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Pediatric Pulmonology Oct 2022Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to...
BACKGROUND AND OBJECTIVES
Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis.
METHODS
A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients.
RESULTS
Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM.
CONCLUSIONS
Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.
Topics: Adolescent; Adult; Arabinose; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cysteine; Cystic Fibrosis; Cytokines; Diabetes Mellitus; Dysbiosis; Glucose Intolerance; Glutamine; Humans; Indoles; Insulin Resistance; Lactates; Lactulose; Mannitol; Pilot Projects; Probiotics; Prospective Studies; Quality of Life; Young Adult
PubMed: 35676769
DOI: 10.1002/ppul.26037 -
Biochimica Et Biophysica Acta.... Sep 2022Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful...
Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful model to study membrane homeostasis and to identify eventual therapeutic routes. The C. elegans gene paqr-2 encodes a homolog of the mammalian AdipoR1 and AdipoR2 proteins that, when mutated, causes a membrane homeostasis defect accompanied by multiple phenotypes such as intolerance to dietary saturated fatty acids, intolerance to cold and a characteristic tail tip morphology defect. We screened a compound library to identify molecules that can suppress the paqr-2 phenotypes. A single positive hit, Tyloxapol, was found that very effectively suppresses multiple paqr-2 phenotypes. Tyloxapol is a non-ionic detergent currently in use clinically as an expectorant. Importantly, we examined the potential of Tyloxapol as a fluidizer in human cells and found that it improves the viability and membrane fluidity of AdipoR2-deficient human cells challenged with palmitic acid, a membrane-rigidifying saturated fatty acid.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Fatty Acids; Mammals; Membrane Proteins; Polyethylene Glycols; Receptors, Adiponectin
PubMed: 35588889
DOI: 10.1016/j.bbamem.2022.183959 -
Nutrients Apr 2022Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this... (Review)
Review
Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this product category has been questioned. In this review, we summarize the safety evidence as well as relevant clinical findings on weight management and metabolic effects of six representative dietary supplement ingredients: caffeine, green tea extract (GTE), green coffee bean extract (GCBE), choline, glucomannan, and capsaicinoids and capsinoids. Of these, caffeine, GTE (specifically epigallocatechin gallate [EGCG]), and choline have recommended intake limits, which appear not to be exceeded when used according to manufacturers' instructions. Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes. As with any dietary component, the potential for gastrointestinal intolerance, as well as possible interactions with concomitant medications/supplements exist, and the health status of the consumer should be considered when consuming these components. Most of the ingredients reviewed also improved markers of metabolic health, such as glucose, lipids, and blood pressure, although the data are limited for some. In summary, weight management supplements containing caffeine, GTE, GCBE, choline, glucomannan, and capsaicinoids and capsinoids are generally safe when taken as directed and demonstrate metabolic health benefits for overweight and obese people.
Topics: Antioxidants; Caffeine; Catechin; Choline; Dietary Supplements; Humans; Overweight; Plant Extracts; Tea
PubMed: 35565754
DOI: 10.3390/nu14091787 -
Microbial Biotechnology Aug 2022Non-wine yeasts could enhance the aroma and organoleptic profile of wines. However, compared to wine strains, they have specific intolerances to winemaking conditions....
Non-wine yeasts could enhance the aroma and organoleptic profile of wines. However, compared to wine strains, they have specific intolerances to winemaking conditions. To solve this problem, we generated intra- and interspecific hybrids using a non-GMO technique (rare-mating) in which non-wine strains of S. uvarum, S. kudriavzevii and S. cerevisiae species were crossed with a wine S. cerevisiae yeast. The hybrid that inherited the wine yeast mitochondrial showed better fermentation capacities, whereas hybrids carrying the non-wine strain mitotype reduced ethanol levels and increased glycerol, 2,3-butanediol and organic acid production. Moreover, all the hybrids produced several fruity and floral aromas compared to the wine yeast: β-phenylethyl acetate, isobutyl acetate, γ-octalactone, ethyl cinnamate in both varietal wines. Sc × Sk crosses produced three- to sixfold higher polyfunctional mercaptans, 4-mercapto-4-methylpentan-2-one (4MMP) and 3-mercaptohexanol (3MH). We proposed that the exceptional 3MH release observed in an S. cerevisiae × S. kudriavzevii hybrid was due to the cleavage of the non-volatile glutathione precursor (Glt-3MH) to detoxify the cell from the presence of methylglyoxal, a compound related to the high glycerol yield reached by this hybrid. In conclusion, hybrid generation allows us to obtain aromatically improved yeasts concerning their wine parent. In addition, they reduced ethanol and increased organic acids yields, which counteracts climate change effect on grapes.
Topics: Ethanol; Fermentation; Glycerol; Saccharomyces; Saccharomyces cerevisiae
PubMed: 35485391
DOI: 10.1111/1751-7915.14068 -
International Journal of Environmental... Apr 2022Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason...
Influence of (rs4680) and (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders.
Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase () and dopamine receptor D2 () gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of (rs4680) and (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of (rs4680) ( = 0.04994) in all ADHD children. No effect of (rs4680) and (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed and gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.
Topics: Attention Deficit Disorder with Hyperactivity; Catechol O-Methyltransferase; Child; Female; Fetal Alcohol Spectrum Disorders; Genotype; Humans; Methylphenidate; Polymorphism, Genetic; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Dopamine D2
PubMed: 35457347
DOI: 10.3390/ijerph19084479 -
Nutrients Mar 2022People that experience prenatal alcohol exposure (PAE) may have behavioral and metabolic impairments, and it is unclear whether these remain stable or change with age....
People that experience prenatal alcohol exposure (PAE) may have behavioral and metabolic impairments, and it is unclear whether these remain stable or change with age. We assessed behavioral and metabolic endpoints across the lifespan in a mouse model of fetal alcohol spectrum disorder (FASD). Pregnant C57BL/6J mice received alcohol (ALC; 3 g/kg) or maltose-dextrin (control, CON) daily from embryonic day 8.5 to 17.5. Offspring were tested on accelerating rotarod, Y-maze, novel object recognition, and fear conditioning at 6 weeks and 10 and 17 months; females were also tested at 24 months. Body composition, fasting glucose, and glucose clearance were assessed at 18 months. Female but not male ALC mice had greater adiposity than age-matched CON from 7 months onward. At 18 months, male but not female ALC mice had reduced glucose clearance and ALC mice were more likely to have elevated fasting glucose. In the rotarod training session, ALC females performed worse than CON. In the Y-maze, significant exposure-age interactions affected ALC performance in both sexes versus age-match CON. For fear conditioning, all animals acquired the task and froze more at older ages. In both the context and cued tasks, there were exposure-age interactions and ALC animals frozen less than CON at 10 months. Correlation analysis revealed that fasting glucose and glucose clearance correlated with % of body fat in ALC but not in CON mice. Additionally, glucose intolerance and % body fat negatively correlated with performance in the rotarod, context learning, and novel object recognition tasks in ALC but not CON mice. All mice exhibit worsening of behavioral performance as they age, and PAE did not further exacerbate this. ALC but not CON mice displayed adiposity and glucose intolerance that correlate with their cognitive impairments, suggesting that these may be mechanistically related in PAE. Findings emphasize that FASD should be considered a whole-body disorder.
Topics: Adiposity; Aging; Animals; Female; Fetal Alcohol Spectrum Disorders; Glucose; Glucose Intolerance; Humans; Male; Mice; Mice, Inbred C57BL; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 35406051
DOI: 10.3390/nu14071438 -
PloS One 2022Two theoretical perspectives have been proffered to explain changes in alcohol use during the pandemic: the 'affordability-availability' mechanism (i.e., drinking...
Two theoretical perspectives have been proffered to explain changes in alcohol use during the pandemic: the 'affordability-availability' mechanism (i.e., drinking decreases due to changes in physical availability and/or reduced disposable income) and the 'psychological-coping' mechanism (i.e., drinking increases as adults attempt to cope with pandemic-related distress). We tested these alternative perspectives via longitudinal analyses of the COVID-19 Psychological Consortium (C19PRC) Study data (spanning three timepoints during March to July 2020). Respondents provided data on psychological measures (e.g., anxiety, depression, posttraumatic stress, paranoia, extraversion, neuroticism, death anxiety, COVID-19 anxiety, intolerance of uncertainty, resilience), changes in socio-economic circumstances (e.g., income loss, reduced working hours), drinking motives, solitary drinking, and 'at-risk' drinking (assessed using a modified version of the AUDIT-C). Structural equation modelling was used to determine (i) whether 'at-risk' drinking during the pandemic differed from that recalled before the pandemic, (ii) dimensions of drinking motives and the psychosocial correlates of these dimensions, (iii) if increased alcohol consumption was predicted by drinking motives, solitary drinking, and socio-economic changes. The proportion of adults who recalled engaging in 'at-risk' drinking decreased significantly from 35.9% pre-pandemic to 32.0% during the pandemic. Drinking to cope was uniquely predicted by experiences of anxiety and/or depression and low resilience levels. Income loss or reduced working hours were not associated with coping, social enhancement, or conformity drinking motives, nor changes in drinking during lockdown. In the earliest stage of the pandemic, psychological-coping mechanisms may have been a stronger driver to changes in adults' alcohol use than 'affordability-availability' alone.
Topics: Adaptation, Psychological; Adult; Alcohol Drinking; COVID-19; Communicable Disease Control; Costs and Cost Analysis; Humans; Motivation; Pandemics
PubMed: 35324964
DOI: 10.1371/journal.pone.0265145 -
Scientific Reports Mar 2022ALDH2 is a key enzyme in alcohol metabolism that protects cells from acetaldehyde toxicity. Using iHS, iSAFE and F statistics, we identified regulatory acting variants...
ALDH2 is a key enzyme in alcohol metabolism that protects cells from acetaldehyde toxicity. Using iHS, iSAFE and F statistics, we identified regulatory acting variants affecting ALDH2 gene expression under positive selection in populations of European ancestry. Several SNPs (rs3184504, rs4766578, rs10774625, rs597808, rs653178, rs847892, rs2013002) that function as eQTLs for ALDH2 in various tissues showed evidence of strong positive selection. Very large pairwise F values indicated high genetic differentiation at these loci between populations of European ancestry and populations of other global ancestries. Estimating the timing of positive selection on the beneficial alleles suggests that these variants were recently adapted approximately 3000-3700 years ago. The derived beneficial alleles are in complete linkage disequilibrium with the derived ALDH2 promoter variant rs886205, which is associated with higher transcriptional activity. The SNPs rs4766578 and rs847892 are located in binding sequences for the transcription factor HNF4A, which is an important regulatory element of ALDH2 gene expression. In contrast to the missense variant ALDH2 rs671 (ALDH2*2), which is common only in East Asian populations and is associated with greatly reduced enzyme activity and alcohol intolerance, the beneficial alleles of the regulatory variants identified in this study are associated with increased expression of ALDH2. This suggests adaptation of Europeans to higher alcohol consumption.
Topics: Alcohol Drinking; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Alleles; Asian People; Gene Expression; Humans; Polymorphism, Single Nucleotide
PubMed: 35296751
DOI: 10.1038/s41598-022-08588-0 -
Molecular Metabolism Jun 2022The recently identified glycerol-3-phosphate (Gro3P) phosphatase (G3PP) in mammalian cells, encoded by the PGP gene, was shown to regulate glucose, lipid and energy...
OBJECTIVE
The recently identified glycerol-3-phosphate (Gro3P) phosphatase (G3PP) in mammalian cells, encoded by the PGP gene, was shown to regulate glucose, lipid and energy metabolism by hydrolyzing Gro3P and to control glucose-stimulated insulin secretion (GSIS) in β-cells, in vitro. However, whether G3PP regulates β-cell function and insulin secretion in vivo is not known.
METHODS
We now examined the role of G3PP in the control of insulin secretion in vivo, β-cell function and glucotoxicity in inducible β-cell specific G3PP-KO (BKO) mice. Inducible BKO mice were generated by crossing floxed-G3PP mice with Mip-Cre-ERT (MCre) mice. All the in vivo studies were done using BKO and control mice fed normal diet and the ex vivo studies were done using pancreatic islets from these mice.
RESULTS
BKO mice, compared to MCre controls, showed increased body weight, adiposity, fed insulinemia, enhanced in vivo GSIS, reduced plasma triglycerides and mild glucose intolerance. Isolated BKO mouse islets incubated at high (16.7 mM), but not at low or intermediate glucose (3 and 8 mM), showed elevated GSIS, Gro3P content as well as increased levels of metabolites and signaling coupling factors known to reflect β-cell activation for insulin secretion. BKO islets also showed reduced glycerol release and increased O consumption and ATP production at high glucose only. BKO islets chronically exposed to elevated glucose levels showed increased apoptosis, reduced insulin content and decreased mRNA expression of β-cell differentiation markers, Pdx-1, MafA and Ins-2.
CONCLUSIONS
The results demonstrate that β-cells are endowed with a "glycerol shunt", operated by G3PP that regulates β-cell metabolism, signaling and insulin secretion in vivo, primarily at elevated glucose concentrations. We propose that the glycerol shunt plays a role in preventing insulin hypersecretion and excess body weight gain and contributes to β-cell mass preservation in the face of hyperglycemia.
Topics: Animals; Glucose; Glycerol; Insulin; Insulin Secretion; Mammals; Mice; Obesity; Phosphates; Phosphoric Monoester Hydrolases; Stress, Physiological; Weight Gain
PubMed: 35272070
DOI: 10.1016/j.molmet.2022.101471 -
Women's Health Issues : Official... 2022Women are experiencing greater unemployment and increased stress from childcare responsibilities than men during the COVID-19 pandemic. Women with these experiences may...
PURPOSE
Women are experiencing greater unemployment and increased stress from childcare responsibilities than men during the COVID-19 pandemic. Women with these experiences may be at particular risk for mental illness and increased substance use during the COVID-19 pandemic. The purpose of the study was to assess women's substance use, mental health, and experiences of COVID-19 pandemic impacts.
METHODS
A national online survey was administered to adult women from September to November 2020. The survey included questionnaires assessing mental health, loneliness, intolerance for uncertainty, social support, substance use, and intimate partner violence (IPV).
RESULTS
A total of 499 women responded; most were White, college educated, and in their mid-30s. Of the 20.24% who acknowledged at least one IPV problem, 29.7% stated that their IPV problems have gotten worse since the pandemic began, and 16.83% said that they have increased their drug or alcohol use to cope with their relationship problems. Anxiety, perceived daily impact of COVID-19, and lower self-efficacy were significant predictors of COVID-19 anxiety. Those with risky alcohol use had significantly higher anxiety (p = .028) and depression (p = .032) than those with low-risk alcohol use.
CONCLUSIONS
Greater anxiety about COVID-19, greater reported changes in daily life due to the pandemic, and high-risk alcohol use are related to greater mental health-related distress among women. For some, IPV has gotten worse during the pandemic and drug or alcohol use is a coping mechanism.
Topics: Adult; Anxiety; COVID-19; Female; Humans; Intimate Partner Violence; Mental Health; Pandemics; Substance-Related Disorders; Women's Health
PubMed: 35246351
DOI: 10.1016/j.whi.2022.01.004