The clinical effect of different vertebral body height restoration rates after percutaneous kyphoplasty for osteoporotic vertebral compression fractures.

OBJECTIVE: This study aimed to evaluate the clinical effect of different vertebral body heights restoration rate after percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures (OVCF). METHODS: The patients were divided into two groups according to the height restoration rate of the anterior edge of the vertebral body fracture after PKP operation using X-Ray imaging. The group A was below 80%, and the group B was above 80%. Clinical preoperative and postoperative efficacy (1st day, 1st month, 6th month, and 12th month after surgery) were evaluated according to VAS, Oswestry Disability Index(ODI), Quality of Life Questionnaire of the European Foundation for Osteoporosis(QUALEFFO), and Back Pain Life Disorder Questionnaire(RQD). Simultaneously, the preoperative and postoperative local Cobb angles and changes in the injured vertebrae in the two groups were calculated and analyzed. RESULTS: The postoperative Cobb angle in group A was significantly higher than that in group B. The correction rate in group B was significantly better than that in group A. The VAS, ODI, QUALEFFO, and RQD scores of group B patients were significantly lower than those of patients in group A at each follow-up time point. The correlation coefficients of vertebral body height restoration rate and VAS, ODI, QUALEFFO, and RQD scores at the last follow-up were - 0.607 (P < 0.01), -0.625 (P < 0.01), -0.696 (P < 0.01), and - 0.662 (P < 0.01), respectively. CONCLUSIONS: The results of the correlation analysis between the vertebral body height restoration rate and the above clinical efficacy scores show that increasing the vertebral body anterior height restoration rate is beneficial for pain relief and improves the clinical efficacy of patients. Simultaneously, improving the height restoration rate of the anterior edge of the vertebral body and restoring the normal spinal structure is beneficial for reducing the incidence of refracture of the adjacent vertebral body.

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

OBJECTIVE: Colon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING). METHODS: Real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-181a-2-3p in colon cancer cell lines and normal intestinal epithelial cells. After overexpression of miR-181a-2-3p in colon cancer cell lines SW480 and HT29, cells were examined by CCK8, Transwell, and flow cytometry assays for alterations in proliferation, migration, apoptosis, and cell cycle. Target genes of miR-181a-2-3p were predicted by bioinformatics and validated by dual luciferase assays. Rescue experiments were performed to explore the role of STING in the effect of miR-181a-2-3p. The effect of miR-181a-2-3p on colon cancer proliferation in vivo was validated by nude mouse tumorigenicity assay. RESULTS: miR-181a-2-3p was lowly expressed in both colon cancer tissues and cell lines. Overexpression of miR-181a-2-3p led to reduced proliferation and migration, increased apoptosis, and altered cell cycle in colon cancer cell lines SW480 and HT29. STING was a target gene of miR-181a-2-3p. Increased STING expression partially counteracted the effect of overexpression of miR-181a-2-3p on colon cancer cell lines. miR-181a-2-3p also suppressed colon cancer proliferation in vivo. CONCLUSION: miR-181a-2-3p inhibits the proliferation and oncogenicity of colon cancer, and its molecular mechanism could be inhibited by STING.

Pairing comparative genomics with tandem mass-based molecular networking allows to highly efficient discovery of nonribosomal peptides from Nocardia spp.

Microbial natural products, particularly nonribosomal peptides (NRPs), have attracted significant attention due to their structural diversity and therapeutic potential. Nocardia, a genus of Actinomyces, is an important reservoir for natural products, especially NRPs. However, rediscovery is a significant challenge for mining new specialized metabolites from Nocardia, as well as from other sources. To overcome this challenge, we developed a strategy that combines comparative genomics with tandem mass-based molecular networking, which allows to efficiently discover new NRPs from Nocardia spp.. As a proof of concept, all genomes of Norcardia in NCBI database, including three strains from our lab, were compared with each other to prioritize unique biosynthetic gene clusters (BGCs) in the three in-house Nocardia strains, particularly those containing nonribosomal peptide synthases (NRPSs). Subsequently, the metabolomics data of those three in-house strains were analyzed employing tandem mass-based molecular networking. This led to the identification of a known lipopeptide, nocarjamide (1), and five new congeners (2-6) of nocarjamide, as well as a new decalipopeptide, nocarlipoamide (7), along with nocardimicin, a known compound found in Nocardia. The structure of the new decalipopeptide 7 was further extensively characterized using NMR, MS/MS, Marfey's analysis, and X-ray. In addition, the biosynthesis pathways for 1-7 were proposed through bioinformatics analysis, and thus the gene clusters responsible for biosynthesizing them were confirmed. Our results indicate that this strategy enables prompt dereplication of known compounds, rapid linkage of identified compounds with their biosynthesis gene cluster, and efficient discovery of new compounds.

Axial Symptoms After Conventional and Modified Laminoplasty: A Meta-analysis.

PURPOSE: The study aims to evaluate the impact of procedural variations in single-door laminoplasty on axial symptoms (AS) and neurologic outcomes. METHODS: A comprehensive literature search was conducted across PubMed, EMBASE, and the Cochrane Library, adhering to specific inclusion criteria. We extracted data on the prevalence of AS in both the modified and conventional laminoplasty groups from the selected studies. Neurologic outcomes were assessed using the Japanese Orthopedic Association (JOA) recovery rate, which was subsequently converted to Hedge's g for analysis. Forest plots were generated to visualize the effect sizes, and publication bias was assessed using both funnel plots and Egger's test. RESULTS: Fourteen studies comprising 1201 patients were included in this meta-analysis focused on AS. The aggregated SMD was -0.891 with a 95% CI of -1.146 to -0.631 (P < 0.01), denoting a statistically significant reduction in AS in the modified laminoplasty group compared with the conventional approach. Of the 14 studies, 10, encompassing 898 patients, contributed data for JOA recovery rate analysis. The overall effect size was 0.089, with a 95% CI ranging from -0.090 to 0.267, and a P value of 0.2901, indicating no significant difference in neurologic outcomes between the 2 techniques. No evidence of publication bias was detected. CONCLUSIONS: This meta-analysis demonstrates that modified laminoplasty is associated with a significant reduction in the incidence and severity of axial symptoms, without compromising neurologic functionality.

Nocaviogua A and B: two lipolanthines from root-nodule-associated Nocardia sp.

Nocaviogua A (1) and B (2), two lipolanthines featuring a non-canonical avionin (Avi)-containing macrocycle and a long acyl chain, were identified from the mutualistic actinomycete Nocardia sp. XZ19_369, which was isolated from the nodules of sea buckthorn collected in Tibet. Their planar structures were elucidated via extensive analyses of 1D and 2D NMR, as well as HRMS data. The absolute configurations were fully elucidated by advanced Marfey's analysis and GIAO NMR calculations, representing the first time that the configurations of this family of lipolanthines have been determined. Nocaviogua A (1) exhibited weak cytotoxicity against human chronic uveal melanoma cells (UM92-1), non-small cell lung cancer (NCI-H2170), and breast cancer (MDA-MB-231). Our work provides valuable information on this burgeoning class of lipolanthines for further investigations.

Are surgical outcomes for one level anterior decompression and fusion associated with MRI parameters for degenerative cervical myelopathy?

Background: Our study is to determine the correlation between preoperative MRI parameters of spinal cord compression and the effects of anterior surgery in patients with degenerative cervical myelopathy (DCM). Methods: 24 normal subjects with no evident abnormalities were selected as group A. 79 patients with DCM underwent single-segment (C4-5/C5-6) ACDF surgery formed the operation group, and separated into group B (without high signal) and group C (with high signal) according to the absence or presence of high signal in the spinal cord on preoperative T2-weighted MRI respectively. MRI parameters (MCC, maximum canal compromise; MSCC, maximum spinal cord compression; CR, spinal cord compression rate; RCSCDS, ratio of cervical spinal cord to dura sac) were measured. The JOA score was used to evaluate cervical spinal cord function and recovery rate (RR) was used to evaluate postoperative efficacy. The relationship between preoperative MRI parameters and postoperative efficacy was analyzed. Results: The preoperative JOA score and RR of group B were higher than that of group C. MCC and MSCC in group B were significantly lower than those in groups C. The multiple linear regression equation was the fitted postoperative JOA score = 13.371-2.940 * MCC -5.660 * RCSCDS +0.471 * preoperative JOA score. The fitted RR = 1.451-0.472 * MCC -1.313 * RCSCDS. Conclusion: The occurrence of high signal on T2-weighted images could reflect more serious spinal cord injury. The postoperative JOA score was significantly correlated with MCC, RCSCDS, and preoperative JOA score, while RR was significantly associated with MCC and RCSCDS.

Identification of a Small Molecule That Inhibits the Interaction of LPS Transporters LptA and LptC.

The need for novel antibiotics has become imperative with the increasing prevalence of antibiotic resistance in Gram-negative bacteria in clinics. Acting as a permeability barrier, lipopolysaccharide (LPS) protects Gram-negative bacteria against drugs. LPS is synthesized in cells and transported to the outer membrane (OM) via seven lipopolysaccharide transport (Lpt) proteins (LptA-LptG). Of these seven Lpt proteins, LptC interacts with LptA to transfer LPS from the inner membrane (IM) to the OM, and assembly is aided by LptD/LptE. This interaction among the Lpt proteins is important for the biosynthesis of LPS; therefore, the Lpt proteins, which are significant in the assembly process of LPS, can be a potential target for new antibiotics. In this study, a yeast two-hybrid (Y2H) system was used to screen compounds that could block LPS transport by inhibiting LptA/LptC interaction, which finally disrupts the biosynthesis of the OM. We selected the compound IMB-0042 for this study. Our results suggest that IMB-0042 disrupts LptA/LptC interaction by binding to both LptA and LptC. Escherichia coli cells, when treated with IMB-0042, showed filament morphology, impaired OM integrity, and an accumulation of LPS in the periplasm. IMB-0042 inhibited the growth of Gram-negative bacteria and showed synergistic sensitization to other antibiotics, with low cytotoxicity. Thus, we successfully identified a potential antibacterial agent by using a Y2H system, which blocks the transport of LPS by targeting LptA/LptC interaction in Escherichia coli.

Alterations and Mechanism of Gut Microbiota in Graves' Disease and Hashimoto's Thyroiditis.

To explore the role of gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2 and lower levels of Bacillaceae and Megamonas. Further analysis of KEGG found that the "ABC transporter" metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that Bacillus, Blautia, and Ornithinimicrobium could be used as potential markers to distinguish GD and HT from the healthy population and that "ABC transporter" metabolic pathway may be involved in the pathogenesis of GD and HT.

Finite Element Analysis of Spinal Cord Stress in a Single Segment Cervical Spondylotic Myelopathy.

Background: Spinal cord ischemia is largely caused by cervical spondylotic myelopathy (CSM), which has a corresponding biomechanical basis. Finite element analysis of spinal cord stress in diseased segments of CSM was performed to provide a biomechanical basis for the pathogenesis of CSM. Methods: A single segment (C4-5) in a patient with CSM was selected for mechanical simulation of three-dimensional (3D) computed tomography scanning, and a 3D finite element model of the cervical vertebra was constructed. Based on the patient's age, sex, height, weight, and other parameters, a finite element analysis model of an individual with healthy cervical vertebrae in our hospital was selected as the control to compare the stress changes between the patient and control groups in the analysis of the cervical vertebrae under anterior flexion, posterior extension, lateral flexion, and rotating load in the diseased spinal cord segment. Results: In the CSM patient, the diseased segment was C4-5. Under loading conditions of forward flexion, posterior extension, left flexion, right flexion, left rotation, and right rotation, the maximum stress on the spinal cord in the control group was 0.0044, 0.0031, 0.00017, 0.00014, 0.0011, and 0.001 MPa, respectively, whereas those in the spinal cord in the CSM group were 0.039, 0.024, 0.02, 0.02, 0.0194, and 0.0196 MPa, respectively. Conclusion: The maximum stress on the diseased segments of the spinal cord in the CSM group was higher than that in the control group, which contributed to verifying the imaging parameters associated with spinal cord compression stress.

[Development of a BLI assay-based method for detecting LptA/LptC interaction].

In Gram-negative bacteria, lipopolysaccharide transport (Lpt) protein LptA and LptC form a complex to transport LPS from the inner membrane (IM) to the outer membrane (OM). Blocking the interaction between LptA and LptC will lead to the defect of OM and cell death. Therefore, Lpt protein interaction could be used as a target to screen new drugs for killing Gram-negative bacteria. Here we used biolayer interferometry (BLI) assay to detect the interaction between LptA and LptC, with the aim to develop a method for screening the LptA/LptC interaction blockers in vitro. Firstly, LptC and LptA with or without signal peptide (LptAfull or LptAno signal) were expressed in E. coli BL21(DE3). The purified proteins were then labeled with biotin and the super streptavidin (SSA) biosensor was blocked with diluent. The biotin labeled protein sample was mixed with the sensor, and then the binding of the protein with a series of diluted non biotinylated protein was detected. At the same time, non-biotinylated protein was used as a control. The binding of biotinylated protein to a small molecule IMB-881 and the blocking of interaction were also detected by the same method. In the blank control, the biosensor without biotinylated protein was used to detect the serially diluted samples. The signal response constant was calculated by using steady analysis. The results showed that biotinylated LptC had a good binding activity with LptAfull and LptAno signal with KD value 2.9e⁻7±7.9e⁻8 and 6.0e⁻7±2.8e⁻8, respectively; biotinylated LptAno signal had a good binding activity with LptC, with a KD value of 9.6e⁻7±7.2e⁻8. All binding curves showed obvious fast binding and fast dissociation morphology. The small molecule compound IMB-881 can bind to LptA to block the interaction between LptA and LptC, but has no binding activity with LptC. In summary, we developed a method for detecting the LptA/LptC interaction based on the BLI technology, and confirmed that this method can be used to evaluate the blocking activity of small molecule blockers, providing a new approach for the screening of LptA/LptC interaction blockers.

Exploring the diagnostic effectiveness for myocardial ischaemia based on CCTA myocardial texture features.

BACKGROUND: To explore the characteristics of myocardial textures on coronary computed tomography angiography (CCTA) images in patients with coronary atherosclerotic heart disease, a classification model was established, and the diagnostic effectiveness of CCTA for myocardial ischaemia patients was explored. METHODS: This was a retrospective analysis of the CCTA images of 155 patients with clinically diagnosed coronary heart disease from September 2019 to January 2020, 79 of whom were considered positive (myocardial ischaemia) and 76 negative (normal myocardial blood supply) according to their clinical diagnoses. By using the deep learning model-based CQK software, the myocardium was automatically segmented from the CCTA images and used to extract texture features. All patients were randomly divided into a training cohort and a test cohort at a 7:3 ratio. The Spearman correlation and least absolute shrinkage and selection operator (LASSO) method were used for feature selection. Based on the selected features of the training cohort, a multivariable logistic regression model was established. Finally, the test cohort was used to verify the regression model. RESULTS: A total of 387 features were extracted from the CCTA images of the 155 coronary heart disease patients. After performing dimensionality reduction with the Spearman correlation and LASSO, three texture features were selected. The accuracy, area under the curve, specificity, sensitivity, positive predictive value and negative predictive value of the constructed multivariable logistic regression model with the test cohort were 0.783, 0.875, 0.733, 0.875, 0.650 and 0.769, respectively. CONCLUSION: CCTA imaging texture features of the myocardium have potential as biomarkers for diagnosing myocardial ischaemia.

A predictive analysis approach for paediatric and adult high-grade glioma: miRNAs and network insight.

BACKGROUND: Brain tumours are the most common solid tumour in children and are a cause of mortality in adults. Most cases of brain tumour-related death are attributed to glioblastoma (GBM), with an elevated rate for high-grade glioma (HGG). Showing strong heterogeneity, the lesion location, molecule expression and type of HGG differ between adults and children. However, with regard to pathogenesis, brain tumours are expected to have the same underlying molecular processes. METHODS: In this study, we obtained data from the Gene Expression Omnibus (GEO) database to analyse molecular expression in HGG between adults and children. The same and different mutations were identified in these groups, and the genes involved were compared using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular analysis revealed the same trend of differences between children and adults, which was verified in The Cancer Genome Atlas (TCGA). RESULTS: A total of 12 microarrays including 455 HGG patients were screened. Through a rigorous intersecting process, we identified miR-10a, miR-10b, and miR-139 as having common differences, as well as 6 target genes, such as CDK6, SOX4 and VEGFA, etc. And 12 long noncoding RNAs (lncRNAs). CONCLUSIONS: We identified that these key molecules are involved in development and progression of HGG between adults and children. The findings provide a comprehensive description of the similarities in advanced diseases between adults and children and molecular diagnostic directions for precision small-molecule medicine to treat HGG in different age populations.

Surgical consideration for thoracolumbar burst fractures with spinal canal compromise without neurological deficit.

BACKGROUND: For thoracolumbar burst fractures with spinal canal compromise but no neurological deficit, is it necessary to perform additional laminectomy decompression after the currently accepted posterior pedicle-screw internal fixation? METHODS: Patients were divided into two groups: decompression group (Group A) and nondecompression group (Group B). A retrospective analysis of the posterior vertebral body height of the fractured vertebral body, the ratio of the volume of the spinal canal, and the change of the Cobb angle, relative to the corresponding preoperative values, was conducted to analyse the reasons for choosing different surgical methods. RESULTS: Compared the intraoperative findings after fixation with the preoperative data, in Group A, the posterior vertebral body height of the fractured vertebral body was not significantly restored, the volume ratio of the spinal canal was not significantly improved, and the Cobb angle was not significantly reduced (p â€‹> â€‹0.05). In comparison, in Group B, the posterior vertebral body height of the fractured vertebral body was significantly restored, the volume ratio of spinal canal was significantly increased, and the Cobb angle was significantly reduced (p â€‹< â€‹0.001). CONCLUSION: For patients with thoracolumbar burst fractures with spinal canal compromise but no neurological deficit, if when the posterior intraoperative fixation is performed, the spinal canal fracture is partially recovered, the posterior vertebral body height of the injured vertebrae is significantly restored, the spinal canal volume ratio is significantly increased, and the large kyphosis is corrected, then the indirect decompression without the posterior laminectomy can be performed. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study contributes to offer treatment â€‹consideration for â€‹patients with thoracolumbar burst fracture without neurological symptoms.

Effects and mechanism of siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells.

Siomycin A is a type of thiopeptide antibiotic that is isolated from the fermentation products of an endophytic actinomycin, which is derived from the medicinal plant Acanthopanax senticosus. The present study investigated whether siomycin A has antitumor effects in vitro on a variety of cell lines. A Cell Counting Kit-8 assay was performed to detect the effects of siomycin A on cell viability; morphological changes in the MiaPaCa-2 cell line were analyzed using an inverted phase contrast microscope. A Transwell migration assay was applied to detect cell migration ability. The cytoskeleton was observed by laser confocal microscopy, and apoptosis was detected using flow cytometry. A western blot assay was used to detect the expression of matrix metalloproteinase (MMP)-2, MMP-9 and α-tubulin. The results revealed that siomycin A inhibited the proliferation of human tumor cell lines of different origins. As the concentration of siomycin A increased, the cell density decreased gradually and cells exhibited a morphological change from spindle to spherical shape. Furthermore, 24 h after administration, the cell migration ability was inhibited. The cytoskeleton complexity and morphological changes were increased after administration of siomycin A. The percentage of apoptotic cells was significantly increased and the expression levels of MMP-2, MMP-9 and α-tubulin were downregulated by siomycin A. Therefore, siomycin A was determined to effectively inhibit the proliferative ability of a variety of human tumor cell lines. Siomycin A was also determined to affect the cytoskeleton of tumor cells by downregulating the expression of α-tubulin protein.

Serum miR-515-3p, a potential new RNA biomarker, is involved in gastric carcinoma.

OBJECTIVES: microRNAs (miRNAs) have provided a new opportunity for developing diagnostic biomarkers and effective therapeutic targets in gastric cancer (GC). In this study, we aimed to investigate the relationship between miR-515-3p and GC development. EXPERIMENTAL DESIGN: The Gene Expression Omnibus (GEO) database was used for screening genes and miRNA and for 2R analysis. miRNA prediction target genes and screening key genes were analyzed using protein interactions (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of miRNA-mRNA interactions was predicated by Cytoscape (v.3.5.1), Institute of Systems Biology & University of California, San Diego & Pasteur institute & University of California, San Francisco. Finally, miR-515-3p levels were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in gastric cells and plasma levels. Then, the association between the expression level of miR-515-3p and the clinicopathological features of patients with GC was further analyzed. OBSERVATIONS AND CONCLUSIONS: We found that miR-515-3p was markedly overexpressed in individuals with GC compared with that in normal gastric cells (NCs) and the surgery group (P < 0.0001). In addition, receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) value of 0.8555 for miR-515-3p. SIGNIFICANCE: Our results present new information to the field of gastric cancer and has done a good job of creating an initial hypothesis using the database as well as validate their initial results. These results suggest that serum miR-515-3p is a novel potential biomarker for the detection of GC.

Combining multi-dimensional data to identify a key signature (gene and miRNA) of cisplatin-resistant gastric cancer.

Gastric cancer (GC) is one of the most lethal malignant tumors; the resistance of this type of tumor is the main source of GC treatment failure. In this study, we used bioinformatics analysis to verify differences in resistant GCs and identify an effective method for reversing drug resistance in GC. Microarray data [gene and microRNA (miRNA)] were analyzed using GEO2R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to further enrich the genetic data. miRNA-gene interactions were determined using Cytoscape (v.3.5.1). Online software was used to analyze protein interactions and predict network structure. The Cancer Genome Atlas (TCGA) database was used to verify the expression levels of genes in GC resistance. miR-604 expression levels were verified by real-time PCR in GC cell lines. We screened 3981 GC resistance-associated genes and 244 miRNAs using bioinformatics methods. Six hub genes were identified and verified in the TCGA database, including five up-regulated genes, POLR2L, POLR2C, POLR2F, APRT, and LMAN2, and a down-regulated gene, NFKB2. The up-regulated genes POLR2L, POLR2C, APRT, and LMAN2 interact with miR-604; therefore, we focused on miR-604, which has low expression in drug-resistant GC. The results of this study indicate that through bioinformatics technologies, we have determined the hub genes and hub miRNAs related to drug resistance in GC. Among them, miR-604 could become a new indicator in the diagnosis of drug-resistant GC and may be used to investigate the pathogenesis of resistance in GC.

Apoptin-derived peptide reverses cisplatin resistance in gastric cancer through the PI3K-AKT signaling pathway.

The prognosis of gastric cancer (GC) remains poor due to clinical drug resistance, and novel drugs are urgently needed. Apoptin-derived peptide (AdP) is an antitumor polypeptide constructed in our laboratory that has been used to combat cisplatin (CDDP) resistance in GC cells. MTT and colony-formation assays and Hoechst 33342 staining were used to measure the cytotoxicity of CDDP and AdP in GC cells. Cell apoptosis was measured using an Annexin-V-FITC/PI dual staining assay. Western blot analysis was conducted to detect the expression of proteins in the PI3K/AKT signaling pathway and resistance-related markers. AdP exerted a specific cytotoxic effect on GC cells and CDDP-resistant GC cells in a concentration- and time-dependent manner. AdP also suppressed cell invasion and migration. Additionally, AdP inhibited the expression of p85, AKT, p-p85, p-AKT, multidrug resistance 1 (MDR1), and aryl hydrocarbon nuclear translocator (ARNT) in the PI3K/AKT/ARNT signaling pathway, which promoted apoptosis and necrosis in GC cells. AdP promoted apoptosis in CDDP-resistant GC cells by suppressing the PI3K/AKT/ARNT signaling pathway and might be considered a candidate agent for the clinical treatment of cisplatin-resistant GC.

A peptide derived from apoptin inhibits glioma growth.

Glioblastoma (GBM) is associated with poor prognosis due to its resistance to surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic approaches for the treatment of GBM are urgently needed. HSP70 is an antiapoptotic protein that participates in the inhibition of both mitochondrial and membrane receptor apoptosis pathways and is highly expressed in glioma tissues. Here, we investigated a derivative of apoptin; specifically, a chicken anemia viral protein with selective toxicity toward cancer cells that can inhibit hyperactive molecules, including HSP70. Our earlier studies demonstrated that apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription, which contributes to HSP70 downregulation. This study provides the first demonstration of the therapeutic potential of an apoptin-derived peptide for the treatment of GBM by identifying the minimal region of the apoptin domain required for interaction with the heat-shock element (HSE). This apoptin-derived peptide (ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an increased ability to promote apoptosis in GBM cells compared with rapamycin and temozolomide. ADP treatment inhibited xenograft tumor growth and increased the overall health and survival of nude mice implanted with GBM cells. These effects were measured in tumors obtained from cell lines and were observed in both intracranial and subcutaneous xenografts. In conclusion, we provide the first demonstration that ADP has therapeutic potential for the treatment of human GBM. Specifically, this study suggests that ADP is a potent candidate for drug development based on its favorable toxicity and pharmacokinetic profiles as well as its time- and cost-saving benefits.

Gene delivery of apoptin-derived peptide using an adeno-associated virus vector inhibits glioma and prolongs animal survival.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors. These data indicate that ssAAV2-ADP injection in the left hemisphere effectively prevented ipsilateral tumor growth but was insufficient to prevent distal tumor growth in the contralateral hemisphere. However, the systemic route is the most effective approach for treating widely dispersed tumors. In summary, systemic delivery of AAV2-ADP is an attractive approach for invasive GBM treatment.

Actinophytocola xanthii sp. nov., an actinomycete isolated from rhizosphere soil of the plant Xanthium sibiricum.

A novel actinomycete strain, 11-183T, was isolated from the rhizosphere soil of Xanthium sibiricum, which was collected in Tangshan, Hebei, China. A phylogenetic analysis based on 16S rRNA gene sequences showed that strain 11-183T formed a clade within the genus Actinophytocola, with a maximum similarity of 98.44 % to Actinophytocola xinjiangensis QAIII60T, followed by 97.76 % similarity to Actinophytocola sediminis YIM M13705T. The average nucleotide identity and digital DNA-DNA hybridization values differed by 79.24 and 23.4 %, respectively, between strain 11-183T and Actinophytocolaxinjiangensis QAIII60T. Strain 11-183T grew well on N-Z-amine agar, and it produced a scant, white aerial mycelium. The isolate formed pale yellow to brown-black colonies and a dense, non-fragmented, branched substrate mycelium, and produced aerial hyphae on which nodular spore chains formed. Growth was observed at salinities ranging from 0 to 2 %, at pH values ranging from pH 6.5 to 8.0 and at temperatures ranging from 15 to 37 °C. The cell-wall amino acids included meso-diaminopimelic acid. Whole cell hydrolysates contained galactose and glucose. The principal fatty acids were iso-C16 : 0, iso-C16 : 1 H and C17 : 1ω6c. Diphosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine were the diagnostic phospholipids. The isoprenoid quinones included MK-9(H4) and MK-10(H4). The G+C content of the genomic DNA was 71.7 mol%. Based on the genotypic and phenotypic data, we conclude that strain 11-183T belongs to a novel species of the genus Actinophytocola. The name proposed for the novel species is Actinophytocola xanthii sp. nov., with the type strain 11-183T (=KCTC 39690T= MCCC 1K02062T).