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Neurobiology of Disease Feb 2021Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD)... (Meta-Analysis)
Meta-Analysis
Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Brain; Energy Metabolism; Frontotemporal Dementia; Humans; Inflammation; Inflammation Mediators; Lewy Body Disease; Neurodegenerative Diseases; Proteostasis; Transcriptome
PubMed: 33347974
DOI: 10.1016/j.nbd.2020.105225 -
Evidence-based Complementary and... 2019At present, the prevention and treatment of cardiovascular disease in the world are facing severe challenges. Xinmailong injection, which is derived from the animal... (Review)
Review
BACKGROUND
At present, the prevention and treatment of cardiovascular disease in the world are facing severe challenges. Xinmailong injection, which is derived from the animal medicine , has certain advantages in the clinical treatment of cardiovascular disease. This study systematically evaluated the basic research reports of Xinmailong Injection on cardiovascular disease and made its pharmacological mechanisms more clear.
METHODS
Basic research reports on the intervention mechanisms of Xinmailong Injection on cardiovascular disease in PubMed, EMBASE, Cochrane Library (No. 2, 2019), CNKI, Wan Fang, and VIP databases were searched. The search time limit was from the establishment of the database to February 2019. The literature was screened according to inclusion and exclusion criteria, and then the data were extracted and a descriptive analysis of the pharmacological mechanisms of Xinmailong Injection on cardiovascular disease was performed.
RESULTS
Finally, twenty-two basic research reports were included. The intervention mechanisms of Xinmailong Injection on cardiovascular disease mainly includes the following: inhibiting oxidative stress and inflammatory reaction; regulating autophagy; promoting Ca influx by activating excitability of excitation-contraction coupling (ECC); inhibiting overexpressions of transforming growth factor-1 (TGF-1) and connective tissue growth factor (CTGF) to regulate the dynamic balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs); inhibiting the phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (AKT), and glycogen synthase kinase 3 (GSK3) proteins and overexpression of the downstream transcription factor GATA4 in the nucleus; regulating vascular endothelial factors and so on.
CONCLUSIONS
Xinmailong Injection can protect cardiomyocytes and maintain the normal function of the heart in various ways, thus effectively preventing the development of cardiovascular disease. Therefore, Xinmailong Injection has great potential for clinical application, and more basic researches need to be carried out to explore the medicinal value of Xinmailong Injection.
PubMed: 32454845
DOI: 10.1155/2019/8512405 -
Cancers May 2020Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available... (Review)
Review
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.
PubMed: 32375310
DOI: 10.3390/cancers12051153 -
BioMed Research International 2019Chemical structures derived from marine foods are highly diverse and pharmacologically promising. In particular, chitooligosaccharides (COS) present a safe...
Chemical structures derived from marine foods are highly diverse and pharmacologically promising. In particular, chitooligosaccharides (COS) present a safe pharmacokinetic profile and a great source of new bioactive polymers. This review describes the antioxidant, anti-inflammatory, and antidiabetic properties of COS from recent publications. Thus, COS constitute an effective agent against oxidative stress, cellular damage, and inflammatory pathogenesis. The mechanisms of action and targeted therapeutic pathways of COS are summarized and discussed. COS may act as antioxidants their radical scavenging activity and by decreasing oxidative stress markers. The mechanism of COS antidiabetic effect is characterized by an acceleration of pancreatic islets proliferation, an increase in insulin secretion and sensitivity, a reduction of postprandial glucose, and an improvement of glucose uptake. COS upregulate the GLUT2 and inhibit digestive enzyme and glucose transporters. Furthermore, they resulted in reduction of gluconeogenesis and promotion of glucose conversion. On the other hand, the COS decrease inflammatory mediators, suppress the activation of NF-B, increase the phosphorylation of kinase, and stimulate the proliferation of lymphocytes. Overall, this review brings evidence from experimental data about protective effect of COS.
Topics: Animals; Anti-Inflammatory Agents; Chitin; Chitosan; Free Radical Scavengers; Gluconeogenesis; Glucose; Glucose Transporter Type 2; Humans; Hypoglycemic Agents; Oligosaccharides
PubMed: 31781615
DOI: 10.1155/2019/4568039 -
Neuropsychopharmacology : Official... Jul 2018Converging evidence from molecular to neuroimaging studies suggests brain energy metabolism abnormalities in both schizophrenia and bipolar disorder. One emerging...
Converging evidence from molecular to neuroimaging studies suggests brain energy metabolism abnormalities in both schizophrenia and bipolar disorder. One emerging hypothesis is: decreased oxidative phosphorylation leading to accumulation of lactic acid from glycolysis and subsequent acidification of tissue. In this regard, integrating lactate and pH data from magnetic resonance spectroscopy (MRS) studies in both diseases may help us understand underlying neurobiological mechanisms. In order to achieve this goal, we performed a systematic search of case-control studies examining brain lactate or pH among schizophrenia and/or bipolar patients by using MRS. Medline/Pubmed and EBSCO databases were searched separately for both diseases and outcomes. Our search yielded 33 studies in total composed of 7 lactate and 26 pH studies. In bipolar disorder, 5 out of 6 studies have found elevated lactate levels especially in the cingulate cortex and 4 out of 13 studies reported reduced pH in the frontal lobe. In contrast, in schizophrenia a single study has examined lactate and reported elevation, while only 2 out of 13 studies examining pH have reported reduction in this measure. There were no consistent patterns for the relationship between lactate or pH levels and medication use, disease type, mood state, and other clinical variables. We highlight the need for future studies combining H-MRS and P-MRS approaches, using longitudinal designs to examine lactate and pH in disease progression across both schizophrenia and bipolar disorders.
Topics: Bipolar Disorder; Brain; Humans; Hydrogen-Ion Concentration; Lactic Acid; Schizophrenia
PubMed: 29581538
DOI: 10.1038/s41386-018-0041-9 -
Oncotarget Aug 2017Oxidative stress results from an imbalance of the reactive oxygen species/reactive nitrogen species (ROS/RNS) production and the oxidants defense system. Extensive... (Review)
Review
Oxidative stress results from an imbalance of the reactive oxygen species/reactive nitrogen species (ROS/RNS) production and the oxidants defense system. Extensive research during the last decades has revealed that oxidative stress can mediate cancer initiation and development by leading not only to molecular damage but also to a disruption of reduction-oxidation (redox) signaling. In order to provide a global overview of the redox signaling pathways, which play a role in cancer formation, we conducted a systematic literature search in PubMed and ISI Web of Science and identified 185 relevant reviews published in the last 10 years. The 20 most frequently described pathways were selected to be presented in this systematic review and could be categorized into 3 groups: Intracellular ROS/RNS generating organelles and enzymes, signal transduction cascades kinases/phosphatases and transcription factors. Intracellular ROS/RNS generation organelles are mitochondria, endoplasmic reticulum and peroxisomes. Enzymes, including NOX, COX, LOX and NOS, are the most prominent enzymes generating ROS/RNS. ROS/RNS act as redox messengers of transmembrane receptors and trigger the activation or inhibition of signal transduction kinases/phosphatases, such as the family members of protein tyrosine kinases and protein tyrosine phosphatases. Furthermore, these reactions activate downstream signaling pathways including protein kinase of the MAPK cascade, PI3K and PKC. The kinases and phosphatases regulate the phosphorylation status of transcription factors including APE1/Ref-1, HIF-1α, AP-1, Nrf2, NF-κB, p53, FOXO, STAT, and β-catenin. Finally, we briefly discuss cancer prevention and treatment opportunities, which address redox pathways and further research needs.
PubMed: 28881698
DOI: 10.18632/oncotarget.17128 -
World Journal of Gastroenterology Mar 2016To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression. (Review)
Review
AIM
To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
METHODS
A systematic review of the literature was performed using OvidSP and PubMed databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype.
RESULTS
Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated.
CONCLUSION
Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.
Topics: Animals; Carcinoma, Pancreatic Ductal; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucose; Humans; Pancreatic Neoplasms; Phenotype
PubMed: 27022229
DOI: 10.3748/wjg.v22.i12.3471