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1.
Nature ; 631(8020): 307-312, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38898280

ABSTRACT

Spin accumulation in semiconductor structures at room temperature and without magnetic fields is key to enable a broader range of optoelectronic functionality1. Current efforts are limited owing to inherent inefficiencies associated with spin injection across semiconductor interfaces2. Here we demonstrate spin injection across chiral halide perovskite/III-V interfaces achieving spin accumulation in a standard semiconductor III-V (AlxGa1-x)0.5In0.5P multiple quantum well light-emitting diode. The spin accumulation in the multiple quantum well is detected through emission of circularly polarized light with a degree of polarization of up to 15 ± 4%. The chiral perovskite/III-V interface was characterized with X-ray photoelectron spectroscopy, cross-sectional scanning Kelvin probe force microscopy and cross-sectional transmission electron microscopy imaging, showing a clean semiconductor/semiconductor interface at which the Fermi level can equilibrate. These findings demonstrate that chiral perovskite semiconductors can transform well-developed semiconductor platforms into ones that can also control spin.

2.
Biomolecules ; 14(4)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38672413

ABSTRACT

Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 µg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled.


Subject(s)
Diterpenes , Epoxy Compounds , Insulin Resistance , Mice, Inbred C57BL , Obesity , Phenanthrenes , Animals , Epoxy Compounds/pharmacology , Epoxy Compounds/administration & dosage , Diterpenes/pharmacology , Diterpenes/administration & dosage , Phenanthrenes/pharmacology , Phenanthrenes/administration & dosage , Obesity/metabolism , Obesity/immunology , Mice , Male , Inflammation/metabolism , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Interleukin-17/metabolism , Interleukin-17/genetics , Diet, High-Fat/adverse effects , Tumor Necrosis Factor-alpha/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/immunology , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Energy Metabolism/drug effects
3.
FASEB J ; 38(3): e23460, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38315443

ABSTRACT

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long-lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA-Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus-derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI.


Subject(s)
Brain Injuries, Traumatic , Thymus Extracts , Humans , Rats , Animals , Cattle , Thymus Extracts/pharmacology , Thymus Extracts/therapeutic use , Brain Injuries, Traumatic/drug therapy , Neurons , Neuroglia , Hippocampus , Disease Models, Animal
4.
Metabolites ; 14(1)2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38276304

ABSTRACT

Obesity-resistant (non-responder, NR) phenotypes that exhibit reduced susceptibility to developing obesity despite being exposed to high dietary fat are crucial in exploring the metabolic responses that protect against obesity. Although several efforts have been made to study them in mice and humans, the individual protective mechanisms are poorly understood. In this exploratory study, we used a polygenic C57BL/6J mouse model of diet-induced obesity to show that NR mice developed healthier fat/lean body mass ratios (0.43 ± 0.05) versus the obesity-prone (super-responder, SR) phenotypes (0.69 ± 0.07, p < 0.0001) by upregulating gene expression networks that promote the accumulation of type 2a, fast-twitch, oxidative muscle tissues. This was achieved in part by a metabolic adaptation in the form of blood glucose sparing, thus aggravating glucose tolerance. Resistance to obesity in NR mice was associated with 4.9-fold upregulated mitoferrin 1 (Slc25a37), an essential mitochondrial iron importer. SR mice also showed fecal volatile metabolite signatures of enhanced short-chain fatty acid metabolism, including increases in detrimental methyl formate and ethyl propionate, and these effects were reversed in NR mice. Continued research into obesity-resistant phenotypes can offer valuable insights into the underlying mechanisms of obesity and metabolic health, potentially leading to more personalized and effective approaches for managing weight and related health issues.

5.
Nutrients ; 16(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38202000

ABSTRACT

Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.


Subject(s)
Diet, High-Fat , Lipid Metabolism , Animals , Mice , Diet, High-Fat/adverse effects , Mice, Inbred C57BL , Mice, Obese , Obesity/etiology , Phenotype
6.
Int J Mol Sci ; 22(3)2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33494167

ABSTRACT

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERß receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERß in the hypothalamus of OVX rats, as well as in ERα/ß cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.


Subject(s)
Phytoestrogens/chemistry , Phytoestrogens/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Rheum/chemistry , Vasomotor System/drug effects , Animals , Biomarkers , Disease Models, Animal , Dose-Response Relationship, Drug , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Hot Flashes , Menopause/drug effects , Molecular Structure , Ovariectomy , Postmenopause , Rats
7.
Food Chem Toxicol ; 111: 445-453, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29196236

ABSTRACT

Driven by the need for alternative whole food options to manage metabolic syndrome, multiple dietary interventions are suggested to achieve a better control of metabolic risk factors and molecular networks that regulate cellular energy metabolism. It is generally accepted that anthocyanin-rich diets are beneficial for maintaining healthy body weight, improving glucose and lipid metabolism, and determining inflammatory status of key metabolic tissues. However, anthocyanins are a structurally diverse group of phenolic compounds and their individual contributions to improving metabolic health are not clear. In this study, we show that consumption of berries containing anthocyanins with enhanced methylation profiles (malvidin and petunidin) is more effective at reducing high fat diet-induced metabolic damage in the C57BL/6 mouse model of polygenic obesity. Blueberries and Concord grapes (57% and 33% anthocyanins as malvidin, petunidin, or peonidin, respectively) improved body composition through individual significant effects on energy expenditure and increased activity. Methylated anthocyanins are also more effective at enhancing mitochondrial respiration and dissipation of the mitochondrial proton gradient (proton leak) in adipose tissue, thus counteracting mitochondrial dysfunction associated with metabolic stress. Together, these results provide direct proof of the higher protective potential of methylated anthocyanins against the metabolic consequences of chronic exposure to calorie-dense foods.


Subject(s)
Anthocyanins/chemistry , Diet, High-Fat/adverse effects , Diet , Fruit/chemistry , Rubus/chemistry , Animal Feed , Animals , Energy Metabolism , Lipid Metabolism , Male , Metabolic Diseases , Methylation , Mice , Mice, Inbred C57BL
8.
J Ethnopharmacol ; 203: 171-181, 2017 May 05.
Article in English | MEDLINE | ID: mdl-28344030

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Antimicrobial drug resistance is a growing threat to global public health. Historical records and herbal texts relating to traditional Celtic medicine indicate an extensive pharmacopeia of plants for treating infections likely caused by microbes. However, a major barrier for successful integration of these remedies into mainstream practice is the current lack of accurate interpretation and scientific validation. MATERIALS AND METHODS: We investigated the flora of the Isle of Arran, Scotland, via in situ targeted screening of 83 out of 138 plants identified in Meddygion Myddvai (a 14th century Welsh manuscript) to treat conditions related to microbial infections, and an additional 18 plants from modern ethnobotanical knowledge on the island (Scottish School of Herbal Medicine). In a follow-up proof-of-concept study, bioassay-guided fractionation was performed to identify bioactive constituents from two high scoring hits that inhibited Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacterial growth. RESULTS: 67 historical plants (80.7%) and 14 modern plants (77.8%) were found to have detectable levels of antimicrobial activity when tested using Mobile Discovery kits, with human saliva as a source of bacteria for screening. Sabinene, a natural bicyclic monoterpene from juniper "berries" (Juniperus communis L.) and alliin, a natural sulfoxide from garlic cloves (Allium sativum L.), were isolated and confirmed as primary antibacterial leads. CONCLUSION: Using historical medical sources such as those associated with traditional Celtic medicine to guide rigorous, evidence-based scientific investigation, provides additional leads for new and alternative bioactive molecules for combating bacterial diseases.


Subject(s)
Anti-Bacterial Agents/history , Medicine, Traditional/history , Plant Preparations/history , Plants, Medicinal/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/history , Ethnobotany/history , Ethnopharmacology/history , History, Medieval , Humans , Phytotherapy/history , Phytotherapy/methods , Plant Preparations/pharmacology , Scotland
9.
Int J Mol Sci ; 18(2)2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28212306

ABSTRACT

Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.


Subject(s)
Anthocyanins/chemistry , Anthocyanins/metabolism , Fruit/metabolism , Animal Feed , Animals , Body Composition , Body Weight , Chromatography, High Pressure Liquid , Dietary Supplements , Feces/chemistry , Gastrointestinal Microbiome , Glucose/metabolism , Humans , Insulin Resistance , Mice , Molecular Structure , Oxygen Consumption
10.
J Agric Food Chem ; 63(27): 6172-80, 2015 Jul 15.
Article in English | MEDLINE | ID: mdl-26066489

ABSTRACT

Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 µg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.


Subject(s)
Anthocyanins/administration & dosage , Glucose/metabolism , Obesity/drug therapy , Obesity/metabolism , Plant Extracts/administration & dosage , Ribes/chemistry , Weight Gain/drug effects , Animals , Anthocyanins/chemistry , Fruit/chemistry , Gastrointestinal Microbiome/drug effects , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/microbiology , Obesity/physiopathology , Plant Extracts/chemistry
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