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OBJECTIVE@#To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.@*METHODS@#Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.@*RESULTS@#Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).@*CONCLUSION@#KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.
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Female , Rats , Animals , Humans , Angiotensin II , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Hypertension/drug therapy , Estradiol/pharmacology , Superoxide Dismutase , Ovariectomy , Mammals/metabolismABSTRACT
A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.
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Through the combing of ancient books of Chinese herbal medicine in the past dynasties， a textual research of Coptidis Rhizoma involved the name， origin， medicinal parts， producing area， quality evaluation， harvesting and processing methods in famous classical formulas was conducted in this paper. After textual research， the mainstream varieties of Coptidis Rhizoma in the Ranunculaceae family before Tang and Song dynasties were Coptis chinensis and C. chinensis var. brevisepala， after the Ming and Qing dynasties， C. deltoidea， C. teeta and C. omeiensis were gradually praised. In ancient times， the authentic producing area of Coptidis Rhizoma has the characteristics of gradually moving to the west. The eastern Coptidis Rhizoma was highly praised in the early stage， while in the later stage， western Coptidis Rhizoma like chicken feet was highly praised. In the early stage， western Coptidis Rhizoma probably originated from C. chinensis and its genus， while Coptidis Rhizoma like chicken feet was cultivated， and no wild species has been found so far. As Coptidis Rhizoma has mixed use of multiple origins in ancient books of past dynasties， based on the current shortage of market resources in C. teeta and C. deltoidea， there are also endangered and protected plants of C. chinensis var. brevisepala and C. omeiensis， combined with the mainstream medicines and resources of past generations， it is recommended to choose C. chinensis as the base of the formulas. In ancient times， there were many processing methods for Coptidis Rhizoma， such as frying and wine-， ginger-， honey-processed. In the process of developing famous classical formulas， the appropriate processing specifications of Coptidis Rhizoma should be selected based on the original source records and the requirements of the medicinal material.
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Indication and functions is an important key information in the research and development of the ancient classical formulas, which directly affects the clinical positioning of the compound formulas and their reasonable, effective and safe use after marke-ting. It is also the embodiment of the ultimate vitality of ancient classical formulas. Due to the particularity of ancient classical formulas, it is of great significance to accurately define and describe the functions and indications of classical formulas to exert their unqiue advantages. Based on the analysis of the provenances, classification of clinical indications, and functions of 100 prescriptions in the Catalogue of Ancient Classical Formulas(First Batch), this paper summarized the incompleteness, irregularity and inconsistency in the original text, the differences in terminology between ancient and modern times, and the evolution of the meanings of prescriptions in different dynasties. In addition, under the guidance of the general principle of textual researh on ancient classical formulas, which is to inherit the essence, make the past serve the present, link up the past and the present, and bulid consensus, this paper proposed the following ideas: respecting the original meanings and provenances of ancient classical formulas, taking full consideration of the development and evolution, serving the current clinical application and health needs, accurately linking up the ancient and modern terminologies, standardizing the expression of traditional Chinese medicine(TCM) terminology, highlighting the characteristics of TCM, attaching importance to the textual research principles and suggestions of post-marketing evidence-based and clinical positioning research, so as to determine the the functions and indications of the ancient classical formulas in a scientific, standardized and reasonable way and better guide the clinical application of the classical formulas.
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Drugs, Chinese Herbal , Medicine, Chinese Traditional , Oils, Volatile , PrescriptionsABSTRACT
ObjectiveTo analyze the endemic situation of schistosomiasis in national surveillance sites of Zhenjiang City from 2015 to 2019, so as to provide the scientific basis for the consolidation of schistosomiasis control achievements and timely treatment of risk factors. MethodsA total of 7 national schistosomiasis surveillance sites were assigned in Zhenjiang City from 2015 to 2019. According to the National Scheme for Schistosomiasis Surveillance (2014 version), Schistosoma japonicum infections were monitored in local residents, floating populations and livestock, and snail habitats were surveyed in Zhenjiang City from 2015 to 2019. The results of schistosomaisis surveillance in Zhenjiang City from 2015 to 2019 were analyzed. Results There were 15 848 and 7 779 person-times of local residents and floating populations receiving serological screening of schistosomiasis in 7 national surveillance sites of Zhenjiang City from 2015 to 2019, and the seroprevalence rates were 0.95% to 1.75% and 0.14% to 0.91% among local residents and floating populations, respectively; however, no egg-positives were identified. A total of 1 885 herd-times of livestock were detected, and no egg-positives were found. During the 5-year period, snail survey was conducted in snail habitats and suspected snail habitats covering 3 333.79 hm2, and there were 108.71 hm2 snail habitats identified, including 50.97 hm2 re-emerging snail habitats. The density of living snails was 0.007 to 0.125 snails/0.1 m2 from 2015 to 2019, which showed a trend for a rise year by year (χ2 = 2 732.626, P < 0.01); however, no S. japonicum infections were detected in snails. Conclusions The endemic situation of schistosomiasis has been maintained at a low level in Zhenjiang City, and schistosomiasis control achievements are consolidated. However, snails are widely distributed in the city, and there are still risk factors associated with schistosomiasis transmission. Further integrated interventions require to be reinforced to timely manage the risk of transmission of schistosomiasis and promote the progress towards elimination of schistosomiasis.
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Objective::To systematically review the evolution of Biejia Jianwan in Medical Treasures of the Golden Chamber and its clinical application in ancient and modern times, in order to analyze its application and transformation in modern times. For one thing, it provided ideas for the secondary development of Biejia Jianwan, for another, it provided reference for the transformation and application of classical famous prescriptions. Method::Ancient and modern literature of Biejia Jianwan were collected and summarized to study the ancient and modern clinical application of Biejia Jianwan, and its origin, evolution of prescription meanings and changes of main indications. Based on market research, the market transformation of Biejia Jianwan, and its research and development process and market application were analyzed. Result::Biejia Jianwan has been applied in past dynasties since the Medical Treasures of the Golden Chamber, but with insignificant changes and simple indications. In fact, Biejia Jianwan was specially developed for the treatment of malaria with abdominal mass. According to the drug dosage ratio, Trinycis Carapax and Chixiao are the main drugs in Biejia Jianwan, and insect drugs are also used. Modern literature analysis shows that Biejia Jianwan is mainly used to treat liver diseases, such as liver fibrosis, cirrhosis and liver cancer, whether in clinical or experimental studies. It was found that when Biejia Jianwan was transformed from a classical prescription into a Chinese patent medicine mainly based on its composition, dosage and preparation of the original prescription recorded in the Medical Treasures of the Golden Chamber. Chinese patent medicine preparations have been included in many diseases diagnosis and treatment, medication guidelines and expert consensus. Compared with other traditional Chinese medicines, Biejia Jianwan is more widely used in clinic with lower costs. Conclusion::Biejia Jianwan is used to treat malaria with abdominal mass in ancient times, but in modern times it is mostly used to treat liver diseases, such as liver fibrosis, with a definite efficacy. In addition, Biejia Jianwan have been successfully transformed into a modern Chinese patent medicine preparation, and achieved a better response in the market, providing a reference for the transformation and application of other classical prescriptions.
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Objective To investigate the immunological functions of heat shock protein 40 kDa of Schistosoma japonicum (SjHSP40). Methods The homology of the SjHSP40 protein sequence was analyzed and the B and T cell epitopes of SjHSP40 were predicted using bioinformatics tools. The full-length SjHSP40 gene was amplified using a PCR assay, and cloned into the prokaryotic expression vector pGEX-6P-1, which was transformed into Escherichia coli BL-21. The protein expression was induced with isopropyl β-D-thiogalactoside (IPDG), and then, the recombinant protein was purified with glutathione-sepharose 4B resin to yield the fusion protein GST-SjHSP40, which was checked with SDS-PAGE and Western blotting. Following immunization with GST-SjHSP40, the serum levels of anti-SjHSP40 IgG antibody and IgG1 and IgG2a subtypes were detected in BALB/c mice using ELISA. In addition, the effect of SjHSP40 on CD4+ T-cell subset differentiation was examined using flow cytometry. Results SjHSP40 contained 7 potential B cell epitopes and multiple T cell epitopes (CTL epitopes and Th epitopes). The prokaryotic expression plasmid pGEX-6p-1-SjSHP40 was successfully constructed, and the fusion protein GST-SjHSP40 was obtained following IPDG induction and protein purification. Significantly higher serum levels of anti-SjHSP40 IgG, IgG1 and IgG2a antibodies were detected in mice immunized with GST-SjHSP40 than in other groups; however, SjHSP40 showed no remarkable effects on CD4+ T-cell subset differentiation. Conclusions SjHSP40 may induce specific humoral immune responses in mice; however, it does not affect the balance of Th immune responses. It is suggested that SjHSP40 may be a potential vaccine candidate.
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Objective: To establish a quantitative analysis model for online monitoring of the blending uniformity of hydroxychloroquine sulfate raw and auxiliary materials, so as to accurately and quickly determine the blending endpoint. Methods: A mixture of excipients and hydroxychloroquine sulfate raw material was prepared with a labeling percentage of 70%-130%. The near-infrared spectrum was collected; and the standard normal variate transformation and frst derivative by Norris smoothing were used for spectra pretreating, with 8 372-9 045 cm-1, 5 616-6 058 cm 1 used as the spectral bands. A quantitative analysis model was developed using partial least squares regression. The quantitative analysis model was used to predict the labeling percentage of hydroxychloroquine sulfate in the blending process of raw and auxiliary materials, and the blending endpoint was verified by high-performance liquid chromatography (HPLC) analysis. Results: Five primary factors were used to establish the model. The root mean square error of calibration was 0.96 and the correlation coefficient of calibration set (Rc) was 0.998. The root mean square error of prediction was 0.97 and the correlation coefficient of validation set (Rp) was 0.998. The root mean square error of cross-validation was 1.56 and the correlation coefficient of cross-validation (Rcv) was 0.995. The prediction results of the near-infrared model was consistent with the results of HPLC verification. Conclusion: The near-infrared model in this study can be used for online quantitative analysis of the blending uniformity of hydroxychloroquine sulfate, and it can accurately and quickly determine the blending endpoint.
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Objective To understand the epidemic trend of soil-transmitted nematodiasis in Zhenjiang City from 2006 to 2018, so as to provide evidence for formulating targeted control measures. Methods The permanent residents at ages of 3 years and greater and the immigrants who had lived in Zhenjiang City for more than one year were selected as the study subjects. Fecal samples were collected, and the soil-transmitted nematode eggs were detected in fecal samples with the modified Kato-Katz technique (three smears from one stool sample), while the children at ages of 12 years and lower were tested for Enterobius vermicularis eggs using the adhesive cellophane-tape perianal swab method. The prevalence and intensity of parasitic infections were estimated in Zhenjiang City each year from 2006 to 2018, and the data pertaining to the deworming for soil-transmitted nematode infections were collected during the study period. Results A total of 202 880 person-times were subjected to stool examinations in Zhenjiang City from 2006 to 2018, and 946 persons were detected with soil-transmitted nematode infections, with a mean prevalence of 0.47%. The overall prevalence of human soil-transmitted nematode infections appeared a decline tendency (P < 0.01), with a reduction from 1.10% in 2006 to 0.11% in 2018, and there was a region-specific overall prevalence (P < 0.01), with the highest prevalence seen in Runzhou District (1.65%) and the lowest detected in New District (0.04%). The mean prevalence of human Ascaris lumbricoides, hookworm and Trichuris trichiura infections was 0.33%, 0.09% and 0.04% in Zhenjiang City, respectively, and showed a decline tendency year by year from 2006 to 2018 (P < 0.01). Among all infections, mild infections were predominant. During the period from 2006 through 2018, a total of 45 427 children were examined in Zhenjiang City from 2006 to 2018, and 145 children were positive for E. vermicularis infections, with a mean prevalence of 0.32%. The prevalence of E. vermicularis infections decreased from 1.33% in 2006 to 0.22% in 2018 in children, and the overall prevalence appeared a decline tendency (P < 0.01). A single parasite infection was predominant in soil-transmitted nematode infections (97.46%), and mixed infection of two parasites were mainly detected before 2007. A total of 535 089 person-times received deworming in Zhenjiang City from 2006 to 2018, and the rate of adverse events was 0.002%. Conclusions Currently, the soil-transmitted nematode infection is at a low level in Zhenjiang City, and the overall prevalence of soil-transmitted nematode infections shows a decline tendency year by year. The surveillance and health education of soil-transmitted nematodiasis should be further intensified to consolidate the control achievements.
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Textual research is the first step, ensuring the safety and effectiveness of the clinical application, and also one of the main bases for determining the research scheme and experimental parameters in the development of famous classical formulas. It involves the origin and historical evolution of the prescription, the main function, the meaning of the prescription, the decoction method, as well as the original part, origin, dosage, processing method of the medicinal materials in the prescription. In view of these points, the author believes that the ancient and modern literature information should be comprehensively and accurately collected according to the standardized procedures and methods, combined with the historical continuation and cross-sectional analysis, in order to ensure the efficacy and safety of traditional Chinese medicine (TCM) famous classical formulas. The research and development plan of famous classical formulas was formulated from the perspectives of TCM theoretical characteristics, formula historical evolution, modern clinical value and practical feasibility. Under the premise of "compliance with the ancients", we should understand the common problems in the process of research and development, such as the origin, processing, dosage and decoction of TCM from the perspective of history and development, so as to widely gather the industry consensus and jointly explore the precious treasure of the famous classical formulas.
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Objective To analyze the epidemic situation and epidemiological characteristics of malaria in Zhenjiang City from 2004 to 2017, so as to provide the evidence for formulating the reasonable strategies and measures for malaria prevention and control. Methods The epidemiological data of malaria in Zhenjiang City from 2004 to 2017 were collected and analyzed for the epidemic situation, epidemiological characteristics, species of Plasmodium, blood test status for febrile patients. Results A total of 182 malaria cases were reported in Zhenjiang City between 2004 and 2017, 123 cases (67.58%) were infected with P. vivax, and 55 cases (30.22%) were infected with P. falciparum. Among all the reported cases, 41 (22.53%) were local cases, 66 (36.26%) were imported cases from other provinces in China, 75 (41.21%) were imported cases from abroad. Most of the cases were male (133 cases), and 59.89% of them concentrated in the age groups of 20-50 years. These cases were mainly farmers (24.73%, 45/182) and workers (24.18%, 44/182), and most of the cases occurred from July to September. From 2004 to 2017, the blood tests were conducted for 258 879 febrile patients, with a positive detection rate of 0.007% in the local population and 0.724% in floating population, and there was a statistically significant difference between them (P<0.01). Conclusion Since 2011, no indigenous cases have been reported in Zhenjiang City, and therefore, the control of imported malaria from abroad has become the key of malaria prevention and control in this city.
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Objective To analyze the epidemic situation and epidemiological characteristics of malaria in Zhenjiang City from 2004 to 2017, so as to provide the evidence for formulating the reasonable strategies and measures for malaria prevention and control. Methods The epidemiological data of malaria in Zhenjiang City from 2004 to 2017 were collected and analyzed for the epidemic situation, epidemiological characteristics, species of Plasmodium, blood test status for febrile patients. Results A total of 182 malaria cases were reported in Zhenjiang City between 2004 and 2017, 123 cases (67.58%) were infected with P. vivax, and 55 cases (30.22%) were infected with P. falciparum. Among all the reported cases, 41 (22.53%) were local cases, 66 (36.26%) were imported cases from other provinces in China, 75 (41.21%) were imported cases from abroad. Most of the cases were male (133 cases), and 59.89% of them concentrated in the age groups of 20-50 years. These cases were mainly farmers (24.73%, 45/182) and workers (24.18%, 44/182), and most of the cases occurred from July to September. From 2004 to 2017, the blood tests were conducted for 258 879 febrile patients, with a positive detection rate of 0.007% in the local population and 0.724% in floating population, and there was a statistically significant difference between them (P<0.01). Conclusion Since 2011, no indigenous cases have been reported in Zhenjiang City, and therefore, the control of imported malaria from abroad has become the key of malaria prevention and control in this city.
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Objective To evaluate the effects of the strategy of transmission interruption of schistosomiasis in Runzhou Dis-trict,Zhenjiang City,Jiangsu Province.Methods The comprehensive prevention and control strategy was carried out in Run-zhouDistrict,Zhenjiang City,Jiangsu Province.The strategy was relied mainly on the Oncomelania hupensis snail control,ex-tended chemotherapy of schistosomiasis in residents and the health education.The infection rate of schistosomiasis in residents,area with snails,area with snails controlled,and the rates of awareness and correct behavior of schistosomiasis were as evalua-tion indexes.Results The area with snails controlled was 7 091.50 hm2in Runzhou District,Zhenjiang City from 2001 to 2016.The area with snails reduced year by year from 2001 to 2016.There was a negative correlation between the coverage intensity of snail control and the area with snails(r=-0.874,P=0).There were 1 703 serum positive and 199 fecal positive people of schis-tosomiasis in the permanent residents from 2001 to 2016.These serum and fecal positive people of schistosomiasis were all treat-ed with praziquantel.The serum positive rate of schistosomiasis in the permanent residents dropped to below 1.0％after 2005.The fecal positive patients were not found in 2004 and later.Totally 189 639 people received the questionnaire survey for the knowledge of schistosomiasis control from 2001 to 2016.The rates of awareness and correct behavior of schistosomiasis were raised in the residents year by year.The goal of the transmission interruption of schistosomiasis came to true in Runzhou Dis-trict,Zhenjiang City in 2016.Conclusion The comprehensive prevention and control strategy including mainly the snail con-trol,extended chemotherapy of schistosomiasis and health education could achieve the goal of transmission interruption of schis-tosomiasis in the areas of marshland along the Yangtze River.
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Objective To observe the relationship between serum Klotho levels and the progression of renal function in patients with chronic kidney disease (CKD)and investigate further the feasibility of serum Klotho levels for predicting the progression of renal function in CKD patients.Methods Eighty-one non-dialysis patients with CKD 3 to 5 stages and 30 healthy volunteers in the First People's Hospital of Kunshan were enrolled for a 12 months of follow-up.The levels of Klotho and fibroblast growth factor 23 (FGF23) in serum were detected by ELISA at the beginning and the end of the follow-up.The other related indicators were also tested simultaneously.GFR values were calculated by MDRD and GC formulas.According to the decreasing range of GFR,the CKD patients were subdivided into two groups:deterioration group and stability group for renal function,and the relationships between Klotho levels and progression of kidney function were evaluated.Results The patients were followed up for an average of (9.5 + 2.9) months.GFR in CKD patients decreased from (24.8 ± 12.4) mL/min to (18.7 ± 12.1) mL/min (P ＜ 0.0 1),and serum Klotho level decreased from 2.53 (1.41,3.67)ng/mL to 1.63 (1.07,3.19)ng/mL (P ＜0.01)with more pronounced trend in the patients with renal function deterioration than the patients in stability group (P ＜0.01).Fifteen patients with high Klotho level suffered from adverse kidney outcomes while 26 ones with lower Klotho level suffered from deterioration of renal function (63.4％ vs 36.5％,P =0.02).KaplanMeier analysis revealed the high risk of adverse kidney outcomes arose in the CKD patients with lower Klotho level (P =0.013).Conclusion Klotho level in CKD patients may significantly decrease and should be more apparent with renal function progresses.Lower Klotho level in serum may be associated with high risk of adverse kidney outcomes and become a promising marker to predict CKD progression.
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In the daily life, we perceive the world around us by integrating multiple sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and proprioceptive) to create a coherent, reliable representation that allows us to interact meaningfully with the environment. The integration of different sensory information is necessary for our perception, motor transformation, decision making, learning and memory. In the past decades, many interdisciplinary researchers have been attracted to the field of multisensory research, and tremendous advances have been made in this field. We review the researches on multisensory integration during self-motion perception in the past decades from the candidate areas, the integration principles and the neural correlation of the behaviors, with the intention to provide a comprehensive source for those interested in understanding the neural substrates for multisensory integration. Meanwhile, we also provide a prospect for the future research in this field.
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To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-β-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.
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Humans , Benzofurans , Cell Line, Tumor , Glycosides , Plant Roots , Chemistry , Plants, Medicinal , Chemistry , Rhizome , Chemistry , Veratrum , ChemistryABSTRACT
We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-beta [TGF-beta] /Smad pathway, an important signaling system involved in epithelialmesenchymal transition [EMT], but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting [0]TGF-beta1-induced normal rat kidney proximal tubular epithelial cells [NRK-52E] as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-beta1 in vitro. NRK-52E cells were incubated with the blank vehicle [Dulbecco's modified Eagle's medium and F-12 [DMEM/F12] added with 10% fetal bovine serum [FBS]], 10 ng/ml TGF-beta1 alone or together with 100, 200 or 400microM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h. Cell morphological changes were observed to confirm occurrence of EMT. Protein expressions of two typical markers of EMT, E-cadherin and alpha-smooth muscle actin [alpha-SMA], were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-beta1 induced spindle-like morphological transition, the loss of Ecadherin protein and upregulation of expression of alpha-SMA. However, the TGF-beta1-produced changes in cellular morphology, E-cadherin and alpha-SMA were inversed by tranlilast in concentration-dependent manner. Our findings indicate that tranilast can directly inhibit EMT. Thus, it may be implied that regulation of EMT be the target to prevent renal tubulointerstitial fibrosis.
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Animals , Epithelial-Mesenchymal Transition/drug effects , Kidney Tubules, Proximal/drug effects , ortho-Aminobenzoates/pharmacology , Rats , Cadherins/analysis , Cell Line , Dose-Response Relationship, Drug , Actins/analysisABSTRACT
The paeonol proniosomes ointment and ordinary ointment were administered to rats. Physiological saline served as perfused solution. The perfusion rate was 5 mL x L(-1) and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by HPLC. Investigation of the pharmacokinetics of paeonol proniosomes ointment and ordinary ointment by the skin-blood synchronous microdialysis coupled with HPLC is reported in this study. The results show that the recovery was (54.80 +/- 1.50)% in vitro and (54.58 +/- 4.61)% in vivo. The results showed that paeonol proniosomes ointment significantly raised the drug concentrations in skin more than the paeonol ordinary ointment. The paeono proniosomes ointment has less drugs into the blood as the ordinary ointments in blood, but its blood drug concentrations were steadier. The paeonol proniosomes ointment may be developed into a new preparation.
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Animals , Male , Rats , Acetophenones , Blood , Chemistry , Pharmacokinetics , Drug Delivery Systems , Methods , Drugs, Chinese Herbal , Chemistry , Pharmacokinetics , Microdialysis , Ointments , Chemistry , Pharmacokinetics , Paeonia , Chemistry , Rats, Wistar , Skin , MetabolismABSTRACT
To confirm the hypothesis that the high frequency sequences of high throughput sequencing are the terminal sequences of the bacteriophage genome. An adaptor of specific sequence was linked to the end of the bacteriophage T3 genomic DNA, which was then subject to high throughput sequencing; as a control, the same T3 genomic DNA without adaptor was also analyzed by high throughput sequencing. The sequencing results were examined with bioinformatics software. Similar high throughput sequencing technique was applied to analyze the genomic sequence of N4-like bacteriophage IME11. Bioinformatics study showed that the sequences tagged with adaptors were consistent with the high frequency sequences without adaptor labeling. Our analysis also indicated that the end of the T4-like phage genome had specific sequences instead of random sequences, disagreeing with the previous assertion. Evidences were provided that N4-like bacteriophage had a particular terminal sequence: the left end of the genome was unique while the right end was permuted. The high throughput sequencing technique was convenient and practical to be used to simultaneously detect the terminal sequence and the complete sequence of bacteriophage genome.
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Caudovirales , Genetics , Computational Biology , Genome, Viral , High-Throughput Nucleotide Sequencing , MethodsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect and mechanism of signal transducers and activators of transcription 3 (STAT-3) modulates human tongue squamous cell carcinoma invasion ability via targeting mircoRNA-21.</p><p><b>METHODS</b>Tscca and Tca8113P160 human tongue squamous cell carcinoma cell lines were used.WP1066 (STAT-3 inhibitor) , the small molecule inhibitor of STAT-3 was used to suppress the STAT-3 expression. The half maximal inhibitory concentration (IC50 value) of WP1066 in the two cell lines was determined by methyl thiazolyl tetrazolium (MTT) assay. The expression level of STAT-3 and phosphorylation of STAT-3 (pSTAT-3) was examined by Western blotting. Real-time PCR was used to detect the mircoRNA-21 expression after treated with WP1066. Matrigel matrix and transwell assay were used to determine cancer cell colony formation and invasion ability after treated with WP1066. Tumor invasion related proteins in Tscca and Tca8113P160 cell lines were measured by Western blotting. Luciferase reporter gene assay was conducted to detect the relationship between STAT-3 and mircoRNA-21.</p><p><b>RESULTS</b>The IC50 to WP1066 in Tscca cell was 3.1 and 3.5 µmol/L for Tca8113P160 cell respectively. STAT-3/pSTAT-3 protein level was suppressed significantly (Tscca: STAT-3: F = 887.154, P = 0.000; pSTAT-3: F = 332.212, P = 0.000; Tca8113P160: STAT-3: F = 322.895, P = 0.000; pSTAT-3:F = 788.357, P = 0.000). mircoRNA-21 expression was down-regulated (Tscca:F = 32.157, P = 0.000; Tca8113P160: F = 11.349, P = 0.007). The diameters of culture clone in cell treated with WP1066 were less than control groups (Tscca:F = 15.751, P = 0.004; Tca8113P160: F = 12.964, P = 0.007). The number of tongue cancer cell migrating through the transwell membrane in WP1066 treated group was less than in control groups (Tscca: F = 1688.926, P = 0.000; Tca8113P160: F = 327.528, P = 0.000). In addition, MMP-2/9 protein expression was decreased in both of the cell lines treated with WP1066, while TIMP-3 was up regulated dramatically. STAT-3 could modulate mircoRNA-21 directly.</p><p><b>CONCLUSIONS</b>Reduction of STAT-3 can inhibit tongue cancer cell invasion ability via targeting mircoRNA-21.</p>