Myelodysplastic syndrome (MDS) is a group of heterogeneous hematopoietic stem cell malignancies with a high risk of transformation into acute myeloid leukemia (AML). Clonal evolutions are significantly associated with transformation to AML. According to a gene expression microarray, atg3 is downregulated in MDS patients progressing to leukemia, but less is known about the function of Atg3 in the survival and death of MSD/AML cells. Moreover, the role of autophagy as a result of bortezomib treatment is controversial. The current study was designed to investigate the function of Atg3 in SKM-1 cells and to study the effect of Atg3 on cell viability and cell death following bortezomib treatment.

The influence of atrial fibrillation (AF) on the clinical outcomes of patients with ischemic stroke (IS) has not been completely determined. We aimed to perform a systematic review and meta-analysis to assess the relationship between AF and adverse events in patients with acute IS treated with thrombolysis.PubMed, EMBASE, and the Cochrane Library were searched for relevant studies regarding the association between AF and the outcomes of patients with IS treated with thrombolysis. Random and fixed effect models were used for pooling data.Twelve cohort studies involving 14,801 patients with acute IS were included. Meta-analysis revealed that patients with AF were more likely to die within 90 days after thrombolysis (odds ratio [OR], 2.13; 95% confidence interval [CI]: 1.68-2.70, P < 0.001), whereas this association was not observed in hospitalized patients (OR, 1.50; 95% CI, 0.86-2.60; P = 0.150). AF was associated with a reduced incidence of favorable outcomes (modified Rankin Scale ≤ 2) (OR, 1.95; 95% CI: 1.33-2.85, P = 0.001) and an increased risk of symptomatic intracerebral hemorrhage (OR, 1.28; 95% CI: 1.08-1.52, P = 0.006). No evident publication bias was found by Begg's test or Egger's test.Comorbidity of AF may increase the risk of adverse outcomes for patients with IS undergoing thrombolysis. Further well-designed trials are warranted to confirm this association.

MicroRNAs have crucial roles in development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-124 was down-regulated in many cancers; however, the role of miR-124 in osteosarcoma development is unknown. In this study, we demonstrate that expression of miR-124 is significantly downregulated in osteosarcoma tissues and cell lines, compared to the adjacent tissues. The expression of miR-124 in the metastases osteosarcoma tissues was lower than that in non- metastases tissues. We identified and confirmed Rac1 as a novel, direct target of miR-124 using prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed Rac1 protein expression and attenuated cell proliferation, migration, and invasion and induced apoptosis in MG-63 and U2OS in vitro. Moreover, overexpression of Rac1 in miR-124-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion caused by miR-124. Therefore, our results demonstrate that miR-124 is a tumor suppressor miRNA and suggest that this miRNA could be a potential target for the treatment of osteosarcoma in future.

Data-independent acquisition (DIA) in liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) provides comprehensive untargeted acquisition of molecular data. We provide an open-source software pipeline, which we call MS-DIAL, for DIA-based identification and quantification of small molecules by mass spectral deconvolution. For a reversed-phase LC-MS/MS analysis of nine algal strains, MS-DIAL using an enriched LipidBlast library identified 1,023 lipid compounds, highlighting the chemotaxonomic relationships between the algal strains.

Food allergy can influence the development of colorectal cancer, although the underlying mechanisms are unclear. While mast cells (MC) store and secrete histamine, immature myeloid cells (IMC) are the major site of histidine decarboxylase (HDC) expression, the enzyme responsible for histamine production. From our earlier work, we hypothesized that histamine is central to the association between allergy and colorectal carcinogenesis through its influence on the MC-MDSC axis. Here, we show that in wild type (WT) mice, ovalbumin (OVA) immunization elicits a typical TH2 response. In contrast, in HDC-/- mice, the response to OVA allergy is skewed towards infiltration by IL-17 expressing MCs. This response is inhibited by histamine treatment. The HDC-/- allergic IL-17-expressing MCs promote MDSC proliferation and upregulation of Cox-2 and Arg-1. OVA allergy in HDC-/- mice increases the growth of colon tumor cells in both the MC38 tumor cell implantation model and the AOM/DSS carcinogenesis model. Taken together, our results show that histamine represses IL-17-expressing MCs and their subsequent activation of MDSCs, attenuating the risk of colorectal cancer in the setting of food allergy. Targeting the MC-MDSC axis may be useful for cancer prevention and treatment in patients, particularly in those with food allergy.

Olaratumab (LY3012207/IMC-3G3/Lartruvo™) is a fully human monoclonal antibody specific for platelet-derived growth factor receptor alpha (PDGFRα). Phase Ib/II trial results of olaratumab plus doxorubicin in adult patients with advanced soft tissue sarcoma (STS) supported accelerated FDA approval of this regimen. Radiation therapy (RT) is frequently used for high-risk localized STS. However, olaratumab has not been tested with concurrent RT. Here, we evaluate the chimeric anti-mouse PDGFRα antibody 1E10Fc as a radiosensitizer in a primary mouse model of STS.

Cisplatin is the most commonly used antitumor drug in the chemotherapy of a variety of malignancies. However, the severe side effects and drug resistance limit its clinical application. The aim of this study was to develop PLGA-based cisplatin-loaded implants and evaluate the antitumor efficacy of continuous intratumoral chemotherapy with the implants. The cisplatin-loaded implants were prepared by the direct compression method and characterized regarding drug content, micromorphology, in vitro and in vivo drug release profiles. Furthermore, the antitumor activity of the implants was conducted in sarcoma 180 tumor-bearing mice. The SEM images showed smooth surface of the implants and the mean drug content of the tested implants was (37.7% ± 0.5%, w/w). Both in vitro and in vivo release profiles of the implants were characterized by initial burst release followed by the sustained-release of cisplatin. Intratumoral implantation of the cisplatin-loaded implants could effectively inhibit the tumor growth. Additionally, intratumoral chemotherapy with the implants significantly reduced the systemic toxicity compared with intravenous injection of cisplatin. It is worth noting that an increase in the dose of the implants led to a higher tumor suppression rate without additional systemic toxicity. These results demonstrated that cisplatin-loaded implants enhanced the antitumor efficacy and reduced the dose-related side effects in sarcoma 180 tumor-bearing mice.

Shengmai injection (SMI) is a classical traditional Chinese medicine (TCM) officially recorded in Pharmacopoeia of the People's Republic of China (version 2015) and has long been used to treat heart failure in China. However scientific evidence for the anti-oxidative stress potential of SMI used in traditional medicine is lacking.

Gastric cancer (GC) is the fourth most common malignant neoplasm and the second leading cause of cancer death. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression facilitates early GC diagnosis and the development of targeted therapies for advanced GC patients. Emerging evidence has revealed a close correlation between forkhead box (FOX) proteins and cancer development. However, the prognostic significance of forkhead box S1 (FOXS1) in patients with GC and the function of FOXS1 in GC progression remain undefined. In this study, we found that upregulation of FOXS1 was frequently detected in GC tissues and strongly correlated with an aggressive phenotype and poor prognosis. Functional assays confirmed that FOXS1 knockdown suppressed cell proliferation and colony numbers, with induction of cell arrest in the G0/G1 phase of the cell cycle, whereas forced expression of FOXS1 had the opposite effect. Additionally, forced expression of FOXS1 accelerated tumor growth in vivo and increased cell migration and invasion through promoting epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, the core promoter region of FOXS1 was identified at nucleotides -660~ +1, and NFKB1 indirectly bind the motif on FOXS1 promoters and inhibit FOXS1 expression. Gene set enrichment analysis revealed that the FOXS1 gene was most abundantly enriched in the hedgehog signaling pathway and that GLI1 expression was significantly correlated with FOXS1 expression in GC. GLI1 directly bound to the promoter motif of FOXS1 and significantly decreased FOXS1 expression. Finally, we found that miR-125a-5p repressed FOXS1 expression at the translational level by binding to the 3' untranslated region (UTR) of FOXS1. Together, these results suggest that FOXS1 can promote GC development and could be exploited as a diagnostic and prognostic biomarker for GC.

Aplysin, a kind of phytochemicals or phytonutrients, is purified from red alga Laurencia tristicha. The present study aims to investigate the influence of aplysin on changes of intestinal permeability and microbiota induced by excessive ethanol and iron. Thirty male rats were randomly divided into three groups (10/group): control group (normal saline); ethanol + iron group as EI treated with ethanol (8⁻12 mL/kg/day) and iron (1000 mg/kg) in diet; EI supplemented with aplysin (150 mg/kg/day) group as AEI; the trial lasts for 12 weeks. The result showed that levels of plasma endotoxin, fatty acid-binding protein 2, D-lactic acid, diamine oxidase were increased in rats in the EI group; and significantly decreased by 14%, 17%, 26%, 16%, respectively (p < 0.05) in the AEI group after the 12-week aplysin treatment. Moreover, in the AEI group the amount of Escherichia coli and Bacteroides fragilis were higher, while the amount of Lactobacillus, Bifidobacterium and Clostridium were lower than those in the EI group. The expressions of iron transporters divalent-metal transporter 1(DMT1) and ferroportin 1(FPN1) were significantly upregulated in the EI group compared to those in the control group. In conclusion, aplysin could effectively improve intestinal permeability and intestinal flora disorder induced with excessive ethanol and iron.

This experiment was conducted to investigate the effect of exposure to high altitude and low oxygen on intestinal microbial communities using mice as an animal model. Fecal microbiota from mice housed in a control environment representing 2,200 meters (NC group) above sea level with 16% Oxygen and mice that were placed in a hypobaric chamber representing 5000 meters (HC group) above sea level with 11% Oxygen for 30 days, were analyzed by the HiSeq Illumina sequencing platform. The results showed a significant difference in beta diversity observed between the two groups, while no significant difference was observed in alpha diversity. Compared with the NC group, the relative abundance of class Epsilonproteobacteria, phlym Actinobacteria, class Erysipelotrichia and genus Helicobacter were significantly lower (P<0.05), while the relative abundance of genus Alistipes was increased in the HC group; Phenotypic analysis showed no significant difference in aerobic, anaerobic, facultatively anaerobic, potentially pathogenic, stress tolerant, mobile element, biofilms formation, gram negative and gram positive between HC group and NC group; Functional analysis results showed significant differences in 34 gene functional metabolic pathways (carbohydrate digestion and absorption, energy metabolism, arachidonic acid metabolism, flavonoid biosynthesis, RIG-I-like receptor signaling pathway, etc) between HC group and NC group. Together, these findings suggest that exposure to high altitude and low oxygen had the potential to change the intestinal microbial communities, which potentially may modulate metabolic processes in mice.

Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers1,2. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues. For example, blocking insulin signalling promotes glycogen breakdown in the liver and prevents glucose uptake in the skeletal muscle and adipose tissue, resulting in transient hyperglycaemia within a few hours of PI3K inhibition. The effect is usually transient because compensatory insulin release from the pancreas (insulin feedback) restores normal glucose homeostasis3. However, the hyperglycaemia may be exacerbated or prolonged in patients with any degree of insulin resistance and, in these cases, necessitates discontinuation of therapy3-6. We hypothesized that insulin feedback induced by PI3K inhibitors may reactivate the PI3K-mTOR signalling axis in tumours, thereby compromising treatment effectiveness7,8. Here we show, in several model tumours in mice, that systemic glucose-insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence of PI3K inhibitors. This insulin feedback can be prevented using dietary or pharmaceutical approaches, which greatly enhance the efficacy/toxicity ratios of PI3K inhibitors. These findings have direct clinical implications for the multiple p110α inhibitors that are in clinical trials and provide a way to increase treatment efficacy for patients with many types of tumour.

Gastric cancer can be a fatal tumor and therefore represents one of the primary challenges in modern oncology. Survivin and X-linked inhibitor of apoptosis protein (XIAP) are members of the IAP family, which exerts a strong inhibitory effect on cellular apoptosis. In previous studies, the expression levels of survivin and XIAP have been demonstrated to influence the prognosis of patients with gastric cancer; therefore, the present study investigated the effect of silencing survivin and XIAP on the biological activity of the gastric cancer HGC-27 cell line. It was demonstrated that the expression levels of survivin and XIAP were significantly increased in gastric cancer tissues, compared with the adjacent non-tumor tissues. Furthermore, it was observed that the expression levels of survivin and XIAP were similarly elevated in gastric cancer HGC-27 cells, compared with normal gastric epithelial GES-1cells. Furthermore, small interfering RNA-mediated surviving- or XIAP-knockdown, in addition to the dual knockdown of survivin and XIAP, inhibited the proliferation and promoted the apoptosis of HGC-27 cells. Simultaneous inhibition of XIAP and survivin expression was more effective, compared with inhibition of XIAP or survivin alone. These results indicated that the dual knockdown of survivin and XIAP may be an effective strategy for treating gastric cancer in the future.

Hydrogen sulfide (H2 S) has traditionally been viewed as a highly toxic gas; however, recent studies have implicated H2 S as a third member of the gasotransmitter family, exhibiting properties similar to NO and carbon monoxide. Accumulating evidence has suggested that H2 S influences a wide range of physiological and pathological processes, among which blood vessel relaxation, cardioprotection and atherosclerosis have been particularly studied. In the cardiovascular system, H2 S production is predominantly catalyzed by cystathionine γ-lyase (CSE). Decreased endogenous H2 S levels have been found in hypertensive patients and animals, and CSE(-/-) mice develop hypertension with age, suggesting that a deficiency in H2 S contributes importantly to BP regulation. H2 S supplementation attenuates hypertension in different hypertensive animal models. The mechanism by which H2 S was originally proposed to attenuate hypertension was by virtue of its action on vascular tone, which may be related to effects on different ion channels. Both H2 S and NO cause vasodilatation and there is cross-talk between these two molecules to regulate BP. Suppression of oxidative stress may also contribute to antihypertensive effects of H2 S. This review also summarizes the state of research on H2 S and hypertension in China. A better understanding of the role of H2 S in hypertension and related cardiovascular diseases will allow novel strategies to be devised for their treatment.

Systematic analysis and interpretation of the large number of tandem mass spectra (MS/MS) obtained in metabolomics experiments is a bottleneck in discovery-driven research. MS/MS mass spectral libraries are small compared to all known small molecule structures and are often not freely available. MS2Analyzer was therefore developed to enable user-defined searches of thousands of spectra for mass spectral features such as neutral losses, m/z differences, and product and precursor ions from MS/MS spectra in MSP/MGF files. The software is freely available at http://fiehnlab.ucdavis.edu/projects/MS2Analyzer/ . As the reference query set, 147 literature-reported neutral losses and their corresponding substructures were collected. This set was tested for accuracy of linking neutral loss analysis to substructure annotations using 19 329 accurate mass tandem mass spectra of structurally known compounds from the NIST11 MS/MS library. Validation studies showed that 92.1 ± 6.4% of 13 typical neutral losses such as acetylations, cysteine conjugates, or glycosylations are correct annotating the associated substructures, while the absence of mass spectra features does not necessarily imply the absence of such substructures. Use of this tool has been successfully demonstrated for complex lipids in microalgae.

Bombyx mori nucleopolyhedrovirus (BmNPV) has been identified as a major pathogen responsible for severe economic loss. Most silkworm strains are susceptible to BmNPV, with only a few highly resistant strains thus far identified. Here we investigated the molecular basis of silkworm resistance to BmNPV using susceptible (the recurrent parent P50) and resistant (near-isogenic line BC9) strains and a combination of iTRAQ-based quantitative proteomics, reverse-transcription quantitative PCR and Western blotting. By comparing the proteomes of infected and non-infected P50 and BC9 silkworms, we identified 793 differentially expressed proteins (DEPs). By gene ontology and KEGG enrichment analyses, we found that these DEPs are preferentially involved in metabolism, catalytic activity, amino sugar and nucleotide sugar metabolism and carbon metabolism. 114 (14.38%) DEPs were associated with the cytoskeleton, immune response, apoptosis, ubiquitination, translation, ion transport, endocytosis and endopeptidase activity. After removing the genetic background and individual immune stress response proteins, we identified 84 DEPs were found that are potentially involved in resistance to BmNPV. Further studies showed that a serine protease was down-regulated in P50 and up-regulated in BC9 after BmNPV infection. Taken together, these results provide insights into the molecular mechanism of silkworm response to BmNPV.

The prevalence of differentiated thyroid carcinoma (DTC) in children is increasing. However, the clinical features and recurrence of DTC in children in different age groups, especially those less than 14 years old, are not well studied. We retrospectively investigated 73 children diagnosed with DTC in our hospital between January 1998 and July 2014. Data were reviewed for different age groups based on the age at initial diagnosis: 5-9, 10-14, or 15-19 years. The mean age of the recurrence group (10.6±4.1 years) was lower than that of the non-recurrence group (12.6±6.2 years; P=0.004). The main symptom at initial diagnosis was local invasion in the recurrence group, but was thyroid nodules in the non-recurrence group (P<0.001). The recurrence and non-recurrence groups did not differ in TNM stage or risk level. However, according to our age classification, the American Thyroid Association pediatric risk level was significantly different in three age groups (P=0.024). The DTC recurrence rate in each age group decreased as the age of the children increased (P=0.011). Thus, a high risk of recurrence and a high proportion of local invasion cases were observed in the youngest age group, suggesting that younger age is an important risk factor for DTC recurrence in children.

This study aims to investigate the prognostic value of pretreatment C-reactive protein/albumin ratio (CAR) in human malignancies by an updated meta-analysis.

The ribosomal proteins play important roles in the growth and development of organisms. This study aimed to explore the function of NlRPL5 (GenBank KX379234), a ribosomal protein L5 gene, in the brown planthopper Nilaparvata lugens. The open reading frame of NlRPL5 was cloned from N. lugens based on a previous transcriptome analysis. The results revealed that the open reading frame of NlRPL5 is of 900 bp, encoding 299 amino acid residues. The reverse transcription quantitative PCR results suggested that the expression of NlRPL5 gene was stronger in gravid females, but was relatively low in nymphs, males, and newly emerged females. The expression level of NlRPL5 in the ovary was about twofolds of that in the head, thorax, or fat body. RNAi of dsNlRPL5 resulted in a significant reduction of mRNA levels, ∼50% decrease in comparison with the dsGFP control at day 6. Treatment of dsNlRPL5 significantly restricted the ovarian development, and decreased the number of eggs laid on the rice (Oryza sativa) plants. This study provided a new clue for further study on the function and regulation mechanism of NlRPL5 in N. lugens.

The causal agent of pine wilt disease, pine wood nematode (PWN) (Bursaphelenchus xylophilus), revealed extended lifespan at low temperature. To discover the molecular mechanism of this phenomenon, we attempted to study the molecular characterization, transcript abundance, and functions of three genes of the cyclic guanosine monophosphate (cGMP) pathway from B. xylophilus. Three cGMP pathway genes were identified from B. xylophilus. Bioinformatic software was utilized to analyze the characteristics of the three putative proteins. Function of the three genes in cold tolerance was studied with RNA interference (RNAi). The results showed that the deduced protein of Bx-DAF-11 has an adenylate and guanylate cyclase catalytic domain, indicating an ability to bind to extracellular ligands and synthesizing cGMP. Both Bx-TAX-2 and Bx-TAX-4 have cyclic nucleotide-binding domains and ion transport protein domains, illustrating that they are cGMP-gated ion channels. The transcript level of Bx-daf-11, Bx-tax-2, and Bx-tax-4 increased at low temperature. The survival rates of three gene silenced B. xylophilus revealed a significant decrease at low temperature. This study illustrated that the cGMP pathway plays a key role in low-temperature-induced lifespan extension in B. xylophilus.