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Artigo em Inglês | MEDLINE | ID: mdl-31713023


PBC is a chronic progressive autoimmune disorder involving the destruction of intrahepatic small bile ducts, cholestasis, fibrosis, and ultimately cirrhosis if left untreated. It is largely driven by the autoimmune response, but bile acids and the intestinal microbiota are implicated in disease progression as well. The only drugs licensed for PBC are UDCA and OCA. UDCA as a first-line and OCA as a second-line therapy are safe and effective, but the lack of response in a significant portion of patients and inadequate control of symptoms such as fatigue and pruritus remain as concerns. Liver transplantation is an end-stage therapy for many patients refractory to UDCA, which gives excellent survival rates but also moderate to high recurrence rates. The limited options for FDA-approved PBC therapies necessitate the development of alternative approaches. Currently, a wide variety of experimental drugs exist targeting immunological and physiological aspects of PBC to suppress inflammation. Immunological therapies include drugs targeting immune molecules in the B cell and T cell response, and specific cytokines and chemokines implicated in inflammation. Drugs targeting bile acids are also noteworthy as bile acids can perpetuate hepatic inflammation and lead to fibrosis over time. These include FXR agonists, ASBT inhibitors, and PPAR agonists such as bezafibrate and fenofibrate. Nonetheless, many of these drugs can only delay disease progression and fail to enhance patients' quality of life. Nanomedicine shows great potential for treatment of autoimmune diseases, as it provides a new approach that focuses on tolerance induction rather than immunosuppression. Tolerogenic nanoparticles carrying immune-modifying agents can be engineered to safely and effectively target the antigen-specific immune response in autoimmune diseases. These may work well with PBC especially, given the anatomical features and immunological specificity of the disease. Nanobiological therapy is thus an area of highly promising research for future treatment of PBC.

Bioresour Technol ; 206: 141-149, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26851898


Rhodosporidium toruloides AS 2.1389 was tested using different concentrations of acetic acid as a low-cost carbon source for the production of microbial lipids, which are good raw materials for biodiesel production. It grew and had higher lipid contents in media containing 4-20 g/L acetic acid as the sole carbon source, compared with that in glucose-containing media under the same culture conditions. At acetic acid concentrations as high as 20 g/L and the optimal carbon-to-nitrogen ratio (C/N) of 200 in a batch culture, the highest biomass production was 4.35 g/L, with a lipid content of 48.2%. At acetic acid concentrations as low as 4 g/L, a sequencing batch culture (SBC) with a C/N of 100 increased biomass production to 4.21 g/L, with a lipid content of 38.6%. These results provide usable culture strategies for lipid production by R. toruloides AS 2.1389 when using diverse waste-derived volatile fatty acids.

Ácido Acético/metabolismo , Basidiomycota/metabolismo , Técnicas de Cultura Celular por Lotes/métodos , Lipídeos/biossíntese , Biocombustíveis , Biomassa , Carbono/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbiologia Industrial/métodos , Nitrogênio/metabolismo
Acta Pharmacol Sin ; 35(2): 175-84, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24389946


AIM: To examine whether co-activation of nAChR and mGluR1 induced γ oscillation (20-60 Hz) in rat medial septum diagonal band of Broca (MSDB) slices. METHODS: Rat brain sagittal slices containing the MSDB were prepared. Extracellular field potentials were recorded with glass microelectrodes. The nAChR and mGluR1 agonists were applied to the slices to induce network activity. Data analysis was performed off-line using software Spike 2. RESULTS: Co-application of the nAChR agonist nicotine (1 µmol/L) and the mGluR1 agonist dihydroxyphenylglycine (DHPG, 25 µmol/L) was able to induce γ oscillation in MSDB slices. The intensity of nAChR and mGluR1 activation was critical for induction of network oscillation at a low (θ oscillation) or high frequency (γ oscillation): co-application of low concentrations of the two agonists only increased the power and frequency of oscillation within the range of θ, whereas γ oscillation mostly appeared when high concentrations of the two agonists were applied. CONCLUSION: Activation of mGluR1 and nAChR is able to program slow or fast network oscillation by altering the intensity of receptor activation, which may provide a mechanism for modulation of learning and memory.

Feixe Diagonal de Broca/metabolismo , Feixe Diagonal de Broca/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
Acta Pharmacol Sin ; 34(4): 464-72, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23474704


AIM: Spiking activities and neuronal network oscillations in the theta frequency range have been found in many cortical areas during information processing. The aim of this study is to determine whether nicotinic acetylcholine receptors (nAChRs) mediate neuronal network activity in rat medial septum diagonal band Broca (MSDB) slices. METHODS: Extracellular field potentials were recorded in the slices using an Axoprobe 1A amplifier. Data analysis was performed off-line. Spike sorting and local field potential (LFP) analyses were performed using Spike2 software. The role of spiking activity in the generation of LFP oscillations in the slices was determined by analyzing the phase-time relationship between the spikes and LFP oscillations. Circular statistic analysis based on the Rayleigh test was used to determine the significance of phase relationships between the spikes and LFP oscillations. The timing relationship was examined by quantifying the spike-field coherence (SFC). RESULTS: Application of nicotine (250 nmol/L) induced prominent LFP oscillations in the theta frequency band and both small- and large-amplitude population spiking activity in the slices. These spikes were phase-locked to theta oscillations at specific phases. The Rayleigh test showed a statistically significant relationship in phase-locking between the spikes and theta oscillations. Larger changes in the SFC were observed for large-amplitude spikes, indicating an accurate timing relationship between this type of spike and LFP oscillations. The nicotine-induced spiking activity (large-amplitude population spikes) was suppressed by the nAChR antagonist dihydro-ß-erythroidine (0.3 µmol/L). CONCLUSION: The results demonstrate that large-amplitude spikes are phase-locked to theta oscillations and have a high spike-timing accuracy, which are likely a main contributor to the theta oscillations generated in MSDB during nicotine receptor activation.

Potenciais de Ação/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nicotina/farmacologia , Núcleos Septais/efeitos dos fármacos , Ritmo Teta/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Lobo Frontal/metabolismo , Lobo Frontal/fisiologia , Técnicas In Vitro , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Wistar , Receptores Nicotínicos/metabolismo , Núcleos Septais/metabolismo , Núcleos Septais/fisiologia , Estimulação Química , Ritmo Teta/fisiologia