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Purpose The efficacy of immune checkpoint inhibitors such as programmed cell death ligand 1 (PD-L1) antibodies in non-small cell lung cancer (NSCLC) is limited, and combined use with other therapies is recommended. Dipeptidyl peptidase 4 (DPP4) inhibitors, a class of small molecule inhibitors, are highly effective for treating type 2 diabetes. Emerging evidence implicates DPP4 inhibitors as immunomodulators that modify aspects of innate and adaptive immunity. We evaluated the combination of a DPP4 inhibitor (anagliptin) and PD-L1 blockade in an NSCLC mouse model. Methods The effect of the combination of anti-PD-L1 and anagliptin was evaluated in subcutaneous mouse models of NSCLC. Tumor-infiltrating immune cells were analyzed by flow cytometry. Bone marrow-derived monocytes of C57BL/6 mice were isolated in vitro to examine the underlying mechanism of anagliptin on the differentiation and polarization of macrophage. Results Anagliptin dramatically improved the efficacy of PD-L1 antibody monotherapy by inhibiting macrophage formation and M2 polarization in the tumor microenvironment. Mechanistically, anagliptin suppressed the production of reactive oxygen species in bone marrow monocytes by inhibiting NOX1 and NOX2 expression induced by macrophage colony-stimulating factor, reduced late ERK signaling pathway activation, and inhibited monocyte-macrophage differentiation. However, the inhibitory effect was reactivated by lipopolysaccharide and interferon-gamma interacting with corresponding receptors during M1 macrophage polarization, but not M2. Conclusions Anagliptin can enhance PD-L1 blockade efficacy in NSCLC by inhibiting macrophage differentiation and M2 macrophage polarization, and combination therapy may be a promising strategy for treating PD-L1 blockade therapy-resistant patients with NSCLC.

Konjac powder has the effect of improving blood lipids in the general population, but there is no research on schizophrenic patients who are susceptible to dyslipidemia. The aim of our study is to evaluate the effects of konjac powder on blood lipid, glucose levels, body weight, and blood pressure in schizophrenia inpatients with dyslipidemia.After a two-week adaptation period, 76 people with schizophrenia were enrolled in a 30-day double-blind randomized controlled trial. The subjects in the experimental group were given a beverage containing konjac powder 30 minutes before each meal, whereas those in the control group were given a beverage containing resistant maltodextrin.The lipid profile, plasma glucose, blood pressure, and body weight were measured at baseline and at the end of 30-day treatment. Fiftynine subjects completed the study. There was a substantial decrease in total serum cholesterol in the experimental group, but an increase in the control group. Likewise, apolipoprotein B decreased in the experimental group but increased in the control group.We concluded that a diet supplemented with konjac powder may prevent the deterioration of dyslipidemia in people with schizophrenia, demonstrating its potential value in the treatment of metabolic disorders in schizophrenia as a new therapeutic method.

Escherichia coli (E. coli) is a common opportunistic pathogen for nosocomial infection. The aim of the study was to examine the phenotype, genotype and epidemiology of plasmid-mediated AmpC β-lactamases in E. coli. In total, 96 clinical isolates of repeated E. coli were collected from different hospitals between August and October 2012. Using a cefoxitin disk diffusion method to identify the phenotype of AmpC β-lactamases in E. coli, the plasmid was extracted, and multiplex polymerase chain reaction (PCR) was used to determine the amp gene. The PCR products were purified and sequenced. Of the 96 isolates strains, 43 strains were cefoxitin-resistant. Twelve (12.5%) isolates were detected to produce AmpC β-lactamases with multiplex PCR, 11 strains carried DHA type ampC-resistant genes, and one strain carried ACC type ampC-resistant genes. In conclusion, the incidence of producing a plasmid-mediated AmpC enzyme of E. coli strains was relatively high. Therefore, antibiotics such as imipenem, a carbapenem, potentially serve as the treatment of choice for the infection.

The expression of human transfer ribonucleic acid (tRNA) methyltransferase 9-like (KIAA1456) protein in lung cancer tissue and its effects on certain genes involved in the proliferation, migration and invasion of lung cancer cells were investigated. Immunohistochemistry was applied to stain lung cancer tissue and adjacent tissue sections of 90 lung cancer patients, so as to evaluate the difference in the expression level of KIAA1456 between two tissues. The correlation of KIAA1456 expression with clinicopathological parameters of lung cancer was analyzed. Kaplan-Meier survival curves were used to analyze the relationship between KIAA1456 and postoperative survival in patients with lung cancer. KIAA1456 gene was overexpressed in lung cancer cell lines (A549 and GLC-15), and the influence of KIAA1456 gene on the expression of cyclin D1, neural cadherin (N-cadherin) and epithelial cadherin (E-cadherin) and their involvement in lung cancer cell proliferation, migration and invasion were observed. Compared with that in adjacent tissue, the expression of KIAA1456 in lung cancer tissue was significantly decreased (p

The aim of the present study was to determine the prevalence and related drug resistance of AmpC β-lactamases in Acinetobacter baumannii in tertiary-level hospitals in the Xuzhou region in China. A total of 134 clinical isolates of non-repetitive Acinetobacter baumannii were collected from different hospitals in the Xuzhou region, and multiplex polymerase chain reaction (PCR) was employed to determine the genotype of AmpC. The PCR products were purified and sequenced. The susceptibility to antibiotics was tested using the biometrics automated microbiological-assay system, VITEK-2. Amongst the 134 isolated strains, 96 strains were found to produce AmpC β-lactamases, and the positive rate was 72%, all of which carried acinetobacter-derived cephalosporinase (ADC) type AmpC resistance genes. The drug sensitivity tests indicated that the positive Acinetobacter baumannii strains were resistant to the majority of extended-spectrum β-lactam antibiotics, but were only sensitive to polymyxin. In conclusion, the incidence of AmpC enzymes in Acinetobacter baumannii strains in tertiary-level hospitals in the Xuzhou area is relatively high, and resistance to the majority of extended-spectrum β-lactam antibiotics may be related to the ADC type of AmpC.

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer.

Several studies have reported a significant role of high mobility group box protein 1 (HMGB1) in lung cancer. Nevertheless, there is a lack of knowledge regarding the expression of HMGB1 and its correlation with the clinicopathological features of lung cancer. In addition, the potential molecular mechanisms underlying the role of HMGB1 in lung cancer are still unknown. We therefore investigated the clinicopathological and prognostic significance as well as the potential role of HMGB1 in the development and progression of lung cancer. HMGB1 expression in the tumor tissues of the cohort correlated with clinicopathological features. Moreover, lung cell migration and invasion were significantly increased after treatment with HMGB1. The matrix metalloproteinase-2 (MMP-2) expression and activity were upregulated after treatment with HMGB1, while the upregulated expression of MMP-2 stimulated by HMGB1 in lung cancer cells was significantly reduced with the blockage of si-p65. These results indicated that HMGB1 expression was significantly associated with lung cancer progression. We also showed that HMGB1 promoted lung cancer invasion and metastasis by upregulating the expression and activity of MMP-2 in an NF-κB-dependent manner. Taken together, these data suggested that HMGB1 may be a potential prognosis and therapeutic marker for lung cancer.

Several studies have reported a significant role of high mobility group box protein 1 (HMGB1) in lung cancer. Nevertheless, there is a lack of knowledge regarding the expression of HMGB1 and its correlation with the clinicopathological features of lung cancer. In addition, the potential molecular mechanisms underlying the role of HMGB1 in lung cancer are still unknown. We therefore investigated the clinicopathological and prognostic significance as well as the potential role of HMGB1 in the development and progression of lung cancer. HMGB1 expression in the tumor tissues of the cohort correlated with clinicopathological features. Moreover, lung cell migration and invasion were significantly increased after treatment with HMGB1. The matrix metalloproteinase-2 (MMP-2) expression and activity were upregulated after treatment with HMGB1, while the upregulated expression of MMP-2 stimulated by HMGB1 in lung cancer cells was significantly reduced with the blockage of si-p65. These results indicated that HMGB1 expression was significantly associated with lung cancer progression. We also showed that HMGB1 promoted lung cancer invasion and metastasis by upregulating the expression and activity of MMP-2 in an NF-κB-dependent manner. Taken together, these data suggested that HMGB1 may be a potential prognosis and therapeutic marker for lung cancer.

Integrin alphavbeta6 is up-regulated in a variety of human carcinomas and plays a crucial role in tumor invasion and metastasis. However, the function of alphavbeta6 in pancreatic carcinoma and its potential role in gemcitabine resistance remain unknown.Small interfering RNA (siRNA) targeting alphavbeta6 was constructed and transfected into PANC-1 cells. Effects of alphavbeta6 knockdown on cell proliferation, invasion, cell cycle progression, apoptosis and chemosensitivity to gemcitabine were investigated.Expression of alphavbeta6 in PANC-1 cells was markedly suppressed by siRNA. Silencing of alphavbeta6 expression significantly inhibited cell proliferation and invasiveness, resulted in cell cycle arrest, and induced cell apoptosis. More importantly, alphavbeta6 knockdown enhanced chemosensitivity to gemcitabine and increased gemcitabine-induced caspase-mediated apoptosis.These findings suggest a novel mechanism by which alphavbeta6 contributes to pancreatic carcinoma progression. The combination of alphavbeta6 silencing and gemcitabine treatment may provide an effective therapeutic strategy for highly resistant pancreatic carcinoma.

Norcantharidin has been used as an efficacious anticancer drug in China for many years, but its true mechanism remains poorly understood. Intriguingly, in an in vitro series study of anticancer drugs, we found that norcantharidin can effectively inhibit epithelial tumor cells from expressing integrin alphavbeta6. Our previous studies have confirmed that integrin alphavbeta6 is closely relevant to malignant epithelial cell tumor biology behavior, and it can promote cancer cells to invade and metastasize through a special alphavbeta6-extracellular signal-related kinase (ERK) direct signaling pathway. In this study, we investigated the relationship between the norcantharidin anticancer mechanism and integrin alphavbeta6. After HT-29 colon cancer cells were treated with norcantharidin, cell apoptosis increased remarkably. The expression of alphavbeta6 and the amount of p-ERK decreased substantially; simultaneously, the linkage between alphavbeta6 and ERK was barely detectable. However, the expression of other integrins and the levels of mitogen-activated protein kinase hardly changed. On these grounds, we presumed that norcantharidin induced HT-29 colon cancer cell apoptosis through the alphavbeta6-ERK signaling pathway. This finding elicited a novel strategy for targeting the whole alphavbeta6-ERK signal pathway, rather than simply blocking the combining site of alphavbeta6-ERK in colon cancer treatment.