Summary
Aims
Baicalin (BAI), a flavonoid compound isolated from the root of
Scutellaria baicalensis
Georgi, has been established to have potent anti‐inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (
AD
) treatment have not been well studied. This study aimed to investigate the effects of
BAI
pretreatment on cognitive impairment and neuronal protection against microglia‐induced neuroinflammation and to explore the mechanisms underlying its anti‐inflammation effects.
Methods
To determine whether
BAI
plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin‐1) mice, behavioral experiments were conducted. We assessed the effects of
BAI
on microglial activation, the production of proinflammatory cytokines, and neuroinflammation‐mediated neuron apoptosis in vivo and in vitro using Western blot,
RT
‐
PCR
,
ELISA
, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti‐inflammation mechanisms underlying the effects of
BAI
, the protein expression of
NLRP
3 inflammasomes and the expression of proteins involved in the
TLR
4/
NF
‐κB signaling pathway were measured using Western blot and immunofluorescence.
Results
The results indicated that
BAI
treatment attenuated spatial memory dysfunction in
APP
/
PS
1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally,
BAI
administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation‐mediated neuron apoptosis, in
APP
/
PS
1 mice and LPS (lipopolysaccharides)/Aβ‐stimulated
BV
2 microglial cells. Lastly, the molecular mechanistic study revealed that
BAI
inhibited microglia‐induced neuroinflammation via suppression of the activation of
NLRP
3 inflammasomes and the
TLR
4/
NF
‐κB signaling pathway.
Conclusion
Overall, the results of the present study indicated that
BAI
is a promising neuroprotective compound for use in the prevention and treatment of microglia‐mediated neuroinflammation during
AD
progression.
The aim of this study was to investigate the prognostic value of tumor markers in operable non-small cell lung cancer (NSCLC) patients. A total of 481 NSCLC patients were enrolled in the present study. High levels of neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) were detected in 306 (63.6%), 89 (18.5%) and 125 (26.0%) patients, respectively. Seventy-eight of 481 patients died of disease progression, and the median disease-free survival (DFS) and overall survival (OS) were 16.0 and 21.0 months, respectively. The three-year DFS rate was 56.7%, and the OS rate was 75.3%. For serum NSE, the three-year cumulative DFS rate for the normal and elevated group was 67.7% and 51.8% (p = 0.007). The OS in patients with high and normal levels of NSE was 34.0 months and 48.0 months, respectively. The median DFS was 46.0 months versus 32.0 months (p = 0.001), and the OS was 48.0 months versus 44.0 months (p = 0.001) in patients with normal and high levels of CA125. For patients with squamous cell carcinoma, the overall survival was significantly shorter in patients with elevated levels of SCC (p = 0.041). In the multivariate analysis high levels of NSE, CA125 and clinical stage were significantly correlated with worse prognosis (p < 0.05). Patients with all three tumor markers elevated presented the worst prognosis (p < 0.05). In our analysis, high levels of preoperative serum NSE and CA125 are correlated with worse survival in operable NSCLC patients.
Platelets play a significant role in cancer cell growth, progression and metastasis. However, in non-small cell lung cancer (NSCLC), the association between a patient’s platelet count and prognosis has not previously been fully elucidated. The aim of the present study was to investigate the correlation between platelet count, patients’ characteristics and prognosis in patients with NSCLC. A total of 510 NSCLC patients were enrolled in the present study. The median platelet count in the NSCLC patients was 203×109/l (95% CI, 115–358×109/l). The median platelet count in T3 and T4 patients was significantly higher than that of T1 and T2 patients (median, 263×109/l and 253.5×109/l vs. 199.5×109/l and 196.5×109/l, respectively; P<0.001). The 3-year cumulative overall survival (OS) probability was 75.3% for patients with normal platelet counts and 59.2% for patients with elevated platelet counts. When compared with the patients with normal platelet counts, the patients with elevated platelet counts had an increased risk of disease progression (HR, 1.568; 95% CI, 1.015–2.453). Pre-operative platelet counts are a novel independent prognostic biomarker in operable NSCLC.
Scope: In this study, it has been investigated whether the neuroprotective efficacy of epigallocatechin-3-gallate (EGCG) is mediated by inhibition of canonical and noncanonical inflammasome activation via toll-like receptor 4 (TLR4)/NF-κB pathway both in LPS+Aβ-induced microglia in vitro and in APP/PS1 mice in vivo.Methods and results: In BV2 cells, EGCG inhibits the expressions of Iba-1, cleaved IL-1β, and cleaved IL-18 induced by LPS+Aβ. Then, the supernatants are used to treat SH-SY5Y cells, and EGCG treatment significantly recovers the neurotoxicity from LPS+Aβ-induced microglial conditioned media. Subsequently, it has been found that EGCG reduces the microglial expressions of caspase-1 p20, NLRP3, and caspase-11 p26. Furthermore, the expression levels of Toll-like receptor 4 (TLR4), p-IKK/IKK, and p-NF-κB/NF-κB were decreased after EGCG treatment. As expected, when a caspase-1 specific inhibitor Z-YVAD-FMK, and an IKK and caspase-11 inhibitor wedelolactone are used for blocking, Z-YVAD-FMK and wedelolactone exacerbate the inhibitory efficacy than using EGCG alone.
Background: The anesthetic characteristics of ultrasound-guided bi-level erector spinae plane block (ESPB) plus dexmedetomidine (Dex) remain unclear. We compared the efficacy and safety of ultrasound-guided bi-level ESPB plus different doses of Dex in patients undergoing video-assisted thoracic surgery (VATS).Methods: One-hundred eight patients undergoing VATS were randomized into three groups: R group (n = 38, 15 ml of 0.375% ropivacaine with 0.1 mg/kg dexamethasone), RD1 group (n = 38, 15 ml of 0.375% ropivacaine plus 0.5 μg/kg DEX with 0.1 mg/kg dexamethasone) and RD2 group (n = 38, 15 ml of 0.375% ropivacaine plus 1.0 μg/kg DEX with 0.1 mg/kg dexamethasone). The primary outcome was the pain 12 h after surgery. Secondary outcomes included the Prince Henry Hospital Pain Score; hemodynamics; consumption of sufentanil; anesthetized dermatomal distribution; recovery time; rescue analgesia; satisfaction scores of patients and surgeon; quick recovery index; adverse effects; the prevalence of chronic pain and quality of recovery.Results: The visual analog scale (VAS) and the Prince Henry pain score were significantly lower in both the RD1 and RD2 groups during the first 24 h after surgery (P
< 0.05). Both VAS with coughing and the Prince Henry pain score were significantly lower in the RD2 group than in the RD1 group 8–24 h after surgery (P < 0.05). Both heart rate and mean arterial pressure were significantly different from T2 to T6 in the RD1 and RD2 groups (P < 0.05). The receipt of remifentanil, propofol, Dex, and recovery time was significantly reduced in the RD2 group (P < 0.05). The requirement for sufentanil during the 8–72 h after surgery, less rescue medication, and total press times were significantly lower in the RD2 group (P < 0.05). The time to the first dose of rescue ketorolac was significantly longer in the RD2 group (P < 0.05). Further, anal exhaust, removal of chest tubes, and ambulation were significantly shorter in the RD2 group (P < 0.05). The incidence of tachycardia, post-operative nausea and vomiting, and chronic pain was significantly reduced in the RD2 group, while the QoR-40 score was significantly higher in the RD2 group (P < 0.05).Conclusions: Pre-operative bi-level, single-injection ESPB plus 1 μg/kg DEX provided superior pain relief and long-term post-operative recovery for patients undergoing VATS.Clinical Trial Registration:http://www.chictr.org.cn/searchproj.aspx.
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