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1.
Mol Psychiatry ; 26(11): 6912-6925, 2021 11.
Article in English | MEDLINE | ID: mdl-33981006

ABSTRACT

Reduced activity of the mediodorsal thalamus (MD) and abnormal functional connectivity of the MD with the prefrontal cortex (PFC) cause cognitive deficits in schizophrenia. However, the molecular basis of MD hypofunction in schizophrenia is not known. Here, we identified leucine-rich-repeat transmembrane neuronal protein 1 (LRRTM1), a postsynaptic cell-adhesion molecule, as a key regulator of excitatory synaptic function and excitation-inhibition balance in the MD. LRRTM1 is strongly associated with schizophrenia and is highly expressed in the thalamus. Conditional deletion of Lrrtm1 in the MD in adult mice reduced excitatory synaptic function and caused a parallel reduction in the afferent synaptic activity of the PFC, which was reversed by the reintroduction of LRRTM1 in the MD. Our results indicate that chronic reduction of synaptic strength in the MD by targeted deletion of Lrrtm1 functionally disengages the MD from the PFC and may account for cognitive, social, and sensorimotor gating deficits, reminiscent of schizophrenia.


Subject(s)
Schizophrenia , Animals , Cognition/physiology , Membrane Proteins , Mice , Nerve Tissue Proteins/genetics , Prefrontal Cortex , Schizophrenia/genetics , Sensory Gating , Thalamus
2.
J Sci Food Agric ; 102(10): 3952-3963, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-34958458

ABSTRACT

BACKGROUND: Polymethoxylated flavones (PMFs) show multiple biological functions, while their high hydrophobicity leads to a low bioaccessibility and limits their wide applications. The design of a reasonable food-grade drug delivery system is an effective strategy to improve the low bioaccessibility of PMFs. In this study, sinensetin, tangeretin and nobiletin were encapsulated in Pickering emulsions stabilized by zein/pullulan complex colloidal particles (ZPPs), and the protection effect and in vitro digestion were characterized. RESULTS: Rheological analysis revealed that ZPP-Pickering emulsion loading with PMFs maintained a strong gel-like network structure. Moreover, the ability to scavenge free radicals of PMFs was improved by the emulsion delivery system. The antioxidant activity of PMFs encapsulated in Pickering emulsion was positively correlated with the oil volume fraction (φ). ZPP-Pickering emulsion loading with PMFs can effectively delay lipid oxidation, and the φ (70%) of Pickering emulsion showed the most pronounced effects, in which the lipid hydroperoxide content and malondialdehyde content decreased by 64.3% and 38.3% after 15 days of storage, compared with the bulk oil group, respectively. The bioaccessibility of the three PMFs has been increased by ZPP-Pickering emulsion simultaneously and it presented the highest values as its φ was 50%, in which the bioaccessibility of sinensetin, tangeretin and nobiletin increased by 2.5, 3.2 and 3.9 times, compared with the bulk oil group, respectively. CONCLUSION: Pickering emulsion stabilized by ZPPs is an excellent nutrient delivery system for delivering three PMFs simultaneously and imparting functional properties to bioactive delivery systems. © 2022 Society of Chemical Industry.


Subject(s)
Flavones , Zein , Digestion , Emulsions/chemistry , Glucans , Particle Size
3.
Mov Disord ; 36(4): 938-947, 2021 04.
Article in English | MEDLINE | ID: mdl-33135810

ABSTRACT

BACKGROUND: Levodopa (l-dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of l-dopa results in a motor complication known as levodopa-induced dyskinesia (LID) in ~50% of patients over 5 years. OBJECTIVES: We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine-dependent vessel diameter changes. METHODS: Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6-OHDA lesion) treated with 2 doses of l-dopa (saline, 2, and 10 mg/kg/day subcutaneous l-dopa treatment for 22 days) by 5-bromo-2'-deoxyuridine (BrdU)-RECA1 co-immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2-photon laser scanning microscopy and Dodt gradient imaging. RESULTS: We found that the 10 mg/kg l-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22-day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non-LID animals. Dopamine-induced vasodilatory responses were exaggerated only in rats that show LID-like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA-induced vasodilation is preceded by increased Ca2+ release in the adjacent astrocytes. CONCLUSION: This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Dyskinesia, Drug-Induced , Parkinson Disease , Animals , Antiparkinson Agents/toxicity , Corpus Striatum , Disease Models, Animal , Dopamine , Humans , Levodopa/toxicity , Oxidopamine/toxicity , Parkinson Disease/drug therapy , Rats
4.
Biochem Biophys Res Commun ; 521(2): 485-491, 2020 01 08.
Article in English | MEDLINE | ID: mdl-31677784

ABSTRACT

Oxidative stress and cardiomyocyte apoptosis contributed to the progression of doxorubicin (Dox)-induced cardiotoxicity. Recent studies identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that functioned as a key regulator in stress-induced cardiac injury. The present study aimed to investigate the role and possible mechanism of miR-22 on Dox-induced oxidative stress and cardiomyocyte apoptosis. Mice were exposed to reduplicative injections of Dox (i.p., 4 mg/kg) weekly for consecutive 4 weeks to generate Dox-induced cardiotoxicity. Herein, we found that miR-22 level was significantly increased in murine hearts subjected to chronic Dox treatment. MiR-22 inhibition attenuated oxidative stress and cardiomyocyte apoptosis in vivo and in vitro, thereby preventing Dox-induced cardiac dysfunction. Mechanistically, we observed that miR-22 directly bound to the 3'-UTR of Sirt1 and caused SIRT1 downregulation. Conversely, miR-22 antagomir upregulated SIRT1 expression and SIRT1 inhibitor abolished the beneficial effects of miR-22 antagomir. In conclusion, miR-22 inhibition prevented oxidative stress and cardiomyocyte apoptosis via upregulating SIRT1 and miR-22 might be a new target for treating Dox-induced cardiotoxicity.


Subject(s)
Cardiotoxicity/prevention & control , Doxorubicin/adverse effects , MicroRNAs/antagonists & inhibitors , Sirtuin 1/metabolism , 3' Untranslated Regions , Animals , Antagomirs/pharmacology , Apoptosis/drug effects , Cardiotoxicity/etiology , Mice , MicroRNAs/metabolism , Oxidative Stress/drug effects , Sirtuin 1/genetics , Up-Regulation
5.
Med Sci Monit ; 26: e928849, 2020 Dec 19.
Article in English | MEDLINE | ID: mdl-33339813

ABSTRACT

BACKGROUND Emerging studies noted that liver injury in coronavirus disease 2019 (COVID-19) patients may be induced by virus-mediated inflammation, which was confirmed by liver pathology. The aim of this study was to observe clinical characteristics and explore risk factors in COVID-19 patients with liver injury. MATERIAL AND METHODS In this retrospective study, 40 confirmed COVID-19 patients with normal alanine transaminase (ALT) on admission were divided into a group of normal ALT patients whose ALT was always less than 40 U/l during hospitalization and a group of elevated ALT patients whose ALT was at least once more than 40 U/l after admission. Clinical data, especially virus-induced inflammatory parameters, were analyzed for risk factors and predictive value. The Mann-Whitney U test and t test for comparing means and logistic regression were performed for analysis of risk factors. Area under the ROC curve was used for predictive values. RESULTS Sixteen of 40 (40.0%) patients developed elevated ALT, many of them with more severe COVID-19. The highest ALT level was 101 U/l. The risk factors for liver injury were C-reactive protein (CRP), interleukin 6 (IL6), erythrocyte sedimentation rate (ESR), CD8+T cell count, and severity of disease, and CRP (OR 1.13, 95% CI 1.045-1.222, p=0.002) was the independent risk factor. CONCLUSIONS Liver injury in COVID-19 patients was mild and associated with inflammatory markers, especially CRP, which suggests that liver injury may be induced by virus-mediated inflammation in COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Liver/metabolism , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/metabolism , China/epidemiology , Coronavirus/pathogenicity , Female , Hospitalization , Humans , Interleukin-6/analysis , Liver/injuries , Lymphocyte Count , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity
6.
Environ Microbiol ; 21(11): 4212-4232, 2019 11.
Article in English | MEDLINE | ID: mdl-31418995

ABSTRACT

Almost all bacterial genomes harbour prophages, yet it remains unknown why prophages integrate into tRNA-related genes. Approximately 1/3 of Shewanella isolates harbour a prophage at the tmRNA (ssrA) gene. Here, we discovered a P2-family prophage integrated at the 3'-end of ssrA in the deep-sea bacterium S. putrefaciens. We found that ~0.1% of host cells are lysed to release P2 constitutively during host growth. P2 phage production is induced by a prophage-encoded Rep protein and its excision is induced by the Cox protein. We also found that P2 genome excision leads to the disruption of wobble base pairing of SsrA due to site-specific recombination, thus disrupting the trans-translation function of SsrA. We further demonstrated that P2 excision greatly hinders growth in seawater medium and inhibits biofilm formation. Complementation with a functional SsrA in the P2-excised strain completely restores the growth defects in seawater medium and partially restores biofilm formation. Additionally, we found that products of the P2 genes also increase biofilm formation. Taken together, this study illustrates a symbiotic relationship between P2 and its marine host, thus providing multiple benefits for both sides when a phage is integrated but suffers from reduced fitness when the prophage is excised.


Subject(s)
Bacteriophage P2/physiology , Shewanella putrefaciens/virology , Symbiosis/genetics , Aquatic Organisms/genetics , Genome, Bacterial/genetics , Prophages/genetics , RNA, Bacterial/genetics , Shewanella putrefaciens/genetics
7.
J Pharmacol Exp Ther ; 358(1): 31-8, 2016 07.
Article in English | MEDLINE | ID: mdl-27189965

ABSTRACT

Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity.


Subject(s)
5'-Nucleotidase/metabolism , Adenosine/metabolism , Drug Tolerance , Ethanol/pharmacology , Hippocampus/drug effects , Signal Transduction/drug effects , 5'-Nucleotidase/genetics , Animals , Ethanol/blood , Hippocampus/enzymology , Hippocampus/metabolism , Male , Mice, Knockout , Receptor, Adenosine A1/genetics , Receptor, Adenosine A1/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Synaptic Transmission/drug effects
8.
J Sep Sci ; 38(19): 3390-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26227076

ABSTRACT

In chromatographic processes, molecular collisions between the mobile phase and the solute result in the transfer of kinetic energy. Based on these interactions, the relationship between the gauge pressure of the carrier gas at the column inlet and the partition frequency of the solute is derived; consequently, the relationship between the column temperature and partition frequency can be obtained. These relationships have been experimentally validated. The change in the peak shape described herein has been successfully explained using this relationship: the partition frequency was calculated from the theoretical plate number of a tailing peak. We propose a new mechanism for peak tailing using plate theory, which states that as the number of plates increases, the symmetry of the peak increases.


Subject(s)
Chromatography, Gas/methods , Energy Transfer , Hydrocarbons/chemistry , Normal Distribution , Solutions/chemistry , Temperature
9.
Zhonghua Nei Ke Za Zhi ; 54(12): 1023-7, 2015 Dec.
Article in Zh | MEDLINE | ID: mdl-26887368

ABSTRACT

OBJECTIVE: To analyze the clinical outcome and complications of orthotopic liver transplantation (OLT) for patients with primary biliary cirrhosis(PBC). METHODS: Clinical data of 25 patients with PBC who underwent OLT were analyzed retrospectively. The postoperative cumulative survival rate of the patients was calculated. The postoperative recurrence of PBC, de novo diseases and other complications were analyzed. RESULTS: A total of 25 patients were recruited including 22 females and 3 males. The average age was 49.1 years (range from 40 to 64 years). The score of model for end-stage liver disease (MELD) was 21.80±5.49, and the Mayo score 8.01±1.38. Four patients died after liver transplantation. The 1-year, 2-year and 7-year patient cumulative survival rates were 92.0%, 87.8% and 75.3%, respectively. Eight cases (32.0%) developed recurrent PBC based on histological evidence. The median time to recurrence was 17.5 months. One of the eight patients with recurrent PBC was diagnosed with de novo auto-immune hepatitis (AIH) simultaneously, who eventually died. Acute rejection and de novo hepatitis B virus (HBV) infection developed in thirteen (52.0%) patients and five (20.0%) patients, respectively. Two cases (8.0%) of de novo AIH were diagnosed, one of which was fatal. CONCLUSIONS: OLT is an effective procedure for end-stage PBC. Much attention needs to be paid to the post-transplantation complications, including recurrence of primary disease, combined de novo HBV infection, de novo AIH, etc.


Subject(s)
Hepatitis, Autoimmune/etiology , Liver Cirrhosis, Biliary/etiology , Liver Cirrhosis, Biliary/surgery , Liver Transplantation , Postoperative Complications/etiology , Adult , Female , Hepatitis B virus , Humans , Liver Cirrhosis, Biliary/diagnosis , Liver Cirrhosis, Biliary/mortality , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Period , Recurrence , Retrospective Studies , Survival Rate
10.
Angew Chem Int Ed Engl ; 54(41): 12127-33, 2015 Oct 05.
Article in English | MEDLINE | ID: mdl-26305271

ABSTRACT

Healable, electrically conductive materials are highly desirable and valuable for the development of various modern electronics. But the preparation of a material combining good mechanical elasticity, functional properties, and intrinsic self-healing ability remains a great challenge. Here, we design composites by connecting a polymer network and single-walled carbon nanotubes (SWCNTs) through host-guest interactions. The resulting materials show bulk electrical conductivity, proximity sensitivity, humidity sensitivity and are able to self-heal without external stimulus under ambient conditions rapidly. Furthermore, they also possess elasticity comparable to commercial rubbers.


Subject(s)
Elastomers/chemistry , Nanotubes, Carbon/chemistry , Elasticity , Electric Conductivity , Nanotechnology/methods , Nanotubes, Carbon/ultrastructure
11.
Bioorg Chem ; 52: 24-30, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24300390

ABSTRACT

A series of diacyltanshinol derivatives were synthesized by esterifying the corresponding o-hydroquinones of tanshinones. The suppressive effects of the synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results indicated that the nicotinate derivatives 1a and 2a, modified from tanshinone IIA and cryptotanshinone, showed stronger suppressive activity on oxLDL uptake and the resultant foam cell formation relative to tanshinone IIA. Western Blot analysis indicated that derivatives 1a and 2a could dose-dependently inhibit the expression of oxLDL-induced LOX-1, implying that the suppressive effects of 1a and 2a on oxLDL uptake and foam cell formation could be at least partially attributed to the inhibition of LOX-1 expression in macrophages.


Subject(s)
Caffeic Acids/chemistry , Foam Cells/drug effects , Lipoproteins, LDL/metabolism , Protective Agents/chemistry , Protective Agents/pharmacology , Abietanes/chemistry , Animals , Cell Line , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/methods , Foam Cells/metabolism , Macrophages/drug effects , Macrophages/physiology , Mice , Protective Agents/chemical synthesis , Scavenger Receptors, Class E/antagonists & inhibitors
12.
Pharmazie ; 69(3): 163-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24716403

ABSTRACT

We synthesized eight tanshinone anhydrides and the alcoholytic derivatives through a mild oxygen-insertion under Pd/C catalytic hydrogenation conditions. The suppressive effects of the anhydrides on the oxidized low-density lipoprotein (oxLDL) uptake and the oxLDL-induced macrophage-derived foam cell formation were studied. Our results revealed that both anhydrides 1a and 2a could significantly suppress the oxLDL uptake in macrophages and the foam cell formation at micromolar level, which might be partially attributed to their inhibition of oxLDL-induced LOX-1 expression in macrophages.


Subject(s)
Abietanes/chemical synthesis , Antineoplastic Agents, Phytogenic/chemical synthesis , Foam Cells/metabolism , Lipoproteins, LDL/metabolism , Macrophages/metabolism , Anhydrides/chemical synthesis , Animals , Azo Compounds , Catalysis , Cell Line, Tumor , Cholesterol, LDL/metabolism , Coloring Agents , Indicators and Reagents , Magnetic Resonance Spectroscopy , Mice , Tetrazolium Salts , Thiazoles
13.
Cir Esp (Engl Ed) ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39393491

ABSTRACT

BACKGROUND AND AIMS: Total bile acid (TBA) is associated with portal hypertension, a risk factor for post-hepatectomy liver failure (PHLF). We conducted this study to clarify whether TBA is also associated with PHLF in patients with hepatocellular carcinoma (HCC). METHODS: We recruited patients with HCC and Child-Pugh class A, who underwent liver resection, and applied multivariate analyses to identify risk factors for PHLF. RESULTS: We analyzed data from 154 patients. The prevalence of PHLF was 14.3%. The median maximum tumor diameter was 5.1 cm (2.9-6.9 cm). The proportions of patients with elevated TBA levels (P = 0.001), severe albumin-bilirubin (AIBL) grades (P = 0.033), and low platelet counts (P = 0.031) were significantly higher within the subgroup of patients with PHLF than in the subgroup without PHLF. The multivariate analysis results suggest that TBA level (OR, 1.08; 951.03-1.14; P = 0.003) and MRI tumor diameter (OR, 1.17; 95% CI, 1.01-1.35; P = 0.038) are independent preoperative risk factors for PHLF. The TBA levels correlated with the indocyanine green retention rate at 15 minutes (P = 0.001) and the effective hepatic blood flow (P < 0.001), two markers of portal hypertension. However, TBA levels did not correlate with tumor diameter (P = 0.536). CONCLUSIONS: Compared to ICG R15 and AIBL score, preoperative TBA was risk factor for PHLF in Chinese patients with HCC, and it may impact PHLF through its potential role as a marker of portal hypertension.

14.
Atherosclerosis ; 390: 117395, 2024 03.
Article in English | MEDLINE | ID: mdl-38114408

ABSTRACT

BACKGROUND AND AIMS: Elderly patients with acute coronary syndrome (ACS) tend to choose clopidogrel over potent P2Y12 receptor inhibitor such as ticagrelor after percutaneous coronary intervention (PCI) in China considering higher risks of bleeding. CYP2C19 genotype is regarded as a major factor influencing the efficacy of clopidogrel. The present study aims to investigate the efficacy and safety of ticagrelor relative to clopidogrel in elderly ACS patients after PCI in China with reduced CYP2C19 metabolism. METHODS: Between January 2016 and March 2019, 2751 ACS patients over 65 years old with CYP2C19 loss-of-function (LOF) variants after PCI were enrolled. All patients were treated with aspirin and P2Y12 receptor inhibitor, among whom 2056 received clopidogrel and 695 received ticagrelor. Net adverse clinical events (NACE), a composite of cardiac death, myocardial infarction (MI), ischemic stroke, target vessel revascularization and clinically relevant bleeding including Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding, were compared between the two groups at 12 months after PCI. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the two groups. RESULTS: Before and after PSM, NACE was significantly increased in ticagrelor group compared with clopidogrel group at 12 months post PCI (Before PSM, 15.18% vs. 25.61% p<0.001; After PSM, 11.66% vs. 26.01% p<0.001). MACE was comparable between the two groups (Before PSM, 5.45% vs. 5.32% p>0.999; After PSM, 3.59% vs. 5.38% p=0.146). BARC types 2, 3, 5 bleeding events were significantly increased in patients treated with ticagrelor relative to clopidogrel (Before PSM, 10.31% vs. 21.01% p<0.001; After PSM, 8.22% vs. 21.38% p<0.001), which was mainly attributed to a higher incidence of BARC type 2 bleeding events in ticagrelor group (Before PSM, 8.12% vs. 18.56% p<0.001; After PSM, 6.43% vs. 18.83% p<0.001). CONCLUSIONS: In the present real-world study, selection of ticagrelor over clopidogrel showed a significant increase in NACE with a higher incidence of bleeding and similar ischemic events in elderly ACS patients carrying CYP2C19 LOF variants after PCI.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Humans , Aged , Clopidogrel/adverse effects , Ticagrelor/adverse effects , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/genetics , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/adverse effects , Percutaneous Coronary Intervention/adverse effects , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/therapeutic use , Treatment Outcome , Hemorrhage/chemically induced
15.
Theranostics ; 14(1): 265-282, 2024.
Article in English | MEDLINE | ID: mdl-38164153

ABSTRACT

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions. Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases. In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA. In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA. Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells. At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.


Subject(s)
Arthritis, Rheumatoid , Lymphatic Vessels , Osteoarthritis , Humans , Arthritis, Rheumatoid/pathology , Osteoarthritis/metabolism , Lymphatic Vessels/metabolism , Inflammation/metabolism , Lymphangiogenesis
16.
Acta Pharmacol Sin ; 34(1): 60-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23064722

ABSTRACT

Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury. Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes. Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption, cellular release of ATP, metabolism of extracellular ATP (and other adenine nucleotides), adenosine influx, adenosine efflux and adenosine metabolism. Recent studies have used genetically modified mice to investigate the relative contributions of intra- and extracellular pathways for adenosine formation. The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase. From these studies, we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures, but not in hippocampal slices or in vivo mice exposed to ischemic conditions.


Subject(s)
Adenosine/metabolism , Brain Ischemia/metabolism , Brain Ischemia/pathology , Brain/metabolism , Brain/pathology , Adenosine Triphosphate/metabolism , Animals , Brain/blood supply , Humans , Neurons/metabolism , Neurons/pathology , Nucleoside Transport Proteins/metabolism
17.
Sensors (Basel) ; 13(7): 9070-84, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23860316

ABSTRACT

The measurement and control strategy of a piezo-based platform by using strain gauge sensors (SGS) and a robust composite controller is investigated in this paper. First, the experimental setup is constructed by using a piezo-based platform, SGS sensors, an AD5435 platform and two voltage amplifiers. Then, the measurement strategy to measure the tip/tilt angles accurately in the order of sub-µrad is presented. A comprehensive composite control strategy design to enhance the tracking accuracy with a novel driving principle is also proposed. Finally, an experiment is presented to validate the measurement and control strategy. The experimental results demonstrate that the proposed measurement and control strategy provides accurate angle motion with a root mean square (RMS) error of 0.21 µrad, which is approximately equal to the noise level.


Subject(s)
Algorithms , Micro-Electrical-Mechanical Systems/instrumentation , Transducers, Pressure , Equipment Design , Equipment Failure Analysis , Feedback , Motion
18.
Cell Death Dis ; 14(1): 64, 2023 01 27.
Article in English | MEDLINE | ID: mdl-36707511

ABSTRACT

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Pregnane X Receptor/genetics , Sorafenib/pharmacology , Sorafenib/therapeutic use , Transcription Factors/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Cytochrome P-450 CYP3A/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Microtubule-Associated Proteins/genetics , Cell Cycle Proteins/genetics
19.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 8): o2548, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22904980

ABSTRACT

In the title mol-ecule, C(18)H(11)FN(2)O(4), the fused four- ring system is essentially planar, with an r.m.s. deviation of 0.032 Å. In the crystal, mol-ecules are connected by π-π stacking inter-actions [centroid-centroid distances = 3.5684 (9) and 3.8247 (9) Å] into chains along [100].

20.
Food Sci Nutr ; 10(10): 3395-3404, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36249967

ABSTRACT

The present work investigated the effects of high-pressure processing (200 and 400 MPa, 5 min) combined with chitosan-tea polyphenol (1.5% and 0.5% [w/v], respectively) coating to improve the quality and stability of shrimp (Penaeus monodon) during 28 days of storage. The chemical (pH, TVB-N, TBARS), microbiological, textural, chromatic characteristics, protein oxidation, and endogenous enzyme activities of shrimps were regularly evaluated. Results showed that the combination treatment exerted a better intense antimicrobial effect, stabilized shrimp's freshness, and resulted in lower pH and TVB-N than the control sample. Also, combined treated samples had better oxidative stability than a single treatment until the end of shelf life. Although combination treatment had no significant effect on endogenous proteases, the combined use of 400 MPa high-pressure and chitosan-tea polyphenol coating was most effective in inhibiting the bacteria and improved the hardness and chromatic characteristics of shrimp within the storage.

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