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Cureus Apr 2024Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted treatments, this disease remains a major puzzle in the public health systems worldwide. The initial part of this article provides an overview and illustration of the primary mechanisms responsible for neuronal damage in AD. Subsequently, it offers a critical evaluation of the most noteworthy studies on pharmacological therapy for AD and outlines recent advancements and novel approaches to managing this condition. Main properties, categorization, Food and Drug Administration (FDA) status, mechanisms of action, benefits, and common side effects of the classical and the most recently proposed pharmacological treatments for AD are described. The conventional pharmacological agents revised comprise cholinesterase inhibitors, monoclonal antibodies, and other therapies, such as memantine, valproic acid, and rosiglitazone. The innovative reviewed pharmacological agents comprise the monoclonal antibodies: donanemab, gantenerumab, solanezumab, bapineuzumab, crenezumab, and semorinemab. Nutritional supplements such as alpha-tocopherol (vitamin E) and caprylidene are also revised. Tau and amyloid-targeting treatments include methylthioninium moiety (MT), leuco-methylthioninium bis (LMTM), an oxidized form of MT, and tramiprosate, which inhibits the beta-amyloid (Aβ) monomer aggregation into toxic oligomers. Antidiabetic and anti-neuroinflammation drugs recently proposed for AD treatment are discussed. The antidiabetic drugs include NE3107, an anti-inflammatory and insulin sensitizer, and the diabetes mainstream drug metformin. The anti-neuroinflammatory AD therapies include the use of sodium oligomannate (GV-971), infusions with intravenous immunoglobulin aiming to decrease plasma levels of the constituents of Aβ plaques, and masitinib, a tyrosine kinase inhibitor that impacts mast and microglia cells. Additional anti-inflammatory agents being currently tested in phase-2 clinical trials, such as atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), and benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, drugs targeting Alzheimer's-associated symptoms, such as brexpiprazole (serotonin dopamine activity modulator) and suvorexant (orexin receptor antagonist), respectively, used for agitation and insomnia in AD patients, are reviewed. As experimental investigations and clinical research progress, there is a possibility that a combination of newly tested medications and traditional ones may emerge as a promising treatment option for AD in the future.
PubMed: 38756263
DOI: 10.7759/cureus.58416 -
International Journal of Chronic... 2023Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum...
PURPOSE
Vitamins and carotenoids are essential in preventing and treating chronic obstructive pulmonary disease (COPD). This study investigated the associations between serum vitamins, carotenoids, and COPD in adults aged ≥ 40 years in the United States.
METHODS
We selected 3487 participants aged ≥40 from the NHANES (2017-2018) and used demographic analysis, sensitivity tests, and different weighted multivariate regression models to investigate the relationship between serum vitamins, carotenoids, and COPD.
RESULTS
Subjects in the highest tertile of serum vitamin C, vitamin E (α-tocopherol), α-carotene, trans-β-carotene, and cis-β-carotene had a 50%, 35%, 51%, 54%, and 51% lower risk of COPD than those in the lowest tertile (P for trend: P=0.0005, <0.0001, 0.0054, 0.0066, and 0.0049). Unfortunately, no significant correlation was found for serum vitamin D levels.
CONCLUSION
Our analysis of nationally representative data from 3487 participants showed that serum levels of vitamin C, vitamin E (α-tocopherol), α-carotene, and β-carotene were negatively associated with the incidence of COPD in adults over 40 years of age in the US The findings highlighted the importance of antioxidant vitamins and carotenoids in respiratory health, while the data showed no significant correlation between vitamin D (25-OHD) and the incidence of COPD.
Topics: Adult; Humans; United States; Middle Aged; beta Carotene; alpha-Tocopherol; Pulmonary Disease, Chronic Obstructive; Nutrition Surveys; Carotenoids; Antioxidants; Vitamins; Vitamin E; Vitamin A; Ascorbic Acid; Vitamin D
PubMed: 38107596
DOI: 10.2147/COPD.S432995 -
JAMA Network Open Aug 2023Research suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date...
IMPORTANCE
Research suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date have evaluated whether the mitochondrial DNA fraction with breaks (mtDNAfb) is associated with risk of NHL.
OBJECTIVE
To evaluate the association of mtDNAfb with NHL risk.
DESIGN, SETTING, AND PARTICIPANTS
This nested case-control study, which used prospectively collected samples as part of baseline enrollment (from 1985 through 1988) of 29 133 men who smoked for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study conducted in southwest Finland, included 107 incident NHL cases and 107 controls (matched on date of birth ±5 years). Analyses were conducted from January to September 2022.
EXPOSURE
High-throughput real-time polymerase chain reaction assays quantifying mtDNAfb.
MAIN OUTCOMES AND MEASURES
Incident NHL cases were identified in the ATBC Study through April 30, 2002, using the Finnish Cancer Registry and the Register of Causes of Death. The mtDNAfb was quantified and categorized based on the median, tertile, and quartile distributions among controls. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression models to assess the associations between categorized mtDNAfb and future risk of NHL, controlling for age, body mass index, number of cigarettes smoked per day, number of pack-years, and mtDNAcn.
RESULTS
A total of 29 133 men (median [IQR] age, 57.2 [52.6-62.5] years) participated in ATBC Study. Higher mtDNAfb was associated with an increased risk of NHL (median OR, 2.89; 95% CI, 1.40-5.93) in a dose-dependent manner (quartile 2 vs 1 OR, 1.24; 95% CI, 0.43-3.40; quartile 3 vs 1 OR, 3.58; 95% CI, 1.39-9.24; quartile 4 vs 1 OR, 3.42; 95% CI, 1.30- 8.99; P = .004 for trend).
CONCLUSIONS AND RELEVANCE
This study's findings suggest that increased mtDNAfb is associated with an increased future risk of NHL. Additional studies are needed to confirm these findings, particularly among women and nonsmokers.
Topics: Male; Humans; Female; Middle Aged; DNA, Mitochondrial; Risk Factors; Case-Control Studies; DNA Fragmentation; Lymphoma, Non-Hodgkin
PubMed: 37531109
DOI: 10.1001/jamanetworkopen.2023.26885 -
Frontiers in Nutrition 2023Although well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective...
BACKGROUND
Although well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk.
METHODS
Single-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, β-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed.
RESULTS
Genetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24-0.68, FDR-corrected = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75-0.86, FDR-corrected = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68-0.84, FDR-corrected = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76-0.89, FDR-corrected = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI.
CONCLUSION
Evidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk.
PubMed: 38178976
DOI: 10.3389/fnut.2023.1233086 -
Advanced Science (Weinheim,... Oct 2023Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane...
Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100 mg mL . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α-tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm within 24 h), while no detectable drug permeates when CTX is dissolved in α-tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α-tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL ), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α-tocopherol solvent warrants further study as a treatment for skin malignancies.
Topics: Mice; Animals; Humans; alpha-Tocopherol; Dimethyl Sulfoxide; Mice, Nude; Taxoids; Skin Neoplasms
PubMed: 37555802
DOI: 10.1002/advs.202302658 -
Foods (Basel, Switzerland) Oct 2023Mediterranean diets (MedDiets) are linked to substantial health benefits. However, there is also growing evidence that the intensification of food production over the... (Review)
Review
INTRODUCTION
Mediterranean diets (MedDiets) are linked to substantial health benefits. However, there is also growing evidence that the intensification of food production over the last 60 years has resulted in nutritionally relevant changes in the composition of foods that may augment the health benefits of MedDiets.
OBJECTIVE
To synthesize, summarize, and critically evaluate the currently available evidence for changes in food composition resulting from agricultural intensification practices and their potential impact on the health benefits of MedDiets.
METHODS
We summarized/synthesized information from (i) systematic literature reviews/meta-analyses and more recently published articles on composition differences between conventional and organic foods, (ii) desk studies which compared food composition data from before and after agricultural intensification, (iii) recent retail and farm surveys and/or factorial field experiments that identified specific agronomic practices responsible for nutritionally relevant changes in food composition, and (iv) a recent systematic literature review and a small number of subsequently published observational and dietary intervention studies that investigated the potential health impacts of changes in food composition resulting from agricultural intensification.
RESULTS AND DISCUSSION
There has been growing evidence that the intensification of food production has resulted in (i) lower concentrations of nutritionally desirable compounds (e.g., phenolics, certain vitamins, mineral micronutrients including Se, Zn, and omega-3 fatty acids, α-tocopherol) and/or (ii) higher concentrations of nutritionally undesirable or toxic compounds (pesticide residues, cadmium, omega-6 fatty acids) in many of the foods (including wholegrain cereals, fruit and vegetables, olive oil, dairy products and meat from small ruminants, and fish) that are thought to contribute to the health benefits associated with MedDiets. The evidence for negative health impacts of consuming foods from intensified conventional production systems has also increased but is still limited and based primarily on evidence from observational studies. Limitations and gaps in the current evidence base are discussed. There is now substantial evidence that the intensification of agricultural food production has resulted in a decline in the nutritional quality of many of the foods that are recognized to contribute to the positive health impacts associated with adhering to traditional MedDiets. Further research is needed to quantify to what extent this decline augments the positive health impacts of adhering to a traditional MedDiet.
PubMed: 37893672
DOI: 10.3390/foods12203779 -
European Journal of Epidemiology Jul 2023Pancreatic ductal carcinoma (PDAC) is highly fatal with limited understanding of mechanisms underlying its carcinogenesis. We comprehensively investigated whether...
Pancreatic ductal carcinoma (PDAC) is highly fatal with limited understanding of mechanisms underlying its carcinogenesis. We comprehensively investigated whether lipidomic measures were associated with PDAC in two prospective studies. We measured 904 lipid species and 252 fatty acids across 15 lipid classes in pre-diagnostic serum (up to 24 years) in a PDAC nested-case control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, NCT00002540) with 332 matched case-control sets including 272 having serial blood samples and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC, NCT00342992) with 374 matched case-control sets. Controls were matched to cases by cohort, age, sex, race, and date at blood draw. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) per one-standard deviation increase in log-lipid concentrations within each cohort, and combined ORs using fixed-effects meta-analyses. Forty-three lipid species were associated with PDAC (false discovery rate, FDR ≤ 0.10), including lysophosphatidylcholines (LPC, n = 2), phosphatidylethanolamines (PE, n = 17), triacylglycerols (n = 13), phosphatidylcholines (PC, n = 3), diacylglycerols (n = 4), monoacylglycerols (MAG, n = 2), cholesteryl esters (CE, n = 1), and sphingomyelins (n = 1). LPC(18:2) and PE(O-16:0/18:2) showed significant inverse associations with PDAC at the Bonferroni threshold (P value < 5.5 × 10). The fatty acids LPC[18:2], LPC[16:0], PC[15:0], MAG[18:1] and CE[22:0] were significantly associated with PDAC (FDR < 0.10). Similar associations were observed in both cohorts. There was no significant association for the differences between PLCO serial lipidomic measures or heterogeneity by follow-up time overall. Results support that the pre-diagnostic serum lipidome, including 43 lipid species from 8 lipid classes and 5 fatty acids, is associated with PDAC.
Topics: Male; Humans; Prospective Studies; Lipidomics; Risk Factors; Case-Control Studies; Pancreatic Neoplasms; Fatty Acids
PubMed: 37169992
DOI: 10.1007/s10654-023-01014-3 -
Cureus Nov 2023This article conducts a thorough investigation into the potential role of vitamin E in preventing cardiovascular diseases (CVDs) in the context of shifting mortality... (Review)
Review
This article conducts a thorough investigation into the potential role of vitamin E in preventing cardiovascular diseases (CVDs) in the context of shifting mortality patterns from infectious diseases to the continued prominence of CVDs in modern medicine. The primary focus is on vitamin E's antioxidant properties and its specific ability to counter lipid peroxidation, a pivotal process in the early stages of atherosclerosis, a precursor to CVDs. The research spans a wide range of methodologies, including in vitro, in vivo, clinical, and experimental studies, examining how vitamin E affects critical aspects of cardiovascular health, such as signaling pathways, gene expression, inflammation, and cholesterol metabolism. It also explores vitamin E's influence on complex processes like smooth muscle cell development, oxidative stress reduction, foam cell formation, and the stability of atherosclerotic plaques. In the context of clinical studies, the article presents findings that both support and yield inconclusive results regarding the impact of vitamin E supplementation on CVDs. It acknowledges the intricate interplay of factors such as patient selection, pathophysiological conditions, and genetic variations, all of which can significantly influence the efficacy of vitamin E. The article underscores the need for ongoing research, with a specific focus on understanding the regulatory metabolites of vitamin E and their roles in modulating cellular processes relevant to CVDs. It highlights the potential for innovative therapeutic approaches based on a deeper comprehension of vitamin E's multifaceted effects. However, it also candidly addresses the challenges of translating clinical trial findings into practical applications and emphasizes the importance of considering diverse variables to optimize therapeutic outcomes. In summary, this meticulously conducted study provides a comprehensive examination of vitamin E's potential as a preventive agent against CVDs, recognizing the complexity of the subject and the need for continued research to unlock its full potential in cardiovascular health.
PubMed: 38046702
DOI: 10.7759/cureus.48142 -
Cureus Dec 2023Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be...
Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.
PubMed: 38222238
DOI: 10.7759/cureus.50474 -
The Journal of Nutrition Jul 2023Vitamin E (vit E) is an essential nutrient that functions as a lipophilic antioxidant and is used clinically to treat nonalcoholic fatty liver disease, where it...
BACKGROUND
Vitamin E (vit E) is an essential nutrient that functions as a lipophilic antioxidant and is used clinically to treat nonalcoholic fatty liver disease, where it suppresses oxidative damage and impedes the progression of steatosis and fibrosis. Mice lacking a critical liver iron-trafficking protein also manifest steatosis because of iron-mediated oxidative damage and are protected from liver disease by oral vit E supplements.
OBJECTIVES
We aimed to examine the role of dietary vit E supplementation in modulating iron-sensing regulatory systems and nonheme iron levels in mouse liver.
METHODS
C57Bl/6 male mice, aged 6 wk, were fed purified diets containing normal amounts of iron and either control (45 mg/kg) or elevated (450 mg/kg) levels of 2R-α-tocopherol (vit E) for 18 d. Mouse plasma and liver were analyzed for nonheme iron, levels and activity of iron homeostatic proteins, and markers of oxidative stress. We compared means ± SD for iron and oxidative stress parameters between mice fed the control diet and those fed the vit E diet.
RESULTS
The Vit E-fed mice exhibited lower levels of liver nonheme iron (38% reduction, P < 0.0001) and ferritin (74% reduction, P < 0.01) than control-fed mice. The levels of liver mRNA for transferrin receptor 1 and divalent metal transporter 1 were reduced to 42% and 57% of the control, respectively. The mRNA levels for targets of nuclear factor erythroid 2-related factor (Nrf2), a major regulator of the oxidative stress response and iron-responsive genes, were also suppressed in vit E livers. Hepcidin, an iron regulatory hormone, levels were lower in the plasma (P < 0.05), and ferroportin (FPN), the iron exporter regulated by hepcidin, was expressed at higher levels in the liver (P < 0.05).
CONCLUSIONS
Oral vit E supplementation in mice can lead to depletion of liver iron stores by suppressing the iron- and redox-sensing transcription factor Nrf2, leading to enhanced iron efflux through liver FPN. Iron depletion may indirectly enhance the antioxidative effects of vit E.
Topics: Mice; Male; Animals; Iron; Vitamin E; Hepcidins; NF-E2-Related Factor 2; Liver; Antioxidants; RNA, Messenger; Mice, Inbred C57BL
PubMed: 37127137
DOI: 10.1016/j.tjnut.2023.04.018