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Proceedings of the National Academy of... Jun 2024Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, is highly expressed both in adipose tissue and liver. Its...
Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, is highly expressed both in adipose tissue and liver. Its expression in adipose tissue is reduced in obesity and increased by insulin stimulation. Interference with expression has also been reported to impair adipocyte function. To better understand the role of ADH1B in adipocytes, we used CRISPR/Cas9 to delete in human adipose stem cells (ASC). Cells lacking ADH1B failed to differentiate into mature adipocytes manifested by minimal triglyceride accumulation and a marked reduction in expression of established adipocyte markers. As ADH1B is capable of converting retinol to retinoic acid (RA), we conducted rescue experiments. Incubation of ADH1B-deficient preadipocytes with 9-cis-RA, but not with all-transretinol, significantly rescued their ability to accumulate lipids and express markers of adipocyte differentiation. A homozygous missense variant in (p.Arg313Cys) was found in a patient with congenital lipodystrophy of unknown cause. This variant significantly impaired the protein's dimerization, enzymatic activity, and its ability to rescue differentiation in ADH1B-deficient ASC. The allele frequency of this variant in the Middle Eastern population suggests that it is unlikely to be a fully penetrant cause of severe lipodystrophy. In conclusion, ADH1B appears to play an unexpected, crucial and cell-autonomous role in human adipocyte differentiation by serving as a necessary source of endogenous retinoic acid.
Topics: Humans; Alcohol Dehydrogenase; Adipogenesis; Adipocytes; Tretinoin; Cell Differentiation; CRISPR-Cas Systems; Mutation, Missense; Adipose Tissue
PubMed: 38838011
DOI: 10.1073/pnas.2319301121 -
Cureus May 2024Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be... (Review)
Review
Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be multifactorial in origin, betel quid chewing appears to be the main etiologic factor. Various treatment strategies have been attempted but none proven to cure the disorder because of its multimodal pathogenesis. Reactive oxygen species (ROS) appear to have a role in cancer formation. As OSMF is an oral premalignant disorder and found to be associated with carcinogens like areca nut and tobacco, it is believed to have some relationship with ROS. Tissue damage due to ROS along with other mechanisms may result in the complex pathophysiology of OSMF. The antioxidant system in the body helps to prevent damage caused by highly reactive ROS and helps in the repair of tissues. To study the levels of oxidative stress and antioxidant vitamins in OSMF condition, the present review was done. We carried out a thorough literature search to identify original reports and studies determining the status of oxidative stress and antioxidant vitamins in OSMF condition using several databases including Google Scholar, PubMed, and Scopus. Our review observed that the oxidative stress increased in the condition of OSMF as shown by an increase in malonaldehyde (MDA) and a decrease in antioxidant vitamins like vitamin A, vitamin C, and vitamin E. Also, after the intake of antioxidant vitamins, there was symptomatic improvement in OSMF patients. With the help of identifying oxidative stress and antioxidant status, we can assess the clinical stage of OSMF and can develop a comprehensive treatment plan.
PubMed: 38832153
DOI: 10.7759/cureus.59596 -
Scientific Reports Jun 2024Studies on the beneficial role of dietary antioxidants in preventing or managing hypertension in postmenopausal women are infrequent. The present cross-sectional study...
Studies on the beneficial role of dietary antioxidants in preventing or managing hypertension in postmenopausal women are infrequent. The present cross-sectional study aimed to assess the association between dietary antioxidants and hypertension among menopausal women in Rafsanjan, a city located in the southeast of Iran. This study was based on data from the Rafsanjan Cohort Study (RCS), as part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). Among 2359 postmenopausal women, finally, 1936 women were included in this study. Participants were grouped as having normal blood pressure (BP), elevated BP, stage 1 hypertension, or stage 2 hypertension as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline. A food frequency questionnaire (FFQ), was utilized to ascertain the levels of various nutrients and dietary antioxidants in the diet. The association between dietary intakes of antioxidants and blood pressure groups was evaluated by crude and adjusted models in the multinominal logistics regression analysis. Normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension were observed in 35.69%, 3.62%, 10.59%, and 50.10% of postmenopausal women respectively. In the adjusted model, in subjects with higher consumption of β-carotene, the odds ratios of elevated BP in the 3rd quartile was about 2 times (OR: 2.04 (1.06-3.93) higher than 1st quartile. Also, in subjects with medium quality of DAQS, the odds ratios of elevated BP and stage 1 blood pressure were about 2 times (OR: 2.09 (1.05-4.17) and 1.69 times (OR: 1.69 (1.09-2.63) higher than subjects with low quality respectively. Furthermore, we did not find any statistically significant association between increased intake of dietary antioxidants and decreased odds of hypertension. After controlling the effects of confounding variables, increased dietary intake of selenium, carotenoids, vitamin A, vitamin C, and vitamin E did not decrease the odds of hypertension in postmenopausal women. Accordingly, it is suggested that this association be further investigated in the follow-up phase of this prospective study.
Topics: Humans; Female; Hypertension; Antioxidants; Middle Aged; Iran; Cross-Sectional Studies; Diet; Postmenopause; Blood Pressure; Cohort Studies; Menopause; Prospective Studies; Aged
PubMed: 38830913
DOI: 10.1038/s41598-024-63401-4 -
Frontiers in Nutrition 2024It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally...
It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally vulnerable, with nearly half of the population stunted, and parts of the country facing emergency, near famine-like conditions (IPC4). Although Madagascar is generally considered among the most undernourished of countries, empirical data in the form of biological samples to validate these claims are extremely limited. Our research drew data from three studies conducted between 2013-2020 and provided comprehensive biomarker profile information for 4,710 individuals from 30 communities in five different ecological regions during at least one time-point. Estimated prevalences of nutrient deficiencies and inflammation across various regions of rural Madagascar were of concern for both sexes and across all ages, with 66.5% of the population estimated to be deficient in zinc, 15.6% depleted in vitamin B (3.6% deficient), 11.6% deficient in retinol, and lower levels of iron deficiency (as indicated by 11.7% deficient in ferritin and 2.3% deficient assessed by soluble transferrin receptors). Beyond nutrient status biomarkers, nearly one quarter of the population (24.0%) exhibited chronic inflammation based on high values of α-1-acid glycoprotein, and 12.3% exhibited acute inflammation based on high values of C-reactive protein. There is an 8-fold difference between the lowest and highest regional observed prevalence of vitamin B deficiency, a 10-fold difference in vitamin A deficiency (based on retinol), and a 2-fold difference in acute inflammation (CRP) and deficiencies of zinc and iron (based on ferritin), highlighting strong geographical variations in micronutrient deficiencies across Madagascar.
PubMed: 38826583
DOI: 10.3389/fnut.2024.1389080 -
Nature Communications Jun 2024Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad...
Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.
Topics: Animals; Hematopoietic Stem Cells; Tretinoin; NF-KappaB Inhibitor alpha; Cell Proliferation; Mice; Signal Transduction; Embryonic Development; Mice, Knockout; Polycomb Repressive Complex 2; Mice, Inbred C57BL; Gene Expression Regulation, Developmental; Female
PubMed: 38824124
DOI: 10.1038/s41467-024-48854-5 -
Ultrasonics Sonochemistry Jul 2024A novel approach to ultrasound-assisted Pickering interfacial biocatalysis (PIB) has been proposed and implemented for the efficient enzymatic transesterification...
A novel approach to ultrasound-assisted Pickering interfacial biocatalysis (PIB) has been proposed and implemented for the efficient enzymatic transesterification production of vitamin A fatty acid esters. This is the first instance of exploiting the synergistic effect of ultrasound and the bifunctional modification of enzyme supports to accelerate biocatalytic performance in PIB systems. The optimal conditions were determined to be ultrasound power of 70 W, on/off time of 5 s/5 s, substrate molar ratio of 1:1, enzyme addition of 2 %, and a volume ratio of n-hexane to PBS of 3:1, a temperature of 40 °C, and a time of 30 min. The application of ultrasound technology not only improved lipase activity but also allowed for a reduction in emulsion droplet size to enhance interfacial mass transfer.Bifunctional modification of silica-based supports enhanced stability of immobilized enzymes by increasing hydrogen bonding while maintaining the active interface microenvironment. Compared with a non-ultrasound-assisted PIB system stabilized by mono-modified immobilized enzyme particles, the catalytic efficacy (CE) of the novel system reached 8.18 mmol g min, which was enhanced by 3.33-fold, while the interfacial area was found to have increased by 17.5-fold. The results facilitated the conversion of vitamin A palmitate (VAP), vitamin A oleate (VAO), vitamin A linoleate (VAL), and vitamin A linolenate (VALn), with conversion rates of approximately 98.2 %, 97.4 %, 96.1 %, and 94.7 %, respectively. This represents the most efficient example that has been reported to our knowledge. Furthermore, the system demonstrated improved reusability, with a conversion rate of 62.1 % maintained even after 10 cycles. The findings presented in this paper provide valuable insights into an efficient and conveniently promising protocol for the development of PIB systems.
Topics: Biocatalysis; Vitamin A; Esters; Lipase; Ultrasonic Waves; Enzymes, Immobilized; Esterification; Temperature; Silicon Dioxide
PubMed: 38820933
DOI: 10.1016/j.ultsonch.2024.106929 -
Phytomedicine : International Journal... Jul 2024Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly.
PURPOSE
There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking.
STUDY DESIGN AND METHODS
PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods.
RESULTS
The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies.
CONCLUSION
Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.
Topics: Macular Degeneration; Humans; Biological Products; Oxidative Stress; Animals; Phytotherapy; Vitamin A; Retina; Phenols; Functional Food
PubMed: 38820665
DOI: 10.1016/j.phymed.2024.155522 -
Cureus Apr 2024Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently...
Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently in adults, with no apparent predilection for sex or weight. Headache, papilledema, and possibly sixth nerve palsy with visual field defects are the typical symptoms of this syndrome. Vitamin A toxicity is a rare cause of BIH. We report the case of a previously healthy 13-year-old girl presenting with photophobia, a frontal headache, and vomiting. She had bilateral papilledema discovered by fundoscopy. Both magnetic resonance imaging and brain CT were normal. At admission, a lumbar puncture (LP) revealed an opening pressure of 26 cm HO with normal cerebrospinal fluid (CSF) analysis. The diagnosis of BIH was established, and treatment with acetazolamide was started, with good clinical results. Regular eye evaluations showed a regression of papilledema. Elevated serum vitamin A levels were the only positive findings. Within two weeks, the patient was discharged without any symptoms. This study aims to attract the attention of clinicians to the importance of evaluating vitamin A toxicity in the context of papilledema and oculomotor problems in a child who has undergone normal neuroradiological investigations.
PubMed: 38817456
DOI: 10.7759/cureus.59401 -
BMJ Open May 2024This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically... (Meta-Analysis)
Meta-Analysis
Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.
OBJECTIVES
This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically important outcomes, in people of any age.
METHODS
We searched different electronic databases and other resources for randomised clinical trials that had compared vitamin A supplements versus placebo or no intervention (last search 16 April 2024). We used Cochrane methodology. We used the random-effects model to calculate risk ratios (RRs), with 95% CIs. We analysed individually and cluster randomised trials separately. Our primary outcomes were mortality, adverse events and quality of life. We assessed risks of bias in the trials and used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of the evidence.
RESULTS
We included 120 randomised trials (1 671 672 participants); 105 trials allocated individuals and 15 allocated clusters. 92 trials included children (78 individually; 14 cluster randomised) and 28 adults (27 individually; 1 cluster randomised). 14/105 individually randomised trials (13%) and none of the cluster randomised trials were at overall low risk of bias. Vitamin A did not reduce mortality in individually randomised trials (RR 0.99, 95% CI 0.93 to 1.05; I=32%; p=0.19; 105 trials; moderate certainty), and this effect was not affected by the risk of bias. In individually randomised trials, vitamin A had no effect on mortality in children (RR 0.96, 95% CI 0.88 to 1.04; I=24%; p=0.28; 78 trials, 178 094 participants) nor in adults (RR 1.04, 95% CI 0.97 to 1.13; I=24%; p=0.27; 27 trials, 61 880 participants). Vitamin A reduced mortality in the cluster randomised trials (0.84, 95% CI 0.76 to 0.93; I=66%; p=0.0008; 15 trials, 14 in children and 1 in adults; 364 343 participants; very low certainty). No trial reported serious adverse events or quality of life. Vitamin A slightly increased bulging fontanelle of neonates and infants. We are uncertain whether vitamin A influences blindness under the conditions examined.
CONCLUSIONS
Based on moderate certainty of evidence, vitamin A had no effect on mortality in the individually randomised trials. Very low certainty evidence obtained from cluster randomised trials suggested a beneficial effect of vitamin A on mortality. If preventive vitamin A programmes are to be continued, supporting evidence should come from randomised trials allocating individuals and assessing patient-meaningful outcomes.
PROSPERO REGISTRATION NUMBER
CRD42018104347.
Topics: Humans; Vitamin A; Randomized Controlled Trials as Topic; Dietary Supplements; Primary Prevention; Secondary Prevention; Quality of Life; Vitamins
PubMed: 38816049
DOI: 10.1136/bmjopen-2023-078053 -
Turkish Journal of Medical Sciences 2023Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous...
BACKGROUND/AIM
Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous hypersecretion and colonization. Vitamin D plays a crucial role in the pathogenesis of various inflammatory skin disorders, including AV, due to its immunomodulatory effects and involvement in keratinocyte growth and maturity. However, adequate sun exposure is required for optimal vitamin D synthesis. Isotretinoin (IOS), a vitamin A derivative, is a commonly used medication for severe acne, acting by binding to retinoid receptors. It can also form heterodimers with vitamin D receptors, potentially increasing vitamin D catabolism. Previous studies examining the impact of oral IOS on serum vitamin D levels have yielded inconsistent results. Therefore, this study aimed to assess changes in 25-hydroxy (OH) vitamin D serum levels in individuals with severe AV before and after IOS treatment.
MATERIALS AND METHODS
One hundred patients with severe AV were enrolled, each receiving 0.75 mg/kg IOS treatment daily for 4 months. Serum 25 OH vitamin D levels were measured before, during, and after treatment.
RESULTS
This study found a significant increase in serum 25 OH vitamin D levels among patients with severe AV following IOS treatment (p < 0.001).
CONCLUSION
This study suggests that AV may negatively impact vitamin D synthesis, but IOS treatment appears to raise vitamin D serum levels in individuals with severe AV. Further research is needed to confirm the potential relationship between AV and vitamin D levels.
Topics: Humans; Isotretinoin; Acne Vulgaris; Vitamin D; Male; Female; Dermatologic Agents; Prospective Studies; Young Adult; Adult; Adolescent
PubMed: 38813517
DOI: 10.55730/1300-0144.5742