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Nutrients Apr 2024Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease... (Meta-Analysis)
Meta-Analysis
Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.
Topics: Animals; Humans; Antioxidants; Cytochrome P-450 CYP2E1; Cytokines; Disease Models, Animal; Fatty Liver, Alcoholic; Lipid Peroxidation; Liver; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
PubMed: 38674865
DOI: 10.3390/nu16081174 -
International Journal of Molecular... Apr 2024Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal... (Review)
Review
Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia's genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Topics: Female; Humans; Pregnancy; Biomarkers; Hormones; MicroRNAs; Placenta; Pre-Eclampsia; Trophoblasts
PubMed: 38674114
DOI: 10.3390/ijms25084532 -
Frontiers in Nutrition 2023There is some debate about the effects of omega-3 fatty acids on the regulation of adipose tissue related genes. This systematic review and meta-analysis aimed to...
Impact of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors-, and fibroblast growth factor-21 serum levels in patients with various presentation of metabolic conditions: a GRADE assessed systematic review and dose-response meta-analysis of...
UNLABELLED
There is some debate about the effects of omega-3 fatty acids on the regulation of adipose tissue related genes. This systematic review and meta-analysis aimed to evaluate the effects of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors ( and ) and serum fibroblast growth factor-21 (FGF-21) levels in adults with different presentation of metabolic conditions. To identify eligible studies, a systematic search was conducted in the Cochrane Library of clinical trials, Medline, Scopus, ISI Web of Science, and Google Scholar up to April 2022. Eligibility criteria included a clinical trial design, omega-3 fatty acids supplementation in adults, and reporting of at least one of the study outcomes. Effect sizes were synthesized using either fixed or random methods based on the level of heterogeneity. Fifteen studies met the inclusion criteria. Omega-3 fatty acids supplementation significantly increased the (10 studies) and (2 studies) gene expression compared to the control group (WMD: 0.24; 95% CI: 0.12, 0.35; < 0.001 and 0.09; 95% CI: 0.04, 0.13; p < 0.001, respectively). Serum FGF-21 (8 studies) levels exhibited no significant change following omega-3 fatty acids supplementation ( = 0.542). However, a dose-response relationship emerged between the dose of omega-3 fatty acids and both gene expression and serum FGF-21 levels. Overall, this study suggests that omega-3 fatty acids supplementation may have positive effects on the regulation of adipose tissue related genes in patients with various presentation of metabolic condition. Further research is needed to validate these findings and ascertain the effectiveness of this supplementation approach in this population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?, CRD42022338344.
PubMed: 38035345
DOI: 10.3389/fnut.2023.1202688 -
Phytotherapy Research : PTR Nov 2023Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid... (Review)
Review
Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.
Topics: Humans; Cardiovascular Diseases; Heart; Medicine, Chinese Traditional; PPAR alpha; Fatty Acids; Energy Metabolism
PubMed: 37533230
DOI: 10.1002/ptr.7965 -
Clinical Nutrition ESPEN Jun 2023The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have... (Review)
Review
BACKGROUND AND AIMS
The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults.
METHODS
The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish.
RESULTS
1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated.
CONCLUSION
The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.
Topics: Male; Adult; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Inflammation; Anti-Inflammatory Agents; Dietary Supplements
PubMed: 37202035
DOI: 10.1016/j.clnesp.2023.02.028 -
Adolescent Psychiatry (Hilversum,... 2023Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This...
BACKGROUND
Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This systematic review evaluated preclinical and clinical research on the effects of CBD on depressive and anxiety disorders in adolescence and young adulthood. To provide context, we discuss CBD's mechanism of action and neurodevelopmental effects.
METHODS
PubMed was searched for articles published through June 2022. Preclinical or clinical CBD administration studies with > 1 that examined depressive and/or anxiety disorders were eligible.
RESULTS
Initially, 224 publications were identified. After excluding duplicates and applying eligibility criteria, 6 preclinical (depression: ≈133; anxiety: ≈161) and 4 clinical (anxiety: =113) articles remained. Due to the low number of studies, results were synthesized qualitatively. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence were used to rate each study's evidence. The preclinical effects of CBD on depression-like behavior appear to differ by sex, early life stress, and duration of use. Despite no evidence that CBD exerts anxiolytic effects in preclinical adolescent models, CBD may reduce anxiety symptoms in human adolescents and young adults with anxiety disorders.
CONCLUSIONS
The existing evidence suggests that CBD may reduce symptoms of anxiety in adolescents and young adults. However, the evidence is sparse and limited by variations in samples and CBD dosing duration. Further research is needed to understand the potential benefits and/or harms of CBD for depression and anxiety disorders in this population. Implications for clinical practice and research are discussed.
PubMed: 38919887
DOI: 10.2174/0122106766233339230919143924 -
Frontiers in Psychiatry 2022Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and...
Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate βamyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.
PubMed: 36387000
DOI: 10.3389/fpsyt.2022.1038122 -
Nutrients Nov 2022The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an... (Meta-Analysis)
Meta-Analysis Review
The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an overview of the results from randomized controlled trials is lacking. This study aimed to conduct a meta-analysis to evaluate the effect of omega-3 fatty acid intake on MS (based on the criteria of the Expanded Disability Status Scale (EDSS)) and inflammatory gene expression (IGE). A search was conducted of PubMed, EMBASE, and Web of Science for cohort studies published from the inception of the database up to May 2022 that assessed the associations of omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) with EDSS and inflammatory gene expression (peroxisome proliferator-activated receptor gamma (PPAR-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)) outcomes. For the highest vs. lowest comparison, the relative risk (RR) estimates with a 95% confidence interval (CI) were pooled using the random-effect model. In total, 13 cohort studies with 1353 participants were included in the meta-analysis during periods of 3 to 144 weeks. A significant inverse relationship was found between DHA and EDSS scores (RR: 1.05; 95% CI: 0.62, 1.48; p < 0.00001). Our results also showed that omega-3 FAs significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38; p < 0.03) and downregulated the expression of TNF-α (RR: −0.15; 95% CI: −0.99, 0.70; p < 0.00001) and IL-1 (RR: −0.60; 95% CI: −1.02, −0.18; p < 0.003). There was no clear evidence of publication bias with Egger’s tests for inflammatory gene expression (p = 0.266). Moreover, n-3 PUFAs and EPA were not significantly associated with EDSS scores (p > 0.05). In this meta-analysis of cohort studies, blood omega-3 FA concentrations were inversely related to inflammatory gene expression (IGE) and EDSS score, which indicates that they may hold great potential markers for the diagnosis, prognosis, and management of MS. However, further clinical trials are required to confirm the potential effects of the omega-3 FAs on MS disease management.
Topics: Humans; Multiple Sclerosis; Tumor Necrosis Factor-alpha; Peroxisome Proliferator-Activated Receptors; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Docosahexaenoic Acids; Interleukin-1; Gene Expression; Immunoglobulin E
PubMed: 36364885
DOI: 10.3390/nu14214627 -
Clinical & Translational Oncology :... Mar 2023Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism... (Review)
Review
Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism and has been implicated in cancer development. It has been shown that some cell types other than adipocytes can express leptin and leptin receptors in tumor microenvironments. It has been shown that peroxisome proliferator-activated receptors (PPAR) agonists can affect leptin levels and vice versa leptin can affect PPARs. Activation of PPARs affects the expression of several genes involved in aspects of lipid metabolism. In addition, PPARs regulate cancer cell progression through their action on the tumor cell proliferation, metabolism, and cellular environment. Some studies have shown an association between obesity and several types of cancer, including breast cancer. There is some evidence that suggests that there is crosstalk between PPARs and leptin during the development of breast cancer. Through a systematic review of previous studies, we have reviewed the published relevant articles regarding leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.
Topics: Humans; Female; Peroxisome Proliferator-Activated Receptors; Leptin; PPAR alpha; Breast Neoplasms; Obesity; Signal Transduction; Tumor Microenvironment
PubMed: 36348225
DOI: 10.1007/s12094-022-02988-4 -
Phytotherapy Research : PTR Mar 2022The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases,... (Meta-Analysis)
Meta-Analysis Review
The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases, diet-induced cardiac injury, antihypertensive and anti-platelet activities through various mechanisms. However, there is no meta-analysis performed on the cardioprotective activity of naringin. This systematic review and meta-analysis were focused to summarize and conclude the therapeutic benefits of naringin in various cardiovascular disorders using pre-clinical evidence. The online search was performed using electronic databases such as PubMed/Medline, Scopus, ScienceDirect, and Google scholar. The search was mainly focused on the role of naringin in various cardiovascular disorders in experimental animals. Based on the inclusion and exclusion criteria 34 studies were selected. The meta-analysis revealed that naringin could significantly alleviate various physical and chemical stimuli induced cardiovascular disorders such as diabetic cardiomyopathy, ischemic heart diseases, oxidative stress-induced cardiac injury, diet-induced cardiovascular dysfunctions in experimental models involving multiple mechanisms such as antioxidant (ROS/RNS pathways), anti-inflammatory (COX-2, IL-6, TNF-α, NF-κB pathways), enhancing angiogenic factors (VEGF, VCAM, HIF-1α, iNO), suppressing the apoptotic factors (BCL-2, BAX, caspases) and modulation of PCSK-9, PKCα/β, PPAR-α, JAK/STAT, MAPKs (p38α, ERK1/2, JNK), and PI3K/AKT/mTOR/p70S6K associated pathways. Further, these changes at the cellular and molecular levels were manifested as improvement in the structural, functional, and physiology of the heart upon the naringin treatment. In conclusion, this systematic review and meta-analysis support the available scientific evidence on the therapeutic benefits of naringin in the management of various cardiovascular conditions.
Topics: Animals; Flavanones; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases
PubMed: 35084066
DOI: 10.1002/ptr.7368