Effect of lncRNA HIF1A-AS1 on chemotherapy sensitivity of vincristine-resistant in retinoblastoma cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of long non-coding RNA-HIF1A-AS1(lncRNA HIF1A-AS1)on the chemotherapy sensitivity of vincristine(VCR)-resistant in retinoblastoma(RB)cells by regulating the expression of hypoxia-inducible factor-1α(HIF-1α).METHODS: The human RB VCR-resistant cell line SO-RB50/VCR was established, expression of lncRNA HIF1A-AS1 in SO-RB50 and SO-RB50/VCR cells were detected by reverse transcription-quantitative real-time PCR(RT-qPCR); inhibition of lncRNA HIF1A-AS1 expression or simultaneous overexpression of HIF-1α in SO-RB50/VCR cells, and then median inhibitory concentration(IC50)of VCR and cell proliferation and apoptosis were detected in SO-RB50/VCR cells; the protein expressions of HIF-1α, multidrug resistance associate protein(MRP)and P-glycoprotein(P-gp)were measured by Western blot.RESULTS: Compared with SO-RB50 cells, the expression levels of lncRNA HIF1A-AS1 and HIF-1α protein in SO-RB50/VCR cells were increased(P<0.05); after inhibiting the expression of lncRNA HIF1A-AS1 in SO-RB50/VCR cells, the apoptosis rate was significantly increased(P<0.05), optical density(OD450), the IC50 value of VCR on cells and the expression levels of HIF-1α, MRP and P-gp proteins were significantly reduced(P<0.05); overexpression of HIF-1α attenuates the inhibitory effect of down-regulated lncRNA HIF1A-AS1 expression on drug resistance in SO-RB50/VCR cells.CONCLUSION: The lncRNA HIF1A-AS1 was highly expressed in SO-RB50/VCR cells, and inhibition of lncRNA HIF1A-AS1 expression reduced VCR resistance in SO-RB50/VCR cells by down-regulating HIF-1α expression.

Quantitative determination of selected heavy metals and micronutrients in branded dairy products sold in Nigeria using atomic absorption spectroscopy (AAS)

Quantitative analysis of heavy metals and nutrients in food helps indicate the safety and quality of food for final consumers. The present study was conducted to assess the presence of heavy metals (arsenic, copper, mercury, chromium, and lead) and the nutritional value of calcium in branded milk and yogurt to evaluate health risks for consumers. Ten (10) samples of branded milk and dairy products manufactured in Nigeria were purchased. The metal contents of the samples were determined using atomic absorption spectroscopy. The concentrations of calcium in the milk samples were between 9.33 ± 0.0023 and 18 ± 0.0071 ppm and were detected in all samples. Arsenic concentrations ranged from 0.45 ± 0.00042 to 2.48 ± 0.00064 ppm in eight branded samples but were undetected in two samples. Chromium levels were undetected in most samples, except for two with concentrations of 0.12±0.00049 ppm and 0.23±0.00021 ppm, respectively. Copper ranged from 0.032±0.00021 ppm to 0.129±0.00021 ppm in six samples. Mercury levels were detected in six samples at a concentration of 1.0±1.0 ppm. Lead concentrations ranged from 0.15±0.00064 to 0.29±0.00028 ppm in three samples. The study found heavy metals above the ideal concentration in branded milk and dairy products in Nigeria, highlighting the need for quality control measures during production to prevent contamination.

Evaluation of Elemental and Volatile Compounds of Three Selected Plants of Genus Hibiscus

Aims: The present study aims to evaluate the minerals, bioactive compounds of 3 selected Hibiscus Genus i,e. Hibiscus sabdariffa L., Hibiscus cannabinus L., and Hibiscus acetosella Welw. Place and Duration of Study: The selected plants were collected during May to October 2018 from Imphal (24°37’N and 93°39’E) Manipur North Eastern State of India, which lies 2590 feet above sea level, and study were carried out in Genetics Laboratory, Department of Life Sciences, Manipur University. Methodology: The minerals composition and bioactive compounds were evaluated by using Graphite Flame Atomic Absorption Spectrometer (GF-AAS) method and Gas Chromatography-Mass Spectrometry (GCMS), respectively. Results: The elemental analysis shows the presence of Calcium, Magnesium, Iron, Zinc, Copper, Sodium, Potassium, Selenium, Chromium, Cobalt. By using the GC-MS method, the compounds are identified with Retention time (RT) and area percentage. The two compounds are identified for methanol extract and four compounds for chloroform extract of Hibiscus sabdariffa L. For Hibiscus cannabinus L., three compounds are identified for methanol extract and four compounds for chloroform extract and for Hibiscus acetosella Welw. eleven compounds for methanol extract and three compounds for chloroform extract. Conclusion: The selected plants are good source of Sodium, Potassium, Selenium, Chromium, Cobalt, Calcium, Magnesium, Iron, Zinc, Copper and bioactive compounds which had antibacterial, anticancer, antioxidant properties and renal related disorders protection effects. However, it is needed to study the pharmacological activity for further evaluation.

Expression and clinical significance of LncRNA HIF1A-AS1 in proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and diagnostic value of long non-coding RNA(LncRNA)hypoxia-inducible factor 1 alpha antisense RNA 1(HIF1A-AS1)in serum of patients with proliferative diabetic retinopathy(PDR).METHODS: A total of 160 patients with diabetic retinopathy(DR)admitted to our hospital from July 2019 to July 2021 were selected as the research objects. According to the degree of disease, they were divided into PDR group(80 cases)and nonproliferative diabetic retinopathy(NPDR)group(80 cases). At the same time, 100 healthy cases in our hospital were selected as the control group. Detect and compare serum triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting blood glucose(FBG)and the level of glycosylated hemoglobin A1c(HbA1c); The expression level of LncRNA HIF1A-AS1 in serum was detected by real-time fluorescence quantitative PCR(qRT-PCR)method; Logistic regression was used to analyze the risk factors that affected the occurrence of PDR; Receiver operating characteristic curve(ROC)was used to analyze the clinical value of LncRNA HIF1A-AS1 level in the diagnosis of PDR. RESULTS: The expression level of LncRNA HIF1A-AS1 in the serum of the patients in the PDR group was significantly higher than that in the NPDR group and the control group, and the NPDR group was higher than the control group(P<0.05); The course of disease, HbA1c, TC, TG, LDL-C, FBG levels in the PDR group and the NPDR group were significantly higher than those of the control group, the HDL-C level in the PDR group was significantly lower than that in the control group(P<0.05); The level of LncRNA HIF1A-AS1 was positively correlated with the course of disease, HbA1c, TC, TG, LDL-C and FBG(P<0.05), and negatively correlated with HDL-C(P<0.05); Logistic regression analysis showed that the LncRNA HIF1A-AS1, course of disease, FBG, HbA1c, TC, TG, LDL-C were all risk factors for PDR(P<0.05); ROC results showed that the area under the curve(AUC)of the LncRNA HIF1A-AS1 level predicting PDR was 0.766(95%CI: 0.692～0.829), the corresponding sensitivity was 66.25% and the specificity was 78.75%.CONCLUSION: The level of LncRNA HIF1A-AS1 in the serum of PDR patients is up-regulated, it is a risk factor for the occurrence of PDR and it can be used as a potential serological indicator for predicting the occurrence of PDR.

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Evaluation of soil contamination by heavy metals at public cemeteries in the municipality of Lages, southern Brazil / Avaliação da contaminação de solos por metais tóxicos em cemitérios públicos do município de Lages, Sul do Brasil

ABSTRACT The burial of bodies is a potentially polluting activity. Taking this into consideration, the aim of the present study was to verify the compliance of two cemeteries with environmental legislation and to quantify the concentrations of heavy metals in soils affected by burial activities. Physicochemical characterization of the soil was performed by analyzing control samples from areas near the cemeteries. Concentrations of cadmium, lead, chromium, nickel, zinc and copper were determined using high-resolution continuum source atomic absorption spectrometry. The two cemeteries had unsatisfactory properties for the retention of metal cations, with clay percentages ranging from 15.40 to 41.40% and sand percentages ranging from 28.75 to 66.85%. The control samples presented low cation exchange capacity (12.27 to 22.73 cmolc/dm³) and high aluminum (Al3+) saturation (66.74 to 90.16%). Although neither of the two cemeteries had concentrations above the limits established for the metals analyzed by Resolution No. 420/2009 of the National Environment Council, the contaminants may be leaching to groundwater due to inadequate soil characteristics.

RESUMO O sepultamento de corpos é uma atividade potencialmente poluidora. Este trabalho teve como objetivo verificar a adequação das áreas de dois cemitérios públicos à legislação ambiental e à atividade cemiterial e quantificar a concentração de metais pesados nos solos que estão sob influência desses empreendimentos. Realizou-se a caracterização físico-química do solo, com a análise de amostras testemunha de solo de cada cemitério. Também foram determinadas as concentrações dos metais pesados: cádmio, chumbo, cromo, níquel, zinco e cobre, por meio de espectrometria de absorção atômica de alta resolução com fonte contínua. As áreas dos cemitérios apresentam condições insatisfatórias para a retenção de íons catiônicos metálicos, com percentuais de argila variando entre 15,40 e 41,40% e de areia entre 28,75 e 66,85%. Os solos testemunha apresentaram reduzida capacidade de troca de cátions entre 12,27 e 22,73 cmolc/dm³) e elevada saturação por alumínio entre 66,74 e 90,16%. Apesar de nenhum dos cemitérios apresentar concentrações dos metais analisados acima dos limites de prevenção estabelecidos pela Resolução nº 420/2009 do Conselho Nacional do Meio Ambiente, em função das características dos solos, os contaminantes podem estar sendo lixiviados para os recursos hídricos subjacentes.

Effect of Arsenic in Realgar on Rat Ability in Novel Objects Recognition Test / 中国实验方剂学杂志

Objective:To determine the contents of inorganic arsenic（iAs），monomethylarsonic acid（MMA） and dimethylarsinic acid（DMA） in brain tissues and blood by using hydride generation-cold trap-atomic absorptionspectrometry（HG-CT-AAS）， and to explore the toxic effects of Realgar on central nervous system of rats. Method:The 96 Wistar rats were randomly divided into 4 groups：normal control group，0.3，0.9 and 2.7 g·kg^-1 Realgar groups. They then received intragastric administration for 14，28 and 42 days respectively， so a total of 12 groups were formed， with 8 animals in each group. The normal group was given the same dose of sodium carboxymethyl cellulose （CMC-Na） by gavage. The contents of iAs，MMA and DMA in blood and brain tissues were determined by HG-CT-AAS. The novel object recognition test was conducted to observe the learning and memory ability of rats. The changes of hippocampal neuron ultrastructure were observed by transmission electron microscopy. Result:There was no difference in the growth，weight and hippocampal coefficient of the experimental animals. The method of HG-CT-AAS showed a good linearity，precision，accuracy and recovery in content determination of arsenic （at various forms） in rat brain and blood. MMA and DMA were detected in the brain of realgar groups at time-dose-effect relationship. iAs，MMA and DMA were detected in the blood of Realgar groups. The nuclear membrane， mitochondria and endoplasmic reticulum in hippocampus neurons of rats were gradually damaged with the increase of Rhubarb exposure dose and time. After 14 days of exposure to Realgar，compared with the normal control group，there was no significant difference in the novel object recognition index among Realgar groups. After 28 days of exposure，only 2.7 g·kg^-1 Realgar group showed statistically significant difference with the control group （<italic>P</italic><0.05）. After 42 days of exposure， the novel object recognition index of 0.9 and 2.7 g·kg^-1 Realgar groups was significantly lower than that in normal control group（<italic>P</italic><0.05）. Conclusion:The metabolites of Realgar in rats are iAs，MMA and DMA. MMA and DMA can be accumulated in the brain tissue through the blood-brain barrier，causing the decline of the ability of learning and memory and leading to damage of hippocampal neurons.

Silencing long non-coding RNA HIF1A-AS2 inhibits proliferation, invasion and migration of cervical cancer cells / 南方医科大学学报

OBJECTIVE@#To explore the inhibitory effects of silencing long non-coding RNA (LncRNA) HIF1A-AS2 on epithelialmesenchymal transition (EMT) and tumor stem cell-like phenotype in cervical cancer cells.@*METHODS@#We designed 3 shRNA constructs for silencing HIF1A-AS2 in CaSki cells, and the shRNA with the strongest interference effect was selected for subsequent experiment. CaSki cells were transfected with shRNA-NC or Sh-HIF1A-AS2, and the changes in cell viability, invasion ability, EMT, expressions of EMT-related proteins, formation of cell spheres and expressions of stem cell markers were detected.@*RESULTS@#Transfection with shRNA-NC and Sh-HIF1A-AS2 did not significantly affected the viability of CaSki cells (@*CONCLUSIONS@#Silencing HIF1A-AS2 can inhibit proliferation, invasion and migration of cervical cancer cells

Phytochemical Analysis and Antiplasmodial (curative) Activities of Methanolic Leaf Extract of Morinda lucida (Ewe Oruwo) in Male Swiss Mice Infected with Plasmodium berghei NK65

Aim:Medicinal plants have been used for the treatment of many infections and diseases including malaria. The study was conducted to determine the effect of in vivoanti-plasmodialand antioxidant properties of the methanolic leaf extract of Morinda lucidain male Swiss albino mice infected with Plasmodium Berghei NK65. Study Design and Methodology:Phytochemical, GC-MS and AAS analyses were determined in the plant. Swiss albino mice were inoculated intraperitoneally with Plasmodium bergheiNK65. Thirty-five (35) mice were grouped into seven groups, five per group. Group A were not infected with P.bergheiNK65.Group B, C and D served as the negative and positive control groups while Group E, F and G mice were treated with 400, 600 and 800 mg/kg body weight of methanolic leaf extract of M. lucida. Haematological parameters were determined in the whole blood using BC-3200 Auto Hematology Analyzer. TP, MDA, CAT, SOD % inhibition, SOD unit and vitamin A were all determined in the liver homogenateusing standard procedures.Results:The GC-MS result of the M. lucidashows the presence of five bioactive compounds. It was also observed that the plant contains the following minerals: iron, magnesium, potassium, phosphorus and copper. Acute toxicity shows that the LD50>000mg/Kg b.wt. The extract caused 30.96%, 32.93% and 67.23% reduction in parasitemia at 400, 600 and 800 mg/kg body weight respectively while chloroquine exerted 96.53% and artesunate exerted 92.03% reduction at 10 mg/kg body weight respectively. The Haematological parameters showed that the plant extractis nothaematotoxic since it significantly (P<0.05) reduced WBC count, and increase RBC, HGB, and HCT values in the treated mice compared to the infected untreated mice. This study shows that the mean lipid peroxidation (MDA) level was significantly decreased in the malaria treated mice (group C, D, E, F and G) compared to the untreated mice (group B). There was also a significant increase in the total protein, catalase, SOD % inhibition, SOD unit and Vitamin A levels in the liver homogenate of animals treated with chloroquine, artesunate and extract of M. lucidacompared to the untreated mice. Conclusions: The study shows that Morinda lucidapossess antiplasmodial activity in male Swiss mice infected with Plasmodium berghei NK 65.

A Comparative Analysis Of Two Different Samples Of Siddha Classical Formulation-padigalinga Chenduram

Siddha is the traditional system of medicine in India which is practiced in southern part. This traditional system has many polyherbal and herbo-mineral formulation which is more effective but they lack standardization procedures. Standardization of a herbo- mineral formulation is essential to assess the quality, efficacy, purity and safety of the drug. The present paper deals with standardization of Padigalinga Chenduram, the Siddha formulation which is used for treating menorrhagia, diarrhoea, dysentry etc. In-house preparation and one marketed sample were subjected to standardization techniques like organoleptic study, physicochemical screening and heavy metal analysis. It was observed that both the samples differ in their organoleptic character, physicochemical analysis and heavy metal analysis like colour variance, percent weight loss on drying or moisture content was found to be less in market sample and total ash value was high as well. And the market sample was found to be better than the in-house sample in water-soluble and alcohol-soluble extractive values. The toxic heavy metals as per AAS is found in both formulations and the values are not matching with each other, and it may be due to the raw material collection time and geographical variation, etc. which can be further investigated for its pharmacological activity. More number of samples from different pharmas has to be studied to arrive at definite standard for manufacturing Padigalinga Chenduram. When a definite standard is arrived from future studies, Padigalinga Chenduram will be a cost effective Siddha formulation for the treatment of various ailments.

Diagnóstico e tratamento da DREA: realidades da prática clínica / Diagnosis and treatment of AERD: clinical practice reality

Introdução: A doença respiratória exacerbada por aspirina (DREA), caracterizada por asma, rinossinusite, polipose nasal e hipersensibilidade à aspirina, pode ser sugerida pela história, porém, o teste de provocação oral com a aspirina é o padrão ouro para o diagnóstico, e a dessensibilização com aspirina, uma boa opção terapêutica. O objetivo do trabalho foi avaliar as características clínicas e os resultados dos procedimentos de provocação e/ou de dessensibilização com aspirina nos pacientes com suspeita de DREA, bem como observar se houve correlação com a literatura. Métodos: Neste estudo retrospectivo, foram avaliados prontuários de pacientes adultos com suspeita de DREA, em acompanhamento em um hospital terciário e que foram submetidos à provocação e/ ou dessensibilização com aspirina. Dois protocolos foram utilizados para o teste de provocação: (a) cetorolaco nasal/aspirina oral, e (b) apenas aspirina oral. Foram avaliados: características clínicas, a positividade do teste e da dessensibilização e a comparação deste resultado com a história prévia. Resultados: Participaram do estudo 24 pacientes, com média de idade de 50,8 anos, sendo 54,2% do sexo feminino. Treze pacientes (54,2%) tinham asma grave, e seis (25%), asma alérgica. Média do volume expiratório forçado no primeiro segundo (VEF1) foi de 81,5% do valor predito. Dezenove pacientes (79,2%) referiam broncoespasmo e/ou urticária com anti-inflamatórios não esteroidais. Cinco pacientes não faziam associação com essas medicações. Independente do protocolo usado, onze pacientes (45,8%) apresentaram teste positivo, confirmando a DREA, sendo que seis pacientes (25%) foram submetidos à dessensibilização com aspirina. Oito pacientes (33,3%) apresentaram provocação negativa, e cinco (20,8%) não conseguiram completar a investigação devido à presença de urticária. Conclusões: Pacientes com suspeita de DREA deveriam ser submetidos à provocação com aspirina para confirmar o diagnóstico. Um quarto dos pacientes foi submetido à dessensibilização, entretanto, para a maioria dos pacientes não foi possível confirmar o diagnóstico ou o teste foi negativo.

Introduction: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, rhinosinusitis, nasal polyps, and aspirin hypersensitivity. The condition may be suggested by the patient's medical history; however, oral provocation test with aspirin is the gold standard for diagnosis, and desensitization with aspirin, a good therapeutic option. The aim of this study was to evaluate the clinical characteristics and results obtained with aspirin provocation tests and/or desensitization in patients with suspected AERD, as well as to correlate these data with the literature available. Methods: In this retrospective study, the medical records of adult patients with suspected AERD followed at a tertiary hospital who underwent aspirin challenge and/or desensitization were evaluated. Two protocols were used for the challenge test: (a) nasal ketorolac/ oral aspirin; and (b) oral aspirin alone. Clinical characteristics and both test and desensitization positivity were evaluated, and the results were compared with data from the patient's history. Results: Twenty-four patients participated in the study, with a mean age of 50.8 years; 54.2% were female. Thirteen patients (54.2%) had severe asthma, and six (25%) had allergic asthma. Mean forced expiratory volume in 1 second (FEV1) was 81.5% of the predicted value. Nineteen patients (79.2%) reported bronchospasm and/or urticaria with nonsteroidal anti-inflammatory drugs. Five patients had no association with these medications. Regardless of the protocol used, eleven patients (45.8%) presented positive tests, confirming the diagnosis of AERD, and six patients (25%) underwent aspirin desensitization. Eight patients (33.3%) had negative results in the provocation test, and five (20.8%) failed to complete the investigation due to the presence of urticaria. Conclusions: Patients with suspected AERD should undergo aspirin challenge to confirm the diagnosis. One-fourth of our patients underwent desensitization, but for most patients, either it was not possible to confirm the diagnosis or the test resulted negative.

Methodological evaluation of urinary mercury detection using Zeeman atomic absorption mercury analyzer / 中国比较医学杂志

Objective To evaluate the method for detection of urinary mercury using a Zeeman atomic absorption mercury analyzer and to provide a reference for selecting a convenient method for mercury detection in experiments and clinical diagnoses. Methods Urinary mercury was detected by Zeeman atomic absorption spectroscopy (ZAAS) and hydride generation atomic absorption spectrometry (HG-AAS), and the detection limit, accuracy, precision and consistency of the two methods were compared. Results The Data collected by ZAAS and HG-AAS showed a good linear relationship in the range of 0 -1000 ng/mL (ZASS, R2 =1. 0000) and 0 -20 ng/mL (HG-AAS, R2 =0. 9990). The detection limits of ZAAS was 0. 156 ng/mL and that of HG-AAS was 1. 593 ng/mL, indicating that ZAAS is more sensitive. The recovery rate of standard addition of ZAAS was between 97. 5％ and 103. 2％, and that of HG-AAS was between 95. 6％ and 104. 5％. After measurement of 10 ng/mL and 100 ng/mL mercury standard solutions repeated for 10 times, the relative standard deviation (RSD) of ZAAS was 0. 30％ and 0. 36％ respectively, and the RSD of HG-AAS was 2. 82％ and 1. 11％, respectively. The accuracy and precision of both the two method met the standards of GBZ/T 210. 5-2008, and the precision of ZAAS was better. A total of 30 urine samples were measured by these two methods. The results were compared with paired-samples t-test and showed a non-significant difference (P ＞ 0. 05), indicating a high consistency of these two method (R2 =0. 9961). Conclusions ZAAS is a convenient and accurate method for the detection of urinary mercury, with a relatively low detection limit and better precision.

Direct determination of manganese in urine by Graphite Furnace Atomic Absorption Spectrometry / 中华劳动卫生职业病杂志

Objective@#To establish a method for the determination of manganese in urine by graphite furnace atomic absorption spectrometry (AAS) without the use of matrix modifier.@*Methods@#The urine samples were 5 times diluted with 1% nitric acid then directly determined by AAS. Zeeman was used for background correction.@*Results@#The linear range for determination of manganese in urine was 5~60 μg/L (urine) . The correlation coefficient was greater than 0.995 with the detection limit of 1.5 μg/L and with the lower limit of quantification of 5.0 μg/L. The relative standard deviations (RSDs) of within-run precision was between 1.1%~4.3%, the RSDs of between-run precision was between 3.3%~7.0%. The average recovery was 102.6%. The samples can be stored for 14 days at room temperature, 4℃, -8 ℃ and -35 ℃.@*Conclusion@#The method is feasible for determination of manganese in urine.

Long noncoding RNA EPB41L4A-AS2 associated with the prognosis of tumors / 实用肿瘤学杂志

Objective The relationship between the clinicopathological features and the prognosis of breast cancer patients was evaluated by the expression of EPB41L4A-AS2 in breast cancer tissues.Methods The relationship between the expression of EPB41L4A-AS2 and the clinical features of breast cancer was evaluated by using the genome meta analysis,TCGA and Gene Expression Library(GEO) datasets.The correlation between EPB41L4A-AS2 and apoptotic pathway was verified by Western blotting.Results The results from Meta -analysis,TCGA and GEO datasets showed that EPB41L4A-AS2 was low in breast cancer tissues and was positively correlated with poor clinical and pathological features.EPB41L4A-AS2 was confirmed an association with the classical apoptosis pathway in breast cancer cell lines.In the meta-analysis of GEO,we found the high expression of EPB41L4A-AS2 with good prognosis.Conclusion EPB41L4A-AS2 inhibits tumor formation and has a high value in clinical prognosis of breast cancer.

Three Cases of Thoracic Endovascular Aortic Repair for Spontaneous Rupture of the Thoracic Aorta / 日本心臓血管外科学会雑誌

<p>Spontaneous rupture of the thoracic aorta without trauma, aneurysm or dissection is a rare but fatal disease. We reported successful endovascular aortic repair of thoracic aortic spontaneous rupture in 3 patients. Generally, it is difficult to accurately identify the rupture site in the spontaneous rupture. However, by detailed planning based on the data of preoperative CT images, thoracic endovascular aortic repair (TEVAR) can be successfully performed, like surgical repair of spontaneous rupture of the distal aortic arch or descending thoracic aorta. TEVAR should be considered as a first-line therapy, especially, in patients with advanced age or significant comorbidities.</p>

Regulatory role of long-chain non-coding RNA HIF1A-AS1 on hypoxia-induced the autophagy of pancreatic cancer PANC1 cells / 中华胰腺病杂志

Objective To observe the regulatory role of long non-coding RNA HIF1A-AS1 on the autophagy of pancreatic cancer PANC1 cells induced by hypoxia.Methods The pancreatic cancer PANC1 cells were cultured in a three-gas incubator filled with hypoxic gas mixture (94% N2,5% CO2,1% O2) for 3, 6, 12, 24, 36 and 48 h.HIF1A-AS1 overexpression and low expression PANC1 cells were obtained by the infection of recombinant adenovirus carrying HIF1A-AS1 and the transfection of HIF1A-AS1 targeting siRNA by liposome, and routinely cultured PANC1 cells served as control.The expression of HIF1A-AS1 of PANC1 cells was detected by real-time quantitative PCR after being cultured in hypoxia-induced condition for 24 h.The apoptosis rate was detected by flow cytometry.The autophagy related proteins Beclin 1 were detected by western blot.Results The expression of HIF1A-AS1 in hypoxic cells was increased as the hypoxic time increased since 6 h and peaked at 36 h, which was significantly higher than that in control group (P<0.01).HIF1A-AS1 relative expression in HIF1A-AS1 overexpression and low expression PANC1 cells was 4.49±0.53 and 0.49±0.07, which were normalized to that of control group with the relative expression of 1.Control group had lower HIF1A-AS1 expression than HIF1A-AS1 overexpression PANC1 cells but higher HIF1A-AS1 in HIF1A-AS1 low expression PANC1 cells, and the differences were statistically significant (P<0.01).The cell apoptosis rate of control, HIF1A-AS1 overexpression and low expression PANC1 cells was (8.27±1.28)%, (6.56±1.49)% and (19.9±2.34)% after 24 h hypoxic culture.Control group had higher HIF1A-AS1 expression than HIF1A-AS1 overexpression PANC1 cells but lower HIF1A-AS1 in HIF1A-AS1 low expression PANC1 cells, and the differences were statistically significant (P<0.01).The expression of Beclin 1 protein was protein 1.05±0.11, 1.29±0.19 and 0.38±0.18, respectively.Control group had lower Beclin 1 expression than HIF1A-AS1 overexpression PANC1 cells but higher Beclin 1 in HIF1A-AS1 low expression PANC1 cells, and the differences were statistically significant (P<0.01).Conclusions HIF1A-AS1 can promote autophagy of pancreatic cancer PANC1 cells induced by hypoxia and participate in the pathogenesis and metastasis of pancreatic cancer.

Determination of heavy metals and harmful elements in Yuanhu zhitong capsule / 中国生化药物杂志

Objective To determine the content of heavy metals and harmful elements in commercially available Yuanhu Zhitong Capsule. Methods The determination of lead, cadmium, arsenic, mercury, copper and chromium by atomic absorption spectrometry and atomic fluorescence spectrometry was established.Results The recovery rate of the method was between 91.2% and 111.2%, and the precision of the experiment was less than 5%, and the range of each element was good.The stability and reproducibility of the method were good.Lead and cadmium and copper of Yuanhu zhitong capsule in different degree exceeded the standard, while the content of arsenic, mercury and chromium was in accordance with the requirements. Conclusion The method is simple and easy to operate, convenient and quick.The content of the current limit of Yuanhu zhitong capsule still need to establish the quality standard of lead and cadmium, arsenic, mercury, copper and chromium.In this paper, the establishment of the heavy metals and harmful elements determination method of Yuanhu zhitong capsule provide quality control and safety evaluation of reference.

Análise transcriptômica de miRNAs em pacientes sob dupla terapia de antiagregação / Transcriptomic analysis of miRNAs on patients in dual antiplatelet therapy

A terapia antiagregante é comumente indicada na prevenção e tratamento de doenças cardiovasculares. A dupla antiagregação com clopidrogrel e ácido acetilsalicílico (AAS) tem sido frequentemente adotada em pacientes com Doença Arterial Coronariana (DAC), mas apresenta ineficácia em uma parcela significativa da população com genótipo de respondedores. Essa falha terapêutica nos leva a questionar se outros mecanismos moleculares podem estar influenciando na resposta a esses fármacos. Recentes estudos sugerem que pequenas sequências de RNA não codificantes denominadas microRNAs (miRNAs) podem estar fortemente relacionadas com resposta ao tratamento fármaco-terapêutico, controlando as proteínas envolvidas na farmacocinética e farmacodinâmica. Entretanto, os principais miRNAs que atuam na dinâmica da resposta medicamentosa ainda não foram bem definidos. O objetivo deste estudo foi avaliar o perfil de miRNAs no sangue total periférico, procurando melhor esclarecer os mecanismos envolvidos na resposta aos antiagregantes plaquetários AAS e clopidogrel. Para isso, selecionou-se pacientes com DAC, os quais apresentavam diferentes respostas à dupla terapia de antiagregação determinadas pelo teste de agregação plaquetária. Baseados nos fenótipos, os perfis de expressão de miRNAs foram comparados entre os valores da taxa de agregação categorizados em tercis (T) de resposta. O grupo T1 foi constituído de pacientes respondedores, o T2 de respondedores intermediários e o T3 de não respondedores. Os perfis de miRNAs foram obtidos após sequenciamento de última geração e os dados obtidos foram analisados pelo pacote Deseq2. Os resultados mostraram 18 miRNAs diferentemente expressos entre os dois tercis extremos. Dentre esses miRNAs, 10 deles apresentaram importantes alvos relacionados com vias de ativação e agregação plaquetária quando analisados pelo software Ingenuity®. Dos 10 miRNAs, 4 deles, os quais apresentaram-se menos expressos no sequenciamento, demonstraram os mesmos perfis de expressão quando analisados pela reação em cadeia pela polimerase quantitativa (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR- 30a-5p e hsa-let-7g-5p. A partir das análises de predição de alvos, pôde-se observar que os quatro miRNAs, quando menos expressos simultaneamente, predizem ativação da agregação plaquetária. Além disso, os miRNAs hsa-miR- 423-5p, hsa-miR-744-5p e hsa-let-7g-5p mostraram correlação com o perfil lipídico dos pacientes que, por sua vez, apresentou influência nos valores de agregação compreendidos no T3 de resposta a ambos os medicamentos. Sendo assim, conclui-se que maiores taxas de agregação plaquetária podem estar indiretamente relacionadas com os padrões de expressão de hsa-miR- 423-3p, hsa-miR-744-5p e hsa-let-7g-5p. Sugere-se que a avaliação do perfil de expressão destes 3 miRNAs no sangue periférico de pacientes com DAC possa predizer resposta terapêutica inadequada ao AAS e ao clopidogrel

The antiplatelet therapy is often indicated for the prevention and treatment of cardiovascular diseases. Dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) has often been adopted in patients with coronary artery disease (CAD), but it has been ineffective in a significant portion of the population with genotype of responders. This fact leads us to question whether other molecular mechanisms may be influencing the response to these drugs. Recent studies suggest that small non-coding RNA sequences known as microRNAs (miRNAs) may be closely related to response to drug-therapeutic treatment, controlling proteins involved in pharmacokinetics and pharmacodynamics. The aim of this study was to evaluate the profile of miRNAs in whole blood, looking to better clarify mechanisms involved in ASA and clopidogrel response. For this purpose, we selected CAD patients who showed different responses to dual antiplatelet therapy determined by aggregation test. Based on the phenotypes, the miRNA expression profiles were compared between the platelet aggregation values categorized into tertiles (T) of response. The T1 group consisted of responding patients, the T2 consisted of intermediate responders and the T3 consisted of non-responders. The miRNA profiles were obtained after next-generation sequencing and data were analyzed by Deseq2 package. Results showed that 18 miRNAs were differentially expressed between the two extreme tertiles. By Ingenuity® software prediction analysis, 10 miRNAs showed important targets related with activation and aggregation of blood platelets. Of the 10 miRNAs, 4 of them, which were down-expressed on sequencing, showed the same fold-regulation when expression profiles were analyzed by quantitative polymerase chain reaction (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR-30a-5p and has-hsa- let-7g-5p. By target prediction analysis, it was observed that, when the four miRNAs are simultaneously down-expressed, they predict activation of platelet aggregation. Furthermore, hsa-miR-423-5p, hsa-miR-744-5p, and hsa-let-7g-5p showed correlation with the lipid profile of patients which, in turn, demonstrated influence in aggregation values reaching T3 of response to both drugs. Therefore, we concluded that increased platelet aggregation rates may be indirectly related to the expression profiles of hsa-miR-423-3p, hsa-miR-744-5p and hsa-let-7g-5p. It is suggested that the evaluation of the expression profile of these three miRNAs in the peripheral blood of patients with CAD may predict inadequate therapeutic response to aspirin and clopidogrel

Análise transcriptômica de miRNAs em pacientes sob dupla terapia de antiagregação / Transcriptomic analysis of miRNAs on patients in dual antiplatelet therapy

A terapia antiagregante é comumente indicada na prevenção e tratamento de doenças cardiovasculares. A dupla antiagregação com clopidrogrel e ácido acetilsalicílico (AAS) tem sido frequentemente adotada em pacientes com Doença Arterial Coronariana (DAC), mas apresenta ineficácia em uma parcela significativa da população com genótipo de respondedores. Essa falha terapêutica nos leva a questionar se outros mecanismos moleculares podem estar influenciando na resposta a esses fármacos. Recentes estudos sugerem que pequenas sequências de RNA não codificantes denominadas microRNAs (miRNAs) podem estar fortemente relacionadas com resposta ao tratamento fármaco-terapêutico, controlando as proteínas envolvidas na farmacocinética e farmacodinâmica. Entretanto, os principais miRNAs que atuam na dinâmica da resposta medicamentosa ainda não foram bem definidos. O objetivo deste estudo foi avaliar o perfil de miRNAs no sangue total periférico, procurando melhor esclarecer os mecanismos envolvidos na resposta aos antiagregantes plaquetários AAS e clopidogrel. Para isso, selecionou-se pacientes com DAC, os quais apresentavam diferentes respostas à dupla terapia de antiagregação determinadas pelo teste de agregação plaquetária. Baseados nos fenótipos, os perfis de expressão de miRNAs foram comparados entre os valores da taxa de agregação categorizados em tercis (T) de resposta. O grupo T1 foi constituído de pacientes respondedores, o T2 de respondedores intermediários e o T3 de não respondedores. Os perfis de miRNAs foram obtidos após sequenciamento de última geração e os dados obtidos foram analisados pelo pacote Deseq2. Os resultados mostraram 18 miRNAs diferentemente expressos entre os dois tercis extremos. Dentre esses miRNAs, 10 deles apresentaram importantes alvos relacionados com vias de ativação e agregação plaquetária quando analisados pelo software Ingenuity®. Dos 10 miRNAs, 4 deles, os quais apresentaram-se menos expressos no sequenciamento, demonstraram os mesmos perfis de expressão quando analisados pela reação em cadeia pela polimerase quantitativa (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR- 30a-5p e hsa-let-7g-5p. A partir das análises de predição de alvos, pôde-se observar que os quatro miRNAs, quando menos expressos simultaneamente, predizem ativação da agregação plaquetária. Além disso, os miRNAs hsa-miR- 423-5p, hsa-miR-744-5p e hsa-let-7g-5p mostraram correlação com o perfil lipídico dos pacientes que, por sua vez, apresentou influência nos valores de agregação compreendidos no T3 de resposta a ambos os medicamentos. Sendo assim, conclui-se que maiores taxas de agregação plaquetária podem estar indiretamente relacionadas com os padrões de expressão de hsa-miR- 423-3p, hsa-miR-744-5p e hsa-let-7g-5p. Sugere-se que a avaliação do perfil de expressão destes 3 miRNAs no sangue periférico de pacientes com DAC possa predizer resposta terapêutica inadequada ao AAS e ao clopidogrel

The antiplatelet therapy is often indicated for the prevention and treatment of cardiovascular diseases. Dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) has often been adopted in patients with coronary artery disease (CAD), but it has been ineffective in a significant portion of the population with genotype of responders. This fact leads us to question whether other molecular mechanisms may be influencing the response to these drugs. Recent studies suggest that small non-coding RNA sequences known as microRNAs (miRNAs) may be closely related to response to drug-therapeutic treatment, controlling proteins involved in pharmacokinetics and pharmacodynamics. The aim of this study was to evaluate the profile of miRNAs in whole blood, looking to better clarify mechanisms involved in ASA and clopidogrel response. For this purpose, we selected CAD patients who showed different responses to dual antiplatelet therapy determined by aggregation test. Based on the phenotypes, the miRNA expression profiles were compared between the platelet aggregation values categorized into tertiles (T) of response. The T1 group consisted of responding patients, the T2 consisted of intermediate responders and the T3 consisted of non-responders. The miRNA profiles were obtained after next-generation sequencing and data were analyzed by Deseq2 package. Results showed that 18 miRNAs were differentially expressed between the two extreme tertiles. By Ingenuity® software prediction analysis, 10 miRNAs showed important targets related with activation and aggregation of blood platelets. Of the 10 miRNAs, 4 of them, which were down-expressed on sequencing, showed the same fold-regulation when expression profiles were analyzed by quantitative polymerase chain reaction (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR-30a-5p and has-hsa- let-7g-5p. By target prediction analysis, it was observed that, when the four miRNAs are simultaneously down-expressed, they predict activation of platelet aggregation. Furthermore, hsa-miR-423-5p, hsa-miR-744-5p, and hsa-let-7g-5p showed correlation with the lipid profile of patients which, in turn, demonstrated influence in aggregation values reaching T3 of response to both drugs. Therefore, we concluded that increased platelet aggregation rates may be indirectly related to the expression profiles of hsa-miR-423-3p, hsa-miR-744-5p and hsa-let-7g-5p. It is suggested that the evaluation of the expression profile of these three miRNAs in the peripheral blood of patients with CAD may predict inadequate therapeutic response to aspirin and clopidogrel

Phytochemical, Pharmacognostic and Elemental Analysis of Cayratia gracilis (Guill. & Perr.) Suesseng.

The plant Cayratia gracilis (Guill. & Perr.) Sues., family Vitaceae, is renowned for its numerous medicinal application in folks medicine especially for its analgesic properties. Phytochemical, physicochemical, microscopic and elemental analyses were carried out on the plant to establish basic monograph information for authentication of the plant samples. The moisture content was 12.7%, water extractive value was 19%, and alcohol extractive value was 3.9% in the leaves and the moisture content of 8.8%, water extractive value of 14.8% and alcohol extractive value of 1.3% in the stem. Phytochemical screening revealed the presence of 8 secondary metabolites for the leaves and 6 for the stem. The thin-layer chromatographic (TLC) profile of the stem revealed 4, 3, and 2 spots for the hexane, ethyl acetate and methanol extracts respectively, while the leave revealed 5, 2 and 4 clear spots for hexane, ethyl acetate and methanol extracts respectively. Atomic Absorption Spectroscopy (AAS) of the plant shows the presence Zn, Cu, Mn, Mg, Fe, Na, and absence of metals like Pb and Cr. The study reveals microscopic characters that are useful as diagnostic parameters for Cayratia gracilis. Information obtained from this study is important in establishing diagnostic indices for identification, standardization, and also in monograph development of the plant which has ethno-medicinal uses.