Effect of Tetrandrine on LPS-induced NF-κB activation in isolated pancreatic acinar cells of rat

AIM: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-kappaB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury. METHODS: Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to LPS (10 mg/L), Tet (50 micromol/L, 100 micromol/L) or normal media. At different time point (30 min, 1 h, 4 h, 10 h) after treatment with the agents, cell viability was determined by MTT, the product and nuclear translocation of subunit p65 of NF-kappaB was visualized by immunofluorescence staining and nuclear protein was extracted to perform EMSA which was used to assay the NF-kappaB binding activity. RESULTS: LPS induced cell damage directly in a time dependent manner and Tet attenuated LPS-induced cell damage (50 micromol/L, P < 0.05; 100 micromol/L, P < 0.01). NF-kappaB p65 immunofluorescence staining in cytoplasm increased and began showing its nuclear translocation within 30 min and the peak was shown at 1 h of LPS 10 mg/L treatment. NF-kappaB DNA binding activity showed the same alteration pattern as p65 immunofluorescence staining. In Tet group, the immunofluorescence staining in cytoplasm and nuclear translocation of NF-kappaB were inhibited significantly. CONCLUSION: NF-kappaB activation is an important early event that may contribute to inflammatory responses and cell injury in pancreatic acinar cells. Tet possesses the protective effect on LPS-induced acinar cell injury by inhibiting NF-kappaB activation.     

Obesity: a disease or a biological adaptation? An update

Obesity is characterized by the accumulation of excess body fat and can be conceptualized as the physical manifestation of chronic energy excess. An important challenge of today's world is that our so‐called obesogenic environment is conducive to the consumption of energy and unfavourable to the expenditure of energy. The modern, computer‐dependent, sleep‐deprived, physically inactive humans live chronically stressed in a society of food abundance. From a physiological standpoint, the excess weight gain observed in prone individuals is perceived as a normal consequence to a changed environment rather than a pathological process. In other words, weight gain is a sign of our contemporary way of living or a ‘collateral damage’ in the physiological struggle against modernity. Additionally, substantial body fat loss can complicate appetite control, decrease energy expenditure to a greater extent than predicted, increase the proneness to hypoglycaemia and its related risk towards depressive symptoms, increase the plasma and tissue levels of persistent organic pollutants that promote hormone disruption and metabolic complications, all of which are adaptations that can increase the risk of weight regain. In contrast, body fat gain generally provides the opposite adaptations, emphasizing that obesity may realistically be perceived as an a priori biological adaptation for most individuals. Accordingly, prevention and treatment strategies for obesity should ideally target the main drivers or root causes of body fat gain in order to be able to improve the health of the population.     

Role of NF-κB in thyroid cancer

Thyroid cancer is the most common neoplasia of the endocrine system and accounts for approximately 1% of all newly diagnosed cancer cases. Its incidence has rapidly grown over the past few decades. Although most thyroid carcinomas are of the well-differentiated papillary histology, and respond well to treatment with surgical resection followed by radioactive iodine ablation, tumors with more aggressive phenotype, such as follicular, poorly differentiated, anaplastic, and medullary cancers, lead to almost 1500 patient deaths annually. Therefore, understanding molecular mechanisms that regulate the biology of these carcinomas could be helpful to identify new molecules acting as novel targets for therapeutic intervention.     

Effect of Tetrandrine on LPS-induced NF-κB activation in isolated pancreatic acinar cells of rat

AIM: To investigate the effect of Tetrandrine (Tet) on LPS-induced NF-κB activation and cell injury in pancreatic acinar cells and to explore the mechanism of Tetrandrine preventing LPS-induced acinar cell injury. METHODS: Male rat pancreatic acinar cells were isolated by collagenase digestion, then exposed to LPS (10 mg/L), Tet (50μmol/L, 100μmol/L) or normal media. At different time point (30 min, 1 h, 4 h, 10 h) after treatment with the agents, cell viability was determined by MTT, the product and nuclear translocation of subunit p65 of NF-κB was visualized by immunofluorescence staining and nuclear protein was extracted to perform EMSA which was used to assay the NF-κB binding activity. RESULTS: LPS induced cell damage directly in a time dependent manner and Tet attenuated LPS-induced cell damage (50μmol/L, P < 0.05; 100μmol/L, P < 0.01). NF-κB p65 immunofluorescence staining in cytoplasm increased and began showing its nuclear translocation within 30 min and the peak was shown at 1 h of LPS 10 mg/L treatment. NF-κB DNA binding activity showed the same alteration pattern as p65 immunofluorescence staining. In Tet group, the immunofluorescence staining in cytoplasm and nuclear translocation of NF-κB were inhibited significantly. CONCLUSION: NF-κB activation is an important early event that may contribute to inflammatory responses and cell injury in pancreatic acinar cells. Tet possesses the protective effect on LPS-induced acinar cell injury by inhibiting NF-κB activation.     

Effect of atorvastatin on expression of TLR4 and NF-κB p65 in atherosclerotic rabbits

ObjectiveTo study the effect of atorvastatin on atherosclerotic rabbits.MethodsA total of 60 New Zealand male rabbits were randomly divided into the normal group, model group and atorvastatin group. The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used. All rabbits were sacrificed after 3 months. TLR4 and NF-κB p65 were observed by HE staining, immunohistochemistry and western blotting.ResultsThe expression of TLR4, NF-κB p65 were significantly increased in the model group compared with the normal group. The expression of TLR4 and NF-κB p65 decreased significantly in the atorvastatin group, and there was no difference compared with the normal group.ConclusionsThe effect of atorvastatin on atherosclerosis may be achieved by the inhibition of the expression of TLR4 and NF-κB p65.     

Expression of NF-κB in Helicobacter pylori Infection

Helicobacter pylori colonizes the gastric mucosa in humans and causes chronic gastritis. NF-κB has a key role as a mediator in mucosal inflammation. In this study, we examined the expression of NF-κB in the antral epithelial cells of H. pylori-infected and H. pylori-uninfected biopsies and examined these processes in relationship with grade and activity of gastritis, density of H. pylori, presence of the intestinal metaplasia, and atrophy. Fifty biopsies (35 H. pylori-positive patients and 15 H. pylori-negative controls) were studied. NF-κB immunohistochemical stain was performed. NF-κB activity in H. pylori-infected biopsies were markedly enhanced compared with uninflamed biopsies (P = 0.001). We also found positive correlation NF-κB expression with severity of gastritis (according to Sydney score) (P = 0.001), activity of gastritis (P = 0.046) and H. pylori load (P < 0.001), and atrophy (P = 0.004). We did not find a significant relationship between NF-κB and the presence of intestinal metaplasia (P = 0.355). These findings suggested that expression of NF-κB has an important role in H. pylori gastritis.     

Screening in Frail Older People: An Ounce of Prevention or a Pound of Trouble?

Screening for subclinical disease has provided benefit to many asymptomatic patients, especially those who are relatively young and otherwise healthy. However, frail older people do not always profit from such maneuvers, for several reasons. First, older individuals usually have less physiological reserve and greater comorbidity and resultant polypharmacy than their younger counterparts. As such, they may tolerate the invasive interventions called for after a positive screening test less easily. In addition, shorter natural life expectancy shifts the focus to quality of life improvement after screening tests rather than simply offering a promise of "more years." Lack of education and cognitive decline may also interfere with the older person's ability to give truly informed consent to these maneuvers. Thus, on the whole, in this rapidly growing subpopulation, screening programs may tilt the balance toward the likelihood of causing more harm than good. For many frail older patients, an individualized approach to screening is recommended, adjusted to comorbidity, life expectancy, and patient preference. One size does not fit all.