ABSTRACT
OBJECTIVE: Traumatic brain injury (TBI) induced neuroinflammation is featured as excessive glial inflammatory activation and violent neurologic destruction and dysfunction. Massive microglia activation in situ and disrupt of blood-brain barrier contribute to severely collapsed nervous system. Tizoxanide (TIZ), a synthetic thiazolide derivative agent possessing a broad-spectrum anti-infective effect, currently shows a potential resistance against pathogens like bacteria, virus and parasites, while its underlying role in neuroinflammation is elusive. The study aimed to explore the effect of TIZ on neuroinflammation in vitro microglia. MATERIALS AND METHODS: Primary microglia were accepted to neuroinflammatory activation via lipopolysaccharide (LPS) administration. TIZ was conducted to pretreatment of microglia. Cell viability, inflammatory cytokines, chemotaxis, nitric oxide release, inflammation-related enzymes, and mitogen-activated protein kinase (MAPK) pathway activation in microglia were investigated respectively. RESULTS: We demonstrated that TIZ administration attenuates inflammatory cytokines and chemokines through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) of medium supernatant. In addition, TIZ reduces pro-inflammatory mediators and nitric oxide release in microglia. Furtherly, TIZ inhibits the level of p38/MAPK pathway in LPS stimuli, indicating that TIZ negatively regulates neuroinflammation via inhibiting p38/MAPK pathway. CONCLUSIONS: TIZ is verified to be an anti-inflammation effect on neuroinflammation in microglia via downregulation of p38/MAPK pathway, which restrains inflammation by reduced inflammatory cytokines, chemokines and mediators and decreased nitric oxide release. To summarize, TIZ is considered to be a promising reagent to alleviate neuroinflammation targeting microglia in nervous system injury.
Subject(s)
Inflammation/drug therapy , Lipopolysaccharides/antagonists & inhibitors , Microglia/drug effects , Thiazoles/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Cell Survival/drug effects , Cells, Cultured , Female , Inflammation/chemically induced , Inflammation/pathology , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred C57BL , Microglia/metabolism , Microglia/pathology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Pregnancy , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
AIMS: The aims of the study were to evaluate whether epidemic strains of streptococcosis infected tilapia can be isolated and identified from dead fish for epidemiological investigation. METHODS AND RESULTS: Firstly, tilapias were inoculated with a lethal dose (1 × 108 CFU per fish) of Streptococcus agalactiae and brain tissues were harvested for bacteriological examination and qPCR assay 3, 12, 24 and 48 h postdeath. Streptococcus agalactiae was the only dominant bacterium cultivated on the brain heart infusion (BHI) plate and the bacterial load was about 107 CFU per mg. Secondly, tilapia were killed via ice water shock and immersed either in an aquarium containing 2·27 × 104 CFU per ml S. agalactiae or in a pond with streptococcosis outbreak. Streptococcus agalactiae failed to grow on the BHI plate but were identified (<6 × 102 CFU per mg) via qPCR assay. Finally, an epidemiological investigation of streptococcosis was conducted in the main tilapia breeding areas of South China. A total of 387 tilapia samples were collected including 24 suspected healthy, 35 moribund and 328 dead fish. The achieved detection rates were 0, 100 and 94·82% via bacteriological examination, and 0, 100 and 98·78% via qPCR assay respectively. The concentration of S. agalactiae in brain tissues ranged between 105 and 107 CFU per mg. CONCLUSIONS: Streptococcus agalactiae can survive for 48 h in the brain of dead fish. Dead tilapia can be a useful alternative for epidemiological investigation when the diagnostic analysis of moribund fish is unavailable or impractical. SIGNIFICANCE AND IMPACT OF THE STUDY: This detection method expands the sampling range, reduces the difficulty of sample collection and improves efficiency. Consequently, this method provides an alternative for epidemiological investigation of tilapia streptococcosis.
Subject(s)
Bacterial Load/methods , Cichlids/microbiology , Fish Diseases/microbiology , Streptococcal Infections/veterinary , Streptococcus agalactiae/isolation & purification , Animals , Brain/microbiology , China/epidemiology , Epidemiological Monitoring/veterinary , Polymerase Chain Reaction , Streptococcal Infections/microbiologyABSTRACT
It is noteworthy that the incidence of thyroid cancer around the world has increased significantly in recent decades, raising an imperative need to research its pathogenesis, diagnosis and treatment. Up to now, fine needle aspiration biopsy (FNAB) of thyroid has been acknowledged to discriminate benign from malignant thyroid nodules with the highest sensitivity and specificity. However, 10% to 40% thyroid nodules cannot be discriminated by FNAB. Therefore, it is vitally important to look for highly-correlated tumor makers in molecule level. BRAF mutation is a focus in thyroid cancer research, and some studies showed that this mutation is essential to the onset and development of thyroid cancer, especially papillary thyroid cancer. Joint detection of BRAF mutation could improve diagnostic sensitivity of thyroid cancer, which is crucial for thyroid cancer diagnosis and classification. As for treatment, the discovery of target gene enabled molecule therapy for thyroid cancer, raising hopes for patients with thyroid cancer that refractory to conventional treatments. Currently, many molecule therapeutics relating to BRAF has already undergone clinical trials. It is believed that further research on BRAF-thyroid cancer relationship could create a new field for diagnosis and treatment of thyroid cancer, and set a mode for discovering others molecule markers.
