ABSTRACT
Grassland is an important part of the regional ecosystem, and its micro ecological structures play key roles in the process of element migration and the evolution of ecological diversity systems. To discover the spatial difference of the grassland soil bacterial community, we collected five total soil samples at 30 cm depth and 60 cm depth in Eastern Ulansuhai Basin in early May (before the beginning of the new growing season, with a minimum influence of human activities and other factors). Based on 16S rRNA gene-based high-throughput sequencing technology, the vertical characteristic of the bacterial community was analyzed in detail. First, Actinobacteriota, Proteobacteria, Chloroflexi, Acidobacteriota, Gemmatimonadota, Planctomycetota, Methylomirabilota, and Crenarchacota all appeared in the 30 cm and 60 cm samples, with the relative contents all being higher than 1%. In addition, there were a total of six phyla, five genera, and eight OTUs in the 60 cm sample with relative contents higher than those in the 30 cm sample. As a result, the relative abundance changes in dominant bacterial phyla, genera, and even OTUs at different sample depths did not correspond to their contribution to the bacterial community structure. Second, because of the unique contribution to the bacterial community structure in 30 cm and 60 cm samples, the norank_f__norank_o__norank_c__norank_p__Armatimonadota and Candidatus_Xiphinematobacter could be utilized as key bacterial genera during ecological system analysis, belonging to the Armatimonadota and Verrucomicrobiota, respectively. Finally, the relative abundances of ko00190, ko00910, and ko01200 were all higher in 60 cm samples than those in 30 cm samples, which showed that through the increase in metabolic function abundance, the relative contents of C, N, and P elements in grassland soil had been reduced with the increase in depth. These results will provide references for further study on the spatial change of bacterial communities in typical grassland.
Subject(s)
Ecosystem , Grassland , Humans , RNA, Ribosomal, 16S , Seasons , SoilABSTRACT
In order to study the bacterial community composition and corresponding function in Wuliangsu Lake at the end of the Hetao Plain during the irrigation gap period, lake samples were collected in September 2020, and the pH, TN, TP, DIP, DTP, NH4+-N, Chla, EC, SAL, and other indicators were analyzed. The 16S rRNA high-throughput sequencing method was used to explore the attached bacteria and bacterioplankton in 15 samples of the surface water in Wuliangsu Lake. The experimental results showed that:â the alpha diversity Chao and Shannon indices of attached bacteria were greater than that of bacterioplankton, but the median of Shannoneven index was the same. â¡ In each sampling point, the bacterioplankton of Proteobacteria and Actinobacteria in the top five dominant bacteria phyla were higher than that of attached bacteria, and the abundance of attached bacteria and bacterioplankton of Bacteroidota were staggered. On the contrary, the contents of attached bacteria of Verrucomicrobiota and Cyanobacteria were all higher than that of bacterioplankton. ⢠Redundant analysis showed that pH had the most significant effect on dominant attached bacteria, and the effect of conductivity and salinity in dominant bacterioplankton was the most significant. ⣠PICRUSt2 function prediction analysis showed that attached bacteria and planktonic bacteria had the strongest metabolic functions, showing abundant metabolic functions. There were 29 nitrogen-related effective KOs and 88 phosphorus-related effective KOs, with the greatest nitrogen-fixing function and strong inorganic phosphorus-dissolving function, and bacterioplankton played a greater role in the two functions.
Subject(s)
Actinobacteria , Cyanobacteria , China , Lakes/microbiology , Plankton , RNA, Ribosomal, 16S/geneticsABSTRACT
Mucuna pruriens is traditional medicinal plant originated in South Africa. We characterize the complete plastid genome of M. pruriens, which is a circular-mapping molecule 152,119 bp in length. The genome has a large single-copy region (LSC) of 78,258 bp and a small single-copy region (SSC) of 18,735 bp, respectively. Additionally, the overall GC content of the chloroplast genome was 35.37%. The genome contains 138 genes, including 96 protein-coding, 38 tRNA, and four rRNA genes. The gene content and structure are conserved compared to other species in the genus Glycine. The chloroplast genome and existing data were used to infer its phylogenetic position. The results showed that M. pruriens clustered together with Glycine max and G. soja. These findings provide potential genetic markers that can aid in understanding the genetic diversity of M. pruriens.
ABSTRACT
Bacteria are the key components of water ecosystems, and play important roles in material and energy cycle processes. To understand the changes in the bacterioplankton community in frozen lakes, we collected 15 "bottom ice" samples and 15 "surface water" samples under the ice sheet from Dali Lake, which is an inland closed lake in the Inner Mongolia Plateau. Combined with comparisons of the physicochemical proxies between "bottom ice" and "surface water" samples, the phylum community characteristics of the bacterioplankton were analyzed in detail. Although the bacterioplankton were mainly comprised of Proteobacteria, Actinobacteria, Cyanobacteria, Bacteroidetes, and 11 other phyla in the "bottom ice" and "surface water", the average relative abundances of the dominant planktonic bacteria were clearly different. For example, the average relative abundance of Proteobacteria was approximately 63.64% in the "bottom ice" samples, but decreased to approximately 26.75% in the surface water samples, which was visibly smaller than the relative abundance of Actinobacteria with an average value of approximately 39.10%. We concluded that the changes in the contents of nutrient elements and physicochemical proxies must be the primary factors influencing the changes in the bacterioplankton community in the frozen Dali Lake. The changes in the physicochemical proxies could have been responsible for the changes in the bacteria community in the "bottom ice" and "surface water". Otherwise, the different physiological characteristics of the planktonic bacteria phyla caused the different responses to the changes in the contents of the nutrient elements and physicochemical proxies in the frozen lake. For example, the major bacterioplankton phyla were mainly influenced by the changes in total phosphorus and dissolved total phosphorus in the "bottom ice" and by the changes in dissolved inorganic phosphorus and ammonia nitrogen in the "surface water". The results will provide basic data to analyze the lake ecological environment in Northern China.
Subject(s)
Ecosystem , Lakes , China , Plankton , WaterABSTRACT
Chronic gut inflammation disposes to an increased risk of colitis-associated cancer. Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane/dextran sodium sulfate model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis (UC) and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis. Flow cytometry analysis of the immunocytes isolated from intraepithelial and lamina propria showed that M10 prevented the infiltration of myeloid-derived suppressor cells and increased CD8+T and CD4+T cells in colorectal tissues. Enzyme-linked immunosorbent analysis revealed the reduction of pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor/macrophage colony-stimulating factor, IL-6 and TNF-α in colonic mucosa. Western blot assay also showed M10 prevention of the NF-κB/IL-6/STAT3 pathways and the biomarkers of inflammation and colorectal tumorigenesis. Electron microscopy analysis revealed that M10 prevent robust endoplasmic reticulum (ER) stress-induced autophagy in inflamed colonic mucosal cells. In conclusion, oral administration of Myricetin derivative M10 exerts chemoprevention of UC and colorectal tumor in mice. The mechanism of chemoprevention is associated with the reduction of biomarkers of chronic inflammation and proliferation through attenuating robust ER stress in inflamed colonic mucosal cells. M10 exerts chemoprevention activity without evidence of toxicity in mice. These results justify further evaluation of M10 in clinical trials. M10 could develop a promising regimen in the chemoprevention of colitis and colorectal cancer.
Subject(s)
Alanine/analogs & derivatives , Colitis, Ulcerative/prevention & control , Colorectal Neoplasms/prevention & control , Endoplasmic Reticulum Stress/drug effects , Flavonoids/pharmacology , Hydroxyquinolines/pharmacology , Alanine/pharmacology , Animals , Anticarcinogenic Agents/pharmacology , Colon/drug effects , Colon/metabolism , Colorectal Neoplasms/metabolism , Disease Models, Animal , Inflammation/metabolism , Inflammation/prevention & control , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Objective To investigate the epidemiological status and the anticoagulation treatment of atrial fibrillation (AF) patients,and to provide evidence for improving anticoagulation therapeutic effect in AF patients.Methods We performed a cross-sectional epidemiological investigation of 1 000 patients and out-patients with AF in Huashan Hospital.The clinical data including clinical feature,coexistent diseases,auxiliary examination,and treatment regimen of these patients were collected.The clinical features and anticoagulation status of AF patients were analyzed based on the stroke history,stroke risk evaluation and CHA2DS2-VASc score stratification.Results The mean age of these AF patients was (72.1 ± 11.1) years old.The most common coexistent diseases were hypertension (65%),coronary heart disease (32%) and diabetes (27%).About 6% of the AF patients were diagosed with non-valvularatrial fibrillation (NVAF),and 22% had stroke history.Patients were divided into two groups according to their stroke history.Compared with the non-stroke group,the stroke group was found to be older,with longer course of AF and poorer hypertension control.The overall anticoagulation rate was 32 % and antiplatelet rate was 46 %.The anticoagulation rate of stroke group was 44%,higher than the non-stroke group (P<0.001) but 78% of these patients began anticoagulation therapy after the occurrence of stroke.When CHA2 DS2-VASc scores of NVAF patients were 2 to 5,the anticoagulation proportion increased gradually.When the scores were 2 to 6,the antiplatelet ratio increased gradually.But when the scores were 7-8 points,both anticoagulation and antiplatelet rates were in decline.Conclusions The anticoagulation rate in AF patients was still low at present,while relatively higher in patients with stroke.Anticoagulation could prevent stroke,AF patients still could benefit from anticoagulation after stroke,but anticoagulation before stroke could get more benefits.
ABSTRACT
A series of novel indazole-based diarylurea derivatives targeting c-kit were designed by structure-based drug design. The derivatives were prepared, and their antiproliferative activities were evaluated against human colon cancer HCT-116 cell line and hepatocellular carcinoma PLC/PRF/5 cell line. The antiproliferative activities demonstrated that six of nine compounds exhibited comparable activities with sorafenib against HCT-116. The structure-activity relationship (SAR) analysis indicated that the indazole ring part tolerated different kinds of substituents, and the N position of the central pyridine ring played key roles in antiproliferative activity. The SAR and interaction mechanisms were further explored using molecular docking method. Compound 1i with N-(2-(pyrrolidin-1-yl)ethyl)-carboxamide possessed improved solubility, 596.1 ng/ml and best activities, IC50 at 1.0 µm against HCT-116, and 3.48 µm against PLC/PRF/5. It is a promising anticancer agent for further development.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Indazoles/chemistry , Indazoles/pharmacology , Urea/analogs & derivatives , Urea/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Computer-Aided Design , Drug Design , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/metabolism , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Phenylurea Compounds/pharmacology , Proto-Oncogene Proteins c-kit/metabolism , Sorafenib , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To understand the status of water contact and labor practice of residents in plateau mountain schisto- somiasis endemic areas in Yunnan Province, so as to provide the evidence for formulating the strategy of prevention and control of schistosomiasis in the next step of work. METHODS: A total of 412 residents aged 6-65 years old in 2 villages were randomly sampled and investigated with questionnaires for their water contacts and labor practices in plateau valley schistosomiasis endem- ic areas. Then the schistosome infection status of the residents was surveyed with the indirect hemagglutination assay (IHA). RE- SULTS: Among the 412 residents investigated, the rate of water contact was 88.35%, and the main causes of water contact were watering, and swimming and playing. The percentages of residents who had schistosomiasis history were 1.16%, 0.00%, 30.80%, 3.85%, and 0 in them who had swimming and playing water-contacts, bathing, watering, washing hands, and others, respectively (χ2 = 38.96, P < 0.01). The positives of IHA in the above-mentioned residents were 18.60%, 0.00%, 37.60%, 23.08%, and 0, respectively (χ2 = 12.61, P < 0.05). CONCLUSIONS: The productive infested water contact is the main way of schistosome infection. Therefore, the changes of labor practices and water contact of the residents are very important for the ef- fective prevention and control of schistosomiasis transmission.
Subject(s)
Endemic Diseases , Schistosomiasis/epidemiology , Adolescent , Adult , Aged , Child , China/epidemiology , Female , Hemagglutination Tests , Humans , Male , Middle Aged , Schistosomiasis/prevention & control , WaterABSTRACT
OBJECTIVE: To evaluate the molluscicidal effect of 5% powder of niclosamide ethanolamine salt granules (NEG) in the field of mountainous areas in Yunnan Province. METHODS: The grasslands with Oncomelania hupensis snail habitats were chosen in Beideng Village, Heqing County, Yunnan Province, and were divided into 7 groups (groups of NEG 30 g/m2, NEG 40 g/m2, NEG 50 g/m2, NEG 40 g/m2 plus obstacle clearing, 50% niclosamide ethanolamine salt wettable powder (WPN) 6 g/m2, WPN 6 g/m2 plus obstacle clearing, and fresh water). The snail death rates and the densities of living snails were investigated and the results were compared in the different groups 7 d, 15 d, and 30 d after the implementation. RESULTS: Seven d, 15 d, and 30 d after the implementation, the snail death rates of the groups of NEG 30 g/m2, 40 g/m2, and 50 g/m2 were from 72.75 % to 95.83%, and the average descent rates of living snail densities were from 72.26% to 95.54%. Seven d, 15 d, and 30 d after the implementation, in the NEG 40 g/m2 group, the snail death rates were from 81.69% to 87.19%, and the average descent rates of living snail densities were from 81.42% to 87.91% ; in the NEG 40 g/m2 plus obstacle clearing group, the snail death rates were from 84.89% to 88.24% and the average descent rates of living snail densities were from 85.63% ~ 88.22%; in the WPN 6 g/m2 group, the snail death rates were from 85.23% to 86.17% and the average descent rates of living snail densities were from 85.76% to 86.05%; in the WPN 6 g/m2 plus obstacle clearing group, the snail death rates were from 88.89% to 92.10% and the average descent rates of living snail densities were from 86.71% to 92.20%. The obstacle clearing improved the molluscicidal effect. CONCLUSION: NEG has a good molluscicidal effect in the field of mountainous areas in Yunnan Province.
Subject(s)
Ethanolamines/pharmacology , Molluscacides/pharmacology , Niclosamide/pharmacology , Snails/drug effects , Animals , China , Population Density , PowdersABSTRACT
OBJECTIVE: To evaluate the effect of comprehensive schistosomiasis control measures based on infection source control in plateau mountain areas of Yunnan Province. METHODS: From 2006 to 2004, four administrative villages were selected as test areas from plateau canyon and plateau basin endemic areas in Jindun Town, Heqing County, two villages each type, and the comprehensive control measures were implemented, including the examination and treatment of schistosomiasis, Oncomelania hupensis snail survey and control, health education, improving drinking water and lavatories, banning grazing, constructing sanitary pen of livestock, replacing cattle with machine, etc. The schistosome infection state and snail status in 2006 were treated as the baseline information, and the effect of the comprehensive measures were evaluated. Results The infection rate of human in plateau canyon areas decreased from 4.94% in 2006 to 0.06% in 2014, and that of livestock decreased from 1.11% to 0. In plateau basin areas, there was only 1 case of schistosomiasis found in Xiaolian Village in 2007, and no any other cases found in the other years, the infection rates of livestock dropped from 7.38% to 0. Compared with 2006, the snail areas in the two type areas decreased by 74.89% and 75.30%, respectively, meanwhile, the percentage of snail area, the occurrence rate of frames with snails, as well as the average density of living snails also decreased, and no infected snails were found since 2008. Xidian and Xinzhuang villages in plateau canyon area reached the criteria of schistosomiasis transmission controlled in 2009, and Xiao-lian and Kangfu villages in plateau basin reached the criteria of transmission interrupted in 2014. CONCLUSIONS: The comprehensive schistosomiasis control measures based on infection source control can effectively control the endemic situation of schistosomiasis in plateau areas of Yunnan Province. In the future, we should pay an equal attention to the infection sources control and snail control to consolidate and amplify the achievement of schistosomiasis control.
Subject(s)
Communicable Disease Control/methods , Schistosomiasis/prevention & control , Schistosomiasis/veterinary , Adolescent , Adult , Aged , Animals , Cattle , Child , China/epidemiology , Disease Reservoirs/parasitology , Evaluation Studies as Topic , Feces/parasitology , Female , Health Education , Humans , Livestock/parasitology , Male , Middle Aged , Rural Population , Schistosoma/physiology , Schistosomiasis/epidemiology , Schistosomiasis/parasitology , Snails/growth & development , Snails/parasitology , Young AdultABSTRACT
OBJECTIVES: Sorafenib is a first multi-kinase inhibitor and one of the most widely used small-molecule oral-targeted drugs. It has been widely used for the treatment of patients with advanced renal cell carcinoma and hepatocellular carcinoma. However, some common adverse effects of sorafenib may impact quality of life. In this study, we evaluated the inhibitory effect on the growth of hepatocellular carcinoma cell line (HepG2) and suppression on angiogenesis of 1118-20, a newly synthesized indazole diarylurea compound. METHODS: We evaluated the activity of 1118-20 against HepG2 cells growth and tumour angiogenesis of human umbilical vascular endothelial cell line (HUVECs) with sorafenib as a positive control. KEY FINDINGS: The cytotoxic efficacy of 1118-20 was higher in HepG2 cells than human normal liver cell line (HL-7702). 1118-20 significantly suppressed the proliferation of HepG2 cells by apoptosis induction via Bcl-2 family-mediated mitochondria pathway and inhibition on Wnt/ß-catenin signalling pathway. 1118-20 effectively blunt the motility and migration, and inhibited the formation of capillary tube of HUVECs through suppression of angiogenic factors expression. Moreover, the results indicated that 1118-20 exerted higher efficacy than sorafenib on tumour cell proliferation and angiogenesis. CONCLUSIONS: Compared with its parent drug sorafenib, we found that 1118-20 possessed more potential on inhibition of angiogenesis and cancer cells growth. Inhibitory effect of 1118-20 on non-tumour liver cell HL-7702 was lower than that on hepatoma carcinoma cell HepG2. These results suggest that 1118-20 is a promising candidate compound that could be developed to a potent anticancer agent.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Indazoles/pharmacology , Liver Neoplasms/drug therapy , Phenylurea Compounds/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Movement/drug effects , Cell Proliferation/drug effects , Hep G2 Cells , Human Umbilical Vein Endothelial Cells , Humans , Liver Neoplasms/pathology , Neovascularization, Pathologic/drug therapy , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Protein Kinase Inhibitors/pharmacology , Receptor Protein-Tyrosine Kinases , Sorafenib , Wnt Signaling Pathway/drug effectsABSTRACT
Stable isotopes have been used to identify the characteristics of precipitation, evaporation, basin hydrology, and residence times. However, lakes in the cold regions are usually covered by ice for 5-6 months. To get a better understanding of stable isotopes characteristics and indications in lake ice bodies, ice and water were sampled during the icebound season in both the ice and water bodies in Dali Lake, and deuterium, oxygen-18 total nitrogen (TN), and the major ions were analyzed. The results showed that deuterium and oxygen-18 compositions (δD-δ¹8O) compositions in the ice body were greater than in the water body beneath, scattered on a straight line, and deviating downward from the global meteoric water line in the top right. The ice profile showed that the δD-δ¹8O compositions increased from the ice surface downward and decreased near to the bottom. In contrast, the TN and the major ions in the ice decreased from the ice surface downward and increased near to the bottom, meaning that the concentrations of δ¹8O had a negative correlation with the concentrations of TN and major ions. These indicated that stable isotopes can be used for tracing the nutriment and ion transport processes in the ice body.
Subject(s)
Deuterium/analysis , Environmental Monitoring , Ice/analysis , Ions/analysis , Lakes/analysis , Nitrogen/analysis , Oxygen/analysis , China , Oxygen Isotopes/analysis , SeasonsABSTRACT
HL-40, N-(4-(1-(4-chlorine indazole)) phenyl)-N-(4-chloro-3-three fluorine methyl phenyl) urea, is a novel diarylurea derivative. In this study, we investigated the kinases activities and binding constants, pharmacokinetics of HL-40, and then evaluated its anticancer efficacy by both in vitro and in vivo methods. Enzyme activities assays in vitro were employed to identify eight candidate kinase targets. The competition binding assays against eight candidate kinases suggested that HL-40 showed strong affinity to c-Kit, PDGFRß and FLT3. The pharmacokinetic studies in Wistar rats showed that HL-40 could maintain high compound concentration and long residence time in the blood circulation. HL-40 possessed strong inhibition activities against 12 human cancer cells. Meanwhile, HL-40 effectively delayed the growth of cancer xenografts without significant toxicity to mice. Based on these in vitro and in vivo results, we suggested that HL-40 might be developed as a potential multi-kinases inhibitor for cancer treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Indazoles/pharmacology , Indazoles/pharmacokinetics , Phenylurea Compounds/pharmacology , Phenylurea Compounds/pharmacokinetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/pharmacokinetics , Urea/pharmacology , Urea/pharmacokinetics , Administration, Oral , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Enzyme Assays , Humans , Indazoles/administration & dosage , Indazoles/chemistry , Inhibitory Concentration 50 , Male , Mice , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/chemistry , Rats, Wistar , Urea/administration & dosage , Urea/chemistry , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To understand the situation of the freely grazing and wild feces behaviors of residents in plateau mountain area of schistosomiasis endemic areas in Yunnan Province. METHODS: Two villages of Xidian and Moguang in Heqing County, Yunnan Province were selected as the study area and the questionnaire surveys were performed to the randomly selected villagers aged 6 to 65 years with the sampling ratio of 30%. Then the respondents were tested for the infection of schistosomiasis by indirect hemagglutination assay (IHA). RESULTS: Totally 412 residents were surveyed. In all the responds, the ratios of "captive breed", "freely grazing "unknown" and "no response" were 55.34%, 4.85%, 26.94% and 12.86% respectively; and the ratios of "no grazing", "less than 5/week" and "no less than 5/week" were 75.49%, 16.02% and 8.50% respectively; and the ratios of "no wild feces", "less than 5/week", "no less than 5/week" and "no answer" were 68.45%, 27.67%, 2.91% and 0.97% respectively. CONCLUSIONS: Freely grazing and wild feces behaviors of residents in schistosomiasis endemic area of Heqing County are widespread, could heavily affect the control of schistosomiasis in Heqing County. The further work is to strengthen the management of human and animal feces and grazing and consolidate the results of the prevention and control of schistosomiasis and finally achieve the aim of the transmission interruption.
Subject(s)
Defecation , Herbivory , Schistosomiasis/epidemiology , Adolescent , Adult , China/epidemiology , Feces , Female , Humans , Male , Middle Aged , Schistosomiasis/transmission , Toilet FacilitiesABSTRACT
PURPOSE: 1082-39, an analogue of sorafenib, is a derivative of indazole diarylurea. We evaluated the activity of 1082-39 against human cancer cell growth. Its effects and mechanisms of action were then compared with those of sorafenib. The experiments were performed in human melanoma M21 cells. METHODS: Cell viability was estimated by using the colorimetric assay. Annexin V-FITC/PI staining assay was used to recognize the apoptotic cells. Further analysis of the mitochondria membrane potential (MMP) was performed by the JC-1 fluorescence probe staining. The levels of apoptotic proteins and kinases related to cancer proliferation were determined by western blotting assay. RESULTS: 1082-39 possessed the activity against cancer cell proliferation with time- and dose-dependent manner. 1082-39 induced M21 cell to apoptosis, showing the increase of annexin V-FITC/PI staining cells, the MMP collapse and releasing cytochrome c from mitochondria. Western blotting analysis showed the activation of the mitochondria-mediated intrinsic pathway, showing the increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Statistical analysis suggested that 1082-39 possessed greater activities than sorafenib in the inhibition of M21 proliferation and induction of apoptosis. These effects of 1082-39 might arise from its activity of regulation the PI3K/Akt and Wnt/ß-catenin signaling pathways. CONCLUSIONS: 1082-39 is a promising candidate compound which could develop as a potent anticancer agent.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Antineoplastic Agents/chemistry , Apoptosis Regulatory Proteins/metabolism , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , Cytosol/drug effects , Cytosol/metabolism , Dose-Response Relationship, Drug , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Structure , Niacinamide/chemistry , Niacinamide/pharmacology , Phenylurea Compounds/chemistry , Protein-Tyrosine Kinases/metabolism , Sorafenib , Structure-Activity RelationshipABSTRACT
UNLABELLED: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. CONCLUSION: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Breast Neoplasms/pathology , Deoxycytidine/analogs & derivatives , Administration, Oral , Animals , Cell Cycle/drug effects , Cell Line, Tumor , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Design , Female , Humans , Mice , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , GemcitabineABSTRACT
New series of indazole based diarylureas were synthesized and their anticancer activity against cancer cells H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901 and MDA-MB-231 were examined. These derivatives of diarylureas, except azaindazole based diarylureas 5f, 5l and 5m, showed superior or similar activity against most of these selected cancer cell lines to the reference compound sorafenib. The effect of substituents on the indazole ring was also investigated. Derivatives with trifluoromenthy or halogen substituent on the indazole ring showed higher activity against the selected cancer cell lines than sorafenib. The acute toxicity assay showed that compounds 5a, 5b and 5i possessed lower toxicity than sorafenib. Compound 5i with 4-(trifluoromenthy)-1H-indazole and 4-(trifluoromenthy) benzene moieties exhibited the most potent anticancer activity.
Subject(s)
Antineoplastic Agents/pharmacology , Indazoles/chemistry , Urea/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HT29 Cells , Hep G2 Cells , Humans , Molecular Structure , Structure-Activity Relationship , Urea/analogs & derivatives , Urea/chemical synthesisABSTRACT
OBJECTIVE: To evaluate the effect of a novel plant molluscicide, 4%"Luo-wei" (Tea-seed distilled saponins, TDS) against Oncomelania hupensis snails in plateau mountain areas in Yunnan Province. METHODS: The immersing and spraying experiments were carried out in the ditches and grassland of Xiaolian Administrative Village in Heqing County, Yunnan Province, to assess the molluscicidal effect of 4% TDS comparing with 50% wettable powder of niclosamide ethanolamine salt (WPN) in different environments and time. RESULTS: After immersion for 24, 48 h and 72 h, the snail death rates were 70.67%, 87.33% and 98.67% in the TDS group, whereas being 77.33%, 96.67% and 100.00% in the WPN group, respectively. The differences of the death rates between the two groups 24 h and 72 h after immersing were not statistically significant ( chi2(24h) =1.73, chi2(72h) = 2.01, both P values > 0.05). Seven days after the immersing experiments, the occurrence rate of frames with living snails and the death rate of snails were 20.00% and 93.03% in the TDS group, while those were 13.33% and 95.76% in the WPN group, and there were no significant differences of the 2 indexes between the 2 groups ( chi(2)(Occurrence rate) = 2.27, chi(2)(Death rate) = 0.94, all P values > 0.05). After spraying for 1, 3, 7 d and 15 d, in both groups, the occurrence rates of frames with living snails and the average densities of living snails gradually declined, while the death rates of snails gradually increased with the extension of time. There were no statistically significant differences of the above 3 indexes between the 2 groups (all P values > 0.05). Fifteen days after the spraying experiment, the occurrence rate of frames with living snails and the adjusted death rate of snails were 15.00% and 87.39% in the TDS group and those were 16.67% and 89.32% in the WPN group, respectively. CONCLUSION: The molluscicidal effect of TDS is satisfying in plateau mountain areas, and the molluscicide is worthy of further extension and application.
Subject(s)
Molluscacides/pharmacology , Saponins/pharmacology , Snails/drug effects , Animals , China , Niclosamide/pharmacology , Population DensityABSTRACT
OBJECTIVE: To evaluate the molluscicidal effect of 26% suspension concentrate of metaldehyde and niclosamide (MNSC) in the fields of mountainous areas in Yunnan Province. METHODS: Some representative Oncomelania snail environments of schistosomiasis endemic regions were selected as study areas in Heqing County, Yunnan Province and 26% MNSC and 50% wettable powder of niclosamide ethanolamine salt (WPN) were used to kill the snails with the mechanical spraying and sprinkler spraying methods respectively. RESULTS: Seven, 15, 30 days after the spraying with the mechanical spraying method, in corn fields, the snail mortality rates were from 88.68% to 92.88% in the MNSC group, and from 89.86% to 90.32% in the WPN group respectively, and in the ditch, the snail mortality rates were from 89.97% to 94.46% in the MNSC group and from 90.08% to 96.74% in the WPN group respectively, and there was no significant difference between the 2 groups (P > 0.05); 7, 15, 30 days after the spraying with the sprinkler spraying method, in corn fields, the snail mortality rates were from 66.14% to 89.11% in the MNSC group, and from 78.40% to 91.22% in the WPN group, respectively, in the ditch, the snail mortality rates were from 84.13% to 94.27% in the MNSC group, and from 85.81% to 95.26% in the WPN group respectively, and there was no significant difference between the 2 groups (P > 0.05). CONCLUSION: 26% MNSC has good molluscicidal effect in the fields of mountainous areas in Yunnan Province
Subject(s)
Acetaldehyde/analogs & derivatives , Molluscacides/toxicity , Niclosamide/toxicity , Pest Control/methods , Snails/drug effects , Acetaldehyde/toxicity , Animals , China , Humans , Pest Control/instrumentation , Rural Population , Schistosomiasis/prevention & control , Snails/growth & developmentABSTRACT
OBJECTIVE: To evaluate the effect of comprehensive control and management of schistosomiasis at plateaus regions in Yunnan Province. METHODS: Xiaolian and Kangfu villages at plateaus regions where schistosomiasis was endemic were selected as study areas from 2006 to 2011, the schistosomiasis comprehensive control measures were conducted, and these measures included the health education, chemotherapy, stool and water management, grazing forbidden, Oncomelania snail control, etc. combined with the infrastructure of farmland water conservancy, agricultural comprehensive development, adjustment of industry structure, returning farmland to forest, ditch hardening, and aquaculture. RESULTS: At Xiaolian Village, no schistosomiasis patient and livestock were found from 2008; and at Kangfu Village, no schistosomiasis patient was detected from 2006 and no schistosomiasis domestic animal was found from 2008. In 2011, the snail area, percent of frames with living snails, the number of snails, average concentration of living snails, and the highest concentration of living snails descended by 69.99%, 81.86%, 88.86%, 89.71%, 57.95% at Xiaolian Village, and descended by 27.65%, 1.11%, 94.71%, 92.16%, 88.00% at Kangfu Village, respectively, compared with those in 2006. The ratios of infected snail area to snail area were 68.91% in 2006 and 69.13% in 2007 at Xiaolian Village, and 61.73% in 2006 and 43.24% in 2007 at Kangfu Village. There were no infected snails from 2008 in the two villages. CONCLUSION: The comprehensive control and management measures can effectively control the schistosomiasis prevalence at plateaus regions.