-
International Journal of Environmental... Sep 2019Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection... (Review)
Review
Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%-13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development ('regressive autism'). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.
Topics: Autistic Disorder; Humans; Hypervitaminosis A; Liver; Liver Diseases; Rubella; Rubella Syndrome, Congenital; Rubella virus; Vitamin A
PubMed: 31546693
DOI: 10.3390/ijerph16193543 -
International Journal of Molecular... May 2023Diabetes mellitus (DM) is a serious chronic metabolic disease that is associated with hyperglycemia and several complications including cardiovascular disease and... (Review)
Review
Diabetes mellitus (DM) is a serious chronic metabolic disease that is associated with hyperglycemia and several complications including cardiovascular disease and chronic kidney disease. DM is caused by high levels of blood sugar in the body associated with the disruption of insulin metabolism and homeostasis. Over time, DM can induce life-threatening health problems such as blindness, heart disease, kidney damage, and stroke. Although the cure of DM has improved over the past decades, its morbidity and mortality rates remain high. Hence, new therapeutic strategies are needed to overcome the burden of this disease. One such prevention and treatment strategy that is easily accessible to diabetic patients at low cost is the use of medicinal plants, vitamins, and essential elements. The research objective of this review article is to study DM and explore its treatment modalities based on medicinal plants and vitamins. To achieve our objective, we searched scientific databases of ongoing trials in PubMed Central, Medline databases, and Google Scholar websites. We also searched databases on World Health Organization International Clinical Trials Registry Platform to collect relevant papers. Results of numerous scientific investigations revealed that phytochemicals present in medicinal plants (, , L., and ) possess anti-hypoglycemic activities and show promise for the prevention and/or control of DM. Results also revealed that intake of vitamins C, D, E, or their combination improves the health of diabetes patients by reducing blood glucose, inflammation, lipid peroxidation, and blood pressure levels. However, very limited studies have addressed the health benefits of medicinal plants and vitamins as chemo-therapeutic/preventive agents for the management of DM. This review paper aims at addressing this knowledge gap by studying DM and highlighting the biomedical significance of the most potent medicinal plants and vitamins with hypoglycemic properties that show a great potential to prevent and/or treat DM.
Topics: Humans; Plants, Medicinal; Vitamins; Diabetes Mellitus; Hypoglycemic Agents; Plant Extracts; Blood Glucose; Vitamin A; Vitamin K
PubMed: 37240430
DOI: 10.3390/ijms24109085 -
Journal of Molecular Endocrinology Nov 2022Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types,... (Review)
Review
Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types, both during embryogenesis and in the adult organism. However, we must obtain vitamin A from food sources. Thus, the uptake and metabolism of vitamin A by intestinal epithelial cells, the storage of vitamin A in the liver, and the metabolism of vitamin A in target cells to more biologically active metabolites, such as retinoic acid (RA) and 4-oxo-RA, must be precisely regulated. Here, I will discuss the enzymes that metabolize vitamin A to RA and the cytochrome P450 Cyp26 family of enzymes that further oxidize RA. Because much progress has been made in understanding the regulation of ALDH1a2 (RALDH2) actions in the intestine, one focus of this review is on the metabolism of vitamin A in intestinal epithelial cells and dendritic cells. Another focus is on recent data that 4-oxo-RA is a ligand required for the maintenance of hematopoietic stem cell dormancy and the important role of RARβ (RARB) in these stem cells. Despite this progress, many questions remain in this research area, which links vitamin A metabolism to nutrition, immune functions, developmental biology, and nuclear receptor pharmacology.
Topics: Cytochrome P-450 Enzyme System; Cytochrome P450 Family 26; Ligands; Micronutrients; Tretinoin; Vitamin A
PubMed: 35900851
DOI: 10.1530/JME-22-0082 -
Danish Medical Journal Jun 2023Lipids are essential in human physiology, triglycerides for energy and cholesterol as a structural component in cells and as a precurser for hormones and vitamins....
Lipids are essential in human physiology, triglycerides for energy and cholesterol as a structural component in cells and as a precurser for hormones and vitamins. However, high blood levels of cholesterol cause atherosclerosis, leading to cardiovascular disease, which is the number one cause of death globally. Genetic evidence suggests that lipoprotein(a) and remnant cholesterol, cholesterol in very low-density and intermediate-density lipoproteins, are causally involved in the development of cardiovascular disease together with low-density lipoproteins and this has spurred the development of drugs potently lowering these.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Atherosclerosis; Triglycerides; Vitamin A
PubMed: 37381868
DOI: No ID Found -
Molecular Psychiatry Sep 2023Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major...
Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.
Topics: Humans; Tandem Mass Spectrometry; Depression; Diet; Metabolome; Vitamin A; Hippurates; Metabolomics
PubMed: 37495887
DOI: 10.1038/s41380-023-02180-2 -
Autophagy Nov 2021Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau...
Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a lysosomal degradative process, which plays an important role in the clearance of Aβ. Failure of autophagic clearance of Aβ is currently acknowledged as a contributing factor to increased accumulation of Aβ in AD brains. In this study, we have identified crocetin, a pharmacologically active constituent from the flower stigmas of , as a potential inducer of autophagy in AD. In the cellular model, crocetin induced autophagy in N9 microglial and primary neuron cells through STK11/LKB1 (serine/threonine kinase 11)-mediated AMP-activated protein kinase (AMPK) pathway activation. Autophagy induction by crocetin significantly increased Aβ clearance in N9 cells. Moreover, crocetin crossed the blood-brain barrier and induced autophagy in the brains' hippocampi of wild-type male C57BL/6 mice. Further studies in transgenic male 5XFAD mice, as a model of AD, revealed that one-month treatment with crocetin significantly reduced Aβ levels and neuroinflammation in the mice brains and improved memory function by inducing autophagy that was mediated by AMPK pathway activation. Our findings support further development of crocetin as a pharmacological inducer of autophagy to prevent, slow down progression, and/or treat AD. Aβ: amyloid-β; ABCB1/P-gp/P-glycoprotein: ATP-binding cassette, subfamily B (MDR/TAP), member 1; AD: Alzheimer disease; AMPK/PRKAA: AMP-activated protein kinase; APP: amyloid beta (A4) precursor protein; ATG: autophagy related; BBB: blood-brain barrier; BECN1: beclin 1, autophagy related; CAMKK2/CaMKKβ: calcium/calmodulin-dependent protein kinase kinase 2, beta; CSE: Crocus sativus extract; CTSB: cathepsin B; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; GFAP: glial fibrillary acidic protein; GSK3B/GSK3β: glycogen synthase kinase 3 beta; Kp: brain partition coefficient; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAP2: microtubule-associated protein 2; MAPK/ERK: mitogen-activated protein kinase; MAPT/tau: microtubule-associated protein tau; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTOR: mechanistic target of rapamycin kinase; MWM: Morris water maze; NFKB/NF-κB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NMDA: N-methyl-d-aspartic acid; RPTOR: regulatory associated protein of MTOR; RPS6KB1/p70S6K: ribosomal protein S6 kinase 1; SQSTM1: sequestosome 1; SRB: sulforhodamine B; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TSC2: TSC complex subunit 2; ULK1: unc-51 like kinase 1.
Topics: AMP-Activated Protein Kinases; Amyloid beta-Peptides; Animals; Autophagy; Carotenoids; Cell Line; Female; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Microglia; Vitamin A
PubMed: 33404280
DOI: 10.1080/15548627.2021.1872187 -
Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Nutrients Dec 2023Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only... (Meta-Analysis)
Meta-Analysis Review
Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements.
Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only affect the quality of life of individuals and their families, but also pose significant economic burdens on healthcare systems. In this context, our comprehensive narrative review critically examines the role of nutritional supplements in mitigating cognitive decline. Amidst growing interest in non-pharmacological interventions for cognitive enhancement, this review delves into the efficacy of vitamins, minerals, antioxidants, and other dietary supplements. Through a systematic evaluation of randomized controlled trials, observational studies, and meta-analysis, this review focuses on outcomes such as memory enhancement, attention improvement, executive function support, and neuroprotection. The findings suggest a complex interplay between nutritional supplementation and cognitive health, with some supplements showing promising results and others displaying limited or context-dependent effectiveness. The review highlights the importance of dosage, bioavailability, and individual differences in response to supplementation. Additionally, it addresses safety concerns and potential interactions with conventional treatments. By providing a clear overview of current scientific knowledge, this review aims to guide healthcare professionals and researchers in making informed decisions about the use of nutritional supplements for cognitive health.
Topics: Humans; Vitamins; Antioxidants; Quality of Life; Dietary Supplements; Minerals; Vitamin A; Cognition; Vitamin K; Aging; Observational Studies as Topic
PubMed: 38140375
DOI: 10.3390/nu15245116 -
BMJ Case Reports May 2021We report a case of a patient who presented complaining of a 1-week history of progressive lower limb weakness and decreased sensation bilaterally suggestive of a...
We report a case of a patient who presented complaining of a 1-week history of progressive lower limb weakness and decreased sensation bilaterally suggestive of a peripheral neuropathy, with vague associated symptoms of fluctuating concentration. Clinically, we suspected a Guillain-Barré variant. However, her functioning continued to decline despite intravenous immunoglobulin therapy, and she had normal spinal imaging studies and CSF analysis. Of note, she had a subtotal oesophagectomy and proximal gastrectomy 20 months previously for oesophageal cancer. We found her to be deficient in vitamin D, vitamin E and copper. She was treated with nutritional supplementation of these vitamins and infusion of trace elements, resulting in a gradual improvement in lower limb power, sensation and coordination, as well as improved cognition and mentation. Monthly outpatient neurology follow-up shows continued improvement in symptoms and return towards baseline functioning with regular infusions of nutritional elements and monitoring of blood levels.
Topics: Dietary Supplements; Female; Guillain-Barre Syndrome; Humans; Peripheral Nervous System Diseases; Vitamin A; Vitamins
PubMed: 34039553
DOI: 10.1136/bcr-2021-242716 -
Nutrients Oct 2022All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and...
All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and post-natal regulation of energy metabolism, glucoregulatory control, organ function, and of the skeletal, immune, nervous and cardiovascular systems, as well as cell proliferation vs [...].
Topics: Pregnancy; Female; Humans; Tretinoin; Vitamin A; Autacoids
PubMed: 36364786
DOI: 10.3390/nu14214526