessons learned from upper gastrointestinal endoscopy in asymptomatic Chinese.

Helicobacter 2021 Mar 29:e12803. Epub 2021 Mar 29.

Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: The Helicobacter pylori (H. pylori) infection-related diseases, peptic ulcer, and gastric cancer are frequently asymptomatic until the onset of complications. This study aimed to investigate the prevalence of H. pylori, erosive esophagitis, peptic ulcer, and precancerous lesions such as atrophic gastritis, intestinal metaplasia, gastric dysplasia, and upper gastrointestinal (GI) malignancy in asymptomatic Chinese.

Methods: From January to December 2017, a questionnaire was administered to consecutive asymptomatic patients undergoing routine physical examination, which included their first screening esophagogastroduodenoscopy. H. pylori infection was determined by one of positive C urea breath tests or rapid urease test and histology. The presence of H. pylori infection, erosive esophagitis, peptic ulcer, precancerous gastric histology, and upper GI malignancy was analyzed in relation to demographic factors.

Results: A total of 1108 subjects (mean age: 48, range 21 to 79, 39.5% men) were included. The findings were: erosive esophagitis 7.8%, active H. pylori infection 44%, peptic ulcer 9.1% (duodenal 5.8%, gastric 2.5% or both 0.8%); 0.5% had gastric cancer. Male, smoking history, and current H. pylori infection were all significantly related to the presence of peptic ulcer. Totally, 1095 patients had gastric histopathology and premalignant gastric lesions were present in 67.4%; atrophic gastritis (67.4%), intestinal metaplasia (27.4%), and gastric dysplasia (0.5%). Age, current and previous H. pylori infection were risk factors significantly associated with precancerous lesions.

Conclusions: Upper GI pathology as a sequelae of H. pylori infection is common in asymptomatic Chinese. These findings support institution of a nationwide test and treat program to eradicate H. pylori in China.
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http://dx.doi.org/10.1111/hel.12803DOI Listing
March 2021

Illuminating the Importance of Studying Interventions on the Propagation Phase of Experimental Mouse Abdominal Aortic Aneurysms.

Arterioscler Thromb Vasc Biol 2021 Apr 24;41(4):1518-1520. Epub 2021 Mar 24.

Saha Cardiovascular Research Center, Saha Aortic Center, Department of Physiology, University of Kentucky (H.S.L., A.D.).

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http://dx.doi.org/10.1161/ATVBAHA.121.316070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996449PMC
April 2021

Clinical implication of aquaporin 9 in non-small cell lung cancer patients: its expression and relationship with clinical features and prognosis.

Ir J Med Sci 2021 Mar 23. Epub 2021 Mar 23.

Department of Respiratory and Critical Care Medicine, Zhuji Affiliated Hospital of Shaoxing University, NO. 9 Jianmin Road, Taozhu Streets, Zhuji, Zhejiang, China.

Background: Aquaporin 9 (AQP9) is recognized as a key regulator in several cancers, whereas little is known about its clinical implication in non-small cell lung cancer (NSCLC). Thus, we aimed to explore AQP9 expression and its relationship with clinical features, prognosis in NSCLC patients.

Methods: One hundred ninety-eight NSCLC patients who received resection were retrospectively enrolled. This study contained two cohorts: in cohort A, AQP9 protein expression (from formalin fixed paraffin embedded tumor and paired adjacent tissue specimens) in 198 patients was detected by immunohistochemistry (IHC). In cohort B, AQP9 mRNA expression (from fresh-frozen tumor and paired adjacent tissues) in 108 patients (out of 198 patients) was detected by RT-qPCR.

Results: In cohort A, increased AQP9 IHC score and greater proportion of AQP9 protein high expression cases were shown in tumor tissue than adjacent tissue (both P < 0.001). Tumor AQP9 protein high expression correlated with lymph node (LYN) metastasis (P = 0.002) and raised TNM stage (P = 0.012). Interestingly, tumor AQP9 protein high expression related to worse disease-free survival (DFS) (P = 0.002) and overall survival (OS) (P = 0.026). In cohort B, AQP9 mRNA expression in tumor tissue was increased than adjacent tissue (P < 0.001), and tumor AQP9 mRNA high expression linked to LYN metastasis (P = 0.024) and increased TNM stage (P = 0.032) as well; tumor AQP9 mRNA high expression was related to shorter DFS (P = 0.009), and it presented with a trend to be correlated with worse OS (P = 0.054), but without statistical significance.

Conclusion: AQP9 serves as a potential indicator for monitoring disease progression and prognostication in NSCLC patients.
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http://dx.doi.org/10.1007/s11845-021-02523-4DOI Listing
March 2021

Family and Child Risk Factors for Early-Life RSV Illness.

Pediatrics 2021 Mar 18. Epub 2021 Mar 18.

ICES, Toronto, Ontario, Canada;

Background And Objectives: Most infants hospitalized with respiratory syncytial virus (RSV) do not meet common "high-risk" criteria and are otherwise healthy. The objective of this study was to quantify the risks and relative importance of socioeconomic factors for severe, early-life RSV-related illness. We hypothesized several of these factors, particularly those indicating severe social vulnerability, would have statistically significant associations with increased RSV hospitalization rates and may offer impactful targets for population-based RSV prevention strategies, such as prophylaxis programs.

Methods: We used linked health, laboratory, and sociodemographic administrative data for all children born in Ontario (2012-2018) to identify all RSV-related hospitalizations occurring before the third birthday or end of follow-up (March 31, 2019). We estimated rate ratios and population attributable fractions using a fully adjusted model.

Results: A total of 11 782 RSV-related hospitalizations were identified among 789 484 children. Multiple socioeconomic factors were independently associated with increased RSV-related admissions, including young maternal age, maternal criminal involvement, and maternal history of serious mental health and/or addiction concerns. For example, an estimated 4.1% (95% confidence interval: 2.2 to 5.9) of RSV-related admissions could be prevented by eliminating the increased admissions risks among children whose mothers used welfare-based drug insurance. Notably, 41.6% (95% confidence interval: 39.6 to 43.5) of admissions may be prevented by targeting older siblings (eg, through vaccination).

Conclusions: Many social factors were independently associated with early-life RSV-related hospitalization. Existing RSV prophylaxis and emerging vaccination programs should consider the importance of both clinical and social risk factors when determining eligibility and promoting compliance.
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http://dx.doi.org/10.1542/peds.2020-029090DOI Listing
March 2021

Associations Between Cytochrome P450 (CYP) Gene Single-Nucleotide Polymorphisms and Second-to-Fourth Digit Ratio in Chinese University Students.

Med Sci Monit 2021 Mar 16;27:e930591. Epub 2021 Mar 16.

Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education/Key Laboratory of Reproduction and Genetics/Basic Medical College, Ningxia Medical University, Yinchuan, Ningxia, China (mainland).

BACKGROUND Cytochrome P450 (CYP) genes are necessary for the production or metabolism of fetal sex hormones during pregnancy. The second-to-fourth digit ratio (2D: 4D) is formed in the early stage of human fetal development and considered an indicator reflecting prenatal sex steroids levels. We explored the association between 2D: 4D and single-nucleotide polymorphisms (SNPs) of CYP. MATERIAL AND METHODS Correlation analysis between 2D: 4D and 8 SNPs, rs2687133 (CPY3A7), rs7173655 (CYP11A1), rs1004467, rs17115149, and rs2486758 (CYP17A1), and rs4646, rs2255192, rs4275794 (CYP19A1), was performed using data from 426 female and 412 male Chinese university students. SNP genotyping was conducted using PCR. Digit lengths were photographed and measured by image processing software. RESULTS rs2486758 (CYP17A1) correlated with left hand 2D: 4D in men (P=0.026), and rs1004467 (CYP17A1) correlated with right hand 2D: 4D in men (P=0.008) and the whole population (P=0.032). In men, allele G rs1004467 decreased right hand 2D: 4D, while allele C of rs2486758 increased left hand 2D: 4D. In women, left hand 2D: 4D was higher in genotypes with allele A of SNP rs4646 (CYP19A1) under the dominant genetic model; female DR-L was higher in genotypes with allele T of rs17115149 (CYP11A1). SNPs rs2687133 (CYP3A7) and rs1004467 (CYP17A1) were significantly correlated with right hand 2D: 4D (P=0.0107). CONCLUSIONS SNPs rs1004467 and rs2486758 of CYP17A1 are significant in the relationship between 2D: 4D and CYP gene polymorphisms under different conditions. SNP interactions between CYP genes probably impact 2D: 4D. The correlation between 2D: 4D and some sex hormone-related diseases may be due to the effect of CYP variants on the 2 phenotypes.
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http://dx.doi.org/10.12659/MSM.930591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980499PMC
March 2021

Comparative Genomic and Transcriptomic Analysis Reveals Specific Features of Gene Regulation in .

Front Microbiol 2021 26;12:598060. Epub 2021 Feb 26.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

is a promising host for producing bioethanol and heterologous proteins. It displays many superior traits to a conventional industrial yeast species, , including fast growth, thermotolerance and the capacity to assimilate a wider variety of sugars. However, little is known about the mechanisms underlying the fast-growing feature of . In this study, we performed a comparative genomic analysis between and other Saccharomycetaceae species. Genes involved in flocculation, iron transport, and biotin biosynthesis have particularly high copies in . In addition, 60 specific genes were identified, 45% of which were upregulated during cultivation in rich medium and these genes may participate in glucose transport and mitochondrion related functions. Furthermore, the transcriptomic analysis revealed that under aerobic condition, normalized levels of genes participating in TCA cycles, respiration chain and ATP biosynthesis in the lag phase were higher in than those in . Levels of highly copied genes, genes involved in the respiratory chain and mitochondrion assembly, were upregulated in , but not in , in later time points during cultivation compared with those in the lag phase. Notably, during the fast-growing phase, genes involved in the respiratory chain, ATP synthesis and glucose transport were co-upregulated in . A few shared motifs in upstream sequences of relevant genes might result in the co-upregulation. Specific features in the co-regulations of gene expressions might contribute to the fast-growing phenotype of . Our study underscores the importance of genome-wide rewiring of the transcriptional network during evolution.
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http://dx.doi.org/10.3389/fmicb.2021.598060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953160PMC
February 2021

The prevalence of Helicobacter pylori infection in inflammatory bowel disease in China: A case-control study.

PLoS One 2021 12;16(3):e0248427. Epub 2021 Mar 12.

Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background & Aims: Helicobacter pylori (H. pylori) infection remains high in China though the incidence of inflammatory bowel disease (IBD) has increased. Our aim was to investigate the relationship between the prevalence of H. pylori and inflammatory bowel disease.

Methods: Hospitalized IBD patients including Crohn's disease (CD) and ulcerative colitis (UC) who had tested H. pylori antibody were enrolled. Controls were chose from age- and sex- matched healthy physical examination people who had H. pylori antibody test in a 1:2 fashion (IBD patients:controls). IBD medical history was recorded. All patients were typed by the Montreal classification. Mayo Clinic score and the Harvey-Bradshaw Severity Index were used to evaluate their disease activity. Patients and controls that had H. pylori eradication therapy before were excluded.

Results: Two hundred and sixty IBD patients including 213 CD patients and 47 UC patients, and 520 controls were involved in this study. The prevalence of H. pylori infection in IBD patients (9.6%, 25/260) and IBD newly diagnosed patients (12.1%, 8/66), as well as CD patients (8.9%, 19/213) including CD newly diagnosed patients (10.6%, 5/47) and UC patients (12.8%, 6/47) was significantly lower than controls (29.8%, 155/520) (p = 2.796*10-10, 0.007, 5.723*10-9, 0.016, 0.014), while there was no statistically difference between UC newly diagnosed patients and the controls, and IBD patients with different disease type, disease activity and treatment history.

Conclusions: H. pylori infection had a negative association with IBD, especially CD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248427PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954320PMC
March 2021

MiR-4729 regulates TIE1 mRNA m6A modification and angiogenesis in hemorrhoids by targeting METTL14.

Ann Transl Med 2021 Feb;9(3):232

Department of Otolaryngology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Hemorrhoids are a frequently-occurring disease of the anorectal system that is often accompanied by vascular hyperplasia and edema. A METTL14-mediated RNA N-6 methyladenosine (m6A) modification can improve mRNA stability and increase its transcriptional and translational activities, closely related to the occurrence of many diseases.

Methods: Western blot, qPCR, and immunofluorescence staining were used to detect the levels of gene and protein expression. Haematoxylin and eosin staining was used for histopathological examination. RNA immunoprecipitation-PCR and RNA dot blotting were used to detect mRNA m6A modification.

Results: Obvious signs of angiogenesis (CD31+/vWF+) were identified in the hemorrhoids. High levels of METTL14 expression on vascular endothelial cells (CD31+) suggested that angiogenesis was accompanied by differential modification of m6A RNA. It was subsequently found that the level of miR-4729 expression was significantly decreased in hemorrhoid tissues. The luciferase reporter enzyme assay results suggested that miR-4729 silenced its expression by targeting the 3'UTR of METTL14 mRNA. MiR-4729 overexpression in human umbilical vein endothelial cells (HUVECs) inhibited the proliferation and migration of HUVECs and vascular structure formation in the outer matrix. MiR-4729 overexpression significantly inhibited endogenous METTL14 expression in HUVECs and reduced the entire m6A RNA modification, especially the level of m6A methylation at the specific site of the 3' UTR of TIE1 mRNA. Moreover, miR-4729 overexpression significantly inhibited the molecular loop of the TIE1/VEGFA signaling pathway in HUVECs.

Conclusions: Our findings confirmed that the down-regulation of miR-4729 in hemorrhoid vascular endothelial cells was one of the main reasons for vascular proliferation. The overexpression of miR-4729 in vascular endothelial cells decreased the global mRNA methylation and TIE1 mRNA 3'UTR-specific site methylation by silencing METTL14 expression, reducing TIE1 mRNA stability, down-regulating the TIE1/VEGFA signal molecular loop expression, and weakening angiogenesis ability.
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http://dx.doi.org/10.21037/atm-20-3399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940907PMC
February 2021

Assessing the validity of administrative health data for the identification of children and youth with autism spectrum disorder in Ontario.

Autism Res 2021 Mar 10. Epub 2021 Mar 10.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Population-level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)-based reference standard, consisting 10,000 individuals aged 1-24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case-finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm's sensitivity was 50.0% (95%CI 40.7-88.7%), specificity 99.6% (99.4-99.7), PPV 56.6% (46.8-66.3), and NPV 99.4% (99.3-99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. LAY SUMMARY: We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources.
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http://dx.doi.org/10.1002/aur.2491DOI Listing
March 2021

The relationship between breast density, age, and mammographic lesion type among Chinese breast cancer patients from a large clinical dataset.

BMC Med Imaging 2021 Mar 8;21(1):43. Epub 2021 Mar 8.

Department of Breast Imaging, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Background: The purpose of this study was to investigate the relationship between breast density, age, and mammographic lesion type among Chinese breast cancer patients included in a large clinical dataset.

Methods: A review of mammographic images acquired between July 2014 and June 2017 from a total of 9716 retrospectively registered breast cancer patients was conducted. Mammographic breast density was defined according to the American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) 4-class density rating. Mammographic lesion types were defined according to the ACR BI-RADS, including mass, mass with calcifications, calcifications, architectural distortion/asymmetries, and architectural distortion/asymmetries with calcifications. Three experienced breast radiologists interpreted all mammograms. The chi-square (χ) test and Pearson correlation analyses were performed to assess the relationship between breast density, age, and mammographic lesion type.

Results: A significant inverse relationship was observed between the BI-RADS breast density rating given by radiologists and patient age (r = - 0.521, p < 0.01). The breast density distribution in breast cancer patients from China reversed at the age of 55 years, and exhibited one age peak in the age 55-59 year group. The percentage of lesions with calcifications decreased with increasing age (p < 0.01), and increased with increasing breast density (p < 0.01).

Conclusions: In general, we identified a relationship between patient breast density, age, and mammographic lesion type. This finding may provide a basis for clinical diagnoses and support development of breast cancer screening programs in China.
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http://dx.doi.org/10.1186/s12880-021-00565-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938487PMC
March 2021

The nucleocapsid protein of rice stripe virus in cell nuclei of vector insect regulates viral replication.

Protein Cell 2021 Mar 6. Epub 2021 Mar 6.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

Rice stripe virus (RSV) transmitted by the small brown planthopper causes severe rice yield losses in Asian countries. Although viral nuclear entry promotes viral replication in host cells, whether this phenomenon occurs in vector cells remains unknown. Therefore, in this study, we systematically evaluated the presence and roles of RSV in the nuclei of vector insect cells. We observed that the nucleocapsid protein (NP) and viral genomic RNAs were partially transported into vector cell nuclei by utilizing the importin α nuclear transport system. When blocking NP nuclear localization, cytoplasmic RSV accumulation significantly increased. In the vector cell nuclei, NP bound the transcription factor YY1 and affected its positive regulation to FAIM. Subsequently, decreased FAIM expression triggered an antiviral caspase-dependent apoptotic reaction. Our results reveal that viral nuclear entry induces completely different immune effects in vector and host cells, providing new insights into the balance between viral load and the immunity pressure in vector insects.
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http://dx.doi.org/10.1007/s13238-021-00822-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936609PMC
March 2021

c-Myc-induced circ-NOTCH1 promotes aggressive phenotypes of nasopharyngeal carcinoma cells by regulating the miR-34c-5p/c-Myc axis.

Cell Biol Int 2021 Mar 6. Epub 2021 Mar 6.

Department of Radiation Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Nasopharyngeal carcinoma (NPC) is the subclass of head and neck cancer with the highest incidence among otolaryngology malignancies. A growing amount of evidence has proven that circular RNAs (circRNAs) play key roles in the progression of multiple cancers. It has been reported that circ-NOTCH1 is a novel circRNA and functions as an oncogene in gastric cancer, while the regulatory mechanism of circ-NOTCH1 in NPC remains unknown. In the present research, our findings revealed that circ-NOTCH1 was overexpressed in NPC tissues and cells. Circ-NOTCH1 knockdown suppressed NPC cell proliferation, invasion, and migration. Subsequently, we discovered that c-Myc can activate circ-NOTCH1 by binding to the NOTCH1 promoter. c-Myc functioned as a tumor promoter in NPC cells. Mechanistically, circ-NOTCH1 served as a competitive endogenous RNA to modulate c-Myc expression by sponging miR-34c-5p. Additionally, overexpression of c-Myc reversed the circ-NOTCH1 knockdown-mediated inhibition of NPC cellular progression. Overall, this study suggested that c-Myc-induced circ-NOTCH1 promoted malignant phenotypes of NPC cells by regulating the miR-34c-5p/c-Myc axis.
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http://dx.doi.org/10.1002/cbin.11582DOI Listing
March 2021

A Population-Based Cohort Study of Respiratory Disease and Long-Term Exposure to Iron and Copper in Fine Particulate Air Pollution and Their Combined Impact on Reactive Oxygen Species Generation in Human Lungs.

Environ Sci Technol 2021 Mar 5;55(6):3807-3818. Epub 2021 Mar 5.

Public Health Ontario, Toronto, ON M5G 1V2, Canada.

Metal components in fine particulate matter (PM) from nontailpipe emissions may play an important role in underlying the adverse respiratory effects of PM. We investigated the associations between long-term exposure to iron (Fe) and copper (Cu) in PM and their combined impact on reactive oxygen species (ROS) generation in human lungs, and the incidence of asthma, chronic obstructive pulmonary disease (COPD), COPD mortality, pneumonia mortality, and respiratory mortality. We conducted a population-based cohort study of ∼0.8 million adults in Toronto, Canada. Land-use regression models were used to estimate the concentrations of Fe, Cu, and ROS. Outcomes were ascertained using validated health administrative databases. We found positive associations between long-term exposure to Fe, Cu, and ROS and the risks of all five respiratory outcomes. The associations were more robust for COPD, pneumonia mortality, and respiratory mortality than for asthma incidence and COPD mortality. Stronger associations were observed for ROS than for either Fe or Cu. In two-pollutant models, adjustment for nitrogen dioxide somewhat attenuated the associations while adjustment for PM had little influence. Long-term exposure to Fe and Cu in PM and estimated ROS concentration in lung fluid was associated with increased incidence of respiratory diseases, suggesting the adverse respiratory effects of nontailpipe emissions.
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http://dx.doi.org/10.1021/acs.est.0c05931DOI Listing
March 2021

Peptidomics analysis revealed that a novel peptide VMP‑19 protects against Ang II‑induced injury in human umbilical vein endothelial cells.

Mol Med Rep 2021 Apr 2;23(4). Epub 2021 Mar 2.

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Vascular endothelial dysfunction is a vital pathological change in hypertension, which is mainly caused by apoptosis and oxidative stress injury of vascular endothelial cells. Peptidomics is a method for the direct analysis of small bioactive peptides in various biological samples using liquid chromatography‑mass spectrometry (MS)/MS. Given the advantages of the low molecular weight, optimum targeting and easy access to cells, peptides have attracted extensive attention in the field of drug research. However, to the best of our knowledge, little is currently known regarding the role of peptides in vascular endothelial injury. In order to investigate the peptides involved in vascular endothelial protection, MS was used to analyze the peptide profiles in the supernatant of human umbilical vein endothelial cells (HUVECs) stimulated by Ang II. The results revealed that 211 peptides were identified, of which six were upregulated and 13 were downregulated when compared with the control group. Subsequently, the present study analyzed the physical and chemical properties and biological functions of identified peptides by bioinformatics, and successfully screened a peptide (LLQDSVDFSLADAINTEFK) named VMP‑19 that could alleviate the apoptosis and oxidative stress injury of HUVECs induced by Ang II. In conclusion, to the best of our knowledge, the present study was the first to use peptidomics to analyze the peptide profiles of supernatant secreted by HUVECs, and revealed that the novel peptide VMP‑19 could protect HUVECs from apoptosis and oxidative stress injury. The results of the present study could provide novel insights into treatment strategies for hypertension.
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http://dx.doi.org/10.3892/mmr.2021.11937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930926PMC
April 2021

GluD to the edge: synaptic organizer competition shapes dendrite arbors.

Neuron 2021 02;109(4):566-568

Djavad Mowafaghian Centre for Brain Health and Department of Psychiatry, University of British Columbia, BC, V6T 2B5, Canada. Electronic address:

The relationship between synaptogenesis and dendritogenesis is poorly understood, particularly in mammals. In this issue of Neuron, Takeo et al. (2021) manipulate synaptic organizers GluD2 and cerebellin-1 to show that Purkinje cells regulate how their dendrites branch by competing with neighboring cells for synaptic real estate.
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http://dx.doi.org/10.1016/j.neuron.2021.01.019DOI Listing
February 2021

Nomogram for Early Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using Dynamic Contrast-enhanced and Diffusion-weighted MRI.

Acad Radiol 2021 Feb 13. Epub 2021 Feb 13.

Department of Breast Imaging, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, P.R. China. Electronic address:

Rationale And Objectives: The study investigated the potential of the combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging in predicting the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) after two cycles of NAC.

Materials And Methods: Eighty-seven patients with breast cancer who underwent MR examination before and after two cycles of NAC were enrolled. The patients were randomly assigned to a training cohort and a validation cohort (3:1 ratio). MRI parameters including tumor longest diameter, time-signal intensity curve, early enhanced ratio (E), maximal enhanced ratio and ADC value were measured, and percentage change in MRI parameters were calculated. Univariate analysis and multivariate logistic regression analysis were used to evaluate independent predictors of pCR in the training cohort. The validation cohort was used to test the prediction model, and the nomogram was created based on the prediction model.

Results: This study demonstrated that the ADC value after two cycles of NAC (OR = 1.041, 95% CI (1.002, 1.081); p = 0.037), percentage decrease in E (OR = 0.927, 95% CI (0.881, 0.977); p =0.004) and percentage decrease in tumor size (OR = 0.948, 95% CI (0.909, 0.988); p = 0.011) were significantly important for independently predicting pCR. The prediction model yielded AUC of 0.939 and 0.944 in the training cohort and the validation cohort, respectively.

Conclusion: The combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging could accurately predict pCR after two cycles of NAC. The prediction model and the nomogram had strong predictive value to NAC.
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http://dx.doi.org/10.1016/j.acra.2021.01.023DOI Listing
February 2021

Immune Responses and Viral Persistence in Simian/Human Immunodeficiency Virus SHIV.C.CH848-Infected Rhesus Macaques.

J Virol 2021 Apr 12;95(9). Epub 2021 Apr 12.

Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA

Chimeric simian/human immunodeficiency viruses (SHIVs) are widely used in nonhuman primate models to recapitulate human immunodeficiency virus (HIV) infection in humans, yet most SHIVs fail to establish persistent viral infection. We investigated immunological and virological events in rhesus macaques infected with the newly developed SHIV.C.CH848 (SHIVC) and treated with combined antiretroviral therapy (cART). Similar to HIV/simian immunodeficiency virus (SIV) infection, SHIV.C.CH848 infection established viral reservoirs in CD4 T cells and myeloid cells, accompanied by productive infection and depletion of CD4 T cells in systemic and lymphoid tissues throughout SHIV infection. Despite 6 months of cART-suppressed viral replication, integrated proviral DNA levels remained stable, especially in CD4 T cells, and the viral rebound was also observed after ART interruption. Autologous neutralizing antibodies to the parental HIV-1 strain CH848 were detected, with limited viral evolution at 5 months postinfection. In comparison, heterogenous neutralizing antibodies in SHIV.C.CH848-infected macaques were not detected except for 1 (1 of 10) animal at 2 years postinfection. These findings suggest that SHIV.C.CH848, a novel class of transmitted/founder SHIVs, can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research. SHIVs have been extensively used in a nonhuman primate (NHP) model for HIV research. In this study, we investigated viral reservoirs in tissues and immune responses in an NHP model inoculated with newly generated transmitted/founder HIV-1 clade C-based SHIV.C.CH848. The data show that transmitted founder (T/F) SHIVC infection of macaques more closely recapitulates the virological and clinical features of HIV infection, including persistent viremia and viral rebound once antiretroviral therapy is discontinued. These results suggest this CCR5-tropic, SHIVC strain is valuable for testing responses to HIV vaccines and therapeutics.
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http://dx.doi.org/10.1128/JVI.02198-20DOI Listing
April 2021

Dynamic changes in monocytes subsets in COVID-19 patients.

Hum Immunol 2021 Mar 26;82(3):170-176. Epub 2020 Dec 26.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) is affecting the whole world and threatening human health. We aim to investigate the immunological characteristics of monocytes in critical patients with COVID-19.

Methods: The number and immune status of monocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals.

Results: In critical patients with COVID-19, the absolute number of total monocytes and CD16 monocytes was significantly decreased but CD16 pro-inflammatory monocytes was increased compared to healthy controls. Antigen presentation potential of monocytes, as measured by HLA-DR expression, was suppressed, while their inflammatory phenotype (CD38 expression) was enhanced. Cytokine levels showed sustained increases in critical patients. And the levels of IL-6 were positively correlated with CD16 monocytes number. IL-6 and IL-10 levels were negatively correlated with HLA-DR expression of monocytes. During the recovery of COVID-19 patients, the count and immune status of monocyte subsets were restored by degrees. HLA-DR monocytes possessed good sensitivity and specificity for predicting the incidence of critical patients with COVID-19.

Conclusions: In critical patients with COVID-19, decline in number and HLA-DR expression of monocytes might lead to decreased antigen presentation potential and thus immunosuppression, while increased CD16 pro-inflammatory monocytes might mediate hyperinflammation. HLA-DR monocytes might be a meaningful assisted indicator to predict the incidence of critical patients with COVID-19.
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http://dx.doi.org/10.1016/j.humimm.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762835PMC
March 2021

Highly activated TRAIL CD56 NK cells are associated with the liver damage in HBV-LC patients.

Immunol Lett 2021 Apr 27;232:9-19. Epub 2021 Jan 27.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address:

Background: Chronic hepatitis B-related liver cirrhosis(HBV-LC)is the most common cirrhosis in China, which is characterized as liver damage and high mortality. We aim to investigate the characteristics of TRAILNK cells in patients with HBV-LC and their relationship with liver damage in patients with HBV-LC.

Methods: Thirty cases each of chronic hepatitis B (CHB), HBV-related compensated liver cirrhosis (HBV-CLC) and HBV-related decompensated liver cirrhosis (HBV-DLC) patients were recruited in this study. Thirty age-and sex-matched healthy individuals were recruited as healthy controls (HCs). NK cell phenotypes were determined using flow cytometry. Serum chemokine concentrations were ascertained using the CBA Flex set. Cell apoptosis was analyzed using the Annexin V-PE/7-AAD apoptosis Kit.

Results: CD56 NK cells increased, but CD56 NK cells reduced in HBV-LC patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was mainly expressed on CD56 NK cells. As the degree of liver damage increased, the frequency and activation of total TRAILNK cells and TRAILNK cell subsets continued to increase, especially in the HBV-LC patients. Furthermore, the difference in frequency and activation of total TRAILNK cells between the HBV-CLC and HBV-DLC groups was mainly due to the highly activation and increase of TRAILCD56 NK cells. With the increasing degree of liver damage, CXCR3-associated chemokines (including CXCL9, CXCL10 and CXCL11) were constantly increased, particularly in the HBV-DLC group. The expression of CXCR3 on CD56 NK cells was almost 100 % in all enrolled cohorts. CXCR3-associated chemokines were negatively correlated with liver function and positively correlated with fibrosis degree. TRAILCD56 NK cells were negatively correlated with liver function, and positively correlated with fibrosis degree and CXCR3-associated chemokines. The apoptosis of K562 cells and hepatocytes was suppressed partially by the TRAIL-neutralizing antibodies.

Conclusions: The increase of CXCR3-related chemokines (including CXCL9, CXCL10 and CXCL11) might be related to the migration of TRAIL CD56 NK cells to the liver. Highly activated TRAIL CD56 NK cells were associated with the liver damage in HBV-LC patients. These findings may provide new perspectives and theoretical basis for future immunotherapy of HBV-LC patients.
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http://dx.doi.org/10.1016/j.imlet.2020.12.008DOI Listing
April 2021

Phosphate Uptake and Transport in Plants: An Elaborate Regulatory System.

Plant Cell Physiol 2021 Jan 28. Epub 2021 Jan 28.

State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

Phosphorus (P) is an essential macronutrient for plant growth and development. Low phosphate (Pi) availability is a limiting factor for plant growth and yield. To cope with a complex and changing environment, plants have evolved elaborate mechanisms for regulating Pi uptake and use. Recently, the molecular mechanisms of plant Pi signaling have become clearer. Plants absorb Pi from the soil through their roots and transfer Pi to various organs or tissues through phosphate transporters, which are precisely controlled at the transcript and protein levels. Here, we summarize the recent progress on the molecular regulatory mechanism of phosphate transporters in Arabidopsis and rice, including the characterization of functional transporters, regulation of transcript levels, protein localization, and turnover of phosphate transporters. A more in-depth understanding of plant adaptation to a changing Pi environment will facilitate the genetic improvement of plant P efficiency.
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http://dx.doi.org/10.1093/pcp/pcab011DOI Listing
January 2021

WiMonitor: Continuous Long-Term Human Vitality Monitoring Using Commodity Wi-Fi Devices.

Sensors (Basel) 2021 Jan 22;21(3). Epub 2021 Jan 22.

Key Laboratory of High Confidence Software Technologies (Ministry of Education), School of Electronics Engineering and Computer Science, Peking University, Beijing 100871, China.

For a large population of elderly who live alone, a continuous long-term daily monitoring system is critical and imminently needed to enhance the quality of their lives. Continuous monitoring of vitality information (i.e., which area the elder is staying in, the motion state and activity intensity of an elder) is essential for elderly care. In this paper, we use existing commodity Wi-Fi devices to design and implement a long-term device-free human daily vitality system, WiMonitor. Our system can continuously capture the target's vitality information in a multi-room home environment without compromising the privacy of the target. In a continuous 22-day experiment, WiMonitor successfully captures the human vitality information accurately. We believe our system can provide valuable long-term monitoring data for both researchers and health care personnel.
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http://dx.doi.org/10.3390/s21030751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865764PMC
January 2021

Investigation of Kluyveromyces marxianus as a novel host for large-scale production of porcine parvovirus virus-like particles.

Microb Cell Fact 2021 Jan 25;20(1):24. Epub 2021 Jan 25.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai, 200438, People's Republic of China.

Background: Porcine Parvovirus (PPV) is a Parvovirinae virus that can cause embryonic and fetal loss and death and mummification in affected fetal pigs. Unlike conventional vaccines, virus-like particles (VLPs) inherit the natural structure of their authentic virions and highly immunostimulatory that can induce strong humoral immune and T cell responses with no risk of pathogenicity. The production of PPV VLPs is still a challenge based on traditional expression platforms due to their low yields and high culture costs. Kluyveromyces marxianus is a safe and fast-growing eukaryote that can get high biomass with low-cost cultures. In this study, we investigated the expression and downstream processes of PPV VLPs in K. marxianus, and the potential for effective stand-alone vaccines.

Results: After optimization according to the codon bias of K. marxianus, the VP2 protein from Kresse strain was highly expressed. In a 5 L fermentator, the yield of PPV VLPs reached 2.5 g/L, quantified by HPLC, using a defined mineral medium after 48 h fermentation. Two strategies were established to purify intracellular PPV VLPs: (i) Using the cation exchange chromatography coupled with Sephacryl® S-500 HR chromatography to purify VLPs from the supernatants of pH adjusted cell lysates. (ii) Using anion exchange chromatography followed by cross-flow diafiltration to recover the VLPs precipitated in pH adjusted cell lysates. The purity of PPV VLPs reached about 95%, and total recovery was more than 60%. Vaccination of mice with the purified PPV VLPs induced high titers of specific IgG antibodies in sera, and showed hemagglutination inhibitions on both swine and guinea pig erythrocytes. Spleen lymphocyte proliferation and cytokines detection suggested the PPV VLPs produced by K. marxianus provoked the cellular immune and humoral immunity responses in mice.

Conclusions: This is the highest production of recombinant PPV VLPs achieved to date. The superiorities, Generally Recognized As Safe (GRAS), high production, short lead time, and low cost, make K. marxianus a greatly competitive platform for bioproduction of PPV VLPs vaccine.
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http://dx.doi.org/10.1186/s12934-021-01514-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836160PMC
January 2021

Effect of immobilized anthraquinone-2-sulfonate on antibiotic resistance genes and microbial community in biofilms of anaerobic reactors.

J Environ Manage 2021 Mar 14;282:111967. Epub 2021 Jan 14.

Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, China.

Quinone compounds could significantly accelerate anaerobic biotransformation of refractory pollutants. However, the effect of quinone compounds application on the propagation of antibiotic resistance genes (ARGs) in the bio-treatment of these pollutants-containing wastewater is not available. In this study, the catalytic performance of anthraquinone-2-sulfonate immobilized on polyurethane foam (AQS-PUF), changes of ARGs, mobile gene elements (MGEs) and microbial community structure attached on AQS-PUF and PUF in the up-flow anaerobic bioreactors were investigated. The results showed that AQS-PUF could significantly accelerate the decolorization of azo dye RR X-3B. Meanwhile, metagenomics analysis showed that the total absolute abundance of ARGs increased in the presence of the immobilized AQS. Among ARGs, the number of the efflux pump-encoding ARGs in the biofilm of AQS-PUF accounted for 35.7% of the total ARGs, which was slightly higher than that of PUF (32.1%) due to the presence of the immobilized AQS. The relative abundances of ARGs conferring resistance to MLS (macrolide, lincosamide and streptogramin), tetracycline and sulfonamide, which were deeply concerned, reduced 10%, 21.7% and 7.3% in the presence of the immobilized AQS, respectively. Moreover, the immobilized AQS resulted in the decreased relative abundance of plasmids, transposons and class I integrons. Among the detected 31 ARG subtypes located in MGEs, the relative abundances of only lnuF, msrE and mphD in the biofilm of AQS-PUF were over 2-fold higher compared with those in the biofilm of PUF. However, the three ARGs and their host Gammaproteobacteria was not dominant in microbial community. The relative abundances of more ARGs including MLS (lnuB and EreA), tetracycline (tetH) resistance genes located in MGEs decreased, which was attributed to the decreased relative abundance of their hosts. These studies showed that the addition of the immobilized AQS (around 0.25 mM) had a beneficial effect on reducing the spread of ARGs during dyeing wastewater bio-treatment.
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http://dx.doi.org/10.1016/j.jenvman.2021.111967DOI Listing
March 2021