Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury

Calcitonin gene-related peptide（CGRP） has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury（TBI） remains poorly understood. In this study, 96 adult patients with TBI（enrolled from September 2015 to December 2016） were divided into a mild/moderate TBI group（36 males and 25 females, aged 38 ± 13 years） and severe TBI group（22 males and 13 females, aged 38 ± 11 years） according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls（15 males and 10 females, aged 39 ± 13 years）. Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.

Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers

Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide,due to late detection and high recurrence rates.Today,these cancers have a heavy socioeconomic burden,for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets.Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers.Over the past decade,emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers,indicating its potential as an independent prognostic indicator in such patients.Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo .Furthermore,OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment,in which many details need further exploration.OPN signaling results in various functions,including prevention of apoptosis,modulation of angiogenesis,malfunction of tumor-associated macrophages,degradation of extracellular matrix,activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways,which lead to tumor formation and progression,particularly in gastric and liver cancers.This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression,its potential as a therapeutic target,and putative mechanisms in gastric and liver cancers.Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.

Polo-like kinase 1 suppresses lung adenocarcinoma immunity throughnecroptosis

Polo-like kinase 1(PLK1)plays a crucial role in cell mitosis and has been associated with necroptosis.However,the role of PLK1 and necroptosis in lung adenocarcinoma(LA)remains unclear.In this study,we analyzed The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression databases to evaluate the prognostic value and mechanistic role of PLK1 in LA.PLK1 was found to be highly expressed in LA and was positively associated with advanced disease staging and poor survival outcomes.Functional enrichment analysis showed that PLK1 was involved in cell mitosis,neurotransmitter transmission,and drug metabolism.Further analysis using single-sample gene set enrichment analysis and ESTIMATE algorithm revealed a correlation between PLK1 expression and immune infiltration in LA.Silencing of PLK1 using miRNA transfection in LA cells reduced cell proliferation and increased apoptosis,as well as upregulating the expression of necroptosis-related proteins,such as RIPK1,RIPK3,and MLKL.Additionally,nude mouse transplantation tumor experiments demonstrated that silencing PLK1 reduced the growth capacity of LA cells.These findings suggest that PLK1 plays a critical role in LA progression by regulating necroptosis and immune infiltration,and may serve as a potential therapeutic target for immunotherapy.Furthermore,PLK1 expression can be used as a prognostic biomarker for LA patients.

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer.

Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication

AIM:To investigate the methylation status of secreted protein acidic and rich in cysteine(SPARC) in human hepatocellular carcinoma(HCC) and evaluate its clinical implication.METHODS:The methylation status of SPARC was analyzed in one HCC cell line(SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing.The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry,respectively.The correlations between the methylation status and the gene expression,the clinicopathological parameters,as well as the prognosis after surgery were analyzed.RESULTS:In the SMMC-7721 cell line,the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2'-deoxycytidine.Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues(45/60 vs 7/60,P < 0.001),and it was correlated with the pathological classification(P = 0.019).The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation(P = 0.040).The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC(28.0 mo vs 41.0 mo,P = 0.043).CONCLUSION:Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer

Background X-linked inhibitor of apoptosis （XlAP）-associated factor 1 （XAF1） is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. Methods Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction （RT-PCR）. The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） method and flow cytometry （FACS）, respectively. Results The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues （P 〈0.05）. The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. Conclusion XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.

Blood Biomarkers in Minor Stroke and Transient Ischemic Attack

Minor stroke and transient ischemic attack（TIA）are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician＇s examination of the patient, supplemented by the results of acute brain imaging.However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment.