PubMed

Related Articles Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach. BMC Cancer. 2020 Sep 02;20(1):835 Authors: Zhang Y, Wang J, Dai N, Han P, Li J, Zhao J, Yuan W, Zhou J, Zhou F Abstract BACKGROUND: To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). METHODS: A total of 46 ESCC patients were included in this study. Gas chromatography time-of- flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis. RESULTS: Five differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid (p = 0.0129), linoleic acid (p = 0.0137), citric acid (p = 0.0473) were upregulated, while L-histidine (p = 0.0155), 3'4 dihydroxyhydrocinnamic acid (p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity. CONCLUSION: The present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy. PMID: 32878621 [PubMed - in process]

Related Articles Targeted Metabolic Profiling of Urine Highlights a Potential Biomarker Panel for the Diagnosis of Alzheimer's Disease and Mild Cognitive Impairment: A Pilot Study. Metabolites. 2020 Aug 31;10(9): Authors: Yilmaz A, Ugur Z, Bisgin H, Akyol S, Bahado-Singh R, Wilson G, Imam K, Maddens ME, Graham SF Abstract The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential biomarkers for MCI and AD. Correlation-based feature selection (CFS) and least absolute shrinkage and selection operator (LASSO) methods were used to develop biomarker panels tested using support vector machine (SVM) and logistic regression models for diagnosis of each disease state. Metabolic changes were investigated to identify which biochemical pathways were perturbed as a direct result of MCI and AD in urine. Using SVM, we developed a model with 94% sensitivity, 78% specificity, and 78% AUC to distinguish healthy controls from AD sufferers. Using logistic regression, we developed a model with 85% sensitivity, 86% specificity, and an AUC of 82% for AD diagnosis as compared to cognitively healthy controls. Further, we identified 11 urinary metabolites that were significantly altered to include glucose, guanidinoacetate, urocanate, hippuric acid, cytosine, 2- and 3-hydroxyisovalerate, 2-ketoisovalerate, tryptophan, trimethylamine N oxide, and malonate in AD patients, which are also capable of diagnosing MCI, with a sensitivity value of 76%, specificity of 75%, and accuracy of 81% as compared to healthy controls. This pilot study suggests that urine metabolomics may be useful for developing a test capable of diagnosing and distinguishing MCI and AD from cognitively healthy controls. PMID: 32878308 [PubMed]

Related Articles Food Phenotyping: Recording and Processing of Non-Targeted Liquid Chromatography Mass Spectrometry Data for Verifying Food Authenticity. Molecules. 2020 Aug 31;25(17): Authors: Creydt M, Fischer M Abstract Experiments based on metabolomics represent powerful approaches to the experimental verification of the integrity of food. In particular, high-resolution non-targeted analyses, which are carried out by means of liquid chromatography-mass spectrometry systems (LC-MS), offer a variety of options. However, an enormous amount of data is recorded, which must be processed in a correspondingly complex manner. The evaluation of LC-MS based non-targeted data is not entirely trivial and a wide variety of strategies have been developed that can be used in this regard. In this paper, an overview of the mandatory steps regarding data acquisition is given first, followed by a presentation of the required preprocessing steps for data evaluation. Then some multivariate analysis methods are discussed, which have proven to be particularly suitable in this context in recent years. The publication closes with information on the identification of marker compounds. PMID: 32878155 [PubMed - in process]

Related Articles 31P-NMR Metabolomics Revealed Species-Specific Use of Phosphorous in Trees of a French Guiana Rainforest. Molecules. 2020 Aug 31;25(17): Authors: Gargallo-Garriga A, Sardans J, Llusià J, Peguero G, Asensio D, Ogaya R, Urbina I, Langenhove LV, Verryckt LT, Courtois EA, Stahl C, Grau O, Urban O, Janssens IA, Nolis P, Pérez-Trujillo M, Parella T, Peñuelas J Abstract Productivity of tropical lowland moist forests is often limited by availability and functional allocation of phosphorus (P) that drives competition among tree species and becomes a key factor in determining forestall community diversity. We used non-target 31P-NMR metabolic profiling to study the foliar P-metabolism of trees of a French Guiana rainforest. The objective was to test the hypotheses that P-use is species-specific, and that species diversity relates to species P-use and concentrations of P-containing compounds, including inorganic phosphates, orthophosphate monoesters and diesters, phosphonates and organic polyphosphates. We found that tree species explained the 59% of variance in 31P-NMR metabolite profiling of leaves. A principal component analysis showed that tree species were separated along PC 1 and PC 2 of detected P-containing compounds, which represented a continuum going from high concentrations of metabolites related to non-active P and P-storage, low total P concentrations and high N:P ratios, to high concentrations of P-containing metabolites related to energy and anabolic metabolism, high total P concentrations and low N:P ratios. These results highlight the species-specific use of P and the existence of species-specific P-use niches that are driven by the distinct species-specific position in a continuum in the P-allocation from P-storage compounds to P-containing molecules related to energy and anabolic metabolism. PMID: 32877991 [PubMed - in process]

26 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 2020/09/03PubMed 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.

28 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 2020/09/02PubMed 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.

28 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 2020/09/02PubMed 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.

18 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 2020/09/01PubMed 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.

18 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 2020/09/01PubMed 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.

DNA methylation downregulated ZDHHC1 suppresses tumor growth by altering cellular metabolism and inducing oxidative/ER stress-mediated apoptosis and pyroptosis. Theranostics. 2020;10(21):9495-9511 Authors: Le X, Mu J, Peng W, Tang J, Xiang Q, Tian S, Feng Y, He S, Qiu Z, Ren G, Huang A, Lin Y, Tao Q, Xiang T Abstract Cancer progression is an intricate biological process profiled by not only unscheduled proliferation, but also altered metabolism mechanisms. In this article, we introduced a novel tumor suppressor gene (TSG), Zinc Finger DHHC-Type Containing 1 (ZDHHC1, also known as ZNF377), frequently silenced due to epigenetic modification among various cancers, which exerts significant anti-tumor effects through metabolic regulation. Methods: Quantitative reversed-transcription PCR (qRT-PCR), reverse transcription PCR (RT-PCR) and Western blot were employed to demonstrate transcriptional and protein levels of targeted regulators. Methylation of ZDHHC1 promoter was detected by bisulfite genomic sequencing (BGS) and methylation specific PCR (MSP). Proteomics were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) and gas chromatography-mass spectrometry (GC-MS) were utilized for metabolomics analysis. Cellular functions were examined via corresponding approaches. Nude mice were used for xenograft tumor models. Indirect immunofluorescence staining was utilized to obtain precise location and expression of target proteins. Oxidative and ER stress indicators were detected using specific kits. Results: We found that ZDHHC1 expression was frequently silenced in multiple tumor cells and specimens due to methylation. Restoration of ZDHHC1 expression can curb cancer cell progression via stimulating apoptosis and cell cycle arrest, repressing metastasis, and reversing EMT transition and cell stemness. ZDHHC1's salient anti-tumor abilities were recognized in vivo as well. Metabolomic and proteomic analyses predicted inhibitory role of ZDHHC1 in glucose metabolism pathways in a CYGB-dependent manner, and in pentose phosphate pathway (PPP), which was validated by examining altered key factors. Moreover, we unraveled that ZDHHC1 dedicates to the increment of oxidative stress and endoplasmic reticulum (ER) stress to promote pyroptosis for anticancer purposes. Conclusion: Our study for the first time indicates ZDHHC1 is a potential tumor-suppressor frequently silenced due to promoter methylation, capable of negatively regulating metabolisms of tumor cells while stimulating oxidative stress and ER stress to expedite cell death through induction of pyroptosis and apoptosis, which can be exploited for development of new cancer prevention and therapies. PMID: 32863941 [PubMed - in process]

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells. Theranostics. 2020;10(21):9458-9476 Authors: Du L, Liu X, Ren Y, Li J, Li P, Jiao Q, Meng P, Wang F, Wang Y, Wang YS, Wang C Abstract Rationale: It has been proposed that cancer stem/progenitor cells (or tumor-initiating cells, TICs) account for breast cancer initiation and progression. Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class-III histone deacetylases and mediate various basic biological processes, including metabolic homeostasis. However, interplay and cross-regulation among the sirtuin family are not fully understood. As one of the least studied sirtuin family members, the mitochondrial sirtuin SIRT4 is a tumor suppressor gene in various cancers. However, its role in cancer stemness, as well as initiation and progression of breast cancer, remains unknown. Methods: The expression of SIRT4 in breast cancer was analyzed using the TCGA breast cancer database and 3 GSEA data. Normal breast epithelial cells MCF10A and breast cancer cell lines MCF-7, MDA-MB-231, BT549, MDA-MB-468 were used to establish SIRT4 gene knockdown and corresponding overexpression cells. Identified MTT cytotoxicity assays, cell invasion and motility assay, sorting of SP, confocal immunofluorescence microscopy, mouse mammary stem cell analysis, glutamine and glucose production, clonogenic and sphere-formation assay, mass spectrometric metabolomics analysis and ChIP-seq to further explore SIRT4 biological role in breast cancer. Results: We elucidated a novel role for SIRT4 in the negative regulation of mammary gland development and stemness, which is related to the mammary tumorigenesis. We also uncovered an inverse correlation between SIRT4 and SIRT1. Most importantly, SIRT4 negatively regulates SIRT1 expression via repressing glutamine metabolism. Besides, we identified H4K16ac and BRCA1 as new prime targets of SIRT4 in breast cancer. Conclusions: These results demonstrate that SIRT4 exerts its tumor-suppressive activity via modulating SIRT1 expression in breast cancer and provide a novel cross-talk between mitochondrial and nuclear sirtuins. PMID: 32863939 [PubMed - in process]

Related Articles GC-MS based metabolomics uncovers the mechanism of Curcumae rhizoma and Sparganii rhizome on blood stasis syndrome in liver dialysis. Pak J Pharm Sci. 2020 Mar;33(2(Supplementary)):771-777 Authors: Lou G, Yan W, Yin F, Li L Abstract Blood stasis syndrome (BSS) is characterized by blood retardation and is the major cause of some deadly diseases. Some factors that affect BSS have been identified. However, the small molecule that related to BSS is still largely unknown. Traditional Chinese Medicine (TCM), such as Sanleng and Ezhu, has been used for a long time in treating BSS and promising outcomes have been achieved. However, the mechanism of how they work is unclear. Thus, we constructed the Rat BSS model and treated them with Sanleng and Ezhu. Then, the liver dialysis of those rats was collected and the small molecule metabolites were analyzed by GC-MS based metabolomics approach. Our results showed after Sanleng and Ezhu treatment, several small molecule metabolites were significantly changed metabolites (VIP>1 and P<0.05). Pathway enrichment analysis also showed that Sanleng and Ezhu share the similar mechanism in treating BSS, such as regulating Glyoxylate and dicarboxylate metabolism pathway and energy metabolism. Besides, we also identified some key metabolites that were significantly correlated with BSS. In conclusion, those findings uncover the mechanism of Sanleng and Ezhu in treating BSS. PMID: 32863251 [PubMed - in process]

Related Articles Effect of donor human milk on host-gut microbiota and metabolic interactions in preterm infants. Clin Nutr. 2020 Aug 19;: Authors: Piñeiro-Ramos JD, Parra-Llorca A, Ten-Doménech I, Gormaz M, Ramón-Beltrán A, Cernada M, Quintás G, Collado MC, Kuligowski J, Vento M Abstract BACKGROUND & AIMS: Human milk is the gold standard for infant nutrition. Preterm infants whose mothers are unable to provide sufficient own mother's milk (OMM), receive pasteurized donor human milk (DHM). We studied metabolic signatures of OMM and DHM and their effect on the interplay of the developing microbiota and infant's metabolism. METHODS: Metabolic fingerprinting of OMM and DHM as well as infant's urine was performed using liquid chromatography-mass spectrometry and the infant's stool microbiota was analyzed by 16S rRNA sequencing. RESULTS: Significant differences in the galactose and starch and sucrose metabolism pathways when comparing OMM and DHM, and alterations of the steroid hormone synthesis and pyrimidine metabolism pathways in urine were observed depending on the type of feeding. Differences in the gut-microbiota composition were also identified. CONCLUSION: The composition of DHM differs from OMM and feeding of DHM has a significant impact on the metabolic phenotype and microbiota of preterm infants. Our data help to understand the origin of the observed changes generating new hypothesis: i) steroid hormones present in HM have a significant influence in the activity of the steroid hormone biosynthesis pathway in preterm infants; ii) the pyrimidine metabolism is modulated in preterm infants by the activity of gut-microbiota. Short- and long-term implications of the observed changes for preterm infants need to be assessed in further studies. PMID: 32863061 [PubMed - as supplied by publisher]

Related Articles Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy: a cross-sectional study of ~ 400 women. BMC Med. 2020 Aug 31;18(1):247 Authors: Al Rashid K, Taylor A, Lumsden MA, Goulding N, Lawlor DA, Nelson SM Abstract BACKGROUND: Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown. METHODS: A cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression. RESULTS: Participants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: - 0.31(- 0.22, - 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner's infertility. CONCLUSIONS: In women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve. PMID: 32862829 [PubMed - in process]

Related Articles Plants endophytes: unveiling hidden agenda for bioprospecting toward sustainable agriculture. Crit Rev Biotechnol. 2020 Aug 30;:1-22 Authors: Dubey A, Malla MA, Kumar A, Dayanandan S, Khan ML Abstract Endophytic microbes are present in nearly all of the plant species known to date but how they enter and flourish inside a host plant and display multiple benefits like plant growth promotion (PGP), biodegradation, and stress alleviation are still unexplored. Until now, the majority of the research has been conducted assuming that the host-endophyte interaction is analogous to the PGP microbes, although, studies related to the mechanisms of their infection, colonization as well as conferring important traits to the plants are limited. It would be fascinating to explore the role of these endophytic microbes in host gene expression, metabolism, and the modulation of phenotypic traits, under abiotic and biotic stress conditions. In this review, we critically focused on the following areas: (i) endophytic lifestyle and the mechanism of their entry into plant tissues, (ii) how endophytes modulate the immune system of plants and affect the genotypic and phenotypic expression of host plants under abiotic and biotic stress condition, and (iii) the role of omics and other integrated genomic approaches in unraveling complex host-endophyte signaling crosstalk. Furthermore, we discussed their role in phytoremediation of heavy metal stress and whole genomic analysis based on an understanding of different metabolic pathways these endophytes utilize to combat stress. PMID: 32862700 [PubMed - as supplied by publisher]

Related Articles Specific Patterns of Spinal Metabolite Ratio Underlying α-Me-5-HT-evoked Pruritus Compared with Compound 48/80 Based on Proton Nuclear Magnetic Resonance Spectroscopy. Curr Med Sci. 2020 Aug;40(4):761-766 Authors: Chen YL, He ZG, Wang Q, Xiang HB, Fan L, Xiong J Abstract Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord. We investigated pruritus behavioral testing in three groups of young adult male C57Bl/6 mice, including one group treated with normal saline, while the other groups intradermally injected with α-Me-5-HT (histamine-independent pruritogen), compound 48/80 (histamine-dependent pruritogen) at the nape skin of the neck, respectively. Proton nuclear magnetic resonance spectroscopy (MRS) was used to compare spinal metabolites from the vertebral cervical among three groups, and to study the association of spinal metabolite ratio and pruritus intensity. The MRS-measured N-acetylaspartate-to-myoinositol ratio (NAA/Ins) was significantly correlated with the number of scratches between normal saline group and 48/80 group or α-Me-5-HT group (both P<0.0001), indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen. There was significant difference in Glu/Ins between normal saline group and 48/80 group (P=0.017), indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen, while GABA/Ins was highly significantly different between normal saline group and α-Me-5-HT group (P=0.008), suggesting that GABA/Ins may be a surrogate marker of histamine-independent pruritogen. MRS may reflect the extent of pruritus intensity elicited by α-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches, and above potential markers need to be further validated in pre-clinical and clinical treatment trials. PMID: 32862388 [PubMed - in process]

Related Articles Protective effect of metformin on BPA-induced liver toxicity in rats through upregulation of cystathionine β synthase and cystathionine γ lyase expression. Sci Total Environ. 2020 Aug 12;750:141685 Authors: Sun Y, Wang X, Zhou Y, Zhang J, Cui W, Wang E, Du J, Wei B, Xu X Abstract Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine β synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats. PMID: 32862004 [PubMed - as supplied by publisher]

Related Articles Arctigenin disrupts NLRP3 inflammasome assembly in colonic macrophages via downregulating fatty acid oxidation to prevent colitis-associated cancer. Cancer Lett. 2020 Aug 27;: Authors: Qiao S, Lv C, Tao Y, Miao Y, Zhu Y, Zhang W, Sun D, Yun X, Xia Y, Wei Z, Dai Y Abstract Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associated cancer (CAC) and explore its mechanisms. Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mice. Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation (FAO) metabolism in macrophages, as determined by untargeted metabolomics. Arctigenin also inhibited the expression of carnitine palmitoyltransferase 1 (CPT1), reduced the acetylation of α-tubulin, and disrupted NLRP3 complex formation, which in turn inactivated the NLRP3 inflammasome. Downregulation of the CPT1-FAO-acetyl-coenzyme A (acetyl-CoA)-acetylated α-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly, as confirmed by CPT1 overexpression. Lastly, arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice, and the effect was significantly diminished by the overexpression of adeno-associated virus (AAV)9-CPT1. Taken together, these results show that the inhibition of NLRP3 inflammasome assembly in macrophages due to FAO downregulation contributes to the preventative effect of arctigenin against CAC. Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis. PMID: 32861708 [PubMed - as supplied by publisher]

Related Articles What Is Responsible for Heterogeneity in Mantle Cell Lymphoma Biology and Outcomes? Hematol Oncol Clin North Am. 2020 Oct;34(5):825-835 Authors: Witzig TE Abstract Mantle cell lymphoma, despite its common derivation from a t(11;14) error that occurs in a naïve B-cell leading to overexpression of cyclin D1 protein, is characterized by substantial heterogeneity in biology and clinical outcome. Unlike other non-Hodgkin lymphoma types, it is more common in men. Clinical presentation patterns vary from nodal to splenomegaly with leukemia to gastrointestinal involvement. Biological variability is linked to tumor cell proliferation. Increased monocyte/macrophages and their associated proinflammatory cytokines are associated with inferior outcomes. These clues mandate that new treatments should target signal pathways that contribute to these adverse outcomes. PMID: 32861280 [PubMed - in process]

Related Articles Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy. iScience. 2020 Aug 13;23(9):101453 Authors: Sperry J, Condro MC, Guo L, Braas D, Vanderveer-Harris N, Kim KKO, Pope WB, Divakaruni AS, Lai A, Christofk H, Castro MG, Lowenstein PR, Le Belle JE, Kornblum HI Abstract Glioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM. PMID: 32861192 [PubMed - as supplied by publisher]