Publications by authors named "Jing Cui"

650 Publications

Activities of daily living as a longitudinal moderator of the effect of autonomic dysfunction on anxiety and depression of Parkinson's patients.

Brain Behav 2021 Aug 1. Epub 2021 Aug 1.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Background: There is no clear time point for the onset of depression and anxiety in Parkinson's disease (PD), and their atypical physical symptoms often overlap with other nonmotor symptoms. Autonomic dysfunction usually appears earlier than motor symptoms, seriously impairing activities of daily living (ADL), even quality of life. Whether autonomic dysfunction can affect depression and anxiety in PD patients through ADL is still unclear.

Methods: We conducted three progressive autoregressive mediation models to evaluate whether ADL may mediate the association between autonomic symptom burden, where the mediation chain with autonomic function as an independent variable, ADL as a mediating variable, and anxiety and depression as dependent variables. The ADL of PD patients were measured by the Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) and Modified Schwab and England ADL scale, respectively, and the status of depression and anxiety were measured by the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI).

Results: There were 338 PD patients, including 220 males and 118 females. Demographic information, including age, gender, and education level, were not correlated with the depression and anxiety. Model III had the smallest AIC (AIC = 12,669.89), and the cross-lagged relations were not statistically significant, so we selected Model II as the optimal model. In Model II, longitudinal autoregressive mediated effect and longitudinal mediated effect of autonomic dysfunction affecting anxiety and depression through ADL were not statistically significant, suggesting longitudinal changes of autonomic dysfunction were independent of anxiety and depression through ADL. Contemporaneous mediated effects of autonomic dysfunction affecting anxiety and depression through ADL were statistically significant, suggesting contemporaneous autonomic dysfunction may contribute to anxiety and depression through ADL.

Conclusions: Targeted prevention and intervention measures for autonomic dysfunction and ADL should be taken to preserve and improve self-perceived life satisfaction in the clinical practice and preventive health care of PD.
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http://dx.doi.org/10.1002/brb3.2297DOI Listing
August 2021

Potassium dependency of enzymes in plant primary metabolism.

Plant Physiol Biochem 2021 Jun 18;166:522-530. Epub 2021 Jun 18.

Research School of Biology, ANU Joint College of Sciences, Australian National University, 2601, Canberra, Australia; Institut de Recherche en Horticulture et Semences, INRAe Angers, Université d'Angers, 42 rue Georges Morel, 49070, Beaucouzé, France. Electronic address:

Potassium is a macroelement essential to many aspects of plant life, such as photosynthesis, phloem transport or cellular electrochemistry. Many enzymes in animals or microbes are known to be stimulated or activated by potassium (K ions). Several plant enzymes are also strictly K-dependent, and this can be critical when plants are under K deficiency and thus intracellular K concentration is low. Although metabolic effects of low K conditions have been documented, there is presently no review focusing on roles of K for enzyme catalysis or activation in plants. In this mini-review, we compile the current knowledge on K-requirement of plant enzymes and take advantage of structural data to present biochemical roles of K. This information is instrumental to explain direct effects of low K content on metabolism and this is illustrated with recent metabolomics data.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.017DOI Listing
June 2021

Risk Assessment During Longitudinal Progression of Cognition in Older Adults: A Community-based Bayesian Networks Model.

Curr Alzheimer Res 2021 Jun 8. Epub 2021 Jun 8.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Background: Cognitive dysfunction, particularly in Alzheimer's disease (AD), serious- ly affects the health and quality of life of older adults. Early detection can prevent and slow cogni- tive decline.

Objective: This study aimed at evaluating the role of socio-demographic variables, lifestyle, and physical characteristics in cognitive decline during AD progression and analyzing the probable causes and predicting stages of the disease.

Methods: By analyzing data of 301 subjects comprising normal elderly and patients with mild cog- nitive impairment (MCI) or AD from six communities in Taiyuan, China, we identified the influ- encing factors during AD progression by a logistic regression model (LR) and then assessed the as- sociations between variables and cognition using a Bayesian Networks (BNs) model.

Results: The LR revealed that age, sex, family status, education, income, character, depression, hy- pertension, disease history, physical exercise, reading, drinking, and job status were significantly associated with cognitive decline. The BNs model revealed that hypertension, education, job status, and depression affected cognitive status directly, while character, exercise, sex, reading, income, and family status had intermediate effects. Furthermore, we predicted probable cognitive stages of AD and analyzed probable causes of these stages using a model of causal and diagnostic reasoning.

Conclusion: The BNs model lays the foundation for causal analysis and causal inference of cogni- tive dysfunction, and the prediction model of cognition in older adults may help the development of strategies to control modifiable risk factors for early intervention in AD.Recent Advances in Anti-Infective Drug Discovery.
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http://dx.doi.org/10.2174/1567205018666210608110329DOI Listing
June 2021

Why is phloem sap nitrate kept low?

Plant Cell Environ 2021 Jun 2. Epub 2021 Jun 2.

Research School of Biology, ANU College of Science, Australian National University, Canberra, Australian Capital Territory, Australia.

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http://dx.doi.org/10.1111/pce.14116DOI Listing
June 2021

Health Conditions, Lifestyle Factors and Depression in Adults in Qingdao, China: A Cross-Sectional Study.

Front Psychiatry 2021 14;12:508810. Epub 2021 May 14.

Biomedical Research Center, Northwest Minzu University, Lanzhou, China.

Depression is a common mental illness. Previous studies suggested that health conditions and lifestyle factors were associated with depression. However, only few studies have explored the risk factors of depression in a large representative sample of the general population in the world. A population-based cross-sectional survey was conducted in the 2006 survey and 2009 survey in Qingdao, China. The participants with insufficient information were excluded: Zung score, body mass index (BMI), diabetes items, physical activity, smoking, or drinking. Finally, a total of 3,300 participants were included in this analysis. The category of depression was used in the Zung self-rating depression scale (ZSDS). The associations between different indicators of health conditions (diabetic status, BMI), lifestyle factors (physical activity, smoking, and alcohol consumption), and depression were assessed by the logistic regression model. The mean Zung scores for all participants, male participants, and female participants were 29.73 ± 7.57, 28.89 ± 7.30, 30.30 ± 7.70, respectively. In all participants, those who were pre-diabetes status (OR: 1.53, 95% CI: 1.04-2.27), and irregular physical activity (OR: 0.39, 95% CI: 0.17-0.89) had an increased risk of depression. In man, the analysis showed an increased risk of depression those with pre-diabetes (OR: 2.49, 95% CI: 1.25-4.97), previously diagnosed diabetes (OR: 4.44, 95% CI: 1.58, 12.48), and in those irregular activities (OR: 0.07, 95% CI: 0.01-0.61). In women, those who were underweight (OR: 5.66, 95% CI: 1.04-30.71) had a greater risk of depression. These results suggested that health conditions and lifestyle factors were the potential risk factors for depression. Men with pre-diabetes, previously diagnosed diabetes, and irregular activity had an increased risk for depression; women with underweight status had a higher risk for depression.
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http://dx.doi.org/10.3389/fpsyt.2021.508810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160228PMC
May 2021

Attitudes toward and Perceptions of Educational Needs for End-of-Life Care among Health Professions Students: A Cross-Sectional Study in China.

J Pain Symptom Manage 2021 May 19. Epub 2021 May 19.

School of Nursing, Naval Medical University, Shanghai, China; School of Nursing, Fudan University, Shanghai, China. Electronic address:

Context: To provide effective end-of-life care education for health professions students, it is important to understand students' views of death in addition to their perceptions of educational needs and preferences. However, there is a lack of studies addressing interindividual variability in perceptions of end-of-life care educational needs among health professions students.

Objectives: This study aimed to identify latent profiles of perceptions of end-of-life care educational needs among health professions students and examine whether the demographic characteristics, death-related events, death attitude, and death anxiety differed by need subgroup.

Methods: Through convenience sampling, health professions students from three universities in China were recruited between March 2020 and June 2020. Data were collected using a demographic information and death-related experience questionnaire, the End-of-Life Care Curriculum Needs Questionnaire, the End-of-Life Care Educational Needs Questionnaire, the Death Attitudes Profile-Revised, and the Templer's Death Anxiety Scale.

Results: A total of 1048 students completed the survey. Two classes of perceptions of end-of-life care educational needs were identified: approximately 29.80% of students belonged to a medium-need group class (1), and 70.20% belonged to a high-need group class (2). Being female and having knowledge of end-of-life care significantly increased the probability of membership in class 2. Students with the two latent profiles reported having varied curriculum needs. In addition, a positive attitude toward death and low death anxiety increased the probability of membership in class 1.

Conclusion: Two classes of perceptions of end-of-life care educational needs were identified, and these classes were significantly associated with sex and death-related knowledge (P < 0.05). Interindividual variability should be considered in the future development of end-of-care curricula.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.05.008DOI Listing
May 2021

Prostaglandin E attenuates macrophage-associated inflammation and prostate tumour growth by modulating polarization.

J Cell Mol Med 2021 Jun 13;25(12):5586-5601. Epub 2021 May 13.

Wuxi School of Medicine, Jiangnan University, Wuxi, China.

Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E (PGE ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE had no direct effect on the growth of prostate cancer cells in vitro, PGE could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer.
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http://dx.doi.org/10.1111/jcmm.16570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184682PMC
June 2021

Luteolin and cancer metastasis suppression: focus on the role of epithelial to mesenchymal transition.

Med Oncol 2021 May 5;38(6):66. Epub 2021 May 5.

Research Unit, Induced Resistance and Plant Bioprotection, EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687, Reims Cedex 2, France.

Epithelial to mesenchymal transition (EMT) is a physiological process that assumes a primary role in the induction of cancer metastasis. This results in increased cell renewal, and resistance to cell death and therapies. EMT, therefore, represents an effective strategy for regulating cancerous cell activity. A need for efficacy and low cytotoxicity epithelial to mesenchymal transition modifying drugs has led to the investigational testing of the efficacy of plethora of different groups of phytonutrients. Luteolin is a natural flavonoid inhibits the growth of cancer cells by various mechanisms, such as the stimulation of cancer cell apoptosis, cell cycle arrest, inhibition of cell replication, tumor growth, improvement of drug resistance, prevention of cancer cell intrusiveness and metastasis. This review article focuses on the anti-cancer and anti-metastatic potential of luteolin targeting various transcription factors, markers and signaling pathways associated with the repression of epithelial to mesenchymal transition.
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http://dx.doi.org/10.1007/s12032-021-01508-8DOI Listing
May 2021

Cross-Sectional Study of the Effects of Job Burnout on Immune Function in 105 Female Oncology Nurses at a Tertiary Oncology Hospital.

Med Sci Monit 2021 May 4;27:e929711. Epub 2021 May 4.

Nursing Department, Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China (mainland).

BACKGROUND Nurses who work in hospitals experience a high level of burnout and the relationship between immune variables and burnout syndrome has yet to be elucidated. The aim of the present study was to investigate the effects of job burnout on immune function in female oncology nurses in a tertiary oncology hospital in Guangxi, China. The aspects of the human immune system evaluated were humoral and cellular immunity and complement components 3 (C3) and 4 (C4). MATERIAL AND METHODS We administered the Maslach Burnout Inventory-General Survey (MBI-GS), which includes scales for emotional exhaustion, depersonalization (DP), and personal accomplishment (PA), to measure variables related to immune function in 105 female nurses in a tertiary oncology hospital in Guangxi, China. Levels of humoral immunity and C3 and C4 were detected with immune turbidimetry. Cellular immunity was assessed with indirect immunofluorescence. RESULTS A Spearman rank correlation analysis revealed that levels of C3, C4, and CD4- and CD8-positive T cells were significantly associated with burnout symptoms (P<0.05, P<0.01, and P<0.05, respectively). Furthermore, there was a correlation between demographic data and humoral and cellular immunity (both P<0.05). Multivariable linear regression analysis showed that C4 levels were closely related to DP (P<0.05) and that CD4 and CD8 levels were closely related to PA (P<0.01). CONCLUSIONS These results suggest that DP and PA have an impact on immune function, and that timely psychological and behavioral interventions can be used to reduce the degree of job burnout among nurses and regulate their immunity, thus enabling them to better serve patients.
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http://dx.doi.org/10.12659/MSM.929711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106256PMC
May 2021

Preparation, Physical Properties, and Applications of Water-Based Functional Polymer Inks.

Polymers (Basel) 2021 Apr 27;13(9). Epub 2021 Apr 27.

Instituto de Estructura de la Materia, IEM-CSIC, C/Serrano 121, 28006 Madrid, Spain.

In this study, water-based functional polymer inks are prepared using different solvent displacement methods, in particular, polymer functional inks based on semiconducting polymer poly(3-hexylthiophene) and the ferroelectric polymer poly(vinylidene fluoride) and its copolymers with trifluoroethylene. The nanoparticles that are included in the inks are prepared by miniemulsion, as well as flash and dialysis nanoprecipitation techniques and we discuss the properties of the inks obtained by each technique. Finally, an example of the functionality of a semiconducting/ferroelectric polymer coating prepared from water-based inks is presented.
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http://dx.doi.org/10.3390/polym13091419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124647PMC
April 2021

Carbon Monoxide Releasing Molecule-3 Enhances Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Carbon Monoxide Release.

Drug Des Devel Ther 2021 22;15:1691-1704. Epub 2021 Apr 22.

Department of VIP Center, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, Shandong, People's Republic of China.

Purpose: Limited intrinsic regeneration capacity following bone destruction remains a significant medical problem. Multiple regulatory effects of carbon monoxide releasing molecule-3 (CORM-3) have been reported. The aim of this study was to investigate the effect of CORM-3 on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) during osteogenesis.

Patients And Methods: hPDLSCs obtained from healthy periodontal ligament tissues were cultured and identified with specific surface antigens by flow cytometry. Effect of CORM-3 on the proliferation of hPDLSCs was determined by CCK-8 assay. Alizarin red staining and alkaline phosphatase (ALP) activity were used to assess the osteogenic differentiation of hPDLSCs. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect the expression of the indicated genes. Critical-sized skull defect was made in Balb/c-nude mice, microcomputed tomography (Micro-CT) and Masson trichrome staining were used to assess the new bone regeneration in mice.

Results: CORM-3 (400 μmol/l) significantly promoted the proliferation of hPDLSCs. CORM-3 pretreatment not only notably enhanced the mRNA and protein expression of osteo-specific marker OPN, Runx2 and ALP, but also increased mineral deposition and ALP activity by the release of CO on day 3, 7 and 14 (P<0.05). Degassed CORM-3 did not show the same effect as CORM-3. In animal model, application of CORM-3 with hPDLSCs transplantation highly increased new bone formation in skull defect region.

Conclusion: CORM-3 promoted osteogenic differentiation of hPDLSCs, and increased hPDLSCs-induced new bone formation in mice with critical-sized skull defect, which suggests an efficient and promising strategy in the treatment of disease with bone defect.
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http://dx.doi.org/10.2147/DDDT.S300356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075314PMC
April 2021

A novel small-molecule fatty acid synthase inhibitor with antitumor activity by cell cycle arrest and cell division inhibition.

Eur J Med Chem 2021 Jul 20;219:113407. Epub 2021 Apr 20.

Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214012, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, 214012, China. Electronic address:

Fatty acid synthase (FASN), the key enzyme in de novo lipogenesis, is an attractive therapeutic target for diseases characterized by excessive lipid accumulation. Many FASN inhibitors have failed in the clinical trial phase, largely because of poor solubility and safety. In this study, we generated a novel small-molecule FASN inhibitor by structure-based virtual screening. PFI09, the lead compound, is easy to synthesize, and inhibits the lipid synthesis in OP9 mammalian cell line and Caenorhabditis elegans as well as the proliferation of several cancer cell lines via the blockade of FASN. Mechanistic investigations show that PFI09 induces S-phase arrest, cell division reduction and apoptosis. We also develop a chemically stable analog of PFI09, MFI03, which reduces the proliferation of PC3 tumor cells both in vitro and in vivo, without toxicity to mice. In summary, our data suggest that MFI03 is an effective FASN inhibitor and a promising antineoplastic drug candidate.
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http://dx.doi.org/10.1016/j.ejmech.2021.113407DOI Listing
July 2021

Involvement of salicylic acid in the response to potassium deficiency revealed by metabolomics.

Plant Physiol Biochem 2021 Jun 6;163:201-204. Epub 2021 Apr 6.

Research School of Biology, ANU College of Science, Australian National University, 2601, Canberra, ACT, Australia; Institut de Recherche en Horticulture et Semences, Université d'Angers, INRAe, 42 rue Georges Morel, 49070, Beaucouzé, France. Electronic address:

Potassium (K) deficiency has consequences not only on cellular ion balance and transmembrane potential but also on metabolism. In fact, several enzymes are K-dependent including enzymes in catabolism, causing an alteration in glycolysis and respiration. In addition, K deficiency is associated with the induction of specific pathways and accumulation of metabolic biomarkers, such as putrescine. However, such drastic changes are usually observed when K deficiency is established. Here, we carried out a kinetic analysis with metabolomics to elucidate early metabolic events when nutrient conditions change from K-sufficiency to K-deficiency in Arabidopsis rosettes from both wild type and mutants affected in both K absorption and low-K signalling (hak5 akt1 cipk23). Our results show that mutants have a metabolomics pattern similar to K-deficient wild-type, showing a constitutive metabolic response to low K. In addition, shifting to low K conditions induces (i) changes in sugar metabolism and (ii) an accumulation of salicylic acid metabolites before the appearance of biomarkers of K deficiency (putrescine and aconitate), and such an accumulation is more pronounced in mutants. Our results suggest that early events in the response to low K conditions involve salicylic acid metabolism.
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http://dx.doi.org/10.1016/j.plaphy.2021.04.002DOI Listing
June 2021

Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer.

J Cancer 2021 10;12(9):2768-2776. Epub 2021 Mar 10.

Graduate School, Kunming Medical University, Kunming, Yunnan, China.

Oncolytic adenovirus-mediated gene therapy is an emerging strategy for cancer treatment. However, oncolytic adenoviruses are mainly administered locally at tumor site. Intravenous administration of oncolytic adenovirus for cancer gene therapy is a problem that needs to be solved urgently. We constructed recombinant oncolytic adenovirus KGHV500 carrying anti-p21Ras scFv and employed CIK cells to deliver KGHV500. TUNEL, wound healing, MTT, and Transwell invasion assays were used to determine the anti-tumor efficacy of KGHV500 on liver cancer cells . Nude mouse xenograft model was used to examine the anti-tumor efficacy of CIK cells combined with KGHV500 . Furthermore, KGHV500 accumulation in different organs was detected to assess the safety. KGHV500 inhibited the migration, proliferation, invasion, and induced the apoptosis of liver cancer cells. CIK cells carrying KGHV500 reached tumor site and exerted much better anti-tumor efficacy than CIK cells or KGHV500 alone in nude mouse xenograft model. Moreover, we detected KGHV500 and anti-p21Ras scFv in different organs of nude mice, with little effects on the organs. We develop a novel strategy for the treatment of Ras-driven liver cancer by combining CIK cells with oncolytic adenovirus expressing anti-p21Ras scFv. Intravenous injection of CIK cells carrying KGHV500 significantly inhibits tumor growth, has little effect on normal organs, and is relatively safe.
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http://dx.doi.org/10.7150/jca.51434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040716PMC
March 2021

Everolimus regulates the activity of gemcitabine-resistant pancreatic cancer cells by targeting the Warburg effect via PI3K/AKT/mTOR signaling.

Mol Med 2021 04 13;27(1):38. Epub 2021 Apr 13.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Gemcitabine (GEM) resistance remains a significant clinical challenge in pancreatic cancer treatment. Here, we investigated the therapeutic utility of everolimus (Evr), an inhibitor of mammalian target of rapamycin (mTOR), in targeting the Warburg effect to overcome GEM resistance in pancreatic cancer.

Methods: The effect of Evr and/or mTOR overexpression or GEM on cell viability, migration, apoptosis, and glucose metabolism (Warburg effect) was evaluated in GEM-sensitive (GEM) and GEM-resistant (GEM) pancreatic cancer cells.

Results: We demonstrated that the upregulation of mTOR enhanced cell viability and favored the Warburg effect in pancreatic cancer cells via the regulation of PI3K/AKT/mTOR signaling. However, this effect was counteracted by Evr, which inhibited aerobic glycolysis by reducing the levels of glucose, lactic acid, and adenosine triphosphate and suppressing the expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in GEM and GEM cells. Evr also promoted apoptosis by upregulating the pro-apoptotic proteins Bax and cytochrome-c and downregulating the anti-apoptotic protein Bcl-2. GEM was minimally effective in suppressing GEM cell activity, but the therapeutic effectiveness of Evr against pancreatic cancer growth was greater in GEM cells than that in GEM cells. In vivo studies confirmed that while GEM failed to inhibit the progression of GEM tumors, Evr significantly decreased the volume of GEM tumors while suppressing tumor cell proliferation and enhancing tumor apoptosis in the presence of GEM.

Conclusions: Evr treatment may be a promising strategy to target the growth and activity of GEM-resistant pancreatic cancer cells by regulating glucose metabolism via inactivation of PI3K/AKT/mTOR signaling.
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http://dx.doi.org/10.1186/s10020-021-00300-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045370PMC
April 2021

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer.

J Exp Clin Cancer Res 2021 Apr 8;40(1):124. Epub 2021 Apr 8.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China.

Background: Pancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear.

Methods: The expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay.

Results: Circ-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo.

Conclusion: Circ-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.1186/s13046-021-01894-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034179PMC
April 2021

Cohort Studies on Chronic Non-communicable Diseases Treated With Traditional Chinese Medicine: A Bibliometric Analysis.

Front Pharmacol 2021 19;12:639860. Epub 2021 Mar 19.

China Center for Evidence-based Medicine of TCM, China Academy of Chinese Medical Sciences, Beijing, China.

Cohort studies investigating the treatment of chronic non-communicable diseases (NCDs) with traditional Chinese medicine (TCM) have considerably accumulated in recent years. To systematically and for the first time present the achievements and dilemmas of cohort studies, strict inclusion and exclusion criteria were used to search publications from the Web of Science, PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for cohort studies on NCDs with TCM since the establishment of these databases. Information on the year of publication, exposure factors, diseases, and outcome indicators was obtained, and a literature quality assessment and bibliometric descriptive analysis were conducted. A total of 182 published articles involving 1,615,106 cases were included. There were 110 non-prospective cohort studies and 72 prospective cohort studies. The diseases involved in the cohort studies were, in the order of the number of published articles, malignant tumors (82 articles, 45.05%), cardiovascular diseases (35 articles, 19.23%), neurological diseases (29 articles, 15.93%), chronic kidney diseases (16 articles, 8.79%), liver cirrhosis (8 articles, 4.40%), diabetes mellitus (8 articles, 4.40%), and chronic respiratory diseases (4 articles, 2.20%). The study participants were mainly from China (177 articles, 97.25%). The number of cohort studies increased significantly in the last 5 years (65 articles, 35.71%), and following the Newcastle-Ottawa Scale (NOS) literature quality evaluation, the number of articles that received a score of four to five was high (116 articles, 63.73%), and the overall quality needs to be improved. The application of cohort studies in the field of TCM for the prevention and treatment of NCDs has developed rapidly in the past 5 years, focusing on the prevention and treatment of tumors as well as cardiovascular and cerebrovascular diseases. However, the design and implementation of cohort studies still have considerable limitations. To provide more clinical evidence, researcher should actively cooperate with evidence-based methodologists and standardize the implementation of cohort studies.
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http://dx.doi.org/10.3389/fphar.2021.639860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017211PMC
March 2021

Porphyrin-based covalent organic framework as bioplatfrom for detection of vascular endothelial growth factor 165 through fluorescence resonance energy transfer.

Talanta 2021 Jun 30;228:122060. Epub 2020 Dec 30.

School of Materials and Chemical Engineering, Zhengzhou University of Light Industry, No. 136, Science Avenue, Zhengzhou, 450001, China. Electronic address:

A fluorescent aptasensor based on porphyrin-based covalent organic framework (p-COF) and carbon dots (CDs) was constructed for detecting vascular endothelial growth factor 165 (VEGF) and for imaging of the breast cancer cell line Michigan cancer foundation-7 (MCF-7). CDs synthesized with strong photoluminescence at λ∼380 nm were used as donors to label the VEGF-targeted aptamers (Apt/CDs). Additionally, the p-COF nanostructure comprised rich functional groups of CN on the surface and π-stacking planar nanostructure, resulting in the CDs adsorption via weakly π-π stacking, hydrogen bond and the Van der Waals force. Thereby, the fluorescence resonance energy transfer (FRET) occurred due to the close distance between the p-COF network and CDs, leading to the quenching of the fluorescence feature of CDs and p-COF. In the presence of VEGF, the G-quadruplex was formed via the specific binding between VEGF and aptamer. It impelled that the release of partial VEGF-Apt/CDs complex, affording the fluorescence recovery of the sensing system to some extent. Consequently, the proposed Apt/CDs/p-COF fluorescence biosensor offered excellent analytical performances for the VEGF detection, displaying a detection limit of 20.9 fg mL within a wide linear range of the VEGF concentration of 1.0 pg mL-100 ng mL. The developed fluorescence biosensor was also used to determine VEGF-overexpressed in MCF-7 cancer cells. Thereby, the present work can greatly widen the application of COFs in the development of aptasensors and cancer diagnosis.
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http://dx.doi.org/10.1016/j.talanta.2020.122060DOI Listing
June 2021

Circulating blood metabolite trajectories and risk of rheumatoid arthritis among military personnel in the Department of Defense Biorepository.

Ann Rheum Dis 2021 Mar 22. Epub 2021 Mar 22.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis.

Methods: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05.

Results: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking.

Conclusions: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.
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http://dx.doi.org/10.1136/annrheumdis-2020-219682DOI Listing
March 2021

Peripheral Monocyte Count and Age-Related Macular Degeneration. The Tongren Health Care Study.

Am J Ophthalmol 2021 07 15;227:143-153. Epub 2021 Mar 15.

From the Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China (C.C.X., Y.X.W., J.B.J.); Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Mannheim, Germany (J.B.J.); Institute of Clinical and Scientific Ophthalmology and Acupuncture Jonas & Panda, Heidelberg, Germany; Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland (J.B.J.).

Purpose: To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population.

Design: Cross-sectional study.

Methods: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines.

Results: The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P < .001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P < .001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P < .001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P < .001; intermediate and late AMD: OR: 6.14, P < .001). Individuals with a monocyte count of ≥0.5 × 10/L as compared to participants with a monocyte of 0.1-0.4 × 10/L had a 1.45-fold increased risk for any AMD (OR: 1.45; 95% CI: 1.27, 1.64; P < .001) and 1.58 fold increase risk for intermediate/late AMD (OR: 1.58; 95% CI: 1.33, 1.87; P < .001).

Conclusion: A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD.
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http://dx.doi.org/10.1016/j.ajo.2021.03.010DOI Listing
July 2021

The path linking disease severity and cognitive function with quality of life in Parkinson's disease: the mediating effect of activities of daily living and depression.

Health Qual Life Outcomes 2021 Mar 17;19(1):92. Epub 2021 Mar 17.

Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, People's Republic of China.

Background: Research on quality of life (QOL) with Parkinson's disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence.

Methods: We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and the physical health and mental health component summary scores measured by the SF36 quality of life instrument.

Results: There was a significant mediating effect of PD severity on physical health via ADL and depression (95% CI: - 0.669, - 0.026), and a significant direct effect (p < 0.001). The mediating effect of PD severity on mental health via ADL and depression was significant (95% CI: - 2.135, - 0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on physical health via ADL and depression (95% CI: 0.025, 0.219) and a significant direct effect (p < 0.001). The mediating effect of cognitive function on mental health via ADL and depression was significant (95% CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The physical health models showed a partial mediation, and the mental health models showed a complete mediation, of ADL and depression.

Conclusions: PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect physical health and mental health through different pathways.
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http://dx.doi.org/10.1186/s12955-021-01740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972188PMC
March 2021

Type 2 Diabetes and Myocardial Infarction: Recent Clinical Evidence and Perspective.

Front Cardiovasc Med 2021 24;8:644189. Epub 2021 Feb 24.

Cardiovascular Centre of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Type 2 diabetes mellitus (T2DM) and its complications are seriously affecting public health worldwide. Myocardial infarction (MI) is the primary cause of death in patients with T2DM. T2DM patients without a history of coronary artery disease (CAD) have the same risk of major coronary events as those with CAD; T2DM patients with a history of MI have >40% risk of recurrence of MI. Thus, CAD in patients with T2DM needs to be treated actively to reduce the risk of MI. The cardiology community focused on the role of T2DM in the development of CAD and on the related issues of T2DM and MI with respect to comorbidities, prognosis, drug therapy, and heredity. In this mini review, the latest progress of clinical evidence-based research between T2DM and MI in recent years was reviewed, and the possible research directions in this field were considered and prospected.
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http://dx.doi.org/10.3389/fcvm.2021.644189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943438PMC
February 2021

Induction of Immune Response Against Metastatic Tumors via Vaccination of Mannan-BAM, TLR Ligands and Anti-CD40 Antibody (MBTA).

Adv Ther (Weinh) 2020 Sep 9;3(9). Epub 2020 Jun 9.

Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.

Emerging evidence is demonstrating the extent of T-cell infiltration within the tumor microenvironment has favorable prognostic and therapeutic implications. Hence, immunotherapeutic strategies that augment the T-cell signature of tumors hold promising therapeutic potential. Recently, immunotherapy based on intratumoral injection of mannan-BAM, toll-like receptor ligands and anti-CD40 antibody (MBTA) demonstrated promising potential to modulate the immune phenotype of injected tumors. The strategy promotes the phagocytosis of tumor cells to facilitate the recognition of tumor antigens and induce a tumor-specific adaptive immune response. Using a syngeneic colon carcinoma model, we demonstrate MBTA's potential to augment CD8 T-cell tumor infiltrate when administered intratumorally or subcutaneously as part of a whole tumor cell vaccine. Both immunotherapeutic strategies proved effective at controlling tumor growth, prolonged survival and induced immunological memory against the parental cell line. Collectively, our investigation demonstrates MBTA's potential to trigger a potent anti-tumor immune response.
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http://dx.doi.org/10.1002/adtp.202000044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942838PMC
September 2020

An observation of the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen in treating acute spinal cord injury.

Pak J Med Sci 2021 Mar-Apr;37(2):320-324

Jian-zhou Tong, Department of Neurosurgery, West Part, Baoding First Central Hospital, Baoding, 071000, Hebei, P.R. China.

Objective: To examine the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen therapy in treating thoracolumbar vertebral fracture-induced acute spinal cord injury (ASCI).

Methods: From June 2015 to May 2018, 80 patients with thoracolumbar fractures and ASCI who were treated at Baoding First Central Hospital were selected. All patients underwent posterior laminectomy and screw fixation, and they were randomly divided into two groups using a random number table method. The control group received conventional postoperative treatment, while the experimental group was treated with riluzole combined with mannitol and hyperbaric oxygen on the basis of conventional treatment. The recovery of nerve function which included motor function and sensory function, and the changes of serum IL-6, CRP, BDNF, BFGF and other factors before treatment and four weeks after treatment of the two groups of patients were observed and evaluated.

Results: After treatment, the motor function scores and sensory function scores of the two groups of patients were improved compared with those before treatment (p<0.05). Compared with the control group, the experimental group improved significantly, and the difference was statistically significant (p<0.05). The levels of IL-6, BDNF and NFGF in the experimental group were significantly lower than those in the control group (p<0.05).

Conclusions: For patients with thoracolumbar fractures and ASCI undergoing laminar decompression and fixation, the comprehensive treatment plan of riluzole combined with mannitol and hyperbaric oxygen has certain advantages. Compared with the conventional therapy, it may significantly improve the movement and sensory functions of patients, relieve the inflammatory response of spinal cord, and promote recovery from the injury.
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http://dx.doi.org/10.12669/pjms.37.2.3418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931319PMC
March 2021

Hierarchically Demineralized Cortical Bone Combined With Stem Cell-Derived Extracellular Matrix for Regeneration of the Tendon-Bone Interface.

Am J Sports Med 2021 04 5;49(5):1323-1332. Epub 2021 Mar 5.

Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

Background: Poor healing of the tendon-bone interface after rotator cuff repair is one of the main causes of surgical failure. Previous studies demonstrated that demineralized cortical bone (DCB) could improve healing of the enthesis.

Purpose: To evaluate the outcomes of hierarchically demineralized cortical bone (hDCB) coated with stem cell-derived extracellular matrix (hDCB-ECM) in the repair of the rotator cuff in a rabbit model.

Study Design: Controlled laboratory study.

Methods: Tendon-derived stem cells (TDSCs) were isolated, cultured, and identified. Then, hDCB was prepared by the graded demineralization procedure. Finally, hDCB-ECM was fabricated via 2-week cell culture and decellularization, and the morphologic features and biochemical compositions of the hDCB-ECM were evaluated. A total of 24 rabbits (48 samples) were randomly divided into 4 groups: control, DCB, hDCB, and hDCB-ECM. All rabbits underwent bilateral detachment of the infraspinatus tendon, and the tendon-bone interface was repaired with or without scaffolds. After surgery, 8 rabbits were assessed by immunofluorescence staining at 2 weeks, and the others were assessed by micro-computed tomography (CT) examination, immunohistochemical staining, histological staining, and biomechanical testing at 12 weeks.

Results: TDSCs were identified to have universal stem cell characteristics including cell markers, clonogenicity, and multilineage differentiation. The hDCB-ECM contained 3 components (bone, partial DCB, and DCB coated with ECM) with a gradient of calcium and phosphorus elements, and the ECM had stromal cell-derived factor 1, biglycan, and fibromodulin. Macroscopic observations demonstrated the absence of infection and rupture around the enthesis. The results of immunofluorescence staining showed that hDCB-ECM promoted stromal cell recruitment. Results of micro-CT analysis, immunohistochemical staining, and histological staining showed that hDCB-ECM enhanced bone and fibrocartilage formation at the tendon-bone interface. Biomechanical analysis showed that the hDCB-ECM group had higher ultimate tensile stress and Young modulus than the DCB group.

Conclusion: The administration of hDCB-ECM promoted healing of the tendon-bone interface.

Clinical Relevance: hDCB-ECM could provide useful information for the design of scaffolds to repair the tendon-bone interface, and further studies are needed to determine its effectiveness.
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http://dx.doi.org/10.1177/0363546521994511DOI Listing
April 2021

Sustainability of SARS-CoV-2 Induced Humoral Immune Responses in COVID-19 Patients from Hospitalization to Convalescence Over Six Months.

Virol Sin 2021 Mar 4. Epub 2021 Mar 4.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence. Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays (CLIA). All patients were positive for the anti-SARS-CoV-2 IgM/IgG at the onset of COVID-19 symptoms, and the IgG antibody persisted in all the patients during the convalescence. However, only approximately 25% of patients can detect the IgM antibodies, IgM against N protein (N-IgM) and receptor binding domain of S protein (RBD-IgM) at the 27th week. The titers of IgM, N-IgM and RBD-IgM reduced to 16.7%, 17.6% and 15.2% of their peak values respectively. In contrast, the titers of IgG, N-IgG and RBD-IgG peaked at 4-5th week and reduced to 85.9%, 62.6% and 87.2% of their peak values respectively at the end of observation. Dynamic behavior of antibodies and their correlation in age, gender and severity groups were investigated. In general, the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients. Only a few patients with antibody reducing to an undetectable level which needs further attention. The humoral immune response against SARS-CoV-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.
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http://dx.doi.org/10.1007/s12250-021-00360-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931792PMC
March 2021

Detection of Inflammasome Activation for Predicting Sepsis Mortality.

Front Immunol 2020 4;11:613745. Epub 2021 Feb 4.

Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.

Sepsis is a severe life-threatening syndrome caused by dysregulated host responses to infection. Biomarkers that allow for monitoring the patient's immune status are needed. Recently, a flow cytometry-based detection of inflammasome activation by formation of cytoplasmic aggregates of ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) has been proposed. Here we report on the frequency of ASC-speck leukocytes correlating with the survival of sepsis. 25 patients with sepsis were sampled consecutively for 7 days. Blood, serum samples and patient data were collected according to the guidelines of the PredARRT-Sep-Trial. Flow cytometric analysis was performed on fresh whole blood samples to investigate the formation of ASC-specks in leukocyte subsets. Serum samples were analyzed for production of IL-1ß, IL-18 and additional inflammatory markers. ASC-speck formation was found to be increased in leukocytes from sepsis patients compared to healthy donor controls. The absolute number of ASC-speck neutrophils peaked on day 1. For monocytes, the highest percentage and maximum absolute number of ASC-speck cells were detected on day 6 and day 7. Inflammatory cytokines were elevated on day 1 and declined thereafter, with exception of IL-18. Survival analysis showed that patients with lower absolute numbers of ASC-speck monocytes (<1,650 cells/ml) on day 6 had a lower probability to survive, with a hazard ratio (HR) of 10.178. Thus, the frequency of ASC-speck monocytes on day 6 after onset of sepsis may serve to identify patients at risk of death from sepsis.
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http://dx.doi.org/10.3389/fimmu.2020.613745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889521PMC
June 2021

Quantitative Characterization of Tumor Proximity to Stem Cell Niches: Implications on Recurrence and Survival in GBM Patients.

Int J Radiat Oncol Biol Phys 2021 Jul 16;110(4):1180-1188. Epub 2021 Feb 16.

Department of Radiation Oncology, University of California - Los Angeles, California. Electronic address:

Purpose: Emerging evidence has linked glioblastoma multiforme (GBM) recurrence and survival to stem cell niches (SCNs). However, the traditional tumor-ventricle distance is insufficiently powered for an accurate prediction. We aimed to use a novel inverse distance map for improved prediction.

Methods And Materials: Two T1-magnetic resonance imaging data sets were included for a total of 237 preoperative scans for prognostic stratification and 55 follow-up scans for recurrent pattern identification. SCN, including the subventricular zone (SVZ) and subgranular zone (SGZ), were manually defined on a standard template. A proximity map was generated using the summed inverse distances to all SCN voxels. The mean and maximum proximity scores (PS and PS) were calculated for each primary/recurrent tumor, deformably transformed into the template. The prognostic capacity of proximity score (PS)-derived metrics was assessed using Cox regression and log-rank tests. To evaluate the impact of SCNs on recurrence patterns, we performed group comparisons of PS-derived metrics between the primary and recurrent tumors. For comparison, the same analyses were conducted on PS derived from SVZ alone and traditional edge/center-to-ventricle metrics.

Results: Among all SCN-derived features, PS was the strongest survival predictor (P < .0001). PS was the best in risk stratification, using either evenly sorted (P = .0001) or k-means clustering methods (P = .0045). PS metrics based on SVZ only also correlated with overall survival and risk stratification, but to a lesser degree of significance. In contrast, edge/center-to-ventricle metrics showed weak to no prediction capacities in either task. Moreover, PS,PS, and center-to-ventricle metrics revealed a significantly closer SCN distribution of recurrence than primary tumors.

Conclusions: We introduced a novel inverse distance-based metric to comprehensively capture the anatomic relationship between GBM tumors and SCN zones. The derived metrics outperformed traditional edge or center distance-based measurements in overall survival prediction, risk stratification, and recurrent pattern differentiation. Our results reveal the potential role of SGZ in recurrence aside from SVZ.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238898PMC
July 2021

NAD depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition.

Proc Natl Acad Sci U S A 2021 02;118(8)

Department of Surgery, University of California, Los Angeles, CA 90095;

Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14. Their individual contributions to this mechanism in PDAC have not been previously delineated. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway, a dominant source of NAD in cancer cells. We found that IFN-induced NAD consumption increased dependence upon NAMPT for its role in recycling NAM to salvage NAD pools, thus sensitizing PDAC cells to pharmacologic NAMPT inhibition. Their combination decreased PDAC cell proliferation and invasion in vitro and suppressed orthotopic tumor growth and liver metastases in vivo.
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http://dx.doi.org/10.1073/pnas.2012469118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923374PMC
February 2021

Genomics accurately predicts antimicrobial resistance in Staphylococcus pseudintermedius collected as part of Vet-LIRN resistance monitoring.

Vet Microbiol 2021 Mar 4;254:109006. Epub 2021 Feb 4.

Indiana Animal Disease Diagnostic Laboratory, United States.

Whole-genome sequencing (WGS) has changed our understanding of bacterial pathogens, aiding outbreak investigations and advancing our knowledge of their genetic features. However, there has been limited use of genomics to understand antimicrobial resistance of veterinary pathogens, which would help identify emerging resistance mechanisms and track their spread. The objectives of this study were to evaluate the correlation between resistance genotypes and phenotypes for Staphylococcus pseudintermedius, a major pathogen of companion animals, by comparing broth microdilution antimicrobial susceptibility testing and WGS. From 2017-2019, we conducted antimicrobial susceptibility testing and WGS on S. pseudintermedius isolates collected from dogs in the United States as a part of the Veterinary Laboratory Investigation and Response Network (Vet-LIRN) antimicrobial resistance monitoring program. Across thirteen antimicrobials in nine classes, resistance genotypes correlated with clinical resistance phenotypes 98.4 % of the time among a collection of 592 isolates. Our findings represent isolates from diverse lineages based on phylogenetic analyses, and these strong correlations are comparable to those from studies of several human pathogens such as Staphylococcus aureus and Salmonella enterica. We uncovered some important findings, including that 32.3 % of isolates had the mecA gene, which correlated with oxacillin resistance 97.0 % of the time. We also identified a novel rpoB mutation likely encoding rifampin resistance. These results show the value in using WGS to assess antimicrobial resistance in veterinary pathogens and to reveal putative new mechanisms of resistance.
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http://dx.doi.org/10.1016/j.vetmic.2021.109006DOI Listing
March 2021
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