RESUMEN

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.

Asunto(s)

RESUMEN

Objective:To observe the effect of early temperature control on the prognosis of brain injury patients after severe carbon monoxide poisoning (COP).Methods:A total of 277 patients hospitalized with severe COP were randomly divided into a fever group ( n=78), a normal temperature group ( n=113) and a mild hypothermia group ( n=86). All were given hyperbaric oxygen therapy and any necessary supportive treatment. The mild hypothermia group were kept in a room at 34 to 35℃. Evaluation was with the Glasgow Coma Scale (GCS), version II of the Acute Physiology and Chronic Health Evaluation (APACHE), the Hasegawa dementia scale (HDS) and the mini mental state examination (MMSE). The incidence of delayed encephalopathy (DEACMP) and mortality were compared among the three groups. The bispectral index (BIS) and neuron-specific enolase (NSE) levels were correlated with DEACMP. Results:After the treatments, improvement was observed in multiple indexes of all three groups compared with before the treatment. Compared with the fever group, the average GCS of the mild hypothermia group was significantly higher on the 2nd, 4th, 8th and 31st day after the intervention. It was significantly higher than the normal temperature group′s averages on the 4th, 8th and 31st day. The average APACHE scores of the normal temperature and the mild hypothermia groups were significantly lower than the fever group′s average, with that of the mild hypothermia group significantly lower than that of the normal group. The average HDS scores of the normal temperature and mild hypothermia groups were significantly higher than the fever group′s average, with that of the mild hypothermia group significantly higher than that of the normal group. The average MMSE score of the mild hypothermia group was significantly improved after 7 days, one month and three months of treatment. That of the normal group showed significant improvement after one and three months, but the mild hypothermia group′s averages were superior. Compared with the fever group, the average BIS score of the mild hypothermia group was significantly better after one, three and seven days, and one month. This was true for the normal group beyond three days after the intervention. The average NSE concentration of the normal group after 7 days and one month was significantly lower than that of the fever group. For the mild hypothermia group this was true after only 3 days. Compared with the other two groups, the average coma time, incidence of DEACMP and nervous system injury were significantly lower in the hypothermia group. The average GCS, BIS and NSE values were closely related to the occurrence of DEACMP.Conclusions:Early temperature control can significantly reduce the severity of brain injury after COP and reduce the incidence of neurological sequelae. Early dynamic detection of GCS, NSE concentration and BIS is of great significance for predicting the incidence of DEACMP.

RESUMEN

Objective:To investigate the role of neurite outgrowth inhibitor (Nogo)-oligodendrocyte myelin glycoprotein (Omgp)/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase (Rock) signaling pathway in acute brain injury of carbon monoxide (CO) poisoning rats and treatment feasibility with Rho kinase inhibitor hydrochloride fasudil.Methods:According to random number table method, 135 healthy male SD rats were divided into three groups: a normal control group, a CO poisoning group and a fasudil treatment group ( n=45). Rat models of acute severe CO poisoning were established in the CO poisoning group and fasudil treatment group by inhalation method in a hyperbaric oxygen chamber. All rats received hyperbaric oxygen therapy for two weeks. Rats in the farsudil treatment group were intraperitoneally injected with hydrochloride farsudil for intervention (15 mg/[kg·d], once a d for 2 weeks), while those in the CO poisoning and normal control groups received the same volume of normal saline. The ultrastructures of rat brain tissues were observed by transmission electron microscopy one week after modeling. Staining intensities of Nogo- and OMgp-positive cells were detected by immunohistochemistry, and those of Rock-positive cells were analyzed by immunofluorescence one d, one week, one month and two months after modeling. The protein expressions of Nogo, OMgp and Rock in brain tissues were detected by Western blotting one d, one week, one month and two months after modeling. Results:In the CO poisoning group, the ultrastructures of brain tissues and blood-brain barrier were damaged obviously, and the changes in nucleus, mitochondria and synaptic structure were obvious; while fasudil treatment could effectively maintain the integrity of ultrastructures and functions of brain tissues, and reduce brain edema. One d, one week, one month and two months after modeling, the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the CO poisoning group were significantly higher than those in the normal control group at the same time point ( P<0.05); the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the fasudil treatment group were significantly lower than those in the CO poisoning group at the same time point ( P<0.05). Conclusion:The activation of Nogo-OMgp/Rho-Rock signaling pathway related molecules (Nogo, OMgp and Rock) is closely related to acute brain injury caused by CO poisoning; hydrochloride fasudil can effectively down-regulate the protein expressions of Nogo, OMgp and Rock, therefore obviously alleviate brain injury after CO poisoning.