ABSTRACT
PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
ABSTRACT
BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.
Subject(s)
Escherichia coli Proteins , Quinolones , Escherichia coli , China/epidemiology , Drug Resistance, Bacterial , Anti-Bacterial Agents/pharmacologyABSTRACT
The characteristics and main factors of causes of haze in Zhoukou in January 2022 were analyzed. Six air pollutants, water-soluble ions, elements, OC, EC, and other parameters in fine particulate matter were monitored and analyzed using a set of online high-time-resolution instruments in an urban area. The results showed that the secondary inorganic aerosols(SNA), carbonaceous aerosols(CA, including organic carbon OC and inorganic carbon EC), and reconstructed crustal materials(CM, such as Al2O3, SiO2, CaO, and Fe2O3, etc.) were the three main components, accounting for 61.3%, 24.3%, and 9.72% in PM2.5, respectively. The concentrations of SNA, CA, CM, and SOA were increased, accompanied with higher AQI. The sulfur oxidation rate(SOR) and nitrogen oxidation rate(NOR) in January were 0.53 and 0.46, respectively. The growth rates[µg·(m3·h)] of sulfate and nitrate were 0.027(-5.89-9.47, range) and 0.051(-23.1-12.4), respectively. During the haze period, the growth rates of sulfate and nitrate were 0.13 µg·(m3·h)-1and 0.24 µg·(m3·h)-1, which were 4.8 and 4.7 times higher than the average value of January, respectively. Although the sulfur oxidation rate was greater than the nitrogen oxidation rate, the growth rate of nitrate was approximately 1.8 times that of sulfate owing to the difference in the concentration of gaseous precursors and the influence of relative humidity. The growth rates of nitrate in SNA were significantly higher than those of sulfate on heavily polluted days. The values of SOR, NOR, and concentrations of SNA and SOA during higher AQI and humidity periods were higher than those in lower AQI and humidity periods. The Ox(NO2+O3) decreased with the increase in relative humidity. The SOA was higher at nighttime, increasing faster with the humidity than that in daytime. Under the situation of lower temperature, higher humidity, and lower wind speed, the emission of gaseous precursors of SNA requires further attention in Zhoukou in winter. Advanced control strategies of emissions of SO2 and NO2, such as mobile sources and coal-burning sources, could reduce the peak of haze in winter efficiently.
ABSTRACT
Porcine sapelovirus (PSV) is a ubiquitous virus in farmed pigs that is associated with SMEDI syndrome, polioencephalomyelitis, and diarrhea. However, there are few reports on the prevalence and molecular characterization of PSV in Fujian Province, Southern China. In this study, the prevalence of PSV and a poetical combinative strain PSV2020 were characterized using real-time PCR, sequencing, and bioinformatics analysis. As a result, an overall sample prevalence of 30.8% was detected in 260 fecal samples, and a farm prevalence of 76.7% was observed in 30 Fujian pig farms, from 2020 to 2022. Noteably, a high rate of PSV was found in sucking pigs. Bioinformatics analysis showed that the full-length genome of PSV2020 was 7550 bp, and the genetic evolution of its ORF region was closest to the G1 subgroup, which was isolated from Asia and America; the similarity of nucleotides and amino acids to other PSVs was 59.5~88.7% and 51.7~97.0%, respectively. However, VP1 genetic evolution analysis showed a distinct phylogenetic topology from the ORF region; PSV2020 VP1 was closer to the DIAPD5469-10 strain isolated from Italy than strains isolated from Asia and America, which comprise the G1 subgroup based on the ORF region. Amino acid discrepancy analysis illustrated that the PSV2020 VP1 gene inserted twelve additional nucleotides, corresponding to four additional amino acids (STAE) at positions 898-902 AAs. Moreover, a potential recombination signal was observed in the 2A coding region, near the 3' end of VP1, owing to recombination analysis. Additionally, 3D genetic evolutionary analysis showed that all reference strains demonstrated, to some degree, regional conservation. These results suggested that PSV was highly prevalent in Fujian pig farms, and PSV2020, a PSV-1 genotype strain, showed gene diversity and recombination in evolutionary progress. This study also laid a scientific foundation for the investigation of PSV epidemiology, molecular genetic characteristics, and vaccine development.
Subject(s)
Amino Acids , Enteroviruses, Porcine , Swine , Animals , Prevalence , Farms , Phylogeny , China/epidemiology , Genetic Variation , Recombination, GeneticABSTRACT
Coral-associated microbial communities play a vital role in underpinning the health and resilience of reef ecosystems. Previous studies have demonstrated that the microbial communities of corals are affected by multiple factors, mainly focusing on host species and geolocation. However, up-to-date, insight into how the coral microbiota is structured by vast geographic distance with rich taxa is deficient. In the present study, the coral microbiota in six stony coral species collected from the coastal area of three countries, including United States of America (USA), Australia and Fiji, was used for analysis. It was found that the geographic influence on the coral microbiota was stronger than the coral host influence, even though both were significant. Interestingly, the contribution of the deterministic process to bacterial community composition increased as geographical distance grew. A total of 65 differentially abundant features of functions in coral microbial communities were identified to be associated with three geolocations. While in the same coastal area of USA, the similar relationship of coral microbiota was consistent with the phylogenetic relationship of coral hosts. In contrast to the phylum Proteobacteria, which was most abundant in other coral species in USA, Cyanobacteria was the most abundant phylum in Orbicella faveolata. The above findings may help to better understand the multiple natural driving forces shaping the coral microbial community to contribute to defining the healthy baseline of the coral microbiome.
ABSTRACT
Lung cancer is an aggressive tumor with high incidence and mortality rate. There was growing evidence supporting that nicotinic acetylcholine receptors (nAChRs) play vital role inlung cancer development. In this study, the expression of α3, α4, α5, α6, α7, α9, α10, ß2, ß3, ß4 nAChR subunits on protein and mRNA level were studied in A549, NCI-H1299, NCI-H1688, DMS114 and normal human embryonic lung fibroblast (HEL) cell lines by real-time quantitative PCR (qPCR) and Western blot assay respectively. The results indicated that most of these nAChR subunits were expressed in these five cell lines. Compared with normal cells, the expression of α3 and ß4 nAChR subunits were upregulated in A549 and NCI-H1299. Thus, we treated A549 and NCI-H1299 with an antagonist α-conotoxin TxID which potently and selectively blocks α3ß4 nAChRs. TxID treatment could inhibit A549 and NCI-H1299â¯cell growth and enhance the inhibitory effect of adriamycin when treated simultaneously. To sum up, our study identified the expression of nAChR subunits in different lung cells and the anti-tumor effect of α-conotoxin TxID, which may provide novel strategies for lung cancer therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Conotoxins/pharmacology , Lung Neoplasms/pathology , Receptors, Nicotinic/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Interactions , Gene Expression Regulation, Neoplastic/drug effects , Humans , RNA, Messenger/genetics , Receptors, Nicotinic/geneticsABSTRACT
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD. METHODS: NMOSD patients with (n = 18) and without CTD (n = 39) were enrolled, and the clinical, laboratory, and magnetic resonance imaging (MRI) features of the two groups were assessed. RESULTS: Most of the demographic and clinical features examined were similar between NMOSD patients with and without CTD. Serum immunoglobulin G (IgG), percentage of γ-globulin and seropositivity for several other autoantibodies were significantly elevated in NMOSD patients with CTD (P < 0.05). NMOSD with CTD was marked by longer spinal cord lesions and a lower frequency of short transverse myelitis (TM) than NMOSD without CTD (P < 0.05). NMOSD with CTD also featured more T1 hypointensity and T2 bright spotty lesions (BSLs) on MRI than NMOSD without CTD (P = 0.001 and 0.011, respectively). There were no other differences in laboratory, MRI and clinical characteristics between different NMOSD subtypes. CONCLUSIONS: A few characteristics differed between NMOSD with and without CTD. NMOSD patients with CTD had higher serum IgG, longer spinal cord lesions, a lower frequency of short TM and more T1 hypointensity and T2 BSLs on spinal MRI than NMOSD patients without CTD.
Subject(s)
Connective Tissue Diseases/complications , Neuromyelitis Optica/complications , Adult , Aged , Connective Tissue Diseases/immunology , Connective Tissue Diseases/pathology , Female , Humans , Male , Middle Aged , Neuromyelitis Optica/immunology , Neuromyelitis Optica/pathologyABSTRACT
Objective We herein present a case involving a prevertebral abscess complicated by a spinal epidural abscess (SEA) secondary to intradiscal oxygen-ozone chemonucleolysis for treatment of a cervical disc herniation. Methods A 67-year-old woman with a history of intradiscal oxygen-ozone chemonucleolysis developed numbness and weakness in her right upper and bilateral lower extremities followed by urinary retention. Her symptoms did not respond to intravenous antibiotics alone. Magnetic resonance imaging of the cervical region revealed an extensive SEA anterior to the spinal cord, spinal cord myelopathy due to anterior compression by the lesion, and a prevertebral abscess extending from C2 to T1. She underwent surgical drainage and irrigation. Results The patient was successfully treated with surgical drainage and systemic antibiotic therapy without kyphosis. Streptococcus intermedius was detected within the abscess. All clinical symptoms except for the sensory deficit in the left leg were relieved. Conclusions The safety of intradiscal oxygen-ozone therapy requires further assessment. High-dose intravenous antibiotics should be initiated empirically at the earliest possible stage of prevertebral and epidural abscesses. Surgical drainage may be a rational treatment choice for patients with a prevertebral abscess complicated by an SEA and spinal cord myelopathy.
Subject(s)
Cervical Vertebrae , Epidural Abscess/etiology , Intervertebral Disc Chemolysis/adverse effects , Intervertebral Disc Displacement/surgery , Abscess/diagnostic imaging , Abscess/etiology , Abscess/therapy , Aged , Anti-Bacterial Agents/therapeutic use , Cervical Vertebrae/microbiology , Cervical Vertebrae/surgery , Decompression, Surgical , Epidural Abscess/diagnostic imaging , Epidural Abscess/therapy , Female , Humans , Intervertebral Disc Chemolysis/methods , Magnetic Resonance Imaging , Oxygen/therapeutic use , Ozone/therapeutic use , Spinal Diseases/diagnostic imaging , Spinal Diseases/etiology , Spinal Diseases/therapy , Streptococcal Infections/diagnostic imaging , Streptococcal Infections/etiology , Streptococcal Infections/therapy , Streptococcus intermedius/isolation & purification , Therapeutic IrrigationABSTRACT
Through the environmental factors impact experiments,such as current intensity,initial pH value of the reaction solution,and the type and concentration of the electrolyte,effect and mechanism of electrochemically enhanced removal of nitrobenzene from aqueous solution on activated carbon fibers (ACF)-ozone technique were studied.The result showed that compared with the ACF-O3 system,the removal efficiency of NB in electrochemically enhanced ACF-O3 system was significantly improved.The effect of current intensity on the NB removal efficiency in the electrochemically enhanced ACF-O3 system was not significant.O3 concentration had some effect on the NB removal efficiency.The pH value of the initial reaction solution had a great influence on the catalytic activity of ACF in ACF-O3 system.The presence of inorganic salts such as sodium sulfate,sodium nitrate and sodium chloride inhibited the catalytic ability of ACF in O3 system.In addition,ACF was destroyed by ozone and the promoting effect of ACF was reduced.When the cathode electric field was applied on the surface of ACF,the removal effect of the organic compounds by ACF-O3 was improved significantly and the structure of ACF was not destroyed by ozone.
ABSTRACT
The integration of porous metal-organic frameworks onto the surface of materials, for use as functional devices, is currently emerging as a promising approach for gas sensing and flexible displays. However, research focused on potential applications in electronic devices is in its infancy. Here we present a facile strategy by which interpenetrated, crystalline metal-organic framework films are deposited onto conductive metal-plate anodes via in situ temperature-controlled electrochemical assembly. The nanostructure of the surface as well as the thickness and uniformity of the film are well controlled. More importantly, the resulting films exhibit enhanced dielectric properties compared to traditional inorganic or organic gate dielectrics. This study demonstrates the successful implementation of the rational design of metal-organic framework thin films on conductive supports with high-performance dielectric properties.
ABSTRACT
Brucellosis is a zoonotic disease that causes animal and human diseases. Vaccination is a major measure for prevention of brucellosis, but it is currently not possible to distinguish vaccinated animals from those that have been naturally infected. Therefore, in this study, we constructed the Brucella (B.) abortus 2380 wbkA mutant (2308ΔwbkA) and evaluated its virulence. The survival of 2308ΔwbkA was attenuated in murine macrophage (RAW 264.7) and BALB/c mice, and it induced high protective immunity in mice. The wbkA mutant elicited an anti-Brucella-specific immunoglobulin G response and induced the secretion of gamma interferon. Antibodies to 2308ΔwbkA could be detected in sera from mice, implying the potential for use of this protein as a diagnostic antigen. The WbkA antigen would allow serological differentiation between infected and vaccinated animals. These results suggest that 2308ΔwbkA is a potential attenuated vaccine against 16M. This vaccine will be further evaluated in sheep.
Subject(s)
Brucella Vaccine/immunology , Brucella abortus/immunology , Brucellosis/immunology , Animals , Female , Immunization/veterinary , Mice , Mice, Inbred BALB C , RAW 264.7 Cells , Vaccines, Attenuated/immunology , VirulenceABSTRACT
BACKGROUND: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. MATERIALS AND METHODS: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose (8 µg, 4 µg and 2 µg/day) triptolide or cisplatin at 40 µg/day or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. RESULTS: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). CONCLUSIONS: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Diterpenes/pharmacology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Phenanthrenes/pharmacology , Animals , Cell Cycle/drug effects , Endometrial Neoplasms/metabolism , Epoxy Compounds/pharmacology , Female , Flow Cytometry , Humans , In Vitro Techniques , Mice , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and timedependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z-VADfmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Apoptosis/drug effects , Diterpenes/pharmacology , Mitochondria/metabolism , Phenanthrenes/pharmacology , Tumor Suppressor Protein p53/metabolism , Amino Acid Chloromethyl Ketones/pharmacology , Caspase 3/chemistry , Caspase 3/metabolism , Caspase 9/chemistry , Caspase 9/metabolism , Cell Line, Tumor , Down-Regulation/drug effects , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Epoxy Compounds/pharmacology , Female , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolismABSTRACT
AIM: To examine lymph nodes obtained after lipolysis and liposuction of subcutaneous fat of the inguinal region of female vulvar cancer patients to explore the feasibility of clinical application. METHODS: The field of operation was on the basis of the range of the conventional resection of inguinal lymph nodes. We injected lipolysis liquid fanwise, started liposuction after 15-20 minutes; then the subcutaneous fatty tissue was sucked out clearly by suction tube. We selected the first puncture holes located on 2-3 cm part below anterior superior spine, the others respectively being located 3cm and 6cm below the first for puncturing into the skin, imbedding a trocar to intorduce CO2 gas and the specular body, and excise the lymph nodes by ultrasonic scalpel. The surgical field chamber was set with negative pressure drainage and was pressured with a soft saline bag after surgery. RESULTS: A lacuna emerged from subcutaneous of the inguinal region after lipolysis and liposuction, with a wide fascia easily exposed at the bottom where lymph nodes could be readily excised. The number of lymph nodes of ten patients excised within the inguinal region on each side was 4-18. The excised average number of lymph nodes was 11 when we had mature technology. CONCLUSION: Most of adipose tissue was removed after lipolysis and liposuction of subcutaneous tissue of inguinal region, so that the included lymph nodes were exposed and easy to excise by endoscope. This surgery avoided the large incision of regular surgery of inguinal region, the results indicating that this approach is feasible and safe for used as an alternative technology.
Subject(s)
Endoscopy/methods , Inguinal Canal/pathology , Lipectomy , Lipolysis , Lymph Node Excision , Lymph Nodes/pathology , Vulvar Neoplasms/surgery , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Female , Follow-Up Studies , Humans , Inguinal Canal/surgery , Lymph Nodes/surgery , Middle Aged , Neoplasm Staging , Prognosis , Vulvar Neoplasms/pathologyABSTRACT
The hemocompatibility of La(2)O(3)-doped TiO(2) films with different concentration prepared by radio frequency (RF) sputtering was studied. The microstructures and blood compatibility of TiO(2) films were investigated by scan electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and UV-visible optical absorption spectroscopy, respectively. With the increasing of the La(2)O(3) concentrations, the TiO(2) films become smooth, and the grain size becomes smaller. Meanwhile, the band gap of the samples increases from 2.85 to 3.3 eV with increasing of the La(2)O(3) content in TiO(2) films from 0 to 3.64%. La(2)O(3)-doped TiO(2) films exhibit n-type semiconductor properties due to the existence of Ti(2+) and Ti(3+). The mechanism of hemocompatibility of TiO(2) film doped with La(2)O(3) was analyzed and discussed.
ABSTRACT
Recombinant human endostatin (rh-endostatin), a potential antiangiogenic agent, is used in non-small cell lung carcinoma treatment and represses vascular endothelial cell growth factor (VEGF) levels in tumor cell. However, precise affection of rh-endostatin on the proangiogenic VEGF isoforms (VEGF(165)) or antiangiogenic VEGF isoforms (VEGF(165)b) is not clear. We therefore tested the hypothesis that rh-endostatin could alter expression of these isoforms to regulate tumor growth. A549 cells were exposed to rh-endostatin, and the expression of VEGF(165) and VEGF(165)b was detected. The role of SP1 as a regulator of isoform expression was investigated. We then examined the anticancer and antiangiogenic efficacy of rh-endostatin in combination with exogenous VEGF(165)b against A549 cells, EA.HY 926 cells and xenograft model of human lung cancer. rh-Endostatin reduced VEGF(165) and induced VEGF(165)b as well as inhibited SP1 in A549 cells. SP1 inhibitor (betulinic acid) also developed those changes. VEGF(165)b-rh-endostatin combination was highly synergistic and inhibited growth, survival, and migration of A549 cells, VEGF-mediated VEGFR2 phosphorylation in EA.HY 926 cells, and tumor growth in xenograft model of human lung cancer. rh-Endostatin downregulates proangiogenic vascular endothelial growth factor A (VEGFA) isoform and upregulates antiangiogenic VEGFA isoform, possibly through inhibition of SP1. Furthermore, VEGF(165)b sensitizes A549 to rh-endostatin treatment and enhances the anticancer effect of rh-endostatin.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , Endostatins/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Blotting, Western , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/physiology , Humans , Immunohistochemistry , Mice , Mice, Nude , Neovascularization, Pathologic/metabolism , Protein Isoforms/biosynthesis , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation , Xenograft Model Antitumor AssaysABSTRACT
A new xanthone, 1,5-dihydroxy-2,3,4-trimethoxyxanthone (1), together with 15 known compounds (2-16), was isolated from an ethanolic extract of Halenia elliptica D. Don. Their structures were elucidated by spectroscopic methods. Among the known compounds, the (13)C NMR spectroscopic data of 2,3,4,5-tetramethoxyxanthone-1-O-gentiobioside (2) were reported for the first time.
Subject(s)
Drugs, Chinese Herbal/isolation & purification , Glucosides/isolation & purification , Xanthones/isolation & purification , Drugs, Chinese Herbal/chemistry , Gentianaceae/chemistry , Glucosides/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Xanthones/chemistryABSTRACT
Tumor-targeting bacteria have been developed as powerful anticancer agents. Salmonella typhimurium VNP20009, a representative tumor-targeting strain, has been systemically administered as a single-agent therapy at doses of 1 x 10(6) to 3 x 10(6) colony-forming unit (cfu)/mouse, or in combination with other antitumor agents at doses of 1 x 10(4) to 2 x 10(5) cfu/mouse. Recently, we reported that oral delivery of VNP20009 at the dose of 1 x 10(9) cfu/mouse induced significant anticancer effects comparable to that induced by systemic administration of this strain at 1 x 10(4) cfu/mouse. To further address the efficacy and safety of oral administration of bacteria, here we performed a systemically comparative analysis of anticancer efficacy and toxicity of VNP20009 administered: (i) orally at a dose of 1 x 10(9) cfu/mouse (VNP9-oral); (ii) intraperitoneally at a dose of 1 x 10(4) cfu/mouse (VNP4-i.p.); or (iii) intraperitoneally at a dose of 1 x 10(6) cfu/mouse in tumor-free and tumor-bearing murine models. The results showed that VNP9-oral, similar to VNP4-i.p., induced significant tumor growth inhibition whereas VNP6-i.p. induced better anticancer effect in the B16F10 melanoma model. Among three treatments, VNP9-oral induced the mildest and reversible toxicity whereas VNP6-i.p. resulted in the most serious and irreversible toxicities when compared to other two treatments. Moreover, the combination of VNP9-oral with a low dose of chemotherapeutics produced comparable antitumor effects but displayed significantly reduced toxicity when compared to VNP6-i.p. The findings demonstrated that oral administration, as a novel avenue in the application of bacteria, is highly safe and effective. Moreover, the present preclinical study should facilitate the optimization of bacterial therapies with improved anticancer efficacy and reduced adverse effects in future clinical trials.
Subject(s)
Bacterial Vaccines/administration & dosage , Neoplasms, Experimental/therapy , Salmonella typhimurium/immunology , Administration, Oral , Animals , Bacterial Vaccines/toxicity , Cytokines/biosynthesis , Female , Melanoma, Experimental/therapy , Mice , Mice, Inbred C57BL , Neoplasms, Experimental/immunologyABSTRACT
An efficient and chemoselective deprotection protocol for aryl silyl ethers using LiOAc as a bifunctional Lewis acid-Lewis base catalyst was described. Acetates, epoxides, and aliphatic silyl ethers were preserved, whereas aryl TBS and TBDPS ethers can be differentiated.
ABSTRACT
In the crystal structure of the title compound, C(9)H(14)BNO(4), the boronic acid group and carbamate groups are nearly co-planar with the pyrrole ring, making dihedral angles of 0.1â (2) and 2.2â (2)°, respectively. Intra-molecular and inter-molecular O-Hâ¯O hydrogen bonds help to stabilize the structure, the latter interaction leading to inversion dimers..