Ski ameliorates synovial cell inflammation in monosodium iodoacetate-induced knee osteoarthritis.

Knee osteoarthritis (KOA) is one of the most common degenerative diseases and is characterized by cartilage degeneration, synovial inflammation, joint stiffness and even loss of motor function. In the clinical treatment of arthritis, conventional analgesic and anti-inflammatory drugs have great side effects. We have evaluated the possibility of the endogenous transcription regulator Ski as an anti-inflammatory alternative in OA through experimental studies in animal models and in vivo and in vitro.

Activation of brain lactate receptor GPR81 aggravates exercise-induced central fatigue.

Exercise-induced fatigue is a complex physiological phenomenon and is greatly influenced by central mechanisms in brain. As one of the most abundant circulating carbon metabolites, l-lactate in brain has been considered to be an important supplementary fuel during exercise; however, whether it plays a signaling role in fatigue remains largely obscure. In this study, our results initially revealed that brain l-lactate levels were increased after an exhaustive swimming session in several brain regions including motor cortex, hippocampus, and cerebellum.

Preparation of surface molecularly imprinted polymer and its application for the selective extraction of teicoplanin from water.

In this study, a new surface molecularly imprinted polymer (SMIP) of teicoplanin (TEC) was prepared in an aqueous solution using amino-modified silica gel as a carrier. The molar ratio of the template molecule, functional monomer and cross-linker in the optimized synthesis system was 1 : 15 : 40. The structure and morphology of SMIP were characterized by Fourier-transform infrared spectra and scanning electron microscopy, respectively.

Simultaneous determination of praziquantel and its main metabolites in the tissues of black goats and their residue depletion.

Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the parasitic disease control field. However, PZQ residues caused by non-conforming or excessive use in food-producing animals may pose a serious threat to human health. Herein, a simple, sensitive and reproducible LC-MS/MS method was developed for the simultaneous determination of praziquantel and - and -4-hydroxypraziquantel in black goat tissues to guide the reasonable use of PZQ.

Simultaneous determination of fourteen β-agonist enantiomers in food animal muscles by liquid chromatography coupled with tandem mass spectrometry.

Illegal drug residues in animal derived foods are closely related to human's life and health. Studies on illegal drug residues and the metabolism, such as β-agonists in animals have attracted more and more attention. In most cases, β-agonists are suppliedand used astheracemate.

Inhibition of HIF-1α-AQP4 axis ameliorates brain edema and neurological functional deficits in a rat controlled cortical injury (CCI) model.

Traumatic brain injury (TBI) is an important cause of death in young adults and children. Till now, the treatment of TBI in the short- and long-term complications is still a challenge. Our previous evidence implied aquaporin 4 (AQP4) and hypoxia inducible factor-1α (HIF-1α) might be potential targets for TBI.

Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI.

High glutamate concentration reverses the inhibitory effect of microglial adenosine 2A receptor on NLRP3 inflammasome assembly and activation.

NLRP3 inflammasome plays a crucial role in the innate immune system. Our group previously reported that the microglial adenosine 2A receptor (AR) regulates canonical neuroinflammation, which is affected by the glutamate concentration. However, the regulatory effect of AR on NLRP3 inflammasome and the effects of glutamate concentration remain unknown.

NLRP3 Inflammasome-Dependent Increases in High Mobility Group Box 1 Involved in the Cognitive Dysfunction Caused by Tau-Overexpression.

Tau hyperphosphorylation is a characteristic alteration present in a range of neurological conditions, such as traumatic brain injury (TBI) and neurodegenerative diseases. Treatments targeting high-mobility group box protein 1 (HMGB1) induce neuroprotective effects in these neuropathologic conditions. However, little is known about the interactions between hyperphosphorylated tau and HMGB1 in neuroinflammation.

Novel HIF-1-target gene isthmin1 contributes to hypoxia-induced hyperpermeability of pulmonary microvascular endothelial cells monolayers.

Hypoxia-induced pulmonary microvascular endothelial cell (PMVEC) monolayers hyperpermeability is vital for vascular leakage, which participates in vascular diseases, such as acute lung injury (ALI) and high-altitude pulmonary edema (HAPE). We previously observed that PMVEC permeability was markedly elevated in hypoxia when cocultured with primary type II alveolar epithelial cells (AECII) in which isthmin1 (ISM1) was highly upregulated. However, whether the upregulation of ISM1 plays a role in hypoxia-induced PMVEC hyperpermeability is unclear.

Simultaneous Determination of Multiple Polypeptide Antibiotics Residues in Lake Water by Lyophilization Combined with Liquid Chromatography-Tandem Mass Spectrometry.

It is significant to develop a method for the simultaneous determination of multiple polypeptide antibiotics residues in lake water because of the emergence of multidrug-resistant microorganisms in water. A sensitive, eco-friendly and simple method was developed for the determination of multiple polypeptide antibiotics, including vancomycin, teicoplanin, polymyxin B, colistin and bacitracin A in lake water using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Water samples were lyophilized to enrich them after adjusting the pH to 3.

Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema.

Background: Traumatic brain edema (TBE) is caused by a specific water channel mediated by membrane aquaporins. Aquaporin-4 (AQP4) plays an especially important role in this process, but the relationship between AQP4 and TBE remains unclear. The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury (TBI), as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.

Ski promotes proliferation and inhibits apoptosis in fibroblasts under high-glucose conditions via the FoxO1 pathway.

Objectives: The present study clarified the role and signalling pathway of Ski in regulating proliferation and apoptosis in fibroblasts under high-glucose (HG) conditions.

Materials And Methods: The proliferation and apoptosis of rat primary fibroblasts were assessed using EdU incorporation and TUNEL assays. The protein and phosphorylation levels of the corresponding factors were measured using immunofluorescence staining and Western blotting.

Ski mediates TGF-β1-induced fibrosarcoma cell proliferation and promotes tumor growth.

TGF-β1 promotes cell proliferation in only some tumors and exerts bidirectional regulatory effects on the proliferation of fibroblasts. This study intends to explore whether the mechanism is related to increased expression of Ski. Cell proliferation of the fibrosarcoma cell line L929 was assessed with an ELISA BrdU kit.

PKC Mediates LPS-Induced IL-1β Expression and Participates in the Pro-inflammatory Effect of AR Under High Glutamate Concentrations in Mouse Microglia.

Pathogens such as bacterial lipopolysaccharide (LPS) play an important role in promoting the production of the inflammatory cytokines interleukin-1 beta (IL-1β) and tumour necrosis factor-α (TNF-α) in response to infection or damage in microglia. However, whether different signalling pathways regulate these two inflammatory factors remains unclear. The protein kinase C (PKC) family is involved in the regulation of inflammation, and our previous research showed that the activation of the PKC pathway played a key role in the LPS-induced transformation of the adenosine A receptor (AR) from anti-inflammatory activity to pro-inflammatory activity under high glutamate concentrations.

HIF1α-induced upregulation of KLF4 promotes migration of human vascular smooth muscle cells under hypoxia.

Hypoxia-induced vascular smooth muscle cells (VSMCs) migration plays an important role in vascular remodeling and is implicated in vascular diseases, such as atherosclerosis and pulmonary hypertension. We previously observed the increased expression of krüppel-like factor 4 (KLF4) in VSMCs under hypoxia. However, whether the upregulation of KLF4 participates in hypoxia-induced VSMCs migration is still unknown.

The ERK/CREB pathway is involved in the c-Ski expression induced by low TGF-β1 concentrations during primary fibroblast proliferation.

Increasing evidence has suggested that bidirectional regulation of cell proliferation is one important effect of TGF-β1 in wound healing. Increased c-Ski expression plays a role in promoting fibroblast proliferation at low TGF-β1 concentrations, but the mechanism by which low TGF-β1 concentrations regulate c-Ski levels remains unclear. In this study, the proliferation of rat primary fibroblasts was assessed with an ELISA BrdU kit.

Adenosine A receptor inhibition restores the normal transport of endothelial glutamate transporters in the brain.

Excitatory amino acid transporters (EAATs) on cerebral vascular endothelial cells play an important role in maintaining glutamate homeostasis in the brain. The dysfunction of endothelial EAATs is an important reason for the dramatically elevated brain glutamate levels after brain injury, such as traumatic brain injury (TBI). The adenosine A receptor (AR) plays an important role in regulating the brain glutamate level after brain injury; however, researchers have not clearly determined whether this role was related to its ability to regulate endothelial EAATs.

[Effect of silencing aquaporin 4 on learning and memory dysfunction in rats with traumatic brain injury].

Objective: To observe the protein expression related to cognitive and learning memory function, and to investigate the effect of aquaporin 4 (AQP4) silence on learning and memory function in traumatic brain injury (TBI) rats.

Methods: Ninety-six healthy adult male Wistar rats were divided into groups according to the random number table. (1) Forty-eight rats were divided into sham operation (sham) group, TBI group (by using modified Feeney method), AQP4 RNA interference (RNAi) negative group [TBI+meaningless small interfering RNA (siRNA)-AQP4 liposome solution 10 μL], and AQP4 RNAi group (TBI+siRNA-AQP4 liposome solution 10 μL).

Hsp90 regulation affects the treatment of glucocorticoid for pancreatitis-induced lung injury.

Glucocorticoids are commonly used for the treatment of pancreatitis and complicated acute lung injury and help to reduce the mortality rates of both. The effect of gene variants in heat shock protein 90 (Hsp90), a key chaperone molecule of the glucocorticoid receptor (GR), on the therapeutic effect of glucocorticoids is unclear. Our study aims to investigate the different susceptibility to glucocorticoid treatment in BALB/c and C57BL/6 mice carrying different Hsp90 genotypes in an animal model of pancreatitis-induced lung injury.

Widespread hyperphosphorylated tau in the working memory circuit early after cortical impact injury of brain (Original study).

A series of neurological and psychiatric symptoms occur after traumatic brain injury (TBI), with cognitive dysfunction being one of the most prominent sequela. Given that tau hyperphosphorylation is an important cause of cognitive impairment in patients of Alzheimer's disease, our present study detected the presence of hyperphosphorylated tau (p-tau), mainly at Ser404, in multiple brain regions, including the ipsilateral parietal cortex, contralateral hippocampus and prefrontal cortex, immediately after the injury in a mouse TBI model; these changes lasted for at least 4w. All of these brain regions play important roles in working memory.

Comparative evaluation of the wound-healing potency of recombinant bFGF and ski gene therapy in rats.

We previously demonstrated that cellular Sloan-Kettering Institute (c-Ski) played a dual role, both promoting wound healing and alleviating scar formation. However, its mechanism and therapeutic effects are not clear, especially compared with widely used treatments, such as basic fibroblast growth factor (bFGF) administration. However, Ski treatment led to an even shorter healing time and a more significant reduction in scar area than bFGF treatment.

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor.

Background/aims: Although it has been reported that somatostatin (SOM) upregulated the level of 90-kD heat shock protein (Hsp90), which participates in the inflammatory regulation by its client proteins, such as glucocorticoid receptor (GR), it remains unclear if it has a protective role against acute lung injury (ALI).

Methods: ALI model was established by the injection of oleic acid (OA) into the tail vein of mice. Lung injury was assessed by histological analysis, lung water content and arterial blood gases.