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Schulz JR,Jan I,Sangha G,Azizi E
The high speed radular prey strike of a fish-hunting cone snail.
Curr Biol. 2019 Aug 19;29(16):R788-R789
Cone snails are venomous marine gastropods that hydraulically propel a hollow, chitinous radular harpoon into prey [1,2]. This radular harpoon serves both as projectile and conduit for venom delivery. In the fish-hunting cone snail Conus catus, the radular harpoon is also utilized to tether the snail to its prey, rapidly paralyzed by neuroexcitatory peptides [2,3]. Effective prey capture in C. catus requires both fast-acting neurotoxins and a delivery system quick enough to exceed the prey fish's rapid escape responses [4]. We report here that the cone snail's prey strike is one of the fastest in the animal kingdom. A unique cellular latch mechanism prevents harpoon release until sufficient pressure builds and overcomes the forces of the latch, resulting in rapid acceleration into prey [2]. The radular harpoon then rapidly decelerates as its bulbous base reaches the end of the proboscis, a distensible hydrostatic skeleton extended toward the prey [2], with little slowing during prey impalement. The velocities achieved are the fastest movements of any mollusk and exceed previous estimates by over an order of magnitude [1].
PMID: 31430472

Perraud V,Li X,Smith JN,Finlayson-Pitts BJ
Novel Ionization Reagent for the Measurement of Gas Phase Ammonia and Amines using a Stand-alone Atmospheric Pressure Gas Chromatography (APGC) Source.
Rapid Commun Mass Spectrom. 2019 Aug 19;
Contaminants present in ambient air or in sampling lines can interfere with the target analysis through overlapping peaks or causing a high background. This study presents a positive outcome from the unexpected presence of N-methyl-2-pyrrolidone, released from a PALL HEPA filter, in the analysis of atmospherically relevant gas phase amines using chemical ionization mass spectrometry.
PMID: 31429122

Chen W,Morabito SJ,Kessenbrock K,Enver T,Meyer KB,Teschendorff AE
Single-cell landscape in mammary epithelium reveals bipotent-like cells associated with breast cancer risk and outcome.
Commun Biol. 2019;2:306
Adult stem-cells may serve as the cell-of-origin for cancer, yet their unbiased identification in single cell RNA sequencing data is challenging due to the high dropout rate. In the case of breast, the existence of a bipotent stem-like state is also controversial. Here we apply a marker-free algorithm to scRNA-Seq data from the human mammary epithelium, revealing a high-potency cell-state enriched for an independent mammary stem-cell expression module. We validate this stem-like state in independent scRNA-Seq data. Our algorithm further predicts that the stem-like state is bipotent, a prediction we are able to validate using FACS sorted bulk expression data. The bipotent stem-like state correlates with clinical outcome in basal breast cancer and is characterized by overexpression of and , two modulators of basal breast cancer risk. This study illustrates the power of a marker-free computational framework to identify a novel bipotent stem-like state in the mammary epithelium.
PMID: 31428694

Pham TT,Lester E,Grigorian A,Roditi RE,Nahmias JT
National Analysis of Risk Factors for Nasal Fractures and Associated Injuries in Trauma.
Craniomaxillofac Trauma Reconstr. 2019 Sep;12(3):221-227
Nasal fractures account for up to 58% of facial fractures. However, the literature characterizing associated injuries and risk factors for nasal fractures is sparse and is mostly composed of single-center experiences. This study sought to provide a large descriptive analysis and identify associated injuries and risk factors for nasal fractures in trauma using a national database. A retrospective analysis of the National Trauma Data Bank (NTDB) from 2007 to 2015 was performed. Patients ≥18 years of age with nasal fractures were included. A multivariable logistic regression model was used to identify predictors for nasal fracture in trauma. Of 5,494,609 trauma patients in the NTDB, 255,533 (4.6%) had a nasal fracture. Most were male (74.8%) with a mean age of 45.6 years. Blunt trauma accounted for 90.5% of fractures, with motor vehicle accident being the most common mechanism (27.5%). Closed fractures occurred in 93.0% of patients. Concomitant injuries included traumatic brain injury (TBI; 56.9%), malar/maxillary fracture (27.9%), and open wound of the face (38.6%) and nose (9.5%). Of all patients, 10.1% underwent closed or open reductions at index hospitalization. The strongest associated injuries with nasal fracture included open wound of the nose (odds ratio [OR]: 8.71, 95% confidence interval [CI]: 8.49-8.94, ?
PMID: 31428247

Kreuzer KA,Furman RR,Stilgenbauer S,Dubowy RL,Kim Y,Munugalavadla V,Lilienweiss E,Reinhardt HC,Cramer P,Eichhorst B,Hillmen P,O'Brien SM,Pettitt AR,Hallek M
The impact of complex karyotype on the overall survival of patients with relapsed chronic lymphocytic leukemia treated with idelalisib plus rituximab.
Leukemia. 2019 Aug 19;
PMID: 31427720

Steyvers M,Hawkins GE,Karayanidis F,Brown SD
A large-scale analysis of task switching practice effects across the lifespan.
Proc Natl Acad Sci U S A. 2019 Aug 19;
An important feature of human cognition is the ability to flexibly and efficiently adapt behavior in response to continuously changing contextual demands. We leverage a large-scale dataset from Lumosity, an online cognitive-training platform, to investigate how cognitive processes involved in cued switching between tasks are affected by level of task practice across the adult lifespan. We develop a computational account of task switching that specifies the temporal dynamics of activating task-relevant representations and inhibiting task-irrelevant representations and how they vary with extended task practice across a number of age groups. Practice modulates the level of activation of the task-relevant representation and improves the rate at which this information becomes available, but has little effect on the task-irrelevant representation. While long-term practice improves performance across all age groups, it has a greater effect on older adults. Indeed, extensive task practice can make older individuals functionally similar to less-practiced younger individuals, especially for cognitive measures that focus on the rate at which task-relevant information becomes available.
PMID: 31427513

Spitz DR,Buettner GR,Limoli CL
Response to letter regarding "An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses".
Radiother Oncol. 2019 Aug 16;
PMID: 31427044

Vozella V,Realini N,Misto A,Piomelli D
Feeding Stimulates Sphingosine-1-Phosphate Mobilization in Mouse Hypothalamus.
Int J Mol Sci. 2019 Aug 17;20(16)
Previous studies have shown that the sphingolipid-derived mediator sphingosine-1-phosphate (S1P) reduces food intake by activating G protein-coupled S1P receptor-1 (S1PR1) in the hypothalamus. Here, we examined whether feeding regulates hypothalamic mobilization of S1P and other sphingolipid-derived messengers. We prepared lipid extracts from the hypothalamus of C57Bl6/J male mice subjected to one of four conditions: free feeding, 12 h fasting, and 1 h or 6 h refeeding. Liquid chromatography/tandem mass spectrometry was used to quantify various sphingolipid species, including sphinganine (SA), sphingosine (SO), and their bioactive derivatives SA-1-phosphate (SA1P) and S1P. In parallel experiments, transcription of S1PR1 (encoded in mice by the gene) and of key genes of sphingolipid metabolism (, , , ) was measured by RT-PCR. Feeding increased levels of S1P (in pmol-mg of wet tissue) and SA1P. This response was accompanied by parallel changes in SA and dihydroceramide (d18:0/18:0), and was partially (SA1P) or completely (S1P) reversed by fasting. No such effects were observed with other sphingolipid species targeted by our analysis. Feeding also increased transcription of , , , and . Feeding stimulates mobilization of endogenous S1PR1 agonists S1P and SA1P in mouse hypothalamus, via a mechanism that involves transcriptional up-regulation of de novo sphingolipid biosynthesis. The results support a role for sphingolipid-mediated signaling in the central control of energy balance.
PMID: 31426457

Baxter TW
Reflections on My Stroke Recovery: How I Came Back from a Massive Ischemic Stroke.
World Neurosurg. 2019 Sep;129:451-452
PMID: 31426255

Ricks CJ,Ma MW,Gastelum JR,Rajan GR,Rinehart JB
A Prospective Observational Cohort Study of Calls for Help in a Tertiary Care Academic Operating Room Suite.
Anesth Analg. 2019 Sep;129(3):e83-e85
While significant literature exists on hospital-based "code calls," there is a lack of research on calls for help in the operating room (OR). The purpose of this study was to quantify the rate and nature of calls for help in the OR of a tertiary care hospital. For a 1-year period, all calls were recorded in the main OR at The University of California, Irvine Medical Center. The average rate of calls per 1000 anesthesia hours was 1.4 (95% CI, 1.1-1.8), corresponding to a rate of 5.0 (3.8-6.5) calls per 1000 cases. Airway (44%), cardiac (32%), and hemorrhagic (11%) emergencies were the most common etiologies. Thirty-day mortality approached 11% for patients who required a call for help in the OR.
PMID: 31425214

Xie K,Chen CH,Tsai SP,Lu PJ,Wu H,Zeng Y,Ye Y,Tu H,Wen C,Huang M,Zhang Y,Lee JH,Tsai MK,Wen CP,Wu X
Loss of Life Expectancy by 10 Years or More From Elevated Aspartate Aminotransferase: Finding Aspartate Aminotransferase a Better Mortality Predictor for All-Cause and Liver-Related than Alanine Aminotransferase.
Am J Gastroenterol. 2019 Aug 14;
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled.
PMID: 31425154

Gaut BS,Miller AJ,Seymour DK
Living with Two Genomes: Grafting and Its Implications for Plant Genome-to-Genome Interactions, Phenotypic Variation, and Evolution.
Annu Rev Genet. 2019 Aug 19;
Plant genomes interact when genetically distinct individuals join, or are joined, together. Individuals can fuse in three contexts: artificial grafts, natural grafts, and host-parasite interactions. Artificial grafts have been studied for decades and are important platforms for studying the movement of RNA, DNA, and protein. Yet several mysteries about artificial grafts remain, including the factors that contribute to graft incompatibility, the prevalence of genetic and epigenetic modifications caused by exchanges between graft partners, and the long-term effects of these modifications on phenotype. Host-parasite interactions also lead to the exchange of materials, and RNA exchange actively contributes to an ongoing arms race between parasite virulence and host resistance. Little is known about natural grafts except that they can be frequent and may provide opportunities for evolutionary innovation through genome exchange. In this review, we survey our current understanding about these three mechanisms of contact, the genomic interactions that result, and the potential evolutionary implications. Expected final online publication date for the , Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
PMID: 31424971

Thammavongsy Z,Mercer IP,Yang JY
Promoting proton coupled electron transfer in redox catalysts through molecular design.
Chem Commun (Camb). 2019 Aug 19;
Most bond-forming and -breaking redox reactions require the concomitant transfer of protons. Unassisted proton movement can result in kinetic and thermodynamic barriers that inhibit the rate of these reactions, leading to slow and/or inefficient catalysis. These barriers can be circumvented by effective proton management through molecular design. Different strategies for managing proton movement are discussed with examples from biological and synthetic systems. As proton management is particularly important in redox reactions for chemical fuel generation and utilization, the focus will be on catalysts for H-H and O-O bond formation and cleavage. However, we expect the approaches discussed herein will be general to most multi-electron, multi-proton reactions.
PMID: 31424056

Wu C,Pan LL,Luo Y,Niu W,Fang X,Liang W,Li J,Li H,Pan X,Yang G,Chen W,Zhang H,Lakey JR,Agerberth B,de Vos P,Sun J
Low Methoxyl Pectin Protects Against Autoimmune Diabetes and Associated Caecal Dysfunction.
Mol Nutr Food Res. 2019 Aug 18;:e1900307
This study aims to examine the protective effects of specific low-methoxyl pectin (LMP) on the development of type 1 diabetes (T1D).
PMID: 31423661

Alexander LM,Salum GA,Swanson JM,Milham MP
Measuring strengths and weaknesses in dimensional psychiatry.
J Child Psychol Psychiatry. 2019 Aug 18;
The Extended Strengths and Weaknesses Assessment of Normal Behavior (E-SWAN) reconceptualizes each diagnostic criterion for selected DSM-5 disorders as a behavior, which can range from high (strengths) to low (weaknesses). Initial development focused on Panic Disorder, Social Anxiety, Major Depression, and Disruptive Mood Dysregulation Disorder.
PMID: 31423596

McClintock NC,Gray KE,Neville AL,Kaji AH,Wolfe MM,Calhoun KE,Amersi FF,Donahue TR,Arnell TD,Jarman BT,Inaba K,Melcher ML,Morris JB,Smith BR,Reeves ME,Gauvin JM,Salcedo ES,Sidwell RA,Dent DL,Murayama KM,Damewood RB,Poola VP,de Virgilio CM
Factors associated with general surgery residents' decisions regarding fellowship and subspecialty stratified by burnout and quality of life.
Am J Surg. 2019 Aug 08;
Although most surgery residents pursue fellowships, data regarding those decisions are limited. This study describes associations with interest in fellowship and specific subspecialties.
PMID: 31421896

Lebrun S,Xie Y,Chavez S,Chan R,Jester JV
An in vitro depth of injury prediction model for a histopathologic classification of EPA and GHS eye irritants.
Toxicol In Vitro. 2019 Aug 13;:104628
The purpose of this study was to develop Globally Harmonized System (GHS) and U.S. Environmental Protection Agency (EPA) prediction models for classifying irritant materials based on histopathologic in vitro depth of injury (DoI) measurements. Sixteen different materials were selected, representing all classes of toxicity, according to the GHS and EPA classification systems. Food-source rabbit eyes, similar to eyes used for the widely accepted Bovine Corneal Opacity and Permeability and Isolated Chicken Eye ocular irritation tests, were used. Tissues were exposed to test material for 1?min, and corneas were collected at 3- and 24-hours post-exposure. Tissues were then fixed and processed for live/dead biomarker fluorescent staining using phalloidin. DoI was then measured, and the percent DoI values for the epithelium and stroma were compared to the EPA and GHS classifications. Excluding surfactants, EPA nonclassified (category IV) materials showed no stromal and very slight epithelial damage (≤10%) to the cornea, whereas EPA corrosive (category I) materials showed significantly greater damage (P?10%, P?
PMID: 31419508

Gross TJ,Doran E,Cheema AK,Head E,Lott IT,Mapstone M
Plasma Metabolites Related to Cellular Energy Metabolism Are Altered in Adults with Down Syndrome and Alzheimer's Disease.
Dev Neurobiol. 2019 Aug 16;
Down Syndrome (DS) is a well-known neurodevelopmental disorder most commonly caused by trisomy of chromosome 21. Because individuals with DS almost universally develop heavy amyloid burden and Alzheimer's disease (AD), biomarker discovery in this population may be extremely fruitful. Moreover, any AD biomarker in DS that does not directly involve amyloid pathology may be of high value for understanding broader mechanisms of AD generalizable to the neurotypical population. In this retrospective biomarker discovery study, we examined banked peripheral plasma samples from 78 individuals with DS who met clinical criteria for AD at the time of the blood draw (DS-AD) and 68 individuals with DS who did not (DS-NAD). We measured the relative abundance of approximately 5000 putative features in the plasma using untargeted mass spectrometry (MS). We found significantly higher levels of a peak putatively annotated as lactic acid in the DS-dementia group (q = 0.014), a finding confirmed using targeted MS (q = 0.011). Because lactate is the terminal product of glycolysis and subsequent lactic acid fermentation, we performed additional targeted MS focusing on central carbon metabolism which revealed significantly increased levels of pyruvic (q = 0.03) and methyladipic (q = 0.03) acids in addition to significantly lower levels of uridine (q = 0.007) in the DS-AD group. These data suggest that AD in DS is accompanied by a shift from aerobic respiration toward the less efficient fermentative metabolism and that bio-energetically derived metabolites observable in peripheral blood may be useful for detecting this shift.
PMID: 31419370

Duncan ES,Donovan NJ,Sajjadi SA
Clinical Assessment of Characteristics of Apraxia of Speech in Primary Progressive Aphasia.
Am J Speech Lang Pathol. 2019 Aug 16;:1-13
Purpose We sought to examine interrater reliability in clinical assessment of apraxia of speech (AOS) in individuals with primary progressive aphasia and to identify speech characteristics predictive of AOS diagnosis. Method Fifty-two individuals with primary progressive aphasia were recorded performing a variety of speech tasks. These recordings were viewed by 2 experienced speech-language pathologists, who independently rated them on the presence and severity of AOS as well as 14 associated speech characteristics. We calculated interrater reliability (percent agreement and Cohen's kappa) for these ratings. For each rater, we used stepwise regression to identify speech characteristics significantly predictive of AOS diagnosis. We used the overlap between raters to create a more parsimonious model, which we evaluated with multiple linear regression. Results Results yielded high agreement on the presence (90%) and severity of AOS (weighted Cohen's ? = .834) but lower agreement for specific speech characteristics (weighted Cohen's ? ranging from .036 to .582). Stepwise regression identified 2 speech characteristics predictive of AOS diagnosis for both raters (articulatory groping and increased errors with increased length/complexity). These alone accounted for ≥ 50% of the variance of AOS severity in the constrained model. Conclusions Our study adds to a growing body of research that highlights the difficulty in objective clinical characterization of AOS and perceptual characterization of speech features. It further supports the need for consensus diagnostic criteria with standardized testing tools and for the identification and validation of objective markers of AOS. Additionally, these findings underscore the need for a training protocol if diagnostic tools are to be effective when shared beyond the research teams that develop and test them and disseminated to practicing speech-language pathologists, in order to ensure consistent application.
PMID: 31419154

Berger MH,Tajudeen BA,St John MA,Tjoa T,Kuan EC
Should an elective neck dissection be performed for maxillary sinus squamous cell carcinoma?
Laryngoscope. 2019 Aug 16;
PMID: 31418862

Stieglitz J,Trumble BC, ,Finch C,Li D,Budoff MJ,Kaplan H,Gurven M
Computed tomography shows high fracture prevalence among physically active forager-horticulturalists with high fertility.
Elife. 2019 Aug 16;8
Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on inactivity to explain skeletal fragility. Minimal BMD differences exist between Tsimane and American men, suggesting that systemic factors other than fertility (e.g. diet) do not easily explain Tsimane women's lower BMD. Tsimane fracture prevalence is also higher versus Americans. Lower BMD increases Tsimane fracture risk, but only for women, suggesting a role of weak bone in women's fracture etiology. Our results highlight the role of sex-specific mechanisms underlying skeletal fragility that operate long before menopause.
PMID: 31418688

Tadevosyan NS,Poghosyan SB,Khachatryan BG,Muradyan SA,Guloyan HA,Tshantshapanyan AN,Hutchings NJ,Tadevosyan AE
Residues of xenobiotics in the environment and phytotoxic activity in Armenia.
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2019 Aug 16;:1-8
The article presents the results of a dynamic study (spring, summer, and fall) of the residues of certain xenobiotics such as organochlorine pesticides (OCPs), synthetic surfactants (SSs) in surface water, soil, sludge, snow and phytotoxic activity in Ararat and Lori marzes of Armenia (2016-2017). A comparative analysis of the environmental status showed that all pollutants studied such as ?-hexachlorocyclohexane (?-HCH), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (4,4'-DDT), and p-p'-dichlorodiphenyldichloroethylene (4,4'-DDE) were identified in Ararat marz with the average concentrations and detection rates higher than in Lori marz. The prominent contaminant was ?-HCH. The findings indicated the concentrations of OCPs below of regulatory concern. In Ararat marz an increase in the number of sterile pollen grains of certain wild plants was revealed (14.8-26.0%), compared with Lori marz with the levels within the contingent standard of 5-11%. The phytotoxic activity of soil samples from the Ararat marz studied on seedlings was significantly higher in the summer-fall period. These data correlated with monitoring findings showed an increase in the levels of ?-HCH, 4,4'-DDT, SS in the soil and sludge sampled in summer-fall in Ararat marz. This difference in the environmental status can be considered as the result of active agriculture in Ararat marz, whose share of contribution to a relevant branch of the economy of Armenia is two times higher than in Lori marz, 15.4% and 7.9%, respectively. Mentioned rates of agricultural production may be one of the reasons for the environmental deterioration in Ararat marz. The detection of 4,4-DDT, ?-HCH residues testifies the circulation of these formulations in the environment indicating their use in recent past and confirming their persistence. Although since the 70s of the last century the application of OCPs in the Republic of Armenia has been prohibited. The current situation may be explained by low awareness of farmers on different issues related to the safe management of pesticides. To ensure safe working conditions and raise awareness among the farmers we have developed "Recommendations on Safety requirements when working with pesticides" that are approved by the State Service for Food Safety at the Ministry of Agriculture of RA and included in the reference booklets for farmers as guiding information. Our study shows the understanding of associations between the deterioration of the environmental status and share of agriculture contribution to the economy that provides the evidence for future research programs.
PMID: 31418625

Hursn D,Samu AA,Janovk L,Artyushkova K,Asset T,Atanassov P,Janky C
Morphological Attributes Govern Carbon Dioxide Reduction on N-Doped Carbon Electrodes.
Joule. 2019 Jul 17;3(7):1719-1733
The morphology of electrode materials is often overlooked when comparing different carbon-based electrocatalysts for carbon dioxide reduction. To investigate the role of morphological attributes, we studied polymer-derived, interconnected, N-doped carbon structures with uniformly sized meso or macropores, differing in the pore size. We found that the carbon dioxide reduction selectivity (versus the hydrogen evolution reaction) increased around three times just by introducing the porosity into the carbon structure (with an optimal pore size of 27nm). We attribute this change to alterations in the wetting and CO adsorption properties of the carbon catalysts. These insights offer a new platform to advance CO reduction performance by only morphological engineering of the electrocatalyst.
PMID: 31417986

Hendrick LA,Carter GA,Hilbrands EH,Heubel BP,Schilling TF,Le Pabic P
Bar, stripe and spot development in sand-dwelling cichlids from Lake Malawi.
Evodevo. 2019;10:18
Melanic patterns such as horizontal stripes, vertical bars and spots are common among teleost fishes and often serve roles in camouflage or mimicry. Extensive research in the zebrafish model has shown that the development of horizontal stripes depends on complex cellular interactions between melanophores, xanthophores and iridophores. Little is known about the development of horizontal stripes in other teleosts, and even less is known about bar or spot development. Here, we compare chromatophore composition and development of stripes, bars and spots in two cichlid species of sand-dwellers from Lake Malawi- and .
PMID: 31417669

Wu C,Pan LL,Niu W,Fang X,Liang W,Li J,Li H,Pan X,Chen W,Zhang H,Lakey JRT,Agerberth B,de Vos P,Sun J
Modulation of Gut Microbiota by Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice.
Front Immunol. 2019;10:1733
Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25Foxp3CD4 regulatory T cell (Foxp3 Treg) in the pancreas, pancreatic and mesenteric lymph nodes was analyzed by flow cytometry. We found that LMP supplementation ameliorated T1D development in non-obese diabetic (NOD) mice, as evidenced by decreasing diabetes incidence and fasting glucose levels in LMP fed NOD mice. Further microbiota analysis revealed that LMP supplementation prevented T1D-associated caecal dysbiosis and selectively enriched caecal bacterial species to produce more SCFAs. The LMP-mediated microbial balance further enhanced caecal barrier function and shaped gut-pancreatic immune environment, as characterized by higher expression of tight junction proteins claudin-1, ZO-2 in caecum, increased Foxp3 Treg population and decreased NLRP3 inflammasome activation in both caecum and pancreas. The microbiota-dependent beneficial effect of LMP on T1D was further proven by the fact that aberration of caecal microbiota by ABX treatment worsened T1D autoimmunity and could be restored with transfer of feces of LMP-fed NOD mice. These data demonstrate that this novel LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment. This finding opens a realistic option for gut microbiota manipulation and prevention of T1D in humans.
PMID: 31417546

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