The neutrophil to lymphocyte ratio as a novel predictor of asthma and its exacerbation: a systematic review and meta-analysis.

OBJECTIVE: It is widely known that the main white blood cell populations, and neutrophil to lymphocyte ratio (NLR), are involved in systemic inflammation. The usefulness of NLR measurements has been reported in patients with asthma. We performed a systematic review and meta-analysis of studies to investigate the relationship between the NLR and asthma and its exacerbations. MATERIALS AND METHODS: We systematically searched PubMed and Embase databases for studies (published between Jan 1, 1950 and Jan 2, 2020; no language restrictions) comparing the NLR values in patients with stable asthma or asthma exacerbations to healthy controls. We assessed pooled data by use of a random-effects model. RESULTS: Of 260 identified studies, 6 were eligible and were included in our analysis (N = 2418 participants). Compared with 439 healthy controls, 743 stable asthma patients in four studies showed significantly greater NLR values (standardized mean difference, SMD, 0.567, 95% CI 0.212-0.922; p = 0.002). Furthermore, compared with 1063 stable asthma patients, 402 asthma exacerbation patients yielded significantly greater NLR values (random effects SMD 1.335, 95% CI 0.429-2.241; p < 0.001). CONCLUSIONS: Our meta-analysis showed that the NLR values are a reasonable and easy-to-use marker for asthma and its exacerbations. Further studies, with larger sample sizes and more phenotypes, are required to establish its use as a predictive parameter in asthma.

Neuropilin-1 contributes to esophageal squamous cancer progression via promoting P65-dependent cell proliferation.

Neuropilin-1 (NRP1) is a non-kinase receptor recently implicated in tumor progression. Here we revealed that over-expression of NRP1 correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC). NRP1-knockdown suppressed ESCC cell proliferation and xenograft tumor growth. Reduced NRP1 expression downregulated P65 mRNA and protein expression, and ectopic expression of P65-restored cell proliferation in NRP1-silenced cells. NRP1 regulates P65 transcription by activating cAMP responsive element binding protein (CREB). NRP1 interacted with and activated epidermal growth factor receptor (EGFR), and b1/b2 domain of NRP1 is responsible for the activation of EGFR. We also found that EGFR regulated CREB transcriptional activity via AKT. These data suggest that NRP1 is an upstream regulator in the P65-dependent proliferation signaling pathway and a candidate therapeutic target for ESCC.

Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma.

Cell invasion and migration significantly contribute to tumor metastasis. Microtubule-associated protein 4 (MAP4) protein is one member of microtubule-associate proteins family. It is responsible for stabilization of microtubules by modulation of microtubule dynamics. However, there is little information about the involvement of MAP4 in human cancer. Here we show that MAP4 serves as a regulator of invasion and migration in esophageal squamous cancer cells. By activating the ERK-c-Jun-vascular endothelial growth factor A signaling pathway, MAP4 promotes cell invasion and migration in vitro, tumor growth and metastasis in mouse models. Immunohistochemical staining of operative tissues indicated that MAP4 expression was associated with tumor stage, lymph node metastasis and shorter survival of the patients with esophageal squamous cell carcinoma (ESCC). Multivariate Cox regression analysis showed that MAP4 is an independent prognostic indicator. In the serial sections of ESCC tissues, there was a positive correlation between MAP4 and vascular endothelial growth factor A expression. Notably, an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4-expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease.

Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous cell carcinoma.

We have shown earlier that overexpression of Calreticulin (CRT) contributed to a poor prognosis for patients with esophageal squamous cell carcinoma (ESCC). Here, we have shown an important role of CRT in tumorigenesis through enhancing cell motility and anoikis resistance. SiRNA-mediated knockdown of CRT caused impaired cell migration, invasion and resistance to anoikis. Notably, CRT downregulation decreased the expression of Cortactin (CTTN), which has been previously reported as a candidate oncogene associated with anoikis through the PI3K-Akt pathway. In addition, Akt phosphorylation was abolished after CRT downregulation and its activation can be refreshed by CRT upregulation, suggesting that CRT-enhanced cell resistance to anoikis through the CRT-CTTN-PI3K-Akt pathway. Moreover, the CTTN mRNA level was decreased in CRT-siRNA cells, coupled with the inactivation of STAT3. Expression of both CTTN and p-STAT3 was reduced in tumor cells following incubation with the JAK-specific inhibitor, AG490. Chromatin immunoprecipitation assay showed direct binding of p-STAT3 to the conservative STAT3-binding sequences in CTTN promoter. Furthermore, overexpression of CTTN in CRT-downregulated ESCC cells restored its motility and resistance to anoikis. This study not only reveals a role of CRT in motility promotion and anoikis resistance in ESCC cells, but also identifies CRT as an upstream regulator in the CRT-STAT3-CTTN-Akt pathway.

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/beta-catenin pathway.

xCT, the functional subunit of the cystine/glutamate transporter xc- system, plays a critical role in the maintenance of intracellular glutathione and redox balance. Disruption of xCT significantly inhibits the growth of a variety of carcinomas, including lymphoma, glioma, prostate and breast cancer. However, the role of xCT in tumor metastasis remains largely unknown. In this study, both xCT(+/+) and xCT(-/-) melanocytes were used to evaluate the role of xCT in adhesion. xCT activity was suppressed by an inhibitor, sulfasalazine (SASP), or by xCT siRNA in an esophageal cancer cell line, KYSE150. We found that disruption of xCT enhanced homotypic cell-cell adhesion and attenuated cell-extracellular matrix adhesion. SASP significantly inhibited both cell invasion of KYSE150 in vitro and its experimental metastasis in nude mice. Caveolin-1 was upregulated and beta-catenin was recruited to the plasma membrane when xCT was deficient, which were followed by the inhibition of beta-catenin transcriptional activity. Further study revealed that the upregulation of caveolin-1 and inhibition of tumor cell invasion were mediated by reactive oxygen species-induced p38 MAPK activation. These results first establish the role of xCT in tumor metastasis and implicate a potential target for cancer therapy.

HeLaTG cells have mitochondrial DNA inserted into the c-myc oncogene.

To determine whether mitochondrial DNA (mtDNA) fragments found within the nucleus are transcribed, we have differentially screened a HeLaTG cDNA library. A clone that hybridized to mtDNA as well as to c-myc was identified. Analysis of the cDNA disclosed that it contained a mtDNA sequence, encoding cytochrome-c oxidase subunit III (coxIII) that was contiguous with and 5' of a c-myc sequence corresponding to part of exon 2 and exon 3. Hybridization of ScaI-digested DNA with a 1.05 kb c-myc probe revealed a unique band in HeLaTG cells, as well as a band common to HeLaTG and 13 other cell types examined. Solution hybridization of HeLaTG RNA with a radiolabeled, single-stranded cDNA probe containing the coxIII-c-myc junction demonstrated a nuclease-resistant band that matched the full length of the junctional cDNA probe. A smaller band that equaled the size of the c-myc portion alone was also detected. Only the smaller band coinciding with the c-myc sequences was protected from nuclease digestion by RNA from other cells. When a radiolabeled probe synthesized in the opposite orientation was used, nuclease-resistant bands equal in length to the coxIII portion of the probe were detected after hybridization with RNA from all cells. These results indicate that insertion of mtDNA fragments into nuclear genes occurs and that subsequent transcription of a 'chimaeric' or 'fusion' mRNA containing both mitochondrial and nuclear sequences can ensue.

[Clinical features and imaging findings of posterior cerebral artery infarction].

The clinical features and imaging findings of posterior cerebral artery infarction (PCAI) in 18 cases verified by CT scan and/or MRI, DSA, SPECT were reported, and their interrelation were analyzed. It was found that the main clinical feature of PCAI was visual defect with amnesia syndrome, the lesion was predominant in the right hemisphere. In examining the structure and function of brain and vessels, each of CT, MRI, ECT and DSA had its own advantage and might complement the others, CT and MRI were better in displaying the structure of cerebral parenchyma than ECT and DSA, whereas, MRI was superior in distinguishing the lesions in deep white matter and subtentorial region. DSA was better than MRI and CT in displaying vascular structure, but was inferior in disclosing the occlusion of deep perforating branches or cortical arterioles. ECT, besides its ability to show the morphological changes of brain, was mainly used to disclose the functional changes of cerebral parenchyma, being a method to make early diagnosis for CVD. However, ECT was inferior than MRI and CT, in displaying lacunar infarction and lesions of brain-stem.

The use of Chinese herb medicine in experimental radiotherapy.

Extracts from a group of destagnative herbs, 764-1, and the effective chemical, 764-3, were tested by an in vitro experiment using a HeLa-S3 cell line. Under aerobic conditions, the shoulder of the cell survival curve diminished or disappeared according to the different doses of 764-1 used, but no change in slope was observed. In nitrogen, when the dose of 764-1 increased to 20 mg/ml (ID20), besides the disappearance of the shoulder, the slope of the curve also showed changes at lower doses (4-8 Gy); up to 10-25 Gy the curve became more flattened. 764-3 showed almost a similar effect by mainly affecting the shoulder of the survival curve. At low drug doses a SER as high as 1.87 might be obtained under hypoxic condition. At the same time 764-1 was used in testing the effect on radiation lung damage. It was found that 764-1 could markedly inhibit the change of alveolar surfactant at 1 and 3 weeks after radiation. A wide field of investigation is thus spread out in front of us on radiosensitization and protection. Further studies on 764-3 are carried out.