Diallyl disulfide attenuates pyroptosis via NLRP3/Caspase-1/IL-1ß signaling pathway to exert a protective effect on hypoxic-ischemic brain damage in neonatal rats.

Hypoxic-ischemic encephalopathy (HIE) is a perinatal brain disease caused by hypoxia in neonates. It is one of the leading causes of neonatal death in the perinatal period, as well as disability beyond the neonatal period. Due to the lack of a unified and comprehensive treatment strategy for HIE, research into its pathogenesis is essential. Diallyl disulfide (DADS) is an allicin extract, with detoxifying, antibacterial, and cardiovascular disease protective effects. This study aimed to determine whether DADS can alleviate HIE induced brain damage in rats and oxygen-glucose deprivation (OGD)-induced pyroptosis in PC12 cells, as well as whether it can inhibit pyroptosis via the NLRP3/Caspase-1/IL-1ß signaling pathway. In vivo, DADS significantly reduced the cerebral infarction volume, alleviated inflammatory reaction, reduced astrocyte activation, promoted tissue structure recovery, improved pyroptosis caused by HIE and improved the prognosis following HI injury. In vitro findings indicated that DADS increased cell activity, decreased LDH activity and reduced the expression of pyroptosis-related proteins, including IL-1ß, IL-18, and certain inflammatory factors in PC12 cells caused by OGD. Mechanistically, DADS inhibited pyroptosis and protected against HIE via the NLRP3/Caspase-1/IL-1ß pathway. The specific inhibitor of caspase-1, VX-765, inhibited caspase-1 activation, and IL-1ß expression was determined. Additionally, the overexpression of NLRP3 reversed the protective effect of allicin against OGD-induced pyroptosis. In conclusion, these findings demonstrated that DADS inhibits the NLRP3/Caspase-1/IL-1ß signaling pathway and decreases HI brain damage.

Neuroprotective effect of apigenin against hypoxic-ischemic brain injury in neonatal rats via activation of the PI3K/Akt/Nrf2 signaling pathway.

Neonatal hypoxic-ischemic (HI) brain injury can lead to mortality and severe long-term disabilities including cerebral palsy and brain injury. However, the treatment options for neonatal hypoxic-ischemic (HI) brain injury are limited. Apigenin is abundantly present in vegetables, celery, and chamomile tea with diverse biological functions, such as anti-inflammatory, anti-apoptotic, antioxidant, and anticancer effects. However, it has not yet been reported whether apigenin exerts a neuroprotective effect against neonatal hypoxic-ischemic (HI) brain injury. In this study, we investigated whether apigenin could ameliorate HI brain injury and explored the associated mechanism using in vivo experiments. We found that apigenin remarkably reduced the infarct volume and ameliorated cerebral edema, decreased inflammatory response, inhibited apoptosis, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Mechanistically, we found that apigenin exerted a neuroprotective effect against HI brain injury by activating the PI3K/Akt/Nrf2 pathway. In summary, all these results demonstrate that apigenin could be a potential therapeutic approach for neonatal hypoxic-ischemic (HI) brain injury.

The Expression and Relationship of CD68-Tumor-Associated Macrophages and Microvascular Density With the Prognosis of Patients With Laryngeal Squamous Cell Carcinoma.

OBJECTIVES: We sought to identify the expression of CD68-tumor-associated macrophages (TAMs) and CD34-microvascular density (MVD) in laryngeal squamous cell carcinoma (LSCC), to study the relationship with clinical pathological parameters and to determine whether their expression is predictive of disease. METHODS: Pathologically confirmed 45 LSCC tissue and 20 peritumoral non-tumor tissue were examined. Immunohistochemical studies were used to detect the expression of CD68-TAMs and CD34-MVD. RESULTS: The positive expression rate of CD68 in LSCC tissue was 82% (37/45), which was higher than the 10% (2/20) expression rate of the peritumoral tissue (P<0.05). The CD34-MVD positive expression rate in the LSCC tissue was 26.5±6.4, which obviously higher than 12.2±4.0 expression rate of the peritumoral tissue (P<0.05). The positive expression rates of both CD68 and CD34-MVD were higher in the lymph node metastasis (LNM) positive group than in the LNM negative group. The expression of CD68 had positive correlation with CD34-MVD. The 5-year disease-free survival rate in the group with the low CD68 expression was significantly higher than that in the group with high CD68 expression (76% vs. 42%, respectively). CONCLUSION: The high expression of CD68-TAMs in LSCC and its positive correlation with CD34-MVD illustrates that both play an important role in promoting the metastasis and angiogenesis of this cancer. Their expression was also positively correlated with the prognoses of these patients, suggesting that they could be used as important prognostic markers for LSCC.

Association between MDM2 rs769412 and rs937283 polymorphisms with alcohol drinking and laryngeal carcinoma risk.

TARGET: To investigate the association between the interactions of murine double minute 2 (MDM2) polymorphisms (rs769412 and rs937283) with alcohol drinking and laryngeal carcinoma. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes status of MDM2 rs769412 and rs937283 polymorphisms among 126 cases and 120 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the chi-squared test, which was adopted to analyze the association between MDM2 rs769412 and rs937283 polymorphisms and the susceptibility to larynx carcinoma in the drinking population. RESULTS: Genotypes distributions of MDM2 rs769412 and rs937283 polymorphisms in the control group were in accordance with Hardy-Weinberg equilibrium (HWE). MDM2 rs769412 GG genotype and G allele significantly increased laryngeal carcinoma risk (GG vs. AA: OR=3.17, 95% CI=1.25-8.04; G vs. A: OR=1.88, 95% CI=1.24-2.84). Furthermore, the mutant genotypes of MDM2 rs937283and rs769412 were remarkablely associated with the increased risk for laryngeal carcinoma in drinking population (rs937283: OR=2.67, 95% CI=1.40-5.07; rs769412: OR=3.76, 95% CI=1.62-8.75). CONCLUSION: MDM2 polymorphisms are correlated with the onset of laryngeal carcinoma. The relationship is strengthened by alcohol drinking.

[The expression of tumor related macrophages and matrix solution element in laryngeal squamous carcinoma tissue and the relationship with tumor microvascular density].

OBJECTIVE: To study the expression of CD68 antibody marked tumor associated macrophage TAMs and matrix solution element MMP-7 in laryngeal squamous carcinoma tissue and the relationship with clinicopathological parameters, so that to explore the relationship between the expression of the two molecular markers and laryngeal cancer tissue microvascular density (MVD). METHOD: Immunohistochemical method was employed to detect the expression of CD68 and MMP-7 in 65 cases (laryngeal squamous carcinoma tissue in 45 cases; peritumoral nontumor tissue in 20 cases) and CD 34 antibody marked MVD expression. RESULT: CD68 positive rate in squamous carcinoma tissue (82.2%, 37/45) is obviously higher than that in the peritumoral tissue (15%, 3/20) (P < 0.05), and MMP-7 positive rate in squamous carcinoma tissue is significantly different from that in peritumoral tissue (71.1%; 25%) (P < 0.05). The expression rate of CD34-MVD in laryngeal squamous carcinoma tissue( 26.52 +/- 6.36 )is higher than that in peritumoral tissue (12.23 +/- 4.01) (P < 0.05). In lymph node metastasis group, the positive expression rates of CD68 and MMP-7 are higher than those in the group without lymph node metastasis. MMP-7 showed no correlation with cancer stage, and CD68 was related with cancer stage; CD68, MMP-7 and CD34- MVD have positive correlation. CONCLUSION: The high level of expression of TAMs and MMP-7 in laryngeal cancer tissue and the positive correlation with MVD illustrate that both of the markers play important roles in promoting laryngeal squamous carcinoma tissue metastasis and angiogenesis, which can be used as important markers to evaluate the invasion and metastasis of laryngeal cancer.