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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 -
Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases.Expert Opinion on Drug Metabolism &... Apr 2019Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen...
Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules. The substrates of SULT1E1 include the endogenous and synthetic estrogens. Upon SULT1E1-mediated sulfation, the hydrosolubility of estrogens increases, preventing the binding between the sulfated estrogens and the estrogen receptor (ER). This sulfated state of the estrogens is not irreversible, as the steroid sulfatase (STS) can convert sulfoconjugated estrogens to free estrogens. The expression of SULT1E1 is inducible by several diseases that involve tissue inflammation, such as type 2 diabetes, sepsis, and ischemia-reperfusion injury. Areas covered: This systematic literature review aims to summarize the role of SULT1E1 in the metabolism of estrogenic drugs and xenobiotics, and the role of SULT1E1 in the pathogenesis of several diseases, including cancer, metabolic disease, sepsis, liver injury, and cystic fibrosis. Meanwhile, ablation or pharmacological inhibition of SULT1E1 can affect the outcomes of the aforementioned diseases. Expert opinion: In addition to its role in metabolizing estrogenic drugs, SULT1E1 is unexpectedly being unveiled as a mediator for the disease effect on estrogen metabolism and homeostasis. Meanwhile, because the expression and activity of SULT1E1 can affect the outcome of diseases, the same sulfotransferase and the reversing enzymes STS can be potential therapeutic targets to prevent or manage diseases. Accumulating evidence suggest that the physiological and pathophysiological effects of SULT1E1 can be estrogen-independent and it is necessary to elucidate what other possible substrates may be recognized by the enzyme. Moreover, human studies are paramount to confirm the human relevance of the animal studies.
Topics: Animals; Cytosol; Estrogens; Gene Expression Regulation, Enzymologic; Humans; Liver; Sulfotransferases; Xenobiotics
PubMed: 30822161
DOI: 10.1080/17425255.2019.1588884 -
Journal of Pediatric Gastroenterology... Feb 2018Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known...
Paediatric autoimmune liver disease is characterized by inflammatory liver histology, circulating autoantibodies, and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis, and de novo AIH after liver transplantation. Two types of pediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (AIH-2).Pertinent issues addressing the diagnosis, treatment, and long-term follow-up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate, and Mendeley databases during the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.
Topics: Advisory Committees; Autoantibodies; Child; Female; Gastroenterology; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver; Liver Transplantation; Male; Practice Guidelines as Topic
PubMed: 29356770
DOI: 10.1097/MPG.0000000000001801 -
Briefings in Bioinformatics May 2019In the course of infecting their hosts, pathogenic bacteria secrete numerous effectors, namely, bacterial proteins that pervert host cell biology. Many Gram-negative...
In the course of infecting their hosts, pathogenic bacteria secrete numerous effectors, namely, bacterial proteins that pervert host cell biology. Many Gram-negative bacteria, including context-dependent human pathogens, use a type IV secretion system (T4SS) to translocate effectors directly into the cytosol of host cells. Various type IV secreted effectors (T4SEs) have been experimentally validated to play crucial roles in virulence by manipulating host cell gene expression and other processes. Consequently, the identification of novel effector proteins is an important step in increasing our understanding of host-pathogen interactions and bacterial pathogenesis. Here, we train and compare six machine learning models, namely, Naïve Bayes (NB), K-nearest neighbor (KNN), logistic regression (LR), random forest (RF), support vector machines (SVMs) and multilayer perceptron (MLP), for the identification of T4SEs using 10 types of selected features and 5-fold cross-validation. Our study shows that: (1) including different but complementary features generally enhance the predictive performance of T4SEs; (2) ensemble models, obtained by integrating individual single-feature models, exhibit a significantly improved predictive performance and (3) the 'majority voting strategy' led to a more stable and accurate classification performance when applied to predicting an ensemble learning model with distinct single features. We further developed a new method to effectively predict T4SEs, Bastion4 (Bacterial secretion effector predictor for T4SS), and we show our ensemble classifier clearly outperforms two recent prediction tools. In summary, we developed a state-of-the-art T4SE predictor by conducting a comprehensive performance evaluation of different machine learning algorithms along with a detailed analysis of single- and multi-feature selections.
Topics: Algorithms; Bacterial Proteins; Bacterial Secretion Systems; Bayes Theorem; Machine Learning; Support Vector Machine
PubMed: 29186295
DOI: 10.1093/bib/bbx164 -
Actas Dermo-sifiliograficas Mar 2017Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the... (Review)
Review
Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the administration of anticancer drugs followed by locally applied electrical impulses to achieve an effect known as electroporation, which facilitates entry into the cytosol of drugs that cannot cross the cell membrane. The aim of this review is to evaluate the evidence that supports the use of electrochemotherapy as a therapeutic strategy in melanoma. We conducted a qualitative systematic review of the literature using advanced searches of bibliographic databases and full text reviews. Seven studies (3 systematic reviews and 4 cases series) were selected. The quality of the evidence was not good, but the coincidence of results for certain variables supports their consistency. Results of the meta-analyses favored electrochemotherapy over chemotherapy. Electrochemotherapy appears to be an effective procedure for the local treatment of malignant tumor nodules (evidence of intermediate or low quality). This inexpensive method is simple to apply, well tolerated, and achieves objective responses under certain circumstances. There is no evidence that electrochemotherapy alters the natural course of the disease and it should therefore be considered a palliative treatment. With an evidence level of 1- (minus), electrochemotherapy can be recommended for the palliative treatment of unresectable, locoregionally advanced melanoma (grade B recommendation).
Topics: Antineoplastic Agents; Clinical Trials as Topic; Electrochemotherapy; Evidence-Based Medicine; Humans; Melanoma; Meta-Analysis as Topic; Palliative Care; Skin Neoplasms; Treatment Outcome; Melanoma, Cutaneous Malignant
PubMed: 27769538
DOI: 10.1016/j.ad.2016.08.008 -
Inflammation Research : Official... Feb 2016Calprotectin is calcium-binding protein which can be found in the cytosol of neutrophils. Several studies have studied its levels in preeclamptic women; however, to date... (Review)
Review
BACKGROUND
Calprotectin is calcium-binding protein which can be found in the cytosol of neutrophils. Several studies have studied its levels in preeclamptic women; however, to date there is no consensus regarding its effectiveness in the field.
PURPOSE
To investigate whether serum calprotectin levels are elevated among preeclamptic women compared to healthy controls.
MATERIALS AND METHODS
We used Medline (1966-2015), Scopus (2004-2015), ClinicalTrials.gov (2008-2015), Cochrane Central Register of Controlled Trials CENTRAL (1999-2015) and Google Scholar (2004-2015) search engines in our primary search, together with reference lists from included studies.
RESULTS
Seven studies were finally included in our systematic review which recruited 439 women (245 with preeclampsia and 194 healthy controls). Their methodological quality was relatively high as they reached a score that ranged between 6 and 7 according to the Ottawa-Newcastle classification. All included studies reported that the serum calprotectin levels were significantly elevated among preeclamptic patients (p < 0.05). One study suggested that patients with severe preeclampsia have significantly higher levels of calprotectin than patients with mild preeclampsia (p = 0.01). However, to date there is no evidence regarding specific cut-off values which would help screen women for preeclampsia, or even follow the course of the disease.
CONCLUSION
Current evidence suggests that serum calprotectin is significantly raised among women with preeclampsia during the third trimester. Future research is needed to reach firm conclusions regarding its use as a potential screening and surveillance marker during the pregnancy course of women at risk of developing preeclampsia.
Topics: Biomarkers; Female; Humans; Leukocyte L1 Antigen Complex; Observational Studies as Topic; Pre-Eclampsia; Pregnancy
PubMed: 26603731
DOI: 10.1007/s00011-015-0903-0