Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabonomics study on orthotopic transplantion mice model of colon cancer treated with Astragalus membranaceus-Curcuma wenyujin in different proportions via UPLC-Q-TOF/MS.

Mon, 02/11/2020 - 00:09
Related Articles Metabonomics study on orthotopic transplantion mice model of colon cancer treated with Astragalus membranaceus-Curcuma wenyujin in different proportions via UPLC-Q-TOF/MS. J Pharm Biomed Anal. 2020 Oct 18;193:113708 Authors: Sun R, Gu J, Chang X, Liu F, Liang Y, Yang X, Liang L, Tang D Abstract Metabolomics, an important part of systems biology, can reveal the complex pathogenesis of many diseases and mechanism of Chinese materia medica (CMM). Astragalus membranaceus-Curcuma wenyujin (AC) was a classic drug pair that has a good clinical effect on gastrointestinal inflammation and many tumors. Our previous research proved that AC can inhibit tumor growth and metastasis especially the colorectal cancer (CRC), also promote the normalization of tumor blood vessels, but its optimal ratio and the specific mechanism is still not clear. In this study, colon cancer mice of orthotopic transplantion model was used to screen the best proportion, UPLC-Q-TOF/MS metabolomics analysis method was established to explore the pathogenesis of colon cancer and the molecular mechanism of AC. The correlation analysis of metabolite changes and tumor growth was analyzed by R language. The result showed that AC at the ratio of 2:1 showed the best effect on inhibiting tumor growth, also the liver and spleen metastasis rate. A total of 23 potential biomarkers were detected in the serum of colon cancer mice by the analysis of Progenesis QI (Version 2.4) software. Among this, 11 metabolites including purines, steroids, phytosphingosine and l-palmitoylcarnitine were up-regulated in CC mice, while 12 metabolites like amino acids, deoxyribose and dihydrobiopterin were down-regulated in CC mice. After the treatment of AC for 15 days, 8 biomarkers were up-regulated, and 9 biomarkers down-regulated. Especially, AC at the ratio of 2:1 showed a significant callback effect on metabolic biomarkers, such as hypoxanthine, xanthosine, 7-methylxanthine, all-trans-retinoic acid, dihomo-γ-linolenic acid. 8 metabolic pathways: Aminoacyl-tRNA biosynthesis, Nicotinate and nicotinamide metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Caffeine metabolism, Retinol metabolism, Alanine, aspartate and glutamate metabolism were selected as the model group disturbed metabolic pathways after the enrichment of MetaboAnalyst 4.0 online analysis software. And compared with the model group, Valine, leucine and isoleucine biosynthesis, Aminoacyl-tRNA biosynthesis, Caffeine metabolism pathway and Retinol metabolism pathways were altered after the intervention of AC. The correlation analysis results showed that various endogenous metabolites in serum have a strong correlation with tumor weight, such as hypoxanthine, which provides a basis for the selection of clinical markers. The results showed that AC can partially regulate metabolic disorder of CC mice by reversing the changes of metabolites, so as to inhibit the growth and metastasis of colon cancer, especially at the ratio of 2:1. These findings can provide a scientific basis for exploring the diagnostic biomarkers of colon cancer, and for clinical application of AC in the treatment of CRC program. PMID: 33129117 [PubMed - as supplied by publisher]

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model.

Mon, 02/11/2020 - 00:09
Related Articles Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model. Transl Oncol. 2020 Oct 22;14(1):100882 Authors: Heeran AB, Berrigan HP, Buckley CE, Bottu HM, Prendiville O, Buckley AM, Clarke N, Donlon NE, Nugent TS, Durand M, Dunne C, Larkin JO, Mehigan B, McCormick P, Brennan L, Lynam-Lennon N, O'Sullivan J Abstract Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBE-induction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome. PMID: 33129115 [PubMed - as supplied by publisher]

A Unique Urinary Metabolomic Signature for the Detection of Pancreatic Ductal Adenocarcinoma.

Mon, 02/11/2020 - 00:09
Related Articles A Unique Urinary Metabolomic Signature for the Detection of Pancreatic Ductal Adenocarcinoma. Int J Cancer. 2020 Oct 31;: Authors: Sahni S, Pandya AR, Hadden WJ, Nahm CB, Maloney S, Cook V, Toft JA, Wilkinson-White L, Gill AJ, Samra JS, Dona A, Mittal A Abstract This study aimed to identify a urinary metabolite panel for the detection/diagnosis of pancreatic ductal adenocarcinoma (PDAC). PDAC continues to have poor survival outcomes. One of the major reasons for poor prognosis is the advanced stage of the disease at diagnosis. Hence, identification of a novel and cost-effective biomarker signature for early detection/diagnosis of PDAC could lead to better survival outcomes. Untargeted metabolomics was employed to identify a novel metabolite-based biomarker signature for PDAC diagnosis. Urinary metabolites from 92 PDAC patients (56 discovery cohort and 36 validation cohort) were compared with 56 healthy volunteers using 1 H-nuclear magnetic resonance (1 H-NMR) spectroscopy. Multivariate (Partial-least squares discriminate analysis) and univariate (Mann-Whiney's U-test) analysis were performed to identify a metabolite panel which can be used to detect PDAC. The selected metabolites were further validated for their diagnostic potential using the area under the receiver operating characteristic (AUROC) curve. Statistical analysis identified a six-metabolite panel (trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone) which demonstrated high potential to diagnose PDAC, with AUROC of 0.933 and 0.864 in the discovery and validation cohort, respectively. Notably, the identified panel also demonstrated very high potential to diagnose early stage (I and II) PDAC patients with AUROC of 0.897. These results demonstrate that the selected metabolite signature could be used to detect PDAC and will pave the way for the development of a urinary test for detection/diagnosis of PDAC. PMID: 33128797 [PubMed - as supplied by publisher]

Supplementation of Bacillus sp. DU-106 reduces hypercholesterolemia and ameliorates gut dysbiosis in high-fat diet rats.

Mon, 02/11/2020 - 00:09
Related Articles Supplementation of Bacillus sp. DU-106 reduces hypercholesterolemia and ameliorates gut dysbiosis in high-fat diet rats. Appl Microbiol Biotechnol. 2020 Oct 31;: Authors: Huang J, Xiao N, Sun Y, Wu S, Tian W, Lai Y, Li P, Du B Abstract Gut microbiota modulation by a probiotic is a novel therapy for hypercholesterolemia mitigation. This study initially investigated the potential hypocholesterolemic effect of Bacillus sp. DU-106 in hypercholesterolemic rats and explored its potential relation with gut microbiota. Sprague-Dawley rats received a high-fat diet, or a high-fat diet supplemented with 7.5 × 109 and 1.5 × 1010 CFU/kg bw/day Bacillus sp. DU-106 (low-dose and high-dose groups). At the end of 9 weeks, Bacillus sp. DU-106 treatment significantly decreased the body weight, liver index, and total cholesterol. 16S rRNA sequencing showed that Bacillus sp. DU-106 intervention significantly increased bacterial richness and particularly increased the genus abundance of Turicibacter, Acinetobacter, Brevundimonas, and Bacillus and significantly decreased the abundance of Ralstonia. Metabolomic data further indicated that the supplementation of Bacillus sp. DU-106 remarkably changed the gut metabolic profiles of hypercholesterolemic rats and, in particular, elevated the metabolites of indole-3-acetate, methylsuccinic acid, creatine, glutamic acid, threonine, lysine, ascorbic acid, and pyridoxamine. Spearman's correlation analysis showed the close relation between the different genera and metabolites. In conclusion, Bacillus sp. DU-106 supplement ameliorated high-fat diet-induced hypercholesterolemia and showed potential probiotic benefits for the intestine. KEY POINTS: • A novel potential probiotic Bacillus sp. DU-106 ameliorated hypercholesterolemia in rats. • Bacillus sp. DU-106 supplement regulated gut microbiome structure and richness. • Bacillus sp. DU-106 supplement changed metabolic profiles in high-fat diet rats. • Significant correlations were observed between differential genera and metabolites. PMID: 33128611 [PubMed - as supplied by publisher]

Elevated c-di-GMP levels promote biofilm formation and biodesulfurization capacity of Rhodococcus erythropolis.

Mon, 02/11/2020 - 00:09
Related Articles Elevated c-di-GMP levels promote biofilm formation and biodesulfurization capacity of Rhodococcus erythropolis. Microb Biotechnol. 2020 Oct 31;: Authors: Dorado-Morales P, Martínez I, Rivero-Buceta V, Díaz E, Bähre H, Lasa I, Solano C Abstract Bacterial biofilms provide high cell density and a superior adaptation and protection from stress conditions compared to planktonic cultures, making them a very promising approach for bioremediation. Several Rhodococcus strains can desulfurize dibenzothiophene (DBT), a major sulphur pollutant in fuels, reducing air pollution from fuel combustion. Despite multiple efforts to increase Rhodococcus biodesulfurization activity, there is still an urgent need to develop better biocatalysts. Here, we implemented a new approach that consisted in promoting Rhodococcus erythropolis biofilm formation through the heterologous expression of a diguanylate cyclase that led to the synthesis of the biofilm trigger molecule cyclic di-GMP (c-di-GMP). R. erythropolis biofilm cells displayed a significantly increased DBT desulfurization activity when compared to their planktonic counterparts. The improved biocatalyst formed a biofilm both under batch and continuous flow conditions which turns it into a promising candidate for the development of an efficient bioreactor for the removal of sulphur heterocycles present in fossil fuels. PMID: 33128507 [PubMed - as supplied by publisher]

The Effects of Continuous Albuterol Inhalation on the Serum Metabolome in Healthy Subjects: More than Just Lactic Acid.

Mon, 02/11/2020 - 00:09
Related Articles The Effects of Continuous Albuterol Inhalation on the Serum Metabolome in Healthy Subjects: More than Just Lactic Acid. J Clin Pharmacol. 2020 Oct 30;: Authors: Nowadly CD, Liao SY, Rose JS Abstract Treatment with β2-agonists may cause elevated lactic acid, the end-product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2-agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study is to investigate the impact of one hour of continuous albuterol on the untargeted serum metabolome healthy subjects. 24 healthy participants received 7.5 mg continuous albuterol for 1-hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1-hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (p = 0.02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, p = 0.02) although there was overlap in lactate levels across time points. For metabolomic analysis, fatty acids, organic acids, and sugars elevated and amino acids reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after False Discovery Rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data supports recent hypotheses that Β2-receptor activation stimulates lactic acid production altering aerobic glycolysis, gluconeogenesis, and free fatty acid production. This article is protected by copyright. All rights reserved. PMID: 33128239 [PubMed - as supplied by publisher]

Prediction of response and survival after standardized treatment with 7400 MBq 177Lu-PSMA-617 every 4 weeks in patients with metastatic castration-resistant prostate cancer.

Mon, 02/11/2020 - 00:09
Related Articles Prediction of response and survival after standardized treatment with 7400 MBq 177Lu-PSMA-617 every 4 weeks in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2020 Oct 30;: Authors: Rasul S, Hartenbach M, Wollenweber T, Kretschmer-Chott E, Grubmüller B, Kramer G, Shariat S, Wadsak W, Mitterhauser M, Pichler V, Vraka C, Hacker M, Haug AR Abstract BACKGROUND AND AIMS: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks. PATIENTS AND METHODS: Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0-4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS). RESULTS: Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09-2.09) with an AUC of 0.68 (95% CI: 0.54-0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P < 0.05 (relative risk 1.51 and 0.79, 95% CI: 1.09-2.09 and 0.43-1.46), respectively. In comparison to patients with reduced basal Hb, patients with normal basal Hb levels lived significantly longer (median survival not reached vs. 89 weeks, P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT. CONCLUSION: Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival. PMID: 33128131 [PubMed - as supplied by publisher]

Microbiome-derived metabolome as a potential predictor of response to cancer immunotherapy.

Mon, 02/11/2020 - 00:09
Related Articles Microbiome-derived metabolome as a potential predictor of response to cancer immunotherapy. J Immunother Cancer. 2020 Oct;8(2): Authors: Malczewski AB, Navarro S, Coward JI, Ketheesan N Abstract Cancer immunotherapy with checkpoint blockade has become standard of care treatment for numerous cancer types. Despite this, robust predictive biomarkers are lacking. There is increasing evidence that the host microbiome is a predictor of immunotherapy response, although the optimal host microbiome has not been defined. Metabolomics is a new area of medicine that aims to analyze the metabolic profile of a biological system. The microbiome-derived metabolome (fecal and serum) represents the end products of microbial metabolism and these may be functionally more important than the distinct bacterial species that comprise a favorable microbiome. Short-chain fatty acids (SCFA) are metabolites produced by gut microbiota and have a role in T cell homeostasis, including differentiation of regulatory T cells. Recent studies have confirmed differential expression of SCFA for immunotherapy responders compared with non-responders. We propose that the microbiome metabolome, with a focus on SCFA may be a novel predictive biomarker for immunotherapy efficacy. PMID: 33127655 [PubMed - as supplied by publisher]

Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model.

Mon, 02/11/2020 - 00:09
Related Articles Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model. Neurobiol Dis. 2020 Oct 27;:105151 Authors: Pham L, Wright DK, O'Brien WT, Bain J, Huang C, Sun M, Casillas-Espinosa PM, Shah AD, Schittenhelm RB, Sobey CG, Brady RD, O'Brien TJ, Mychasiuk R, Shultz SR, McDonald SJ Abstract A history of mild traumatic brain injury (mTBI) is linked to a number of chronic neurological conditions, however there is still much unknown about the underlying mechanisms. To provide new insights, this study used a clinically relevant model of repeated mTBI in rats to characterize the acute and chronic neuropathological and neurobehavioral consequences of these injuries. Rats were given four sham-injuries or four mTBIs and allocated to 7-day or 3.5-months post-injury recovery groups. Behavioral analysis assessed sensorimotor function, locomotion, anxiety, and spatial memory. Neuropathological analysis included serum quantification of neurofilament light (NfL), mass spectrometry of the hippocampal proteome, and ex vivo magnetic resonance imaging (MRI). Repeated mTBI rats had evidence of acute cognitive deficits and prolonged sensorimotor impairments. Serum NfL was elevated at 7 days post injury, with levels correlating with sensorimotor deficits; however, no NfL differences were observed at 3.5 months. Several hippocampal proteins were altered by repeated mTBI, including those associated with energy metabolism, neuroinflammation, and impaired neurogenic capacity. Diffusion MRI analysis at 3.5 months found widespread reductions in white matter integrity. Taken together, these findings provide novel insights into the nature and progression of repeated mTBI neuropathology that may underlie lingering or chronic neurobehavioral deficits. PMID: 33127468 [PubMed - as supplied by publisher]

Omics in Myopia.

Mon, 02/11/2020 - 00:09
Related Articles Omics in Myopia. J Clin Med. 2020 Oct 28;9(11): Authors: Grochowski ET, Pietrowska K, Kowalczyk T, Mariak Z, Kretowski A, Ciborowski M, Dmuchowska DA Abstract Myopia is a globally emerging issue, with multiple medical and socio-economic burdens and no well-established causal treatment thus far. A better insight into altered biochemical pathways and underlying pathogenesis might facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the metabolomics and proteomics of myopia in humans and present various experimental approaches and animal models, along with their strengths and weaknesses. We also discuss the potential applicability of these findings to medical practice and suggest directions for future research. PMID: 33126435 [PubMed - as supplied by publisher]

Description of Oceanispirochaeta crateris sp. nov. and reclassification of Spirochaeta perfilievii as Thiospirochaeta perfilievii gen. nov., comb. nov.

Sat, 31/10/2020 - 20:55
Related Articles Description of Oceanispirochaeta crateris sp. nov. and reclassification of Spirochaeta perfilievii as Thiospirochaeta perfilievii gen. nov., comb. nov. Int J Syst Evol Microbiol. 2020 Oct 30;: Authors: Dubinina G, Leshcheva N, Mikheeva N, Spring S, Neumann-Schaal M, Shcherbakova V, Grabovich M Abstract A novel obligately anaerobic spirochete strain K2T was isolated from bottom marine sediments at Crater Bay of Yankicha Island (Kuril Islands, Russia). Strain K2T had helical shape and Gram-negatively stained. The optimal growth conditions were as follows: the optimum temperature was 28-30 °C with range 5-34 °C; optimal pH at 7.0-7.5 with range of 6.8-8.5; NaCl optimum at 3-3.5 % (w/v) and range of 1-7 % (w/v). Strain K2T was catalase- and oxidase-negative. Glucose fermentation products were acetate, lactate, ethanol, CO2, H2. The major fatty acids were C14 : 0, iso-C13 : 0, iso-C15:0, C14 : 0 DMA, iso-C15 : 0 DMA. The G+C content of genomic DNA was 43.2 mol%. Phylogenetic analyses of 16S rRNA genes showed that strain K2T belonged to the genus Oceanispirochaeta of the family Spirochaetaceae. The 16S rRNA gene sequence similarity of strain K2T and O. litoralis DSM 2029T and O. sediminicola DSM 104770T was 96 and 94 %, respectively. Based on the results of our study, we propose the name Oceanispirochaeta crateris sp. nov.; type strain K2T (=DSM 16308T=VKM B-3266T). Also, the taxonomic status of Spirochaeta perfilevii was revised: 16S rRNA genes sequence showed less than 89 % similarity to nearest phylogenetic neighbours. Therefore, we proposed to separate this species into a novel genus Thiospirochaeta - T. perfilievii gen. nov., comb. nov. PMID: 33125316 [PubMed - as supplied by publisher]

Regulation of plasma volume in male lowlanders during four days of exposure to hypobaric hypoxia equivalent to 3,500 m altitude.

Sat, 31/10/2020 - 20:55
Related Articles Regulation of plasma volume in male lowlanders during four days of exposure to hypobaric hypoxia equivalent to 3,500 m altitude. J Physiol. 2020 Oct 30;: Authors: Schlittler M, Gatterer H, Turner R, Regli IB, Woyke S, Strapazzon G, Rasmussen P, Kob M, Mueller T, Goetze JP, Maillard M, van Hall G, Feraille E, Siebenmann C Abstract KEY POINTS: Acclimatization to hypoxia leads to a reduction in plasma volume (PV) that restores arterial O2 content. Studies investigating the mechanisms underlying this PV contraction have made controversial findings, possibly as experimental conditions were inadequately controlled. We examined the mechanisms underlying the PV contraction evoked by four days of exposure to hypobaric hypoxia (HH) in eleven healthy lowlanders, while strictly controlling water intake, diet, temperature and physical activity. Exposure to HH induced a ∼10% PV contraction that was accompanied by a reduction in total circulating protein mass, whereas diuretic fluid loss and total body water remained unchanged. Our data supports an oncotically-driven fluid redistribution from the intra- to the extravascular space, rather than fluid loss, as mechanism underlying HH-induced PV contraction. ABSTRACT: Extended hypoxic exposure reduces plasma volume (PV). The mechanisms underlying this effect are controversial, possibly as previous studies have been confounded by inconsistent experimental conditions. Here, we investigated the effect of hypobaric hypoxia (HH) on PV in a cross-over study that strictly controlled for diet, water intake, physical activity and temperature. Eleven males completed two four-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in HH equivalent to 3,500m altitude. PV, urine output, volume-regulating hormones and plasma protein concentration were determined daily. Total body water (TBW) was determined at the end of both sojourns by deuterium dilution. Although PV was 8.1±5.8% lower in HH than in NX after 24h and remained ∼10% lower thereafter (all P<0.002), no differences were detected in TBW (P = 0.17) or in 24-h urine volumes (all P>0.23). Plasma renin activity and circulating aldosterone were suppressed in HH during the first half of the sojourn (all P<0.05) but thereafter similar to NX, whereas no differences were detected for copeptin between sojourns (all P>0.05). Markers for atrial natriuretic peptide were higher in HH than NX after 30min (P = 0.001) but lower during the last two days (P<0.001). While plasma protein concentration was similar between sojourns, total circulating protein mass (TCP) was reduced in HH at the same time points as PV (all P<0.03). Despite transient hormonal changes favouring increased diuresis, HH did not enhance urine output. Instead, the maintained TBW and reduced TCP support an oncotically-driven fluid redistribution into the extravascular compartment as mechanism underlying PV contraction. This article is protected by copyright. All rights reserved. PMID: 33124686 [PubMed - as supplied by publisher]

The Association Between Obesity and Risk of Acute Kidney Injury After Cardiac Surgery.

Sat, 31/10/2020 - 20:55
Related Articles The Association Between Obesity and Risk of Acute Kidney Injury After Cardiac Surgery. Front Endocrinol (Lausanne). 2020;11:534294 Authors: Shi N, Liu K, Fan Y, Yang L, Zhang S, Li X, Wu H, Li M, Mao H, Xu X, Ma SP, Xiao P, Jiang S Abstract Objective: To determine the relationship between obesity and the risk of AKI after cardiac surgery (CS-AKI) in a cohort study. Methods: A total of 1,601 patients undergoing cardiac surgery were collected and their incidence of CS-AKI was recorded. They were divided into underweight, normal weight, overweight, and obese groups. Logistic regression was used to estimate the association between BMI (body mass index) and CS-AKI risk. Then, a meta-analysis of published cohort studies was conducted to confirm this result using PubMed and Embase databases. Results: A significant association was observed in this independent cohort after adjusting age, gender, hypertension and New York Heart Association classification (NYHA) class. Compared with normal BMI group (18.5 ≤ BMI < 24.0), the individuals with aberrant BMI level had an increased AKI risk (OR: 1.68, 95% CI: 1.01-2.78) for BMI < 18.5 group and (OR: 1.43, 95% CI: 0.96-2.15) for BMI ≥ 28.0. Interestingly, the U-shape curve showed the CS-AKI risk reduced with the increasing of BMI when BMI ≤ 24.0. As BMI increases with BMI > 24.0, the risk of developing CS-AKI increased significantly. In the confirmed meta-analysis, compared with normal weight, overweight group with cardiac surgery had higher AKI risk (OR: 1.28, 95% CI: 1.16-1.41, P heterogeneity = 0.49). The similar association was found in obesity subgroup (OR: 1.79, 95% CI: 1.57-2.03, P heterogeneity = 0.42). Conclusion: In conclusion, the results suggested that abnormal BMI was a risk factor for CS-AKI independently. PMID: 33123083 [PubMed - in process]

Microbial Cleavage of C-F Bonds in Two C6 Per- and Polyfluorinated Compounds via Reductive Defluorination.

Sat, 31/10/2020 - 20:55
Related Articles Microbial Cleavage of C-F Bonds in Two C6 Per- and Polyfluorinated Compounds via Reductive Defluorination. Environ Sci Technol. 2020 Oct 29;: Authors: Yu Y, Zhang K, Li Z, Ren C, Chen J, Lin YH, Liu J, Men Y Abstract The C-F bond is one of the strongest single bonds in nature. Although microbial reductive dehalogenation is well known for the other organohalides, no microbial reductive defluorination has been documented for perfluorinated compounds except for a single, nonreproducible study on trifluoroacetate. Here, we report on C-F bond cleavage in two C6 per- and polyfluorinated compounds via reductive defluorination by an organohalide-respiring microbial community. The reductive defluorination was demonstrated by the release of F- and the formation of the corresponding product when lactate was the electron donor, and the fluorinated compound was the sole electron acceptor. The major dechlorinating species in the seed culture, Dehalococcoides, were not responsible for the defluorination as no growth of Dehalococcoides or active expression of Dehalococcoides-reductive dehalogenases was observed. It suggests that minor phylogenetic groups in the community might be responsible for the reductive defluorination. These findings expand our fundamental knowledge of microbial reductive dehalogenation and warrant further studies on the enrichment, identification, and isolation of responsible microorganisms and enzymes. Given the wide use and emerging concerns of fluorinated organics (e.g., per- and polyfluoroalkyl substances), particularly the perfluorinated ones, the discovery of microbial defluorination under common anaerobic conditions may provide valuable insights into the environmental fate and potential bioremediation strategies of these notorious contaminants. PMID: 33121241 [PubMed - as supplied by publisher]

Effectiveness of Hydrocolloid Dressings for Treating Pressure Ulcers in Adult Patients: A Systematic Review and Meta-Analysis.

Sat, 31/10/2020 - 20:55
Related Articles Effectiveness of Hydrocolloid Dressings for Treating Pressure Ulcers in Adult Patients: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2020 Oct 27;17(21): Authors: Kamińska MS, Cybulska AM, Skonieczna-Żydecka K, Augustyniuk K, Grochans E, Karakiewicz B Abstract The aim of this study was to assess the effectiveness of hydrocolloid dressings in the treatment of grade I, II, III, and IV pressure ulcers in adult patients. We compared the therapeutic effects of hydrocolloids and alternative dressings in pressure ulcer treatment. We conducted a systematic review, using a literature search only in English, from database inception until 20 April 2020, to identify randomized trials comparing various types of dressings applied in the healing of pressure ulcers. The databases were PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The study selection was performed independently by two reviewers. Data were extracted based on the guidelines included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The risk of bias in the included studies was assessed using a standardized critical appraisal instrument developed by the Cochrane Collaboration. Random-effect meta-analysis of data from three or more studies was performed using meta-analysis software (Comprehensive Meta-Analysis V3, Biostat, New Jersey, USA). A total of 1145 records were identified, of which 223 were qualified after further verification, of which eight were finally included in further analysis. Hydrocolloid dressings were not superior to control therapeutics (p = 0.839; Z = 0.203; CI 95%: 0.791-1.334). They were not associated with higher healing rates (p = 0.718; Z = 0.361; OR: 0.067; CI 95%: 0.297-0.431), nor did they decrease the incidence of adverse events compared with control therapeutics (p = 0.300; Z = -1.036; OR: 0.067; CI 95%: 0.394-1.333). In the above cases, Egger's test also did not indicate publication bias (t value = 0.779, p = 0.465; t value = 1.198, p = 0.442; t value = 0.834, p = 0.465, respectively). The present meta-analysis shows that hydrocolloid dressings are not significantly better than alternative ones in the healing of pressure ulcers in adult patients. PMID: 33121151 [PubMed - in process]

Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem.

Sat, 31/10/2020 - 20:55
Related Articles Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem. Proc Natl Acad Sci U S A. 2020 09 08;117(36):22561-22571 Authors: Su YH, Zhou C, Li YJ, Yu Y, Tang LP, Zhang WJ, Yao WJ, Huang R, Laux T, Zhang XS Abstract In the shoot meristem, both WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM), two transcription factors with overlapping spatiotemporal expression patterns, are essential for maintaining stem cells in an undifferentiated state. Despite their importance, it remains unclear how these two pathways are integrated to coordinate stem cell development. Here, we show that the WUS and STM pathways in Arabidopsis thaliana converge through direct interaction between the WUS and STM proteins. STM binds to the promoter of CLAVATA3 (CLV3) and enhances the binding of WUS to the same promoter through the WUS-STM interaction. Both the heterodimerization and simultaneous binding of WUS and STM at two sites on the CLV3 promoter are required to regulate CLV3 expression, which in turn maintains a constant number of stem cells. Furthermore, the expression of STM depends on WUS, and this WUS-activated STM expression enhances the WUS-mediated stem cell activity. Our data provide a framework for understanding how spatial expression patterns within the shoot meristem are translated into regulatory units of stem cell homeostasis. PMID: 32839309 [PubMed - indexed for MEDLINE]

Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes.

Sat, 31/10/2020 - 20:55
Related Articles Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes. Sci Rep. 2019 11 08;9(1):16398 Authors: Tofte N, Suvitaival T, Ahonen L, Winther SA, Theilade S, Frimodt-Møller M, Ahluwalia TS, Rossing P Abstract There is an urgent need for a better molecular understanding of the pathophysiology underlying development and progression of diabetic nephropathy. The aim of the current study was to identify novel associations between serum lipidomics and diabetic nephropathy. Non-targeted serum lipidomic analyses were performed with mass spectrometry in 669 individuals with type 1 diabetes. Cross-sectional associations of lipid species with estimated glomerular filtration rate (eGFR) and urinary albumin excretion were assessed. Moreover, associations with register-based longitudinal follow-up for progression to a combined renal endpoint including ≥30% decline in eGFR, ESRD and all-cause mortality were evaluated. Median follow-up time was 5.0-6.4 years. Adjustments included traditional risk factors and multiple testing correction. In total, 106 lipid species were identified. Primarily, alkyl-acyl phosphatidylcholines, triglycerides and sphingomyelins demonstrated cross-sectional associations with eGFR and macroalbuminuria. In longitudinal analyses, thirteen lipid species were associated with the slope of eGFR or albuminuria. Of these lipids, phosphatidylcholine and sphingomyelin species, PC(O-34:2), PC(O-34:3), SM(d18:1/24:0), SM(d40:1) and SM(d41:1), were associated with lower risk of the combined renal endpoint. PC(O-34:3), SM(d40:1) and SM(d41:1) were associated with lower risk of all-cause mortality while an SM(d18:1/24:0) was associated with lower risk of albuminuria group progression. We report distinct associations between lipid species and risk of renal outcomes in type 1 diabetes, independent of traditional markers of kidney function. PMID: 31705008 [PubMed - indexed for MEDLINE]

Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System.

Sat, 31/10/2020 - 20:55
Related Articles Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System. Front Immunol. 2019;10:2348 Authors: Alessandri G, Ossiprandi MC, MacSharry J, van Sinderen D, Ventura M Abstract Since bifidobacteria are among the pioneering colonizers of the human infant gut, their interaction with their host is believed to start soon following birth. Several members of the Bifidobacterium genus are purported to exert various health-promoting effects at local and systemic levels, e.g., limiting pathogen colonization/invasion, influencing gut homeostasis, and influencing the immune system through changes in innate and/or adaptive immune responses. This has promoted extensive research efforts to shed light on the precise mechanisms by which bifidobacteria are able to stimulate and interact with the host immune system. These studies uncovered a variety of secreted or surface-associated molecules that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue, and that allow interactions with mucosa-associated immune cells. Additionally, the by-products generated from bifidobacterial carbohydrate metabolism act as vectors that directly and indirectly trigger the host immune response, the latter by stimulating growth of other commensal microorganisms such as propionate- or butyrate-producing bacteria. This review is aimed to provide a comprehensive overview on the wide variety of strategies employed by bifidobacteria to engage with the host immune system. PMID: 31632412 [PubMed - indexed for MEDLINE]

Characterization of circadian human facial surface lipid composition.

Sat, 31/10/2020 - 20:55
Related Articles Characterization of circadian human facial surface lipid composition. Exp Dermatol. 2019 07;28(7):858-862 Authors: Jia Y, Zhou M, Huang H, Gan Y, Yang M, Ding R Abstract BACKGROUND: The circadian rhythm is an endogenous clock that governs a wide range of physiological functions. In the skin, rhythmic changes in skin barrier function have been investigated at the physiological level; however, few studies at the molecular level have been reported. Additionally, there is no study on lipidomic profile variations of skin surface lipid (SSL), which could potentially explain the rhythmic changes in skin status. OBJECTIVES: The SSL profile of healthy young women was analysed to assess SSL variations and to assess the skin status during the circadian cycle. METHODS: Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate data analysis were performed to assess SSL variations. RESULTS: The lipidomic profile showed significant differences with the circadian rhythm. Multivariate data analysis indicated that glycerolipids were the lipids majorly affected by the circadian rhythm. Additionally, in the SSL profile, both the average chain length and the content of free fatty acids (FFAs) were higher at 20:00 than at 08:00. CONCLUSIONS: The SSL profile significantly varied with respect to the circadian rhythm. The rhythm-altered triacylglycerol level, FFA chain length and FFA content resulted in rhythmic changes in skin barrier function, including transepidermal water loss alteration and pH variation. PMID: 30972810 [PubMed - indexed for MEDLINE]

metabolomics; +27 new citations

Sat, 31/10/2020 - 11:41
27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/10/31PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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