Prognostic Significance of Pretreatment Prognostic Nutritional Index (PNI) in Patients with Nasopharyngeal Carcinoma: A Meta-Analysis.

OBJECTIVE: Previous studies have investigated the pretreatment prognostic nutritional index (PNI) as a prognostic factor in patients with nasopharyngeal carcinoma (NPC); however, the results remained inconsistent. We aimed to assess the prognostic value of PNI in patients with NPC through conducting meta-analysis. Methods: Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for low PNI of overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), loco-regional recurrence-free survival (LRFS), and cancer-specific survival (CSS). Results: Totally, eight studies involving 4299 patients were included in this meta-analysis. A low pretreatment PNI was associated with poor OS (HR = 1.86, 95% CI = 1.55-2.33, P < 0.001), DMFS (HR = 2.03, 95% CI = 1.69-2.44, P < 0.001), PFS (HR = 1.57, 95% CI = 1.31-1.90, P < 0.001), and CSS (HR = 2.29, 95% CI = 1.54-3.42, P < 0.001). The subgroup analysis showed that low PNI remained a significant factor for poor OS, DMFS, and PFS irrespective of treatment, country, and cutoff value of PNI. In addition, low PNI was correlated to female gender (OR = 1.35, 95% CI = 1.12-1.62, P = 0.002), older age (OR = 1.75, 95% CI = 1.17-2.62, P = 0.007), and T3-T4 stage (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011). Conclusions: A low PNI was associated with poor survival outcomes in patients with NPC. Moreover, PNI could serve as an index to help guide clinical management for older patients.

Comparative Genomics of Bacillus thuringiensis Reveals a Path to Specialized Exploitation of Multiple Invertebrate Hosts.

Understanding the genetic basis of host shifts is a key genomic question for pathogen and parasite biology. The Bacillus cereus group, which encompasses Bacillus thuringiensis and Bacillus anthracis, contains pathogens that can infect insects, nematodes, and vertebrates. Since the target range of the essential virulence factors (Cry toxins) and many isolates is well known, this group presents a powerful system for investigating how pathogens can diversify and adapt to phylogenetically distant hosts. Specialization to exploit insects occurs at the level of the major clade and is associated with substantial changes in the core genome, and host switching between insect orders has occurred repeatedly within subclades. The transfer of plasmids with linked cry genes may account for much of the adaptation to particular insect orders, and network analysis implies that host specialization has produced strong associations between key toxin genes with similar targets. Analysis of the distribution of plasmid minireplicons shows that plasmids with orf156 and orf157, which carry genes encoding toxins against Lepidoptera or Diptera, were contained only by B. thuringiensis in the specialized insect clade (clade 2), indicating that tight genome/plasmid associations have been important in adaptation to invertebrate hosts. Moreover, the accumulation of multiple virulence factors on transposable elements suggests that cotransfer of diverse virulence factors is advantageous in terms of expanding the insecticidal spectrum, overcoming insect resistance, or through gains in pathogenicity via synergistic interactions between toxins.IMPORTANCE Population genomics have provided many new insights into the formation, evolution, and dynamics of bacterial pathogens of humans and other higher animals, but these pathogens usually have very narrow host ranges. As a pathogen of insects and nematodes, Bacillus thuringiensis, which produces toxins showing toxicity to many orders of insects and other invertebrates, can be used as a model to study the evolution of pathogens with wide host ranges. Phylogenomic analysis revealed that host specialization and switching occur at the level of the major clade and subclade, respectively. A toxin gene co-occurrence network indicates that multiple toxins with similar targets were accumulated by the same cell in the whole species. This accumulation may be one of the strategies that B. thuringiensis has used to fight against host resistance. This kind of formation and evolution of pathogens represents a different path used against multiple invertebrate hosts from that used against higher animals.

Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria-mediated pathway.

Metformin is commonly used to treat type II diabetes, although it may also reduce the risk of cancer and improve the associated prognosis. However, its mode of action in cancer remains unclear. The present study evaluated the effects of metformin on lung adenocarcinoma A549 cells and identified molecular mechanisms of metformin activity. The A549 cells were treated with metformin at different concentrations and cell viability was assayed by using an MTT assay. The cell cycle and the apoptosis rate were assayed by flow cytometry. Nude mice were transplanted with A549 cells and the tumor growth inhibition rate was detected. Once the A549 cells had been treated with 20 mM metformin for 48 h, the cell cycle was arrested in the G0/Gl phase and the apoptosis rate was 20.57±3.16%. The expression of the B-cell lymphoma (Bcl)-2 and Bcl-extra large proteins was downregulated following metformin treatment, while Bax protein expression was significantly increased. Tumor size in the high-dose metformin and cisplatin plus metformin groups was significantly smaller, and the inhibition rates were 41.3 and 72.9%, respectively, compared with the control group. These results indicated that metformin displays anticancer activity against lung adenocarcinoma by causing G1 arrest of the cell cycle and subsequent cell apoptosis through the mitochondria-dependent pathway in A549 cells. Furthermore, it was found that metformin dramatically inhibited lung adenocarcinoma tumor growth in vivo. These data suggest that metformin may become a potential cytotoxic drug in the prevention and treatment of lung adenocarcinoma.

Complete genome sequence of Bacillus thuringiensis tenebrionis 4AA1, a typical strain with toxicity to Coleopteran insects.

Bacillus thuringiensis serovar morrisoni biovar tenebrionis has been developed as an bioinsecticide to control Coleopteran insects in agriculture and forestry for a few decades. Its major crystal protein Cry3Aa was also applied to transgenic crops. Here we report the complete genome sequence of strain tenebrionis 4AA1, which has one chromosome of 5,652,292bp and six plasmids. Two crystal protein genes, cry3Aa and cry15Aa, locate on one single plasmid named pBMB51. This strain also possesses plentiful virulence factors besides crystal proteins.

Complete genome sequence of Bacillus thuringiensis serovar galleriae strain HD-29, a typical strain of commercial biopesticide.

Bacillus thuringiensis serovar galleriae is highly toxic to Lepidoptera insect pests, and has been widely used as Bt biopesticide in many countries. Here we reported the complete genome of strain HD-29, a standard serotype strain in galleriae serovariety. More than previous work reported, it harbors ten plasmids, and three large ones carry eight insecticidal protein genes (cry1Aa, cry1Ac, cry1Ca, cry1Da, cry1Ia, cry2Ab, cry9Ea and vip3Aa) and an intact zwittermicin A biosynthetic gene cluster.