Lycium barbarum glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. AIMS: In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. METHODS: SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. RESULTS: In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. CONCLUSIONS: In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem.

Treatment failure occurs in more than 40% of advanced nasopharyngeal carcinoma (NPC) patients including local recurrence and distant metastasis due to chemoradioresistance. Circadian clock genes were identified as regulating cancer progression and chemoradiosensitivity in a time-dependent manner. A novel nanosystem can ensure the accumulation and controllable release of chemotherapeutic agents at the tumour site at a set time. In this study, we investigated the expression of circadian clock genes and identified that period circadian regulator 2 (PER2) as a tumour suppressor plays a key role in NPC progression. A label-free proteomic approach showed that PER2 overexpression can inhibit the ERK/MAPK pathway. The chemotherapeutic effect of PER2 overexpression was assessed in NPC together with the nanosystem comprising folic acid (FA), upconverting nanoparticles covalently coupled with Rose Bengal (UCNPs-RB), 10-hydroxycamptothecin (HCPT) and lipid-perfluorohexane (PFH) (FURH-PFH-NPs). PER2 overexpression combined with the targeted and controlled release of nanoagents elevated chemotherapeutic efficacy in NPC, which has potential application value for the chronotherapy of tumours.

The poly-ADP ribose polymerase-1/apoptosis-inducing factor pathway may help mediate the protective effect of electroacupuncture on early brain injury after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a clinically common, acute, critical cerebrovascular disease associated with high mortality. Here, we investigated the effects of electroacupuncture on early brain injury after SAH. We successfully established a Sprague-Dawley rat model of the SAH model, and randomly divided the rats into four groups: sham-operated group, SAH group, positive control group, and electroacupuncture group. Electroacupuncture effectively decreased the number of transferase UTP nick end labeling-positive cells and extent of DNA fragmentation compared with the control, indicating a decrease in apoptosis. Moreover, electroacupuncture decreased the expression of proteins involved in the poly-ADP ribose polymerase-1/apoptosis-inducing factor (PARP-1/AIF) pathway in vivo, and the difference was statistically significant (P < 0.05). Treatment with electroacupuncture resulted in a significant improvement in neurological function. It inhibited the increase in blood-brain barrier permeability by regulating the protein expression of matrix metalloproteinase-9, occludin, and claudin-5. Additionally, electroacupuncture limited the development of cerebral edema and microglial activation in early brain injury after SAH. In conclusion, electroacupuncture can ameliorate early brain injury after SAH, and this may occur via inhibition of the PARP-1/AIF pathway.

The α-lipoic acid improves high-fat diet-induced cerebral damage through inhibition of oxidative stress and inflammatory reaction.

This study is to clarify the protective role of α-lipoic acid in high-fat diet-induced cerebral damage mice. The mice were divided into 5 groups: normal control group, high-fat diet (HFD) group, low-dose α-lipoic acid group for prevention, high-dose α-lipoic acid group for prevention, and high-dose α-lipoic acid group for treatment. The groups' weights and blood glucose changes were monitored. We used HE staining to observe morphological changes in the cerebral cortex. The expression levels of the oxidative stress proteins SOD2, catalase, and the inflammatory pathway proteins p-JNK, p-ERK were measured by western blot and immunochemistry. Compared with the control group, the quantity of cortical neurons in the HFD group was decreased, and the samples exhibited retrogression. However, the lipoic acid significantly protected and promoted the cortical neurons survival. Moreover, compared with the HFD group, the expression levels of SOD2 and catalase in the three α-lipoic acid obtained groups were significantly increased. However, the expression levels of the inflammatory pathway proteins p-JNK and p-ERK were significantly decreased. These results indicate that theα-lipoic acid greatly protects the cortical neurons, and inhibited the oxidative stress and inflammatory reactions in the high-fat diet mice.

The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway.

The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.