Publications by authors named "Yong Lin"

742 Publications

Rapid detection of Decapod iridescent virus 1 (DIV1) by recombinase polymerase amplification.

J Virol Methods 2021 Nov 18;300:114362. Epub 2021 Nov 18.

Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Sciences, Nanning, 530021, China. Electronic address:

A recombinase polymerase amplification (RPA) assay was established for the rapid detection of Decapod iridescent virus 1 using primers targeted to the virus's ATPase gene (ORF114R). Optimization experiments showed that the optimal amplification temperature of the RPA assay was 37 °C and that the reaction could be completed within only 15 min. The target band of 15 min. is bright enough. In order to shorten the operational reaction time, consequently, 15 min was the optimal amplification time for our new RPA assay for DIV1. Specificity tests showed that the RPA assay did not exhibit any cross-reactivity with other shrimp pathogens(TSV, MrNV, YHV-1, WSSV, EHP, AHPND, EHNV, RSIV, RGV and IHHNV). Sensitivity tests further showed that the detection limit of the new RPA assay was 200 copies/50 μL, indicating that this assay was more sensitive than a nested polymerase chain reaction (PCR) method. A total of 509 clinical samples were assayed using the RPA and the PCR assays; analysis showed that the RPA method could detect weak-positive samples more effectively than the PCR method. Collectively, these findings indicated that the RPA assay was fast, simple, specific, sensitive and has significant potentials for clinical and on-site testing.
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http://dx.doi.org/10.1016/j.jviromet.2021.114362DOI Listing
November 2021

Pathways between objective and perceived neighborhood factors among Black breast cancer survivors.

BMC Public Health 2021 11 6;21(1):2031. Epub 2021 Nov 6.

Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Background: Mounting evidence supports associations between objective neighborhood disorder, perceived neighborhood disorder, and health, yet alternative explanations involving socioeconomic and neighborhood social cohesion have been understudied. We tested pathways between objective and perceived neighborhood disorder, perceived neighborhood social cohesion, and socioeconomic factors within a longitudinal cohort.

Methods: Demographic and socioeconomic information before diagnosis was obtained at interviews conducted approximately 10 months post-diagnosis from participants in the Women's Circle of Health Follow-up Study - a cohort of breast cancer survivors self-identifying as African American or Black women (n = 310). Neighborhood perceptions were obtained during follow-up interviews conducted approximately 24 months after diagnosis. Objective neighborhood disorder was from 9 items audited across 23,276 locations using Google Street View and scored to estimate disorder values at each participant's residential address at diagnosis. Census tract socioeconomic and demographic composition covariates were from the 2010 U.S. Census and American Community Survey. Pathways to perceived neighborhood disorder were built using structural equation modelling. Model fit was assessed from the comparative fit index and root mean square error approximation and associations were reported as standardized coefficients and 95% confidence intervals.

Results: Higher perceived neighborhood disorder was associated with higher objective neighborhood disorder (β = 0.20, 95% CI: 0.06, 0.33), lower neighborhood social cohesion, and lower individual-level socioeconomic factors (final model root mean square error approximation 0.043 (90% CI: 0.013, 0.068)). Perceived neighborhood social cohesion was associated with individual-level socioeconomic factors and objective neighborhood disorder (β = - 0.11, 95% CI: - 0.24, 0.02).

Conclusion: Objective neighborhood disorder might be related to perceived disorder directly and indirectly through perceptions of neighborhood social cohesion.
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http://dx.doi.org/10.1186/s12889-021-12057-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572419PMC
November 2021

Controls Angiogenesis by Targeting VE-PTP Through Interaction With Nucleolin.

Front Cell Dev Biol 2021 11;9:728821. Epub 2021 Oct 11.

Guangxi Key Laboratory for Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Sciences, Nanning, China.

Precise regulation of angiogenesis is required for organ development, wound repair, and tumor progression. Here, we identified a novel gene, (New XingHuo light), that is conserved in vertebrates and that plays a crucial role in vascular integrity and angiogenesis. Bioinformatic analysis uncovered its essential roles in development based on co-expression with several key developmental genes. Knockdown of in zebrafish causes global and pericardial edema, loss of blood circulation, and vascular defects characterized by both reduced vascularization in intersegmental vessels and decreased sprouting in the caudal vein plexus. The gene also affects human endothelial cell behavior . We found that functions in part by targeting VE-PTP through interaction with NCL (nucleolin). Loss of (a VE-PTP ortholo) in zebrafish resulted in defects similar to knockdown. Moreover, deficiency attenuates tumor invasion and proteins (including VE-PTP and NCL) associated with angiogenesis and EMT. These findings illustrate that can regulate angiogenesis via a novel -NCL-VE-PTP axis, providing a new therapeutic target for modulating vascular formation and function, especially for cancer treatment.
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http://dx.doi.org/10.3389/fcell.2021.728821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558974PMC
October 2021

Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p.

Cell Death Discov 2021 Oct 23;7(1):311. Epub 2021 Oct 23.

Departments of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.

A growing body of evidence suggests that long-chain non-coding RNA (lncRNA) plays an important role in the malignant biological behavior and drug resistance of glioblastoma (GBM) cells. In this study, we analyzed the role and potential mechanism of lncRNA TMEM161B-AS1 in the malignant biological behavior of GBM cells and temozolomide (TMZ) resistance. Studies have found that FANCD2 and CD44 are significantly related to the occurrence of GBM, TMZ resistance and the survival of GBM patients. Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. Down-regulation of lncRNA TMEM161B-AS1 and/or over-expression of hsa-miR-27a-3p down-regulated the expression of FANCD2 and CD44, and inhibited the tumor growth in nude mice. These results demonstrated that the lncRNA TMEM161B-AS1-hsa-miR-27a-3p-FANCD2/CD44 signal axis regulated the malignant biological behavior of GBM and TMZ resistance. These findings were expected to provide promising therapeutic targets for the treatment of glioma.
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http://dx.doi.org/10.1038/s41420-021-00709-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542043PMC
October 2021

A phase I study of veliparib with cyclophosphamide and veliparib combined with doxorubicin and cyclophosphamide in advanced malignancies.

Cancer Chemother Pharmacol 2021 Oct 20. Epub 2021 Oct 20.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Purpose: Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C.

Methods: Objectives were to establish the maximum tolerated dose (MTD) of the combinations, characterize V pharmacokinetics (PK) in the presence and absence of C, measure PAR in peripheral blood mononuclear cells (PBMCs) and γH2AX in circulating tumor cells (CTCs). In Group 1, dose escalations of V from 10 to 50 mg every 12 h Days 1-4 plus C 450 to 750 mg/m Day 3 in 21-day cycles were evaluated. In Group 2, V doses ranged from 50 to 150 mg every 12 h Days 1-4 with AC (60/600 mg/m) Day 3 in 21-day cycles. In Group 3, patients received AC Day 1 plus V Days 1-7, and in Group 4, AC Day 1 plus V Days 1-14 was given in 21-day cycles to evaluate effects on γH2AX foci.

Results: Eighty patients were enrolled. MTD was not reached for V and C. MTD for V and AC was V 100 mg every 12 h Days 1-4 with AC (60/600 mg/m2) Day 3 every 21 days. V PK appears to be dose-dependent and has no effect on the PK of C. Overall, neutropenia and anemia were the most common adverse events. Objective response in V and AC treated groups was 22% (11/49). Overall clinical benefit rate was 31% (25/80). PAR decreased in PBMCs. Percentage of γH2AX-positive CTCs increased after treatment with V and AC.

Conclusion: V and AC can be safely combined. Activity was observed in patients with metastatic breast cancer.
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http://dx.doi.org/10.1007/s00280-021-04350-xDOI Listing
October 2021

Construction and Validation of an Immune Cell Signature Score to Evaluate Prognosis and Therapeutic Efficacy in Hepatocellular Carcinoma.

Front Genet 2021 27;12:741226. Epub 2021 Sep 27.

Shanghai Center for Bioinformation Technology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with high morbidity and mortality worldwide. Tumor immune microenvironment (TIME) plays a pivotal role in the outcome and treatment of HCC. However, the effect of immune cell signatures (ICSs) representing the characteristics of TIME on the prognosis and therapeutic benefit of HCC patients remains to be further studied. In total, the gene expression profiles of 1,447 HCC patients from several databases, i.e., The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, and Gene Expression Omnibus, were obtained and applied. Based on a comprehensive collection of marker genes, 182 ICSs were evaluated by single sample gene set enrichment analysis. Then, by performing univariate and multivariate Cox analysis and random forest modeling, four significant signatures were selected to fit an immune cell signature score (ICSscore). In this study, an ICSscore-based prognostic model was constructed to stratify HCC patients into high-risk and low-risk groups in the TCGA-LIHC cohort, which was successfully validated in two independent cohorts. Moreover, the ICSscore values were found to positively correlate with the current American Joint Committee on Cancer staging system, indicating that ICSscore could act as a comparable biomarker for HCC risk stratification. In addition, when setting the four ICSs and ICSscores as features, the classifiers can significantly distinguish treatment-responding and non-responding samples in HCC. Also, in melanoma and breast cancer, the unified ICSscore could verify samples with therapeutic benefits. Overall, we simplified the tedious ICS to develop the ICSscore, which can be applied successfully for prognostic stratification and therapeutic evaluation in HCC. This study provides an insight into the therapeutic predictive efficacy of prognostic ICS, and a novel ICSscore was constructed to allow future expanded application.
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http://dx.doi.org/10.3389/fgene.2021.741226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503558PMC
September 2021

Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects.

Cell Mol Immunol 2021 Oct 13. Epub 2021 Oct 13.

Key Laboratory of Molecular Biology of Infectious Diseases (Chinese Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that poses a great threat to human health worldwide. As the humoral immune response plays essential roles in disease occurrence and development, understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease. In this review, we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARS-CoV-2-specific humoral immunity and the critical role of this immunity in vaccine development. Notably, serological antibody testing based on the humoral immune response can guide public health measures and control strategies; however, it is not recommended for population surveys in areas with very low prevalence. Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection, whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults. The correlations between antibody (especially neutralizing antibody) titers and protection against SARS-CoV-2 reinfection should be further examined. In addition, the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.
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http://dx.doi.org/10.1038/s41423-021-00774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513558PMC
October 2021

Levosimendan administration is not associated with increased risk of bleeding and blood transfusion requirement in patients undergoing off-pump coronary artery bypass grafting: a retrospective study from single center.

Perfusion 2021 Oct 7:2676591211049022. Epub 2021 Oct 7.

Department of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: Levosimendan (LEVO) is a positive inotropic drug which could increase myocardial contractility and reduce the mortality rate in cardiac surgical patients. However, Whether LEVO is associated with postoperative bleeding and blood transfusion in cardiac surgical patients is controversial. Therefore, the current study was designed to investigate the impact of LEVO administration on bleeding and blood transfusion requirement in off-pump coronary artery bypass grafting (OPCAB) patients.

Methods: In a retrospective analysis, a total of 292 patients, aged 40-87 years, undergoing elective OPCAB between January 2019 and July 2019, were divided into LEVO group ( = 151) and Control group ( = 141). Patients in LEVO group continuously received LEVO at a rate of 0.1-0.2 μg kg min after anesthesia induction until 24 hours after OPCAB or patients in Control group received no LEVO. The primary outcome was postoperative chest drainage volume. The secondary outcomes were reoperation for postoperative bleeding, transfusion requirement of red blood cells (RBCs), fresh frozen plasma (FFP) and platelet concentrate (PC), etc. Comparisons of two groups were performed with the Student's -test or Wilcoxon-Mann-Whitney test.

Results: There was no significant difference with respect to chest drainage volume ((956.29 ± 555.45) ml vs (1003.19 ± 572.25) ml, p = 0.478) and the incidence of reoperation for postoperative bleeding (1.32% vs 1.42%, p = 0.945) between LEVO group and Control group. The transfusion incidence and volume of allogeneic RBCs, FFP, and PC were comparable between two groups.

Conclusions: LEVO administration was neither associated with more postoperative blood loss nor increased allogeneic blood transfusion requirement in OPCAB patients.
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http://dx.doi.org/10.1177/02676591211049022DOI Listing
October 2021

Evaluation of the nontreponemal IgM antibodies in syphilis serofast patients: A new serologic marker for active syphilis.

Clin Chim Acta 2021 Dec 27;523:196-200. Epub 2021 Sep 27.

Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, Fujian Province, China. Electronic address:

Background: Serofast status is challenging to interpret in clinical work, and distinguishing active syphilis in serofast patients can provide a reference for clinical diagnosis and treatment. However, effective serologic markers for active syphilis are still lacking.

Objectives: We aimed to explore the possibility of nontreponemal IgM antibodies in distinguishing active syphilis in serofast patients.

Methods: A total of 1501 clinical serum samples were collected from 301 serofast patients, and nontreponemal IgM antibodies were detected by chemiluminescence immunoassay.

Results: The results showed that a total of 29 samples (9.63%) of 301 serofast patients were positive for nontreponemal IgM antibodies, and our limited follow-up data showed that 66.67% (2/3) of the serofast patients progressed to neurosyphilis and cardiovascular syphilis.

Conclusion: These findings demonstrate that most serofast patients with positive nontreponemal IgM antibodies have evidence of progressive syphilis, and nontreponemal IgM antibodies can be used as a new serologic marker for the activity of syphilis. Nontreponemal IgM antibodies may play a role in the management of serofast patients.
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http://dx.doi.org/10.1016/j.cca.2021.09.019DOI Listing
December 2021

ER stress promotes HBV production by enhancing utilization of the autophagosome- multivesicular body axis.

Hepatology 2021 Sep 28. Epub 2021 Sep 28.

Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.

Background & Aims: Hepatitis B virus (HBV) infection has been reported to trigger endoplasmic reticulum (ER) stress and initiate autophagy. However, how ER stress and autophagy influence HBV production remains elusive. Here, we studied the effect of tunicamycin (TM), an N-glycosylation inhibitor and ER stress inducer, on HBV replication and secretion, and examined the underlying mechanisms.

Approach & Results: PDI (an ER marker), LC3 (an autophagosome marker) and p62 (a typical cargo for autophagic degradation) expression were tested in the liver tissues of patients with chronic HBV infection and hepatoma cell lines. The role of TM treatment in HBV production and trafficking was examined in hepatoma cell lines. TM treatment that mimics HBV infection triggered ER stress and increased autophagosome formation, resulting in enhanced HBV replication and the secretion of subviral particles (SVPs) and naked capsids. Additionally, TM reduced the number of early endosomes and HBV surface antigen (HBsAg) localization in this compartment, causing HBsAg/SVPs accumulate in the ER. Thus, TM-induced autophagosome formation serves as an alternative pathway for HBsAg/SVPs trafficking. Importantly, TM inhibited autophagosome-lysosome fusion, accompanied by enhanced autophagosome-late endosome/multivesicular body (MVB) fusion to release HBsAg/SVPs through or along with exosome release. Notably, TM treatment inhibited the HBsAg glycosylation, resulting in impairment of the HBV virions envelopment and secretion, but it was not critical for HBsAg/SVPs trafficking in our cell systems.

Conclusions: TM-induced ER stress and autophagic flux promoted HBV replication and the release of SVPs and naked capsids through the autophagosome-late endosome/MVB axis.
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http://dx.doi.org/10.1002/hep.32178DOI Listing
September 2021

Synergetic valorization of basic oxygen furnace slag and stone coal: Metal recovery and preparation of glass-ceramics.

Waste Manag 2021 Nov 8;135:158-166. Epub 2021 Sep 8.

Process Metallurgy Research Unit, University of Oulu, Oulu 90014, Finland.

A synergetic valorization method was proposed to convert the basic oxygen furnace (BOF) slag and stone coal into ferroalloy and glass-ceramic in this work. Effects of reduction time, temperature, and the mass ratio of BOF slag to stone coal on the reduction were studied. The reduction mechanism was investigated by in-situ observation and dissolution experiments. The effect of sintering temperature on the properties of glass-ceramics prepared from the final slag was further studied. The in-situ observation results indicate that the reduction reactions occurred mainly in the temperature range of 1673-1793 K. The reduction ratio of oxides and size of metal droplets can be improved by increasing reduction time, temperature, and decreasing stone coal addition. The recovered ferroalloys consisted of Fe, Mn, P, and V, which has the potential of returning to the steelmaking process or extracting vanadium. The modified final slag was suitable material for preparing glass-ceramic. Wollastonite-based glass-ceramic with a maximum bending strength of 95.83 MPa was prepared, which could be applied as abrasion-resistant and building decoration materials. Therefore, the present technological route can convert two kinds of industrial solid waste into two kinds of cleaner products and achieve the target of "zero waste".
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http://dx.doi.org/10.1016/j.wasman.2021.08.044DOI Listing
November 2021

Expression of the circular RNAs in astaxanthin promotes cholesterol efflux from THP-1 cells based on RNA-seq.

Genes Nutr 2021 Aug 28;16(1):13. Epub 2021 Aug 28.

Department of Ultrasound, Shunde Women and Children's Hospital of Guangdong Medical University (Maternity & Child Healthcare Hospital of Shunde Foshan), 528300, Foshan, China.

Background: It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux.

Methods: We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student's t test and P < 0.05 was considered statistically significant.

Results: In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR.

Conclusions: The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS.
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http://dx.doi.org/10.1186/s12263-021-00693-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403398PMC
August 2021

Associations of hair dye and relaxer use with breast tumor clinicopathologic features: Findings from the Women's circle of Health Study.

Environ Res 2022 01 11;203:111863. Epub 2021 Aug 11.

Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address:

Background: Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology.

Methods: Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction.

Results: Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall sample. This association was consistent among Black (home kit: OR 2.22, 95 % CI: 1.21-5.00; combination: OR 2.46, 95 % CI: 1.21-5.00), but not White women, and among ER+ (home kit: OR 1.47, 95 % CI: 0.82-2.63; combination: OR 2.98, 95 % CI: 1.62-5.49) but not ER-cases. Combination application of relaxers was associated with increased odds of tumors >2.0 cm vs. <1.0 cm (OR = 1.82, 95 % CI: 1.23-2.69). Longer duration and earlier use of relaxers and combination application of permanent hair dyes and relaxers were associated with breast tumor features including higher tumor grade and larger tumor size, which often denote more aggressive phenotypes, although the findings did not maintain significance with Bonferroni correction.

Conclusions: These novel data support reported associations between hair dye and relaxer use with breast cancer, showing for the first time, associations with breast tumor clinicopathologic features. Improved hair product exposure measurement is essential for fully understanding the impact of these environmental exposure with breast cancer and to guide risk reduction strategies in the future.
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http://dx.doi.org/10.1016/j.envres.2021.111863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616798PMC
January 2022

Effect of switching glatiramer acetate formulation from 20 mg daily to 40 mg three times weekly on immune function in multiple sclerosis.

Mult Scler J Exp Transl Clin 2021 Jul-Sep;7(3):20552173211032323. Epub 2021 Jul 28.

Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Background: Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells.

Objective: To investigate the difference in immunological parameters in response to GA20 and GA40 treatments.

Methods: We analyzed five pro-inflammatory cytokines (IL-1β, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20.

Results: Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups.

Conclusions: The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.
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http://dx.doi.org/10.1177/20552173211032323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330487PMC
July 2021

Alterations of gut microbiome and metabolite profiles in choledocholithiasis concurrent with cholangitis.

Hepatol Int 2021 Jul 27. Epub 2021 Jul 27.

Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China.

Background And Aims: Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to explore the characteristic gut dysbiosis, metabolite profiles and the possible roles in patients with CC.

Methods: A case-control study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with CC (n = 25) compared with healthy controls (HCs) (n = 25) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles.

Results: Significantly reduced Shannon diversity index (p = 0.043) and differential overall fecal microbiota community in CCs were observed. Twelve dominant altered species were identified and analyzed (LDA score > 3.0, p < 0.05) (Q value < 0.05), including unclassified_f_Enterobacteriaceae, Escherichia_coli, Roseburia_faecis and Eubacterium rectale. Moreover, the levels of KEGG pathways related to biofilm formation of Escherichia coli, lipopolysaccharide (LPS) biosynthesis, and the metabolism of propanoate and glutathione in CCs were significantly altered. Finally, 47 markedly changed metabolites (VIP > 1.0 and p < 0.05), including low level of kynurenic acid (KYNA) and high concentration of N-palmitoylsphingosine involving tryptophan metabolism and sphingolipid signaling pathways, were identified to validate aberrant metabolic patterns in CCs, and multiple correlated metabolic modules involving bile inflammation were altered in CCs.

Conclusion: Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in CC and the underlying mechanisms between gut microbiota and bile inflammation.
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http://dx.doi.org/10.1007/s12072-021-10231-5DOI Listing
July 2021

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

Blood Adv 2021 07;5(14):2852-2862

Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.
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http://dx.doi.org/10.1182/bloodadvances.2021004458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341354PMC
July 2021

Cancer cells escape p53's tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation.

Oncogene 2021 Sep 19;40(35):5416-5426. Epub 2021 Jul 19.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations.
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http://dx.doi.org/10.1038/s41388-021-01949-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413129PMC
September 2021

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

Res Pract Thromb Haemost 2021 Jul 14;5(5):e12566. Epub 2021 Jul 14.

Daiichi Sankyo Pharma Development Basking Ridge NJ USA.

Background: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin.

Methods: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire.

Results: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score.

Conclusion: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.
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http://dx.doi.org/10.1002/rth2.12566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279124PMC
July 2021

Changing trends and disparities in 5-year overall survival of women with invasive breast cancer in the United States, 1975-2015.

Am J Cancer Res 2021 15;11(6):3201-3211. Epub 2021 Jun 15.

Department of Pathology, Princeton Medical Center Plainsboro, NJ, USA.

Relative survival is the ratio of overall survival (OS) over survival of the general population, and widely used in epidemiological studies. But it is artificially higher than OS and thus inferior to OS for cancer prognostication of individual patients. Moreover, trend-changes and disparities in OS of breast cancer are unclear while the relative survival of breast cancer has been reported on a regular basis. Therefore, we estimated trends in age-standardized 5-year OS of invasive breast cancer, using data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry program and piecewise-linear regression models. Among 188,052 women with breast cancer diagnosed during 2007-2010 (SEER-18, 155,515 [79.3%] survived by year 5), the 5-year OS significantly differed by age, histology, tumor grade, tumor stage, hormone receptors, race/ethnicity, insurance status, region, rural-urban continuum and selected county-attributes. Among 469,498 women with breast cancer diagnosed during 1975-2010 (SEER-9) in the U.S., we observed an upward trend in the age-standardized 5-year OS (stage- and race/ethnicity-adjusted annual percentage change = 0.97 [95% CI, 0.76-1.18]). The 36-year trends/slopes in age-standardized 5-year OS of breast cancer differed by histology, tumor grade, stage, race/ethnicity, region and socioeconomic attributes of the patient's residence-county, but not by those of rural-urban continuum. The 3-joinpoint model on the 36-year trend identified significant slope changes in 1983, 1987 and 2000, with the largest slope (2.5%/year) during 1983-1987. In conclusion, we here show trends in the age-standardized 5-year OS among U.S. women with breast cancer changed in diagnosis-years of 1983, 1987 and 2000, and differed by tumor characteristics and race/ethnicity. More efforts are needed to understand the trend changes and to address the OS disparities of breast cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263668PMC
June 2021

Radiology report language positively influences adrenal incidentaloma guideline adherence.

Am J Surg 2021 Jun 29. Epub 2021 Jun 29.

Section of Endocrine Surgery, Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA.

Background: Adrenal incidentalomas are common radiographic findings. Guidelines recommend biochemical and radiographic surveillance of adrenal incidentalomas. We investigated if patients were appropriately referred for outpatient evaluation.

Methods: Retrospective chart review was performed to identify patients with adrenal masses on imaging between November 7, 2016 and November 7, 2017. Demographic information, medical history, and outpatient referral information was collected.

Results: 11,723 computed tomography (CT) scans of the chest and/or abdomen/pelvis were performed. 246 patients were noted to have adrenal incidentalomas and met inclusion criteria. The CT report recommended follow-up in 63/246 cases (25.6%). 38/246 (15.4%) patients were referred for evaluation. Age, adrenal nodule size, and type of evaluating provider did not affect referral. A radiology report recommending follow-up was associated with increased referral rate (OR 5.441, 95% CI: 2.491-11.887).

Conclusion: There was low outpatient referral for adrenal incidentalomas. Language in the radiology report significantly influenced referral rates and may be an important resource for improving guideline adherence.
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http://dx.doi.org/10.1016/j.amjsurg.2021.06.015DOI Listing
June 2021

CCDC88A/GIV promotes HBV replication and progeny secretion via enhancing endosomal trafficking and blocking autophagic degradation.

Autophagy 2021 Jun 30:1-18. Epub 2021 Jun 30.

Institute of Biomedical Research, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei province, China.

Hepatitis B virus (HBV) particles are thought to be secreted from hepatocytes through multivesicular bodies (MVBs); however, the cellular trafficking mechanisms prior to this process remain elusive. It has been reported that CCDC88A/GIV expression, which is involved in multiple aspects of vesicular trafficking, changes dynamically at different phases of chronic HBV infection. In this study, we focused on the role of CCDC88A/GIV in HBV replication. In the liver tissues of chronically HBV-infected patients, HBV infection significantly enhanced CCDC88A/GIV expression, and increased endoplasmic reticulum (ER) stress and autophagosome formation without changing endosome formation. Additionally, colocalization of SHBsAg with early endosomes (~30.2%) far exceeded that with autophagosomes (~3.2%). In hepatoma cells, CCDC88A/GIV and its downstream proteins, DNM2 (dynamin 2; a CCDC88A/GIV effector), CLTC and RAB5A significantly enhanced HBV replication and endosome formation but inhibited autophagosome formation. Blocking endocytosis disrupted HBsAg trafficking to endosomes and caused its accumulation in the ER lumen, which triggered ER stress to initiate the unfolded protein response (UPR). Therefore, HBsAg trafficking into autophagosomes was increased, and the lysosomal activity and maturation, which was inhibited by HBV infection, were restored. Meanwhile, core particles were prevented from entering MVBs. CCDC88A/GIV and its other effector, GNAI3, decreased autophagic flux by enhancing the insulin-induced AKT-MTOR pathway, thereby inhibiting HBV antigens autophagic degradation. In conclusion, CCDC88A/GIV enhanced HBV replication by increasing endosomal trafficking and reducing autophagic degradation of HBV antigens, suggesting that CCDC88A/GIV-mediated endosomal trafficking plays an important role in HBV replication and progeny secretion.: ACTB: actin beta; AO: acridine orange; ATF6: activating transcription factor 6; CCDC88A/GIV: coiled-coil domain containing 88A; CLTC: clathrin heavy chain; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DNM2: dynamin 2; ER: endoplasmic reticulum; ERN1: endoplasmic reticulum to nucleus signaling 1; EIF2A: eukaryotic translation initiation factor 2A; FBS: fetal bovine serum; GNAI3: G protein subunit alpha i3; HBV: hepatitis B virus; HBV RIs: HBV replication intermediates; HBcAg: HBV core protein; HBsAg: HBV surface antigen; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MVBs: multivesicular bodies; MTOR: mechanistic target of rapamycin kinase; PDI: protein disulfide isomerase; PHH: primary human hepatocyte; pSM2: a HBV replication-competent plasmid; HSPA5/BIP: heat shock protein family A (Hsp70) member 5; SQSTM1/p62: sequestosome 1; siRNA: small interfering RNA; SEM: standard error of the mean; UPR: unfolded protein response.
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http://dx.doi.org/10.1080/15548627.2021.1934271DOI Listing
June 2021

Sensitive detection of prostate-specific antigen based on dual signal amplification of [email protected] and NH-MIL-101(Fe).

Biosens Bioelectron 2021 Oct 14;190:113437. Epub 2021 Jun 14.

Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China. Electronic address:

An electrochemiluminescence sensor was proposed for detection of prostate-specific antigen (PSA) based on dual-amplification strategy of ferrocenecarboxylic [email protected] layered double hydroxides ([email protected]) and NH-MIL-101(Fe). An (Au NPs/[email protected]) multilayer nanofilm was fabricated by a layer-by-layer self-assembly between positively charged [email protected] nanosheets and negatively charged Au NPs. The multilayer nanofilms acted as nanocarriers for antibody loading and enhancers to catalyze HO decomposition. NH-MIL-101(Fe) promoted the production of reactive oxygen species due to peroxidase-mimicking activity and increased immobilization of antibodies. This sensor showed a linear detection range of 0.05 pg mL to 50 ng mL with a low detection limit of 0.034 pg mL. Moreover, the detection results from this sensor were consistent with data collected from a commercial immunoassay analyzer. The sensor had significant potential for PSA detection in clinical diagnostics.
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http://dx.doi.org/10.1016/j.bios.2021.113437DOI Listing
October 2021

Expression and Diagnostic Value of miR-497 and miR-1246 in Hepatocellular Carcinoma.

Front Genet 2021 7;12:666306. Epub 2021 Jun 7.

Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Objective: Serum microRNAs (miRNAs) may serve as biomarkers in various cancers. Our study aims to explore the roles of miR-497 and miR-1246 in hepatocellular carcinoma (HCC).

Methods: The expression levels of miR-497 and miR-1246 were measured by RT-PCR. A correlation analysis was conducted between the expression levels of miR-497 and miR-1246 and clinicopathological characteristics of patients. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy in HCC. In addition, bioinformatics tools were also utilized to predict the potential targets of miR-497 and miR-1246.

Results: The expression level of miR-497 in HCC was significantly down-regulated compared with the control group while the miR-1246 revealed a significantly higher expression level in HCC. There was a significant correlation demonstrated between the expression levels of miR-497 and miR-1246 in preoperative serum of HCC and the differentiation degree, Tumor Node Metastasis (TNM) classification, and metastasis. The expression levels of serum miR-497 and miR-1246 were significantly associated with the diagnosis, prognosis, and overall survival rate of patients with HCC. Moreover, the potential target genes of miR-497 in HCC include ARL2, UBE2Q1, PHF19, APLN, CHEK1, CASK, SUCO, CCNE1, and KIF23. The low expression of these nine genes is associated with a better prognosis of HCC patients. AUTS2 is a novel target gene of miR-1246, and its low expression is significantly related to the low overall survival rate of HCC patients.

Conclusions: miR-497 and miR-1246 are possibly involved in the progression of HCC by regulating target genes, respectively, and could serve as biomarkers in HCC.
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http://dx.doi.org/10.3389/fgene.2021.666306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215616PMC
June 2021

Mucormycosis: a dreaded complication of COVID-19.

QJM 2021 11;114(9):670-671

School of Medicine, National University of Singapore and Division of Neurology, National University Hospital, Singapore.

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http://dx.doi.org/10.1093/qjmed/hcab166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344851PMC
November 2021

Hydrolyzed seawater pearl tablet modulates the immunity via attenuating Th1/Th2 imbalance in an immunosuppressed mouse model.

J Tradit Chin Med 2021 Jun;41(3):397-405

School of Basic Medical Science, Guangxi University of Chinese Medicine, Nanning 530200, China.

Objective: To investigate whether Hydrolyzed Seawater Pearl tablet (HSPT) could modulate the Th1/Th2 imbalance in an immunosuppressed mouse model with Th1 to Th2 shift induced by Cyclosporine A (CsA) which can be used in the clinical treatment of Th2 to Th1 shift diseases, and explore the possible mechanism for the adjuvant therapeutic efficacy of HSPT on recurrent respiratory infections (RRI) and acquired immune deficiency syndrome (AIDS).

Methods: The mice were randomly divided into six groups of five animals each, namely normal group, model group, lentinan polysaccharide tablet (LPT) group and three HPST treated groups. HPST treated groups were administered with HPST (0.51, 1.02, 2.04 g/kg) via intragastric gavage (i.g) for 30 consecutive days. LPT used as reference drug for positive control, LPT group was administered with LPT (8.2 mg/kg) for 30 consecutive days. Normal group and model group were received distilled water. The animals in model group, LPT group and HPST treated groups were injected intraperitoneally with CsA (50 mg/kg) to establish the immunosuppressed mice model with Th1 to Th2 shift on the 20th, 22nd and 24th day, one hour after the administration of the respective treatment. Animals were sacrificed one hour after the last administration to collect blood and splenic tissue. The proportion of T cells including CD8+ and CD4+ T cells, Th1 and Th2 in peripheral blood of experimental mice were measured by flow cytometric. The protein level in serum and mRNA level in splenic tissue of experimental mice for interleukin (IL)-2, IL-12, interferon-γ (IFN-γ), IL-4, IL-6, IL-10 and IL-13 were measured by enzyme linked immunosorbent assay and fluorescence quantitative polymerase chain reaction respectively.

Results: HSPT elevated the proportion of T cells including both CD8+ and CD4+ T cells, in which the proportion of Th1 and Th2 cells increased, while the ratio of Th1/Th2 cells decreased in peripheral blood of the immunosuppressed mouse model with Th1 to Th2 shift induced by CsA. Furthermore, HSPT elevated both protein and mRNA level of Th1-type cytokines IL-2 and IFN-γ, while had no significant effect on protein and mRNA level of Th1-type cytokine IL-12 and Th2-type cytokines IL-4, IL-6, IL-10, IL- 13 in mouse model.

Conclusion: Our findings suggest that HSPT can increase proportion of T cells including both CD8+ and CD4+ T cells and induce Th2 to Th1 shift in both cells and cytokines, which probably was the mechanism to account for the adjuvant therapeutic efficacy of HSPT on RRI and AIDS.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20210319.001DOI Listing
June 2021

Modeling Cell Survival Fraction and Other Dose-Response Relationships for Immunodeficient C.B-17 SCID Mice Exposed to 320-kV X Rays.

Dose Response 2021 Apr-Jun;19(2):15593258211019887. Epub 2021 May 31.

Lovelace Biomedical Research Institute, Albuquerque, NM, USA.

US homeland security concerns related to potential misuse of γ-ray-emitting radiation sources employed in radiobiological research (eg, shielded cesium-137 irradiators) led to recommendations by the National Research Council to conduct studies into possibly replacing γ-ray irradiators used in research involving small rodent and other models with X-ray instruments. A limiting factor is suitability of the X-ray photon energy spectra. The objective of our research was to demonstrate the suitability of the radiation energy spectrum of 320-kV X rays after filtration (HVL = 4 mm Cu) for in-vivo cytotoxicity studies in immunodeficient C.B-17 SCID mice. By using a previously-published Hazard Function (HF) model to characterize dose-response relationships for in vivo bone marrow and spleen cell survival fractions and also to characterize the acute lethality risk (hematopoietic syndrome mode) we demonstrate that the filtered 320-kV X-ray beam appears suitable for such studies. A key finding for C.B-17 SCID mice when compared to results previously obtained for immunocompetent C.B-17 mice is that the immunodeficient mice appear to be more radioresistant, implicating a possible role of the immune system capacity in radiosensitivity of mammals.
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http://dx.doi.org/10.1177/15593258211019887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170291PMC
May 2021

Association of Body Mass Index, Central Obesity, and Body Composition With Mortality Among Black Breast Cancer Survivors.

JAMA Oncol 2021 Jun 4. Epub 2021 Jun 4.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Importance: Obesity disproportionately affects Black women, who also have a higher risk of death after a breast cancer diagnosis compared with women of other racial/ethnic groups. However, few studies have evaluated the association of measures of adiposity with mortality among Black breast cancer survivors.

Objective: To assess the association of measures of adiposity with survival after a breast cancer diagnosis among Black women.

Design, Setting, And Participants: This prospective population-based cohort study comprised 1891 women with stage 0 to IV breast cancer who self-identified as African American or Black and were ages 20 to 75 years. The New Jersey State Cancer Registry was used to identify women living in 10 counties in New Jersey who were recruited from March 1, 2006, to February 29, 2020, and followed up until September 2, 2020.

Exposures: Measures of adiposity, including body mass index, body fat distribution (waist circumference and waist-to-hip ratio), and body composition (percent body fat and fat mass index), were collected during in-person interviews at approximately 10 months after breast cancer diagnosis.

Main Outcomes And Measures: All-cause and breast cancer-specific mortality.

Results: Among 1891 women, the mean (SD) age at breast cancer diagnosis was 54.5 (10.8) years. During a median follow-up of 5.9 years (range, 0.5-14.8 years), 286 deaths were identified; of those, 175 deaths (61.2%) were associated with breast cancer. A total of 1060 women (56.1%) had obesity, and 1291 women (68.3%) had central obesity. Higher adiposity, particularly higher waist-to-hip ratio, was associated with worse survival. Women in the highest quartile of waist-to-hip ratio had a 61% increased risk of dying from any cause (hazard ratio [HR], 1.61; 95% CI, 1.12-2.33) and a 68% increased risk of breast cancer death (HR, 1.68; 95% CI, 1.04-2.71) compared with women in the lowest quartile. The risks of all-cause and breast cancer-specific death were similarly high among women in the highest quartile for waist circumference (HR, 1.74 [95% CI, 1.26-2.41] and 1.64 [95% CI, 1.08-2.48], respectively), percent body fat (HR, 1.53 [95% CI, 1.09-2.15] and 1.81 [95% CI, 1.17-2.80]), and fat mass index (HR, 1.57 [95% CI, 1.11-2.22] and 1.74 [95% CI, 1.10-2.75]); however, the risk was less substantial for body mass index (HR, 1.26 [95% CI, 0.89-1.79] and 1.33 [95% CI, 0.84-2.10]). In analyses stratified by estrogen receptor status, menopausal status, and age, a higher waist-to-hip ratio was associated with a higher risk of all-cause death among women who had estrogen receptor-negative tumors (HR, 2.24; 95% CI, 1.14-4.41), women who were postmenopausal (HR, 2.15; 95% CI, 1.28-3.61), and women who were 60 years or older at diagnosis (HR per 0.10-U increase, 1.76; 95% CI, 1.37-2.26).

Conclusions And Relevance: In this population-based cohort study, central obesity and higher adiposity were associated with higher all-cause and breast cancer-specific mortality among Black breast cancer survivors. Simple measures of body fat distribution and body composition were found to be useful tools for identifying Black women with a higher risk of death after a breast cancer diagnosis.
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http://dx.doi.org/10.1001/jamaoncol.2021.1499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377573PMC
June 2021

Spark Plasma Sintering of LiFePO: AC Field Suppressing Lithium Migration.

Materials (Basel) 2021 May 25;14(11). Epub 2021 May 25.

Key Laboratory of Advanced technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

Our work proposes a comparison between Spark Plasma Sintering of LiFePO carried out using an Alternating Current (AC) and Direct Current (DC). It quantifies the Li-ion migration using DC, and it validates such hypothesis using impedance spectroscopy, X-ray photoelectron spectroscopy and inductively coupled plasma optical emission spectroscopy. The use of an AC field seems effective to inhibit undesired Li-ion migration and achieve high ionic conductivity as high as 4.5 × 10 S/cm, which exceeds by one order of magnitude samples processed under a DC field. These results anticipate the possibility of fabricating a high-performance all-solid-state Li-ion battery by preventing undesired Li loss during SPS processing.
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http://dx.doi.org/10.3390/ma14112826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198947PMC
May 2021

Plasma interleukin-6 is a potential predictive biomarker for postoperative delirium among acute type a aortic dissection patients treated with open surgical repair.

J Cardiothorac Surg 2021 May 27;16(1):146. Epub 2021 May 27.

Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Xinquan Road No. 29, Fuzhou, 350001, Fujian, China.

Objectives: The relationship between inflammatory cytokines and postoperative delirium (POD) remains to be further investigated, especially in patients undergoing acute type A aortic dissection (AAD). Interleukin-6 (IL-6) is involved in the inflammatory process and has recently been identified as a biomarker of cerebral dysfunction. We explored the hypothesis that IL-6 was one of the critical causes of POD after surgical repair of AAD.

Methods: Plasma IL-6 was measured using electrochemiluminescence technology in patients preoperatively and 24 h, 48 h, and 72 h after surgical repair of acute type A aortic dissection. After the first three postoperative days, delirium was evaluated twice daily using the Confusion Assessment Method. ROC curves were used to evaluate the ability of IL-6 measurements to distinguish POD.

Results: The incidence of POD was 14.03% (31 of 221 patients). The patients in the POD group were significantly older than the patients in the non-POD group (56.48 ± 11.68 years vs 52.22 ± 10.50 years, P = 0.040). Plasma IL-6 concentrations were significantly higher in the POD group than in the non-POD group at three time points: preoperatively, after 24 h, and after 48 h. The AUC values corresponding to IL-6 preoperatively and 24 h after surgery were 0.73 and 0.72, respectively.

Conclusions: Cerebral dysfunction after the surgical repair of AAD shows elevated stress levels and inflammatory responses. Plasma IL-6 is a potential biomarker to predict the onset of POD in acute type A aortic dissection patients following surgical repair.
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http://dx.doi.org/10.1186/s13019-021-01529-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161913PMC
May 2021

miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop.

Cell Mol Biol Lett 2021 May 27;26(1):21. Epub 2021 May 27.

Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, 20040, China.

Recently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR-29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR-29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.
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http://dx.doi.org/10.1186/s11658-021-00266-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161631PMC
May 2021
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