Willingness of joining online support groups among men who have sex with men living with HIV in Shandong Province of China: A mixed methods study.

BACKGROUND: Online support groups afford new opportunities to help individuals affected by HIV/AIDS to seek social support from peers. The study aimed to understand the willingness and associated factors of joining online support groups among men who have sex with men (MSM) living with HIV. METHODS: The study followed a mixed method approach, with qualitative in-depth interviews followed by a quantitative cross-sectional survey in three cities of Shandong Province, China from 2019 to 2020. The in-depth interviews were audio-taped, transcribed verbatim and analyzed using thematic approach. In the quantitative analysis, explanatory variables included sociodemographic, behavioral, clinical, psychological, and demand factors. Univariate and multivariable logistic regressions were conducted to examine the associated factors of willing to join online support groups. RESULTS: A total of 576 and 20 participants were included in the quantitative survey and qualitative interviews, respectively. Only 24.7% (142/576) of participants in the quantitative study were willing to join the online support group. Multivariable analysis showed the associated factors included income level, sexual orientation and availability of information. The barriers to joining online support groups included privacy disclosure concern and psychological pressure exposed to HIV-related information. Facilitators included information acquisition, mutual medication reminding, and emotional support. CONCLUSIONS: MSM living with HIV in China had relatively low willingness to join the online support groups. This study highlighted the importance of safeguarding privacy, involving professional mental health providers, and providing high-quality information when establishing online support groups for people living with HIV.

Exploration for the Priority of HIV Intervention: Modelling Health Impact and Cost-Effectiveness - Six Cities, Eastern China, 2019-2028.

Introduction: In order to enhance the effectiveness of resource allocation, regions must tailor their responses to their specific epidemiological and economic situations. Methods: Utilizing Spectrum software, we projected the cost-effectiveness of 10 chosen HIV interventions in six cities in eastern China from 2019 to 2028. We assessed three scenarios - Base, Achievable, and Idealized - for each city. The analysis included the projected number of HIV infections and deaths averted, as well as the incremental cost-effectiveness ratios for each intervention in the six cities. Results: In Shijiazhuang, Wuxi, Yantai, and Zhenjiang, cities with initially low antiretroviral therapy (ART) coverage, ART showed significant effectiveness, especially for males. Conversely, in Foshan and Ningbo, where ART coverage was notably high, oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) proved effective in the Idealized scenario. MSM outreach, ART for males, and ART for females demonstrated cost-effectiveness across all six cities in both Achievable and Idealized scenarios at the predefined thresholds for each city. Discussion: Maintaining an appropriate coverage rate for outreach to MSM can lead to cost-effectiveness. In cities with low ART coverage, scaling up ART remains a crucial intervention. In regions with high ART coverage, consideration may be given to the utilization of oral PrEP for MSM individuals, requiring budget allocation.

The correlation between serum levels of alkaline phosphatase and bone mineral density in adults aged 20 to 59 years.

Serum alkaline phosphatase (ALP) plays an important role in bone metabolism. However, the association between serum ALP and bone mineral density (BMD) remains inconclusive. Therefore, this study aimed to explore the relationship between serum ALP levels and pelvic BMD in young adults. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey conducted from 2011 to 2016. Serum ALP levels and pelvic BMD were analyzed as independent and dependent variables, respectively. Weighted multivariate linear regression models and stratified analysis by age, sex, and race/ethnicity were applied after controlling for confounding factors to assess the relationship between serum ALP and pelvic BMD. Smooth curve fitting and threshold effect analysis were used to describe the nonlinear relationship between the 2 variables. A total of 7796 participants (4063 males and 3733 females) aged 20 to 59 years were included in this study. When serum ALP was represented as a continuous variable and fully adjusted in the regression model, ALP was significantly negatively correlated with pelvic BMD (ß = -0.0008, 95% confidence interval: -0.0010 to -0.0006, P < .000001); this significant negative correlation persisted when ALP was transformed into a categorical variable, and was consistent in subgroup analyses. Additionally, smooth curve fitting and threshold effect analysis showed a persistent negative correlation between serum ALP and pelvic BMD, with a saturation effect at 97 U/L. Our results revealed a negative correlation between serum ALP levels and pelvic BMD in young adults. Monitoring serum ALP levels could help in the early detection of risks for bone metabolic disorders such as osteoporosis.

Deep Utilization of Low-Grade Heat through Compositional Modulation of Multi-Component Liquid Desiccant.

Low-grade heat is a challenge for deep utilization due to its low temperature. Based on the optimization of the saturated vapor pressure of liquid desiccant in absorption or dehumidification cooling systems, an idea of deep utilization of low-grade heat is proposed in this paper. Instead of optimizing the cycle process or equipment, this paper achieves this goal by obtaining a multi-component salt solution with the advantages of both strong moisture absorption capacity and lower regeneration temperature. The sensitivity of saturated vapor pressure to temperature is defined to evaluate the performance of the salt solution, and the sensitivity mechanism is revealed. The results show that the sensitivity of saturated vapor pressure to temperature increases with the increase of ion charge density, and compositional modulation is proposed to improve the sensitivity. The formula of a multi-component salt solution is taken as an example to illustrate the deep utilization of low-grade heat. As a result, the dehumidification performance of the multi-component dehumidification is equivalent to that of the typical desiccant solution, but its regeneration temperature is about 4 K lower. Furthermore, by using the concept proposed in this paper, it is pointed out that the utilization of low-grade heat can be improved by 40% approximately in an absorption cooling system.

Estimating Costs of the HIV Comprehensive Intervention Using the Spectrum Model - China, 2015-2019.

Introduction: In order to facilitate human immunodeficiency virus (HIV) treatment and prevention, the resource needs for HIV national strategic planning in developing regions were estimated based on Spectrum, the universal HIV cost-effectiveness analysis software. Methods: Based on the theoretical framework of Spectrum, the study developed a cost measurement tool for HIV, and calculated the cost of HIV prevention and control in 6 sampled cities in China during 2015-2019 using the Spectrum model. Results: From 2015 to 2019, the average annual costs for HIV prevention and control for Shijiazhuang, Yantai, Ningbo, Zhenjiang, Foshan, and Wuxi cities were 46.78, 47.55, 137.49, 24.73, 74.37, and 58.30 million Chinese yuan (CNY), respectively. The per capita costs were 4.37, 6.73, 17.33, 7.77, 17.56, and 8.91 CNY, respectively. In terms of the cost structure, the ratio of preventive intervention funds to therapeutic intervention funds (antiviral treatment) varied in sampled cities. Discussion: Developing comprehensive and systematic HIV fund calculation methods can provide a research basis for rational resource allocation in the field of HIV.

Immobilization of iron- and manganese-oxidizing bacteria with a biofilm-forming bacterium for the effective removal of iron and manganese from groundwater.

In this study, three bacteria with high Fe- and Mn-oxidizing capabilities were isolated from groundwater well sludge and identified as Acinetobacter sp., Bacillus megaterium and Sphingobacterium sp. The maximum removal ratios of Fe and Mn (99.75% and 96.69%) were obtained by an optimal combination of the bacteria at a temperature of 20.15°C, pH 7.09 and an inoculum size of 2.08%. Four lab-scale biofilters were tested in parallel for the removal of iron and manganese ions from groundwater. The results indicated that the Fe/Mn removal ratios of biofilter R4, which was inoculated with iron- and manganese-oxidizing bacteria and a biofilm-forming bacterium, were approximately 95% for each metal during continuous operation and were better than the other biofilters. This study demonstrated that the biofilm-forming bacterium could promote the immobilization of the iron- and manganese-oxidizing bacteria on the biofilters and enhance the removal efficiency of iron and manganese ions from groundwater.

Biodegradation of chlorimuron-ethyl and the associated degradation pathway by Rhodococcus sp. D310-1.

Chlorimuron-ethyl is a typical long-term residual sulfonylurea herbicide, and strategies for its removal have attracted increasing attention. Microbial degradation is considered the most acceptable dissipation method. In this study, we optimized the cultivation conditions (substrate concentration, pH, inoculum concentration, and temperature) of the chlorimuron-ethyl-degrading bacterium Rhodococcus sp. D310-1 using response surface methodology (RSM) to improve the biodegradation efficiency. A maximum biodegradation rate of 88.95 % was obtained. The Andrews model was used to describe the changes in the specific degradation rate as the substrate concentration increased. Chlorimuron-ethyl could be transformed with a maximum specific degradation rate (q max), half-saturation constant (K S), and inhibition constant (K i) of 0.4327 day(-1), 63.50045 mg L(-1), and 156.76666 mg L(-1), respectively. Eight biodegradation products (2-amino-4-chloro-6-methoxypyrimidine, ethyl 2-sulfamoyl benzoate, 2-sulfamoyl benzoic acid, o-benzoic sulfimide, 2-[[(4-chloro-6-methoxy-2-pyrimidinyl) carbamoyl] sulfamoyl] benzoic acid, ethyl 2-carbonyl sulfamoyl benzoate, ethyl 2-benzenesulfonyl isocyanate benzoate, and N,N-2(ethyl formate)benzene sulfonylurea) were identified, and three possible degradation pathways were proposed based on the results of high performance liquid chromatography HPLC, liquid chromatography tandem mass spectroscopy (LC-MS/MS), and Fourier transform infrared spectroscopy (FTIR) analyses and the relevant literature. This systematic study is the first to examine the chlorimuron-ethyl degradation pathways of the genus Rhodococcus.

Toxicity of TiO2 nanoparticle to denitrifying strain CFY1 and the impact on microbial community structures in activated sludge.

The antibacterial activity of titanium dioxide nanoparticles (TiO2 NPs) is well described, but little is known of their impact on specific microbial functions such as denitrification, nor on microbial community structure. In this study, a denitrifier (named as Pseudomonas stutzeri CFY1), which was isolated from the activated sludge and could remove up to 111.68 mg/L of NO3(-)-N under aerobic conditions, was utilized to evaluate the influences of TiO2 NPs on its nitrogen removal ability and associated gene expression under aerobic conditions. The variations of the bacterial diversity of activated sludge were also observed. The results showed that antibacterial activity increased with increasing concentrations of TiO2 NPs. Increased production of reactive oxygen species was responsible for TiO2 NPs toxicity. An up-regulation of denitrification genes was observed with increasing concentrations of TiO2 NPs under aerobic conditions. Accordingly, denitrification by P. stutzeri was accelerated when the concentration of TiO2 NPs was increased to 50 mg/L. However, the denitrification of CFY1 was inhibited at low concentrations of TiO2 NPs (5-25 mg/L), indicating that assimilatory and dissimilatory denitrification were synchronized in P. stutzeri CFY1; the latter process plays a major role in denitrification. Further study of the community using 454 pyrosequencing showed that after 7 days of exposure to 50 mg/L TiO2 NPs, the microbial composition of the activated sludge was significantly different and had a lower diversity compared to the controls.

Insights into the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3.

In this study, the effects of cultivation conditions on the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3, which exhibits a high chlorimuron-ethyl-degrading capability, were investigated. To improve the biodegradation efficiency, the cultivation conditions were optimized using response surface methodology (RSM) based on Box-Behnken design (BBD). The maximum biodegradation rate (89.9%) was obtained at the optimal conditions (culture time, 6 d; substrate concentration, 50.21 mg L(-1); pH, 5.95; temperature, 30.15 °C). The Andrews model was used to describe the dynamic change regularity of the specific degradation rate as the substrate concentration increased, and the values of the maximum specific degradation rate (q(max)), half-saturation constant (K(S)) and inhibition constant (K(i)) were 78.87 d(-1), 9180.97 mg L(-1) and 0.28 mg L(-1), respectively. Eight degradation products were captured and identified by liquid chromatography-mass spectrometry (LC-MS) and Fourier transform infrared (FTIR) spectrometry, and three possible degradation pathways are proposed based on the results of high-performance liquid chromatography (HPLC), LC-MS and FTIR analyses as well as results reported in relevant literature. To the best of our knowledge, this is the first systematic study of the degradation pathway of chlorimuron-ethyl by S. maltophilia D310-3. This study provides valuable information for further exploration of the microbial degradation of other sulfonylurea herbicides.

Organic/inorganic composite membranes based on poly(L-lactic-co-glycolic acid) and mesoporous silica for effective bone tissue engineering.

Fabrication of membranes with excellent biocompatibility and bioactivity remains an important technical challenge in bone tissue engineering. In this paper, poly(l-lactic-co-glycolic acid) (PLGA)-SBA15 (Santa Barbara Amorphous 15) composite membranes were prepared by using an electrospinning technique; PLGA was used as a biocompatible and biodegradable polymer and SBA15 was used as a mesoporous silica. The PLGA-SBA15 composite membrane facilitates the cell attachment and the cell proliferation versus pure PLGA membrane where human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded. Furthermore, the analysis of alkaline phosphatase (ALP) activity indicated that this PLGA-SBA15 composite membrane has better osteogenic induction compared with the pure PLGA membrane. Moreover, the presence of SBA15 increased the loading efficiency of the recombinant human bone morphogenetic protein-2 (rhBMP-2) to the membranes. Furthermore, the composite membrane had optimized sustained release of rhBMP-2. Overall, this PLGA-SBA15 composite is an excellent material for bone tissue engineering.

Enhanced bone tissue regeneration by antibacterial and osteoinductive silica-HACC-zein composite scaffolds loaded with rhBMP-2.

Next-generation orthopedic implants with both osteoinductivity and antibacterial ability are greatly needed. In the present study, biodegradable rhBMP-2 loaded zein-based scaffolds with a macroporous structure were synthesized, and SBA-15 nanoparticles and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were incorporated into the scaffolds to produce an anti-infective composite scaffold for delivery of osteogenic factors that facilitate the functional repair of bone defects. The silica/HACC/zein scaffolds developed here showed bioactivity, biocompatibility, and effective antibacterial activity. Confocal laser scanning microscopy (CLSM) was used to quantitatively measure the bactericidal efficacy with respect to bacterial adhesion. Results showed that the sample zein-HACC-S20 exhibited long-lasting antibacterial activity against Escherichia coli and Staphylococcus aureus up to 5 d. At a low dosage of rhBMP-2 (ca. 80 µg), the scaffolds released rhBMP-2 protein efficiently at a relatively slow rate, even after 27 d. An ALP activity and ECM mineralization assay showed that the zein-HACC-S20 scaffolds exhibited significant early osteogenic differentiation by generating enhanced ALP product on day 14 and ECM mineralization on day 21. In a mouse model of thigh muscle pouches, zein-S20 and zein-HACC-S20 groups resulted in obvious bone formation and gave more extensive mineralization to the implants than silica free groups, indicating effective bone induction in vivo. In a rabbit model of critical-sized radius bone defects (20 mm in length and 5 mm in diameter), the bone defects were almost fully repaired and bone marrow cavity recanalization was detectable by 3D micro-CT technique and histological analysis after 12 weeks. In this way, the zein-HACC-S20 scaffolds were proven to significantly promote the bone repair. They also demonstrated considerable promise for tissue engineering. Silica/HACC/zein scaffolds with both antibacterial activity and the ability to induce osteogenesis have immense potential in orthopedics and other biomedical applications.

Selective laser sintering fabrication of nano-hydroxyapatite/poly-ε-caprolactone scaffolds for bone tissue engineering applications.

The regeneration of functional tissue in osseous defects is a formidable challenge in orthopedic surgery. In the present study, a novel biomimetic composite scaffold, here called nano-hydroxyapatite (HA)/poly-ε-caprolactone (PCL) was fabricated using a selective laser sintering technique. The macrostructure, morphology, and mechanical strength of the scaffolds were characterized. Scanning electronic microscopy (SEM) showed that the nano-HA/PCL scaffolds exhibited predesigned, well-ordered macropores and interconnected micropores. The scaffolds have a range of porosity from 78.54% to 70.31%, and a corresponding compressive strength of 1.38 MPa to 3.17 MPa. Human bone marrow stromal cells were seeded onto the nano-HA/PCL or PCL scaffolds and cultured for 28 days in vitro. As indicated by the level of cell attachment and proliferation, the nano-HA/PCL showed excellent biocompatibility, comparable to that of PCL scaffolds. The hydrophilicity, mineralization, alkaline phosphatase activity, and Alizarin Red S staining indicated that the nano-HA/PCL scaffolds are more bioactive than the PCL scaffolds in vitro. Measurements of recombinant human bone morphogenetic protein-2 (rhBMP-2) release kinetics showed that after nano-HA was added, the material increased the rate of rhBMP-2 release. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both nano-HA/PCL scaffolds and PCL scaffolds were implanted in rabbit femur defects for 3, 6, and 9 weeks. The wounds were studied radiographically and histologically. The in vivo results showed that both nano-HA/PCL composite scaffolds and PCL scaffolds exhibited good biocompatibility. However, the nano-HA/PCL scaffolds enhanced the efficiency of new bone formation more than PCL scaffolds and fulfilled all the basic requirements of bone tissue engineering scaffolds. Thus, they show large potential for use in orthopedic and reconstructive surgery.

Survival of GFP-tagged Rhodococcus sp. D310-1 in chlorimuron-ethyl-contaminated soil and its effects on the indigenous microbial community.

The recently isolated bacterial strain Rhodococcus sp. D310-1 can degrade high concentrations of chlorimuron-ethyl (up to 1000 mg L(-1)), indicating its potential for the bioremediation of soil contaminated with high levels of chlorimuron-ethyl. In this study, Rhodococcus sp. D310-1 was tagged with green fluorescent protein gene (gfp) to track its survival in soil. Subsequently, degradation activity of the gfp-tagged strain and its effects on indigenous microbial community were analyzed. Results showed the cell numbers of Rhodococcus sp. D310-1::gfp in non-sterilized soil maintained at 8.5 × 10(4) cells g(-1) dry soil 45 days after inoculation of 7.74 × 10(6) cells g(-1) dry soil and approximately 49% of chlorimuron-ethyl was removed. However, The cell numbers of Rhodococcus sp. D310-1::gfp in sterilized samples increased gradually to 7.85 × 10(7) cells g(-1) dry soil and approximately 78% of chlorimuron-ethyl was removed. PCR-DGGE demonstrated that inoculation of this gfp-tagged strain in chlorimuron-ethyl-contaminated soil has negligible impact on the community structure of bacteria, actinomycetes and fungi. These results indicate that Rhodococcus sp. D310-1 is effective for the remediation of chlorimuron-ethyl-contaminated soil and also provides valuable information about the behavior of the inoculant population during bioremediation, which could be directly used in the risk assessment of inoculant population and optimization of bioremediation process.

Absence of NF-κB subunit p50 ameliorates cold immobilization stress-induced gastric ulcers.

Stress ulcers are a common complication in critically ill patients, but the underlying mechanism is little known. This study characterized the function of the p50 subunit of NF-κB in an experimental model of cold immobilization stress-induced gastric ulcers. Stress-induced gastric mucosal inflammation and gastric injury were examined in wild-type and NF-κB p50-deficient mice. When subjected to cold immobilization stress, NF-κB was rapidly activated in the gastric mucosa in WT mice whereas the majority of κB DNA-binding activity was abrogated from p50(-/-) mice. Deficiency of p50 ameliorated stress-induced expression of TNF-α, MIP-2, and ICAM-1, resulting in reduced mucosal accumulation of neutrophils and gastric injury. These data indicated a critical role for the p50 in the gastric mucosal inflammatory response to cold restraint stress.

Immobilization of Rhodococcus rhodochrous BX2 (an acetonitrile-degrading bacterium) with biofilm-forming bacteria for wastewater treatment.

In this study, a unique biofilm consisting of three bacterial strains with high biofilm-forming capability (Bacillus subtilis E2, E3, and N4) and an acetonitrile-degrading bacterium (Rhodococcus rhodochrous BX2) was established for acetonitrile-containing wastewater treatment. The results indicated that this biofilm exhibited strong resistance to acetonitrile loading shock and displayed a typical spatial and structural heterogeneity and completely depleted the initial concentration of acetonitrile (800mgL(-1)) within 24h in a moving-bed-biofilm reactor (MBBR) after operation for 30days. The immobilization of BX2 cells in the biofilm was confirmed by PCR-DGGE. It has been demonstrated that biofilm-forming bacteria can promote the immobilization of contaminant-degrading bacteria in the biofilms and can subsequently improve the degradation of contaminants in wastewater. This approach offers a novel strategy for enhancing biological oxidation of toxic pollutants in wastewater.

Construction and analysis of an intergeneric fusant able to degrade bensulfuron-methyl and butachlor.

Rhodococcus sp. BX2 degrades bensulfuron-methyl but not butachlor, and Acinetobacter sp. LYC-1 degrades butachlor but not bensulfuron-methyl. Functional strains were constructed through protoplast fusion of Rhodococcus sp. BX2 and Acinetobacter sp. LYC-1 to generate fusants with an improved ability to simultaneously degrade bensulfuron-methyl and butachlor. Initial identification and stability tests of the fusants were performed. Three fusants with eighth transfer on plates containing two antibiotics and two herbicides were obtained. F1 also grew well in an inorganic salt solution containing bensulfuron-methyl and butachlor. F1 was characterized by its parents' morphological and physio-biochemical features. F1 not only had bands in common with BX2 and LYC-1, but also had its own specific bands analyzed by Random Amplified Polymorphic DNA. The genetic similarity indices between F1 and BX2 and F1 and LYC-1 were 0.507 and 0.470, respectively. The percentages bensulfuron-methyl and butachlor degradation by F1 in an inorganic salt solution supplemented with 100 mg/L bensulfuron-methyl and 100 mg/L butachlor were 65.35 and 62.41 %, respectively, and the percentages in soil contaminated with 10 mg/kg bensulfuron-methyl and 10 mg/kg butachlor with an inoculum size of 5 % at 34 °C and at a pH of 7.5 after 35 days were 63.74 and 61.53 %, respectively. It was demonstrated that F1 could simultaneously degrade bensulfuron-methyl and butachlor.

[Identification and biological characterization of an acetonitrile degrading strain].

OBJECTIVE: To identify and characterize an acetonitrile degrading strain BX2, thus to assess its potentials in the treatment of acetonitrile containing wastewater. METHODS: By means of phenotype and physio-biochemical characterization as well as phylogenetic analysis, we identified strain BX2. The optimum culture conditions of the strain were studied with single factor test, and the degradation of acetonitrile under the optimal growth conditions was determined. Additionally, NaCl tolerance was investigated. RESULTS: The phenotype and physio-biochemical characteristics of strain BX2 were similar to those of Rhodococcus sp.. The phylogenetic analysis based on 16S rRNA, gyrB and secA1 gene suggested strain BX2 was the closest relative of Rhodococcus rhodochrous with 99.37%, 99.29% and 97.87% sequence similarity respectively. The optimal conditions for cell growth were 35 degrees C, initial pH 7.5, and 1% inoculum. Under these conditions, the degradation rate of acetonitrile was 95.87% (800mg/L) within 16 h. Strain BX2 was able to grow in defined medium containing NaCl up to 6%. CONCLUSION: Strain BX2 was identified as Rhodococcus rhodochrous and named Rhodococcus rhodochrous BX2. It showed great environmental adaptation and high capability of degrading acetonitrile.

[Effects of allicin on changes of hemorheology in focal cerebral ischemia-reperfusion injury].

OBJECTIVE: To explore the effects of allicin on the changes of hemorheology in focal cerebral ischemia-reperfusion injury in rats. METHOD: Middle cerebral artery occlusion (MCAO) was used to make focal cerebral ischemia-reperfusion model by intravascular nylon filament occlusion. The protective effects of allicin at different doses were evaluated by investigating neurological function score, infarction volume and water content of brain. The changes of blood rheology were detected. RESULT: Compared with model group, allicin (15, 25 mg x kg(-1)) increased the neurological function score and decreased the water content and infarction volume of brain in rats. Allicin (15, 25 mg x kg(-1)) inhibited the increasing of the blood viscosity, high shear rate reduced viscosity, high shear relative reduced viscosity and low shear relative reduced viscosity. CONCLUSION: Allicin has protective effects on cerebral ischemia-reperfusion injuries. The mechanism may be related to inhibit the increasing of hemorheology.

Antiangiogenesis and damaging blood flow by antisense vascular endothelial growth factor oligodeoxynucleotides to suppress lung cancers.

Angiogenesis plays a key role in the growth and metastasis of lung cancers, and vascular endothelial growth factor (VEGF) is one of the major angiogenic factors. The study aims to investigate whether phosphoro thioate-modified antisense VEGF oligodeoxynucleo tides (ASODN) formulated in cationic liposome could inhibit the growth of Lewis lung carcinoma (LLC) tumors by antiangiogenesis. The study demonstrated that ASODN downregulated the expression of VEGF in LLC cells at levels of protein and mRNA in vitro and in vivo. The conditioned media obtained from LLC cells treated with ASODN significantly inhibited the proliferation of bovine aortic endothelial cells. The ASODN therapy significantly suppressed the growth of established subcutaneous LLC tumors in mice by inhibiting angiogenesis and damaging the blood flow of tumors. In conclusion, our results suggest that ASODN targeting VEGF presents a potent therapeutic strategy to combat lung cancers.

[Influence of antisense VEGF oligodeoxynucleotides formulated in cationic liposome on microvessel density and VEGF expression of lung cancer].

BACKGROUND: Vascular endothelial growth factor (VEGF) is known to be one of the most important factors for angiogenesis and tumor cell infiltration. The aim of this study is to determine the influence of phosphorothioate-moeified antisense VEGF oligodeoxynucleotides (ASODN) formulated in cationic liposome on microvessel density (MVD) and VEGF expression of lung cancer. METHODS: Lewis lung carcin- oma model was established by subcutaneous injection of Lewis lung carcinoma cells into 40 C57BL/6 mice. Within 24h after inoculation, mice were randomly assigned to four groups treated with ASODN, sense oligodeoxynucleotides (SODN), mismatch oligodeoxynucleotides (MODN), or liposome alone respectively, twice a week for 4 weeks. The weight and volume of subcutaneous tumors were measured. The morphological and ultrastructural changes of tumor cells were observed under microscope and electron microscope. MVD and expression of VEGF protein and VEGF mRNA were detected by immunohistochemical staining and RT-PCR. RESULTS: The tumor weight in the control group was (7.83±0.78)g, and (4.49±0.43)g in the ASODN group (P < 0.01). The inhibition rate of tumor growth in the ASODN, SODN and MODN groups was 42.6%, 5.1% and 3.2% respectively. MVD and expression of VEGF protein and VEGF mRNA were decreased markedly in the ASODN group compared to the other three groups (P < 0.01). CONCLUSIONS: The results demonstrate that MVD and VEGF expression of lung cancer can be inhibited by VEGF ASODN injected into tumor tissue in C57BL/6 mice.