Nicorandil attenuates cognitive impairment after traumatic brain injury via inhibiting oxidative stress and inflammation: Involvement of BDNF and NGF

Abstract Background and purpose Cognitive impairment is a prevalent adverse consequence of traumatic brain injury (TBI). The neuroprotective effects of nicorandil (N‐(2‐hydroxyethyl)‐nicotinamide nitrate) has been previously documented, yet its protective effects against cognitive dysfunction post‐TBI remain unclear. Hence, the present study was aimed to evaluate whether nicorandil attenuates cognitive dysfunction in TBI rats and the underlying mechanism behind this process. Methods The TBI model was established with a controlled cortical impact (CCI). The effects of nicorandil on cognitive dysfunction of rats with TBI were examined through Novel object recognition (NOR) test, Y‐maze test, and Morris water maze (MWM) task. After behavioral tests, hippocampal tissue was collected for Quantitative real‐time PCR, Western blot analysis, and Enzyme‐linked immunosorbent assay (ELISA) assay. Results We observed that nicorandil administration effectively ameliorates learning and memory impairment in TBI rats. Alongside, nicorandil treatment attenuated oxidative stress in the hippocampus of TBI rats, characterized by the decreased reactive oxygen species generation, malondialdehyde, and protein carbonyls levels, and concurrent promotion of antioxidant‐related factors (including superoxide dismutase, glutathione peroxidase, and catalase) activities. Additionally, nicorandil treatment attenuated the inflammatory response in the hippocampus of TBI rat, as evidenced by the upregulated levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α (TNF‐α), as well as the downregulated level of IL‐10. Mechanistically, nicorandil treatment significantly enhanced the mRNA and protein levels of neurotrophic factors, brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of TBI rats. Conclusion These findings suggest that nicorandil mitigates cognitive impairment after TBI by suppressing oxidative stress and inflammation, potentially through enhancing BDNF and NGF levels

Regulatory effects of saponins from Panax japonicus on colonic epithelial tight junctions in aging rats

Background: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism. Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) were examined by Western blot. NF-κB and phosphorylation of MAPK signaling pathways were also determined by Western blot. Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-1β and tumor necrosis factor-α, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-κB in the colon of aging rats. Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and NF-κB signaling pathways

Surveillance Study of Klebsiella pneumoniae in the Giant Panda Revealed High Genetic Diversity and Antibiotic Therapy Challenge

Klebsiella pneumoniae is not only a worldwide human pathogen, it also effects wildlife, such as the giant panda (Ailuropoda melanoleuca), in which it has recently been evidenced to result in diarrhea, organ failure, and even death. A K. pneumoniae investigation was carried out at the Chengdu Research Base of Giant Panda Breeding in 2018. As part of the investigation, the pulsed-field gel electrophoresis (PFGE) typing, multilocus-sequence typing (MLST), antibiotic resistance profiles (ARPs), and antibiotic resistance genes (ARGs) were studied based on all isolates. Fecal samples were collected from 72 A. melanoleuca from May to December 2018, and a total of 90 K. pneumoniae were isolated from 153 fecal samples. The genotyping results showed that the isolates had high diversity, of which 84 clusters were obtained by PFGE and 57 STs by MLST. The overall trend of the similarity of isolates was the first sample period > second sample period > third sample period, which showed the increasement of genome variability of K. pneumoniae. In addition, 90 isolates showed high resistance to ampicillin, rifampicin, and compound sulfamethoxazole. Of the obtained isolates, 50% carried 6~8 ARPs, and the carrying volume increased during three sample periods, in which we found two isolates carrying 12 and 13 ARPs during the third sample period, respectively. Moreover, a total of 65 ARGs were detected (90.28%, 65/72) in 90 K. pneumoniae samples. Almost all bacteria sampled contained 17 ARGs that belonged to the β-lactamase, Multidrug, MGEs, Aminoglycoside, and Tetracycline, which may be the basis of ARPs of K. pneumoniae. Moreover, the types of Multidrug and MGEs had a greater impact on antibiotic susceptivity of K. pneumoniae. Our results showed that K. pneumoniae has a serious risk of transmission in A. melanoleuca and K. pneumoniae had a high possibility of genome diversity and the risk of drugs tolerance under the large antibiotic usage

Surveillance Study of <i>Klebsiella pneumoniae</i> in the Giant Panda Revealed High Genetic Diversity and Antibiotic Therapy Challenge

Klebsiella pneumoniae is not only a worldwide human pathogen, it also effects wildlife, such as the giant panda (Ailuropoda melanoleuca), in which it has recently been evidenced to result in diarrhea, organ failure, and even death. A K. pneumoniae investigation was carried out at the Chengdu Research Base of Giant Panda Breeding in 2018. As part of the investigation, the pulsed-field gel electrophoresis (PFGE) typing, multilocus-sequence typing (MLST), antibiotic resistance profiles (ARPs), and antibiotic resistance genes (ARGs) were studied based on all isolates. Fecal samples were collected from 72 A. melanoleuca from May to December 2018, and a total of 90 K. pneumoniae were isolated from 153 fecal samples. The genotyping results showed that the isolates had high diversity, of which 84 clusters were obtained by PFGE and 57 STs by MLST. The overall trend of the similarity of isolates was the first sample period > second sample period > third sample period, which showed the increasement of genome variability of K. pneumoniae. In addition, 90 isolates showed high resistance to ampicillin, rifampicin, and compound sulfamethoxazole. Of the obtained isolates, 50% carried 6~8 ARPs, and the carrying volume increased during three sample periods, in which we found two isolates carrying 12 and 13 ARPs during the third sample period, respectively. Moreover, a total of 65 ARGs were detected (90.28%, 65/72) in 90 K. pneumoniae samples. Almost all bacteria sampled contained 17 ARGs that belonged to the β-lactamase, Multidrug, MGEs, Aminoglycoside, and Tetracycline, which may be the basis of ARPs of K. pneumoniae. Moreover, the types of Multidrug and MGEs had a greater impact on antibiotic susceptivity of K. pneumoniae. Our results showed that K. pneumoniae has a serious risk of transmission in A. melanoleuca and K. pneumoniae had a high possibility of genome diversity and the risk of drugs tolerance under the large antibiotic usage