Isolation of Leclercia adecarboxylata Producing Carbapenemases in A Newborn Female.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.

Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING.

Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.

Tetrahydroxy stilbene glucoside alters neurogenesis and neuroinflammation to ameliorate radiation-associated cognitive disability via AMPK/Tet2.

Along with the extensive application of radiation in medical, military and other fields, human beings carry a greater risk of exposure to radiation environment that causes a range of physical injure, particularly to the brain in cognition. However, the radiation-associated cognitive disability is poorly understood and there is no effective prevention or long-term treatment. Here, we demonstrate that neurogenesis and neuroinflammation disorder are primarily involved in the pathophysiological basis of irradiation-induced cognitive decline. Furthermore, we discovered that tetrahydroxy stilbene glucoside (TSG), a natural active ingredient from Heshouwu that has been well known for its unique anti-aging effect as the Chinese herb, can be a promising mitigator to improve learning-memory ability by facilitating the neurogenesis in the proliferation and differentiation of the surviving neural progenitor cells via AMPK/Tet2, and attenuating the neuroinflammation in the microglial NLRP3 inflammasomes activation via AMPK in vivo. Additionally, TSG was also revealed to activate AMPK by molecular docking and kinase enzyme system assay in vitro. Taken together, our findings identify TSG, as the AMPK activator, prevents radiation-induced cognitive dysfunction by regulating neurogenesis and neuroinflammation via AMPK/Tet2 in rodents, and represents a very promising candidate for developing drugs that can be used for radiation-associated brain injury.

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice.

Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD), and amyloid-ß (Aß) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains. This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration. Here, we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage, and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests, and investigated the possible mechanisms by immunohistochemistry and Western blotting. Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test. Furthermore, Aß40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique. Finally, Western blotting showed that TSG primarily decreased the APP expression to avoid the Aß plaque deposition in the cortex and hippocampus of mice. These results reveal the beneficial effects of TSG in APP/PS1-AD mice, which may be associated with the reduction of Aß deposits in the brain.