The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Background: Bacterial metabolism contributes to the generation of uremic toxins in patients with chronic kidney disease (CKD). It has been investigated the use of probiotics in the reduction of uremic toxins intestinal production. Objective: The aim of this pilot study was to evaluate the effect of probiotic supplementation on reducing the production of uremic toxins and the inflammatory profile of CKD patients. Methods: We performed a randomized, blind, placebo-controlled, crossover study on patients with CKD stages 3 and 4. The intervention was a probiotic formulation composed of Lactobacillus acidophilus strains given orally three times a day for 3 months. Changes in uremic toxins (p-Cresylsulfate and Indoxyl Sulfate) and serum inflammatory cytokines were the primary endpoints. Results: Of the 44 patients randomized, 25 completed the study (mean age 51 ± 9.34, 64% female, mean eGFR 36 ± 14.26 mL/min/1.73m², mean BMI 28.5 ± 5.75 kg/m²). At 3 months, there were no significant changes in any of the studied biomarkers including p-cresylsulfate (p = 0.57), Indoxyl sulfate (p = 0.08) and interleukin-6 (p = 0.55). Conclusion: Lactobacillus acidophilus strains given as probiotic were not able to reduce serum levels of uremic toxins and biomarkers of inflammation in CKD patients in stage 3 and 4.

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Anthropometric Variables as Mediators of the Association of Changes in Diet and Physical Activity With Inflammatory Profile

The Journals of Gerontology Series A ◽

10.1093/gerona/glab072 ◽

2021 ◽

Author(s):

Gabriela Cárdenas-Fuentes ◽

Camille Lassale ◽

Miguel Ángel Martínez-González ◽

María Grau ◽

Jordi Salas-Salvadó ◽

...

Keyword(s):

Physical Activity ◽

Body Mass Index ◽

Body Mass ◽

Body Fat ◽

Controlled Trial ◽

High Sensitivity ◽

Linear Regression Models ◽

Mediating Role ◽

Inflammatory Score ◽

Inflammatory Profile

Abstract Background Mechanisms underlying the associations of high levels of physical activity (PA) and adherence to the Mediterranean diet (MedDiet) with a better inflammatory profile remain unclear. Our objective was to assess the mediating role of changes in body mass index (BMI) and waist circumference (WC), as markers of body fat in the association of changes in PA and adherence to the MedDiet, with changes in the inflammatory profile. Method This study included 489 adults, aged 55–75 years, from the PREDIMED-Plus multicenter lifestyle intervention trial. An inflammatory score was calculated, based on 8 blood biomarkers: high-sensitivity C-reactive protein, interleukin 6, interleukin 8, interleukin 18, monocyte chemo-attractant protein-1, C-peptide, leptin, and regulated on activation, normal T-cell–expressed and secreted chemokine. Biomarkers, levels of PA, score of MedDiet adherence, BMI, and WC were measured at baseline and at 1-year follow-up. Linear regression models were fitted according to the Baron and Kenny framework for mediation analysis. Results Changes in BMI and WC mediated the association of both changes in PA and changes in the MedDiet adherence with the inflammatory score. Body mass index mediated 26% of the association of changes in total PA with the inflammatory profile, and 27% of the association of changes in the MedDiet, while WC mediated 13% and 12% of these associations, respectively. Conclusion In older adults at high cardiovascular risk, increasing PA levels and adherence to a MedDiet during 1 year were associated with a lower inflammatory score, which was partly mediated by a reduction in body fat. Clinical Trials Registration Number International Standard Randomized Controlled Trial Number: ISRCTN89898870; registration date July 24, 2014, retrospectively registered.

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Association between dynapenic abdominal obesity and inflammatory profile in diabetic older community-dwelling patients with end-stage renal disease

Experimental Gerontology ◽

10.1016/j.exger.2021.111243 ◽

2021 ◽

Vol 146 ◽

pp. 111243

Author(s):

Hugo de Luca Corrêa ◽

Thiago dos Santos Rosa ◽

Maurílio Tiradentes Dutra ◽

Marcelo Magalhães Sales ◽

Matias Noll ◽

...

Keyword(s):

Renal Disease ◽

Abdominal Obesity ◽

End Stage Renal Disease ◽

Community Dwelling ◽

Inflammatory Profile ◽

Stage Renal Disease ◽

End Stage

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The inflammatory profile of cerebrospinal fluid, plasma, and saliva from patients with severe neuropathic pain and healthy controls-a pilot study

BMC Neuroscience ◽

10.1186/s12868-021-00608-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Mika Jönsson ◽

Björn Gerdle ◽

Bijar Ghafouri ◽

Emmanuel Bäckryd

Keyword(s):

Cerebrospinal Fluid ◽

Neuropathic Pain ◽

Pain Intensity ◽

Principal Component ◽

Partial Least Square ◽

Least Square ◽

Partial Least Square Regression ◽

Therapeutic Interventions ◽

Healthy Controls ◽

Inflammatory Profile

Abstract Background Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. Methods The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. Results We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). Conclusions Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.

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Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

Cancer Causes & Control ◽

10.1007/s10552-021-01469-3 ◽

2021 ◽

Author(s):

Laurie Grieshober ◽

Stefan Graw ◽

Matt J. Barnett ◽

Gary E. Goodman ◽

Chu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Draw ◽

Lymphocyte Ratio ◽

Cox Proportional Hazards Models ◽

Inflammatory Profile ◽

Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

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5FU Delivery through Biocompatible SF/PEG Nanoshuttles Modulates Colorectal Cancer Cells Migration and Invasion Potential and Alters the Inflammatory Cytokines Expression Profile

Proceedings ◽

10.3390/iecp2020-08682 ◽

2020 ◽

Vol 78 (1) ◽

pp. 9

Author(s):

Ariana Hudiță ◽

Ionuț Cristian Radu ◽

Cătălin Zaharia ◽

Octav Ginghină ◽

Bianca Gălățeanu ◽

...

Keyword(s):

Colorectal Cancer ◽

Lethal Dose ◽

Drug Uptake ◽

Morphological Properties ◽

Migration And Invasion ◽

Cancer Management ◽

Invasion Potential ◽

Inflammatory Profile ◽

Ht 29

The past few years have witnessed major developments in nanotechnology with great potential in powering new therapeutic tools for cancer management. Our goal in this study was to develop a biocompatible nanoshuttle for the efficient delivery of 5FU in colorectal cancer patients. Silk fibroin/Poly(ethylene glycol) nanoparticles (SF/PEG NPs) were obtained and further loaded with 5FU. These nanoshuttles were characterized in terms of morphological properties, size and size distribution, drug uptake and release potential as well as in vitro cytotoxicity potential screening. The SF/PEG + 5FU NPs cytotoxicity was determined on HT-29 cells after determination of the lethal dose 50 and targeted the evaluation of the cells viability, proliferation potential and migration and invasion potential. The inflammatory profile of RAW 264.7 macrophage cells was also determined by flow cytometry. The basic cytotoxicity screening revealed that the pristine SF/PEG NPs displayed good biocompatibility while the 5FU-loaded NPs induced cytotoxic effects on HT-29 cells. More, the 5FU-loaded SF/PEG NPs significantly reduced the migration and invasion processes as compared with the unloaded NPs. Lastly, we observed that the cytokine inflammatory profile was significantly altered after the treatment with the 5FU-loaded SF/PEG NPs as compared with the unloaded nanoshuttles.

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Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms22063007 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3007

Author(s):

Isabel Lastres-Becker ◽

Gracia Porras ◽

Marina Arribas-Blázquez ◽

Inés Maestro ◽

Daniel Borrego-Hernández ◽

...

Keyword(s):

Motor Neurons ◽

Molecular Mechanisms ◽

Cell Types ◽

Therapeutic Interventions ◽

Autophagic Flux ◽

Metabolic Disturbances ◽

Molecular Alterations ◽

Healthy Donors ◽

Inflammatory Profile ◽

Als Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily transmitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mitochondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.

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Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells

Marine Drugs ◽

10.3390/md19020079 ◽

2021 ◽

Vol 19 (2) ◽

pp. 79

Author(s):

Hengju Ge ◽

Di Zhang ◽

Muran Shi ◽

Xiaoyuan Lian ◽

Zhizhen Zhang

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Antiproliferative Activity ◽

Lung Cancer Cells ◽

Potential Mechanism ◽

Nucleotide Synthesis ◽

Factor C ◽

Antiglioma Activity

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

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