Search

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (T.sub.H17 cells) or regulatory T cells (T.sub.reg cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice. 3-OxoLCA inhibited the differentiation of T.sub.H17 cells by directly binding to the key transcription factor retinoid-related orphan receptor-[gamma]t (ROR[gamma]t) and isoalloLCA increased the differentiation of T.sub.reg cells through the production of mitochondrial reactive oxygen species (mitoROS), which led to increased expression of FOXP3. The isoalloLCA-mediated enhancement of T.sub.reg cell differentiation required an intronic Foxp3 enhancer, the conserved noncoding sequence (CNS) 3; this represents a mode of action distinct from that of previously identified metabolites that increase T.sub.reg cell differentiation, which require CNS1. The administration of 3-oxoLCA and isoalloLCA to mice reduced T.sub.H17 cell differentiation and increased T.sub.reg cell differentiation, respectively, in the intestinal lamina propria. Our data suggest mechanisms through which bile acid metabolites control host immune responses, by directly modulating the balance of T.sub.H17 and T.sub.reg cells. Screening of a library of bile acid metabolites revealed two derivatives of lithocholic acid that act as regulators of T helper cells that express IL-17a and regulatory T cells, thus influencing host immune responses., Author(s): Saiyu Hang [sup.1] , Donggi Paik [sup.1] , Lina Yao [sup.2] , Eunha Kim [sup.1] , Jamma Trinath [sup.3] , Jingping Lu [sup.4] , Soyoung Ha [sup.1] , Brandon [...]

In this paper, the limit cycles and local bifurcation of critical periods for a class of switching Z 2 equivariant quartic system with two symmetric singularities are investigated. First, through the computation of Lyapunov constants, the conditions of the two singularities to become the centers are determined. Then, we prove that there are at most 18 limit cycles with a distribution pattern of 9-9 around the two symmetric singular points of the system. Numerical simulation is conducted to validate the obtained results. Furthermore, by calculating the period constants, we determine the conditions for the critical point to be a weak center of finite order. Finally, the number of local critical periods that bifurcate from the equilibrium point under the center conditions is discussed. This study presents the first example of a quartic switching smooth system with 18 limit cycles and 4 local critical periods bifurcating from two symmetric singular points. [ABSTRACT FROM AUTHOR]

The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, [...]

Sulfate radicals-based Fenton-like technology has placed more emphasis on effectively dealing with the threat of dye wastewater. In this work, the Zn-doped CuFe2O4@biochar composite (Cu0.9Zn0.1Fe2O4@BC) was prepared through the convenient sol–gel pyrolysis process and applied as heterogeneous persulfate (PS) activator for crystal violet (CV) degradation. The crystal morphology and physicochemical properties of Cu0.9Zn0.1Fe2O4@BC were investigated by scanning electron microscope (SEM), X-ray diffractometer (XRD), vibrating sample magnetometer (VSM), Brunauer–Emmett–Teller method (BET), and X-ray photoelectron spectroscopy (XPS). The morphology of the catalyst changed before and after Zn doping. The crystallite size, lattice constant, saturation magnetization, and oxygen vacancy content increased after doping Zn. Compared with CuFe2O4@BC, the CV degradation efficiency of Cu0.9Zn0.1Fe2O4@BC activating PS increased from 87.7 to 96.9%, and the corresponding reaction rate constant increased by about 3.69 times. The effect of experimental conditions was systematically studied on the degradation progress. The degradation efficiency of CV was 91% after five times cycle experiments. Multiple experiments indicated that SO4•–, •OH and O2•– predominated for CV degradation. The degradation mechanism of CV in the Cu0.9Zn0.1Fe2O4@BC/PS system involved both free radical (SO4•–, •OH and O2•–) and non-free radical pathways (electron transfer). The possible degradation pathways were investigated according to the ultra-performance liquid chromatography mass spectrometry (UPLC-MS) analysis of degradation intermediates. The result showed that Cu0.9Zn0.1Fe2O4@BC have an excellent catalyst performance, which provides a new strategy for improving catalytic activity. [ABSTRACT FROM AUTHOR]

Falls impose substantial health and economic burdens on older adults. Over half of falls in older adults occur at home, with many involving bathroom areas. Limited information is available on the presence of bathroom modifications for those who experience them. Therefore, we examined factors associated with bathroom modifications among older adults with at least one fall in the United States. We analysed the nationally representative 2016 Medicare Current Beneficiary Survey Public Use File of Medicare beneficiaries aged ≥65 years with ≥1 fall (n = 2,404). A survey‐weighted logistic model was used to examine associations between bathroom modifications and factors including socio‐demographic characteristics, health‐related conditions, and fear of falling. Among Medicare beneficiaries with ≥1 fall, 55.5% had bathroom modifications and 50.1% had repeated falls (≥2 falls). Approximately 40.2% of those with repeated falls had no bathroom modifications. In the adjusted model, non‐Hispanic Blacks (odds ratio [OR] = 0.38; p < 0.001) and Hispanics (OR = 0.64; p = 0.039) had lower odds of having bathroom modifications than non‐Hispanic Whites. Fear of falling and activities of daily living limitations had incremental impacts on having bathroom modifications. This study highlights the need to improve disparities in bathroom modifications for non‐Hispanic Black and Hispanic Medicare beneficiaries, including those with repeated falls. With the aging population and growing number of older minorities in the United States, reducing these disparities is vital for fall prevention efforts and aging‐in‐place. [ABSTRACT FROM AUTHOR]

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (TH17 cells) or regulatory T cells (Treg cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice. 3-OxoLCA inhibited the differentiation of TH17 cells by directly binding to the key transcription factor retinoid-related orphan receptor-γt (RORγt) and isoalloLCA increased the differentiation of Treg cells through the production of mitochondrial reactive oxygen species (mitoROS), which led to increased expression of FOXP3. The isoalloLCA-mediated enhancement of Treg cell differentiation required an intronic Foxp3 enhancer, the conserved noncoding sequence (CNS) 3; this represents a mode of action distinct from that of previously identified metabolites that increase Treg cell differentiation, which require CNS1. The administration of 3-oxoLCA and isoalloLCA to mice reduced TH17 cell differentiation and increased Treg cell differentiation, respectively, in the intestinal lamina propria. Our data suggest mechanisms through which bile acid metabolites control host immune responses, by directly modulating the balance of TH17 and Treg cells. Screening of a library of bile acid metabolites revealed two derivatives of lithocholic acid that act as regulators of T helper cells that express IL-17a and regulatory T cells, thus influencing host immune responses. [ABSTRACT FROM AUTHOR]

Though an association between autoimmune diseases and sick sinus syndrome has been reported, there has been no report on the association of hypopituitarism and sick sinus syndrome. Herein, we provide the first case report of hypopituitarism accompanying sick sinus syndrome in a 51-year-old woman presented to our hospital with syncope due to cardiac arrest. The patient was successfully managed by pacemaker installation and hormone replacement therapy.

The expression of NMDA receptor NR1 subunit mRNA was studied in rat auditory cortex (AC) on different postnatal days using digoxigenin-labeled oligonucleotide probes. The results showed that NR1 expression increased from birth to postnatal day 35 (P35) and remained constant until P56. The most significant increases occurred between P7 and P14. Changes in NR1 mRNA expression in rats subjected to monaural hearing deprivation on P7, P21, P35, and P49 were examined on P56. Between P7 and P21, when the rat auditory system was still in a critical period of development, NR1 mRNA expression was lower in the contralateral AC, which received auditory signals from the plugged ear, than in the ipsilateral AC. However, no significant difference was observed between the rats deprived of hearing on P35 and those deprived of hearing on P42, the end of the critical period of auditory development. These results showed that monaural hearing deprivation during early postnatal development was associated with decreased NR1 mRNA expression in the contralateral AC and suggested the involvement of NR1 in auditory function during development. They also indicated that, during postnatal development, environmental factors changed the functional plasticity of neurons in the AC through NR1 receptor expression. Taken together, these findings provide a possible underlying mechanism for the development of postnatal auditory function., (2007 Wiley-Liss, Inc.)