-
Food Research International (Ottawa,... Mar 2023Globally, inflammation and metabolic disorders pose serious public health problems and are major health concerns. It has been shown that natural polyphenols are... (Review)
Review
Globally, inflammation and metabolic disorders pose serious public health problems and are major health concerns. It has been shown that natural polyphenols are effective in the treatment of metabolic diseases, including anti-inflammation, anti-diabetes, anti-obesity, neuron-protection, and cardio-protection. NLRP3 inflammasome, which are multiprotein complexes located within the cytosol, play an important role in the innate immune system. However, aberrant activation of the NLRP3 inflammasome were discovered as essential molecular mechanisms in triggering inflammatory processes as well as implicating it in several major metabolic diseases, such as type 2 diabetes mellitus, obesity, atherosclerosis or cardiovascular disease. Recent studies indicate that natural polyphenols can inhibit NLRP3 inflammasome activation. In this review, the progress of natural polyphenols preventing inflammation and metabolic disorders via targeting NLRP3 inflammasome is systemically summarized. From the viewpoint of interfering NLRP3 inflammasome activation, the health effects of natural polyphenols are explained. Recent advances in other beneficial effects, clinical trials, and nano-delivery systems for targeting NLRP3 inflammasome are also reviewed. NLRP3 inflammasome is targeted by natural polyphenols to exert multiple health effects, which broadens the understanding of polyphenol mechanisms and provides valuable guidance to new researchers in this field.
Topics: Humans; Inflammasomes; Diabetes Mellitus, Type 2; NLR Family, Pyrin Domain-Containing 3 Protein; Atherosclerosis; Inflammation; Obesity; Polyphenols
PubMed: 36869555
DOI: 10.1016/j.foodres.2023.112567 -
Neurochemical Research Jul 2022Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (CHOS) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid,... (Review)
Review
Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (CHOS) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid, DHLA) form of LA. α-LA is a potent anti-oxidative agent that has a significant potential to treat neurodegenerative disorders. α-LA is both hydrophilic and hydrophobic in nature. It is widely distributed in plants and animals in cellular membranes and in the cytosol, which is responsible for LA's action in both the cytosol and plasma membrane. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the α-Lipoic acid for central nervous system diseases. Moreover, α-LA readily crosses the blood-brain barrier, which is a significant factor for CNS activities. The mechanisms of α-LA reduction are highly tissue-specific. α-LA produces its neuroprotective effect by inhibiting reactive oxygen species formation and neuronal damage, modulating protein levels, and promoting neurotransmitters and anti-oxidant levels. Hence, the execution of α-LA as a therapeutic ingredient in the therapy of neurodegenerative disorders is promising. Finally, based on evidence, it can be concluded that α-LA can prevent diseases related to the nervous system.
Topics: Animals; Antioxidants; Neurodegenerative Diseases; Neuroprotective Agents; Oxidation-Reduction; Thioctic Acid
PubMed: 35445914
DOI: 10.1007/s11064-022-03598-w -
Frontiers in Oncology 2022Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully...
Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs' target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.
PubMed: 35330714
DOI: 10.3389/fonc.2022.848199 -
Medicine Aug 2021Obesity strongly affects the prognosis of various malignancies, including breast cancer. Leptin (LEP) may be associated with obesity and breast cancer prognosis. The... (Meta-Analysis)
Meta-Analysis
PURPOSE
Obesity strongly affects the prognosis of various malignancies, including breast cancer. Leptin (LEP) may be associated with obesity and breast cancer prognosis. The purpose of our study was to determine the prognostic value of LEP in breast cancer.
METHOD
We conducted a multi-omic analysis to determine the prognostic role of LEP. Different public bioinformatics platforms (Oncomine, Gene Expression Profiling Interactive Analysis, University of California Santa Cruz Xena, bc-GenExMiner, PrognoScan database, R2-Kaplan-Meier Scanner, UALCAN, Search Tool for the Retrieval of Interacting Genes/Proteins database , and The Database for Annotation, Visualization and Integrated Discovery) were used to evaluate the roles of LEP. Clinicopathological variables were evaluated.
RESULTS
LEP was downregulated in breast cancer tissues compared to levels in normal tissues. By co-expressed gene analysis, a positive correlation between LEP and SLC19A3 was observed. Based on the clinicopathological analysis, low LEP expression was associated with older age, higher stage, lymph node status, human epidermal growth factor receptor 2 (HER2) status, estrogen receptor (ER+) positivity, and progesterone receptor (PR+) positivity. Kaplan-Meier survival analysis showed that low LEP expression indicated a poorer prognosis. LEP is hypermethylated in breast cancer tissues in PrognoScan and R2-Kaplan Meier Scanner, and low LEP expression was correlated with poor prognosis. LEP protein-protein interactions were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins database. Gene ontology analysis results showed that cellular component is mainly associated with the endosome lumen, cytosol, and secretory granules and is upregulated. For the biological process energy reserve, metabolic processes exhibited the greatest regulation compared to the others. In molecular function, it was mainly enriched in a variety of combinations, but hormone activity showed the highest regulation.
CONCLUSION
Our study provides evidence for the prognostic role of LEP in breast cancer and as a novel potential therapeutic target in such malignancies. Nevertheless, further validation is required.
Topics: Female; Humans; Middle Aged; Biomarkers, Tumor; Breast Neoplasms; Correlation of Data; Gene Expression Regulation, Neoplastic; Leptin; Prognosis; Survival Rate
PubMed: 34414945
DOI: 10.1097/MD.0000000000026896 -
International Journal of Cardiology.... Feb 2020Sigma-1 receptors are ligand-regulated chaperone proteins, involved in several cellular mechanisms. The aim of this systematic review was to examine the effects that the... (Review)
Review
Sigma-1 receptors are ligand-regulated chaperone proteins, involved in several cellular mechanisms. The aim of this systematic review was to examine the effects that the sigma-1 receptor has on the cardiovascular system. The interaction targets and proposed mechanisms of action of sigma-1 receptors were explored, with the aim of determining if the sigma-1 receptor is a potential pharmacological target for cardiac pathologies. This systematic review was conducted according to the PRISMA guidelines and these were used to critically appraise eligible studies. Pubmed and Scopus were systematically searched for articles investigating sigma-1 receptors in the cardiovascular system. Papers identified by the search terms were then subject to analysis against pre-determined inclusion criteria. 23 manuscripts met the inclusion criteria and were included in this review. The experimental platforms, experimental techniques utilised and the results of the studies were summarised. The sigma-1 receptor is found to be implicated in cardioprotection, via various mechanisms including stimulating the Akt-eNOS pathway, and reduction of Ca2 + leakage into the cytosol via modulating certain calcium channels. Sigma-1 receptors are also found to modulate other cardiac ion channels including different subtypes of potassium and sodium channels and have been shown to modulate intracardiac neuron excitability. The sigma-1 receptor is a potential therapeutic target for treatment of cardiac pathologies, particularly cardiac hypertrophy. We therefore suggest investigating the cardioprotective mechanisms of sigma-1 receptor function, alongside proposed potential ligands that can stimulate these functions.
PubMed: 31909177
DOI: 10.1016/j.ijcha.2019.100449