bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial Activity of Lactobacillus Strains Isolated from Mongolian Yogurt against Gardnerella vaginalis
Authors: Qian Zhixiang , Zhao Dan , Yin Yu , Zhu Hui , Chen Daijie
Published: April 2020

Worldwide interest in the use of functional foods containing probiotic bacteria such as Lactobacillus and Bifidobacterium for health promotion and disease prevention has increased significantly. Probiotics have demonstrated beneficial properties including strengthening the body’s natural defense system, inhibiting the growth of pathogenic bacteria, and regulating mental activity, but their effects on the human vagina have not been fully elucidated. The primary purpose of our study was to isolate Lactobacillus strains from old yogurt, a traditional dairy product, and investigate their probiotic potential with respect to the human vaginal system. Four Lactobacillus plantarum (L. plantarum) strains, named ZX1, ZX2, ZX27, and ZX69, were isolated from the yogurt samples. Simultaneously, we used a commercial Lactobacillus strain (Lactobacillus delbrueckii DM8909) as a control strain. We tested the antimicrobial activity of Lactobacillus isolates against Escherichia coli and Gardnerella vaginalis by agar spot and well diffusion tests. Then, we tested the antibiotic susceptibility of the 5 strains by using the minimal inhibitory concentration method. We attempted to detect possible bacteriocin genes by PCR sequencing technique. Using a chemically defined medium simulating genital tract secretions, we found that the selected Lactobacillus strains could alter the expression of known virulence genes in Gardnerella vaginalis. Bacteriocins derived from these isolated strains had potent antibacterial activity against G. vaginalis and E. coli, with the most effective activity observed in the case of ZX27. In addition, all strains including the L. delbrueckii DM8909 were positive for the presence of the plantaricin cluster of genes described in L. plantarum C11. The tested stains possessed the pln gene indicating that one of the antibacterial agents was plantaricin. We assume that the production of antimicrobial substances such as bacteriocins induce G. vaginalis to upregulate antimicrobial resistance genes. The new isolated strains have bacteriocin‐related genes and can change the antimicrobial resistance gene transcription of G. vaginalis.
In Silico Analysis Identifies Differently Expressed lncRNAs as Novel Biomarkers for the Prognosis of Thyroid Cancer
Authors: Rao Yuansheng , Liu Haiying , Yan Xiaojuan , Wang Jianhong
Published: April 2020

Background. Thyroid cancer (TC) is one of the most common type of endocrine tumors. Long noncoding RNAs had been demonstrated to play key roles in TC. Material and Methods. The lncRNA expression data were downloaded from Co-lncRNA database. The raw data was normalized using the limma package in R software version 3.3.0. The differentially expressed mRNA and lncRNAs were identified by the linear models for the microarray analysis (Limma) method. The DEGs were obtained with thresholds of ∣logFC∣>1.5 and P<0.001. The hierarchical cluster analysis of differentially expressed mRNAs and lncRNAs was performed using CLUSTER 3.0, and the hierarchical clustering heat map was visualized by Tree View. Results. In the present study, we identified 6 upregulated and 85 downregulated lncRNAs in TC samples. Moreover, we for the first time identified 16 downregulated lncRNAs was correlated to longer disease-free survival time in patients with TC, including ATP1A1-AS1, CATIP-AS1, FAM13A-AS1, LINC00641, LINC00924, MIR22HG, NDUFA6-AS1, RP11-175K6.1, RP11-727A23.5, RP11-774O3.3, RP13-895J2.2, SDCBP2-AS1, SLC26A4-AS1, SNHG15, SRP14-AS1, and ZNF674-AS1. Conclusions. Bioinformatics analysis revealed these lncRNAs were involved in regulating the RNA metabolic process, cell migration, organelle assembly, tRNA modification, and hormone levels. This study will provide useful information to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets for TC.
Streptococcus pseudoporcinus: Case Reports and Review of the Literature
Authors: Khan Shanza , Wong Ting Ting , Prasad Nishant , Lee Benjamin , Urban Carl , Segal-Maurer Sorana , Turett Glenn
Published: April 2020

Streptococcus pseudoporcinus is a beta-hemolytic Gram-positive, catalase-negative, nonmotile coccus arranged in short chains, usually found in the female genitourinary tract and differentiated from Streptococcus porcinus in 2006. Only two human infections associated with this organism have been reported to date: one in a patient with a first digit wound infection and another with lower extremity cellulitis. We describe two novel cases of Streptococcus pseudoporcinus causing endocarditis in one and pneumonia with empyema in another, illustrating the potential of these bacteria to cause severe invasive and life-threatening disease.
Application of the Artificial Neural Network and Support Vector Machines in Forest Fire Prediction in the Guangxi Autonomous Region, China
Authors: Li Yudong , Feng Zhongke , Chen Shilin , Zhao Ziyu , Wang Fengge
Published: April 2020

The study of forest fire prediction is of great environmental and scientific significance. China’s Guangxi Autonomous Region has a high incidence rate of forest fires. At present, there is little research on forest fires in this area. The application of the artificial neural network and support vector machines (SVM) in forest fire prediction in this area can provide data for forest fire prevention and control in Guangxi. In this paper, based on Guangxi’s 2010–2018 satellite monitoring hotspot data, meteorology, terrain, vegetation, infrastructure, and socioeconomic data, the researchers determined the main forest fire driving factors in Guangxi. They used feature selection and backpropagation neural networks and radial basis SVM to build forest fire prediction models. Finally, the researchers use the accuracy, precision, and area under the characteristic curve (ROC-AUC) and other indicators to evaluate the predictive performance of the two models. The results showed that the prediction accuracy of the BP neural network and SVM is 92.16% and 89.89%, respectively. As both results are over 85%, the requirements of prediction accuracy is met. These results can be used for forest fire prediction in the Guangxi Autonomous Region. Specifically, the accuracy of the BP neural network was 0.93, which was higher than that of the SVM model (0.89); the recall of the SVM model was 0.84, which was lower than the BANN model (0.92), and the AUC value of the SVM model was 0.95, which was lower than the BP neural network model. The obtained results confirm that the BP neural network model can provide more prediction accuracy than support vector machines and is therefore more suitable for forest fire prediction in Guangxi, China. This research provides the necessary theoretical basis and data support for application in the field of forestry of the Guangxi Autonomous Region, China.
Positive Solutions for BVP of Fractional Differential Equation with Integral Boundary Conditions
Authors: Li Min , Sun Jian-Ping , Zhao Ya-Hong
Published: April 2020

In this paper, we consider a class of boundary value problems of nonlinear fractional differential equation with integral boundary conditions. By applying the monotone iterative method and some inequalities associated with Green’s function, we obtain the existence of minimal and maximal positive solutions and establish two iterative sequences for approximating the solutions to the above problem. It is worth mentioning that these iterative sequences start off with zero function or linear function, which is useful and feasible for computational purpose. An example is also included to illustrate the main result of this paper.
Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism
Authors: Biswas Ayan , Santra Suman , Bishnu Debasree , Dhali Gopal Krishna , Chowdhury Abhijit , Santra Amal
Published: April 2020

Background & Aims. Chronic hepatitis (CH) has emerged as a distinct outcome of drug-induced liver injury (DILI). Combination therapy of Isoniazid (INH) and Rifampicin (RMP) which is widely used for prolonged periods can cause acute hepatotoxicity and has been also incriminated in chronic DILI. We sought evidence of the production of hepatic fibrosis on long-term INH-RMP treatment through experiments in BALB/c mice exposed to INH-RMP.Methods. A combined dose of INH (50 mg) and RMP (100 mg) per kg body weight per day was administered to mice by oral gavage, 6 days a week, for 4 to 24 weeks for the assessment of liver injury, oxidative stress, and development of hepatic fibrosis, including demonstration of changes in key fibrogenesis linked pathways and mediators.Results. Progressive increase in markers of hepatic stellate cell (HSC) activation associated with changes in matrix turnover was observed between 12 and 24 weeks of INH-RMP treatment along with the elevation of liver collagen content and significant periportal fibrosis. These were associated with concurrent apoptosis of the hepatocytes, increase in hepatic cytochrome P450 2E1 (CYP2E1), NADPH oxidase (NOX) activity, and development of hepatic oxidative stress.Conclusions. INH-RMP can activate HSC through generation of NOX-mediated oxidative stress, leading to the development of liver fibrosis.
Mechanistic Understanding of Cell Recognition and Immune Reaction via CR1/CR3 by HAP‐ and SiO2‐NPs
Authors: Ding Tingting , Sun Jiao
Published: April 2020

Nanodrug carrier will eventually enter the blood when intravenously injected or in other ways. Meanwhile, a series of toxic effects were caused to the body with the formation of nanoparticle protein corona. In our studies, we try to reveal the recognition mechanism of nanoparticle protein corona by monocyte and the damage effect on immune cells by activated complement of hydroxyapatite nanoparticles (HAP‐NPs) and silicon dioxide nanoparticles (SiO2‐NPs). So expressions of TLR4/CR1/CR were analyzed by flow cytometry (FCM) in order to illuminate the recognition mechanism of nanoparticle protein corona by monocyte. And the expression of ROS, cytokines, adhesion molecules, and arachidonic acid was measured when THP‐1 and HUVECs were stimulated by NP‐activated complement. The results showed that HAP‐NPs can be recognized by the opsonin receptor (iC3b/CR3) model, while plasma protein, opsonin receptor, and Toll‐like receptors are all likely launch cell recognition of SiO2‐NPs. And it was considerate that NP‐activated complement can damage THP‐1 and HUVECs, including oxidative stress, inflammation, and increased vascular permeability. So the surface of nanodrug carrier can be modified to avoid being clear and reduce the efficacy according to the three receptors (TLR4/CR1/CR3).
Arenobufagin Promoted Oxidative Stress‐Associated Mitochondrial Pathway Apoptosis in A549 Non‐Small‐Cell Lung Cancer Cell Line
Authors: Kan Jun , Huang Haifu , Jiang Zhangyu , Zhou Ruisheng , Bai Shasha , Liao Caijie , Chen Jiancong , Dong Jun , Zhang Yunlong , Zhang Jingzhi , Zhang Rong , Zhou Daihan , Zhang Enxin
Published: April 2020

Arenobufagin (ARE) has demonstrated potent anticancer activity in various types of tumor, but the role and mechanism of ARE for lung cancer remain unclear. Oxidative stress exists under normal conditions and is an inevitable state in the body. A variety of noxious stimuli can break the equilibrium state of oxidative stress and promote apoptosis. Here, we used a CCK‐8 assay to examine cell viability. We determined oxidative stress damage by measuring levels of intracellular ROS and levels of GSH, SOD, and MDA. Annexin V‐FITC/PI double staining assay, as well as the Hoechst 33258 staining, was used to detect ARE‐induced apoptosis in A549 cell. Evaluation of the expression level of the specified molecule was indicated by Western blot and qRT‐PCR. Loss of function experiment was carried out using NAC pretreatment. The experimental results show that ARE significantly declines in the viability of A549 cells and increases the apoptosis rate of A549 cells. As reflected in cell morphology, the A549 cells showed features of shrinkage and had incompletely packed membranes; the same phenomenon is manifested in Hoechst 33258 staining. Following ARE treatment, the ROS level in A549 cells was rising in a concentration‐dependent manner, and so were MDA and GSH levels, while the SOD level was decreasing. Moreover, we found that ARE can decrease mitochondrial membrane potential (MMP), and a cascade of apoptotic processes can be triggered by decreased MMP. Importantly, we found significant changes in protein expression levels and mRNA levels of apoptosis‐related proteins. Furthermore, when we used NAC to restrain oxidative stress, the expression levels of apoptosis‐related proteins have also changed accordingly. Our data demonstrate that apoptosis in the non‐small‐cell lung cancer (NSCLC) cell line A549 is caused by oxidative stress due to ARE. Our research also shows that ARE may have the potential to become a targeted therapeutic for the treatment of NSCLC in the future.
Quantitative Analysis of Six Phenolic Acids in Artemisia capillaris (Yinchen) by HPLC-DAD and Their Transformation Pathways in Decoction Preparation Process
Authors: Tian Fang , Ruan Qun-Jia , Zhang Ying , Cao Hui , Ma Zhi-Guo , Zhou Gai-Lian , Wu Meng-Hua
Published: April 2020

We aimed to establish a quantitative analysis method of six constituents (5-caffeoylquinic acid, 3-caffeoylquinic acid, 4-caffeoylquinic acid, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid) in Artemisia capillaris (Yinchen) and its decoction by using HPLC coupled with DAD. Besides, the transformation paths of the six constituents were analyzed in decoction preparation processing. The analytical method was fully validated in terms of linearity, sensitivity, precision, repeatability, and recovery and applied to assess the transformation trend and quantitative analysis of the six constituents in Yinchen decoction. The contents of six constituents varied greatly in Yinchen herb and Yinchen decoction, and there were inextricable internal relationships between them. Presumably 3-caffeoylquinic acid was isomerized to generate 5-caffeoylquinic acid and 4-caffeoylquinic acid. Similarly, 1,3-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid were produced by isomerization of 4,5-dicaffeoylquinic acid. In conclusion, this study provides a chemical basis for quality control of Yinchen decoction, and the changes of selected markers in decoction could give us some novel perspectives to study the relationship between substances and drug efficacy.
Experimental Investigation of the Fatigue Behavior of Basalt Fiber Reinforced Polymer Grid‐Concrete Interface
Authors: Wen Bo , Wan Chunfeng , Liu Lin , Fang Da , Yang Caiqian
Published: April 2020

Fatigue behavior is an important factor for mechanical analysis of concrete members reinforced by basalt fiber reinforced polymer (BFRP) grid and polymer cement mortar (PCM) and plays a critical role in ensuring the safety of reinforced concrete bridges and other structures. In this study, on the basis of the static loading test results of concrete specimens reinforced by BFRP grid and PCM, a series of fatigue tests with different loading levels were conducted on interfaces between BFRP grid and concrete to investigate the fatigue behavior of BFRP grid‐concrete interfaces. The test results indicate that with high loading level, the fatigue failure mode of interface is interfacial peeling failure while it transforms to the fatigue fracture of the BFRP grid under low loading level. The fatigue life (S-N) curves of BFRP grid‐concrete interface are obtained and fitted in stages according to different failure modes, and the critical point of the two failure modes is pointed out. The relative slip evolution of interface during fatigue is further revealed in different stages with two failure modes, and the law of interface strain is studied with the increase of fatigue times. The relation of effective bonding length of interface and fatigue times is also described.
Epidemiology and Outcomes from Out-of-Hospital Cardiac Arrest in Kuwait
Authors: Al Hasan Dalal , Yaseen Ameen , El Sayed Mazen
Published: April 2020

Background. Out-of-hospital cardiac arrest (OHCA) survival remains low in most countries. Few studies examine OHCA outcomes out of the Middle East region. This is the first study to describe characteristics and outcomes of patients with OHCA treated by emergency medical services (EMS) in regions of Kuwait.Objectives. To describe characteristics and outcomes of adult patients affected with OHCA in regions of Kuwait.Methods. This was a retrospective observational study on all adult OHCA patients transported by EMS to regional emergency departments over a 10- month period (21 February–31 December 2017). Data were collected from various sources: national emergency medical services archived data, emergency department, intensive care unit, and cardiac care unit of two hospitals.Results. A total of 332 EMS-treated OHCA cases were reviewed, and 286 incidents with OHCA from cardiac aetiology were included in the study. Most were non-Kuwaiti (60.8%) males (67.1%) with mean age 61 (+−16) years. Most OHCA cases occurred at home (76%) but with low witness rate (11.5%). Bystander CPR rate was low (8.7%). ROSC was achieved in ten patients (3.5%), but only 1 (0.3%) patient survived to hospital discharge.Conclusion. OHCA survival rates in this region of Kuwait are low. Targeted measures such as creating cardiac registry, dispatcher-assisted CPR with ongoing training and quality improvement, and community-based CPR education program are needed to improve the survival rates of OHCA victims.
Mouse Models of Oncoimmunology in Hepatocellular Carcinoma
Authors: Bresnahan Erin , Lindblad Katherine E. , Ruiz de Galarreta Marina , Lujambio Amaia
Published: April 2020

Liver cancer is the fourth leading cause of cancer-related mortality worldwide and incidence is on the rise. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with a complex etiology and limited treatment options. The standard-of-care treatment for patients with advanced HCC is sorafenib, a tyrosine kinase inhibitor that offers limited survival benefit. In the past years, therapeutic options for the treatment of advanced HCC have increased substantially, including additional multikinase inhibitors as well as immune checkpoint inhibitors. Nivolumab and pembrolizumab were approved in 2017 and 2018, respectively, as second-line treatment in advanced HCC. These drugs, both targeting the programmed death-1 pathway, demonstrate unprecedented results, with objective response rates of approximately 20%. However, the majority of patients do not respond, necessitating the identification of biomarkers of response and resistance to immunotherapy. With the recent success of immunotherapies in oncology, mouse models that better recapitulate the human disease and antitumor immune response are needed. This review lists ongoing clinical trials testing immunotherapy in HCC, briefly discusses the unique immunosuppressive environment of the liver, and then delves into the most applicable current murine model systems to study oncoimmunology within the context of HCC, including syngeneic, genetically engineered, and humanized models.
Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity
Authors: da Fonseca Ana Carolina Proença  , da Fonseca Guilherme Proença  , Marchesini Bruna , Voigt Danielle Dutra , Campos Junior Mario , Zembrzuski Verônica Marques , Carneiro João Regis Ivar , Nogueira Neto José Firmino , Cabello Pedro Hernan , Cabello Giselda Maria Kalil
Published: April 2020

Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.
Study of the Enzymatic Capacity of Kluyveromyces marxianus for the Synthesis of Esters
Authors: Reyes-Sánchez Francisco Javier , Páez-Lerma Jesús Bernardo , Rojas-Contreras Juan Antonio , López-Miranda Javier , Soto-Cruz Nicolás Óscar , Reinhart-Kirchmayr Manuel
Published: April 2020

Recently, biotechnological opportunities have been found in non-Saccharomyces yeasts because they possess metabolic characteristics that lead to the production of compounds of interest. It has been observed that Kluyveromyces marxianus has a great potential in the production of esters, which are aromatic compounds of industrial importance. The genetic bases that govern the synthesis of esters include a large group of enzymes, among which the most important are alcohol acetyl transferases (AATases) and esterases (AEATases), and it is known that some are present in K. marxianus, because it has genetic characteristics like S. cerevisiae. It also has a physiology suitable for biotechnological use since it is the eukaryotic microorganism with the fastest growth rate and has a wide range of thermotolerance with respect to other yeasts. In this work, the enzymatic background of K. marxianus involved in the synthesis of esters is analyzed, based on the sequences reported in the NCBI database.
ВИЗНАЧЕННЯ ЗАЛИШКОВИХ КІЛЬКОСТЕЙ МИЙНОГО ЗАСОБУ NEODISHER LABOCLEAN PLM НА ЛАБОРАТОРНОМУ ПОСУДІ
Authors: Tarasenko N. L. , Savina N. O. , Britsun V. M. , Оstanina N. V.
Published: April 2020

Мета роботи. Опрацювання простих експрес-підходів для визначення залишкової кількості мийного засобу Neodisher LaboСlean PLM в лабораторному посуді, заснованих на використанні фармакопейних методів (перевірки питомої електропровідності і теста «речовин, що окиснюються»), і оцінювання якості миття посуду дезінфекційно-мийним автоматом. Матеріали і методи. Воду дистильовану і дейонізовану отримано, відповідно, з аквадистилятора GFL2008 і системи Millipore Direct-Q 3 UV. Використовували розчини мийного засобу Neodisher LaboСlean PLM. Кондуктометричні дослідження проводили на кондуктометрі Hanna HI 2300. Миття лабораторного посуду здійснювали в дезінфекційно-миючому автоматі G7883. Результати й обговорення. Визначено питому електропровідність розчинів різної концентрації Neodisher Laboclean PLM. Отримані дані оброблені Excel з метою побудови калібрувальних графіків та створення математичних рівнянь. Ці підходи, хоча не є селективними, проте дозволяють ідентифікувати остаточні забруднення посуду мийним засобом Neodisher LaboСlean PLM в концентраціях, відповідно, 10-5 % і 10-2 %, в тому числі – і кількісно (за питомою електропровідністю, з використанням калібрувального графіка). Подібним чином отримано калібровочний графік для однієї з солей жорсткості водопровідної води – CaCO3. На основі отриманих даних були проведені дослідження чистоти лабораторного посуду після відмивання у дезінфекційно-мийному автоматі. Висновки. Отримані дані (0,8–3,2 і 2,3–10,0 мкг/одиницю на посуду, відповідно, для мийного засобу Neodisher LaboClean PLM і для CaCO3) свідчать, що чистота лабораторного посуду після мийки в дезінфекційно-мийному автоматі G7883 є задовільною для вирішення більшості завдань, які стоять перед аналітичною та фармацевтичною хімією.
МОДЕЛЮВАННЯ КОНЦЕПЦІЇ ФАРМАЦЕВТИЧНОЇ ДОПОМОГИ ХВОРИМ НА ХРОНІЧНИЙ ПРОСТАТИТ
Authors: Hromovyk B. P. , Gadyak I. V.
Published: April 2020

Мета роботи. Здійснити моделювання концепції фармацевтичної допомоги (ФД) хворим на хронічний простатит (ХП). Матеріали і методи. Матеріалом дослідження були теоретичні питання організації ФД, зокрема хворим на ХП. Використано методи інформаційного пошуку, критичного аналізу, конкретизації, узагальнення, аналізу системи менеджменту якості (діаграма К. Ісікави), моделювання. Результати й обговорення. Опрацьовано причинно-наслідкову модель ФД хворим на ХП на основі діаграми К. Ісікави, реалізація якої через інтеграцію шести головних чинників (ключові цінності, асортимент лікарських засобів (ЛЗ), терапевтичний конкорданс, вибір ЛЗ, нормативно-інформаційні документи, моніторинг фармакотерапії) та їх складових очікувано матиме позитивний вплив на якість життя обстежуваного контингенту хворих завдяки покращенню якості їх медикаментозного забезпечення, підвищенню фізичної та економічної доступності необхідних для пацієнтів ЛЗ та в кінцевому результаті дозволить вирішити важливу медичну, соціальну та економічну проблему з оптимізації ФД хворим на ХП. Висновок. На засадах діаграми К. Ісікави змодельовано концепцію ФД хворим на ХП, яка уможливлює виявлення та групування умов і чинників, котрі впливають на процес ФД хворим на ХП, та здійснення аналізу причинно-наслідкового звʼязку у цьому процесі.
ВИВЧЕННЯ АСОРТИМЕНТУ М’ЯКИХ ЛІКАРСЬКИХ ЗАСОБІВ, ЩО СПРИЯЮТЬ ЗАГОЄННЮ РАН, НА ФАРМАЦЕВТИЧНОМУ РИНКУ УКРАЇНИ
Authors: Glushchenko O. M.
Published: April 2020

Мета роботи. Дослідити асортимент м’яких лікарських засобів, що сприяють загоєнню ран, на фармацевтичному ринку України за фазами ранового процесу, фармакологічною дією, допоміжними речовинами, застосуванням у педіатричній практиці.

Матеріали і методи. Об’єкти досліджень : Державний реєстр лікарських засобів, інструкції для медичного застосування препаратів. При проведенні досліджень використовували маркетинговий, статистичний та графічний методи аналізу.

Результати й обговорення. Встановлено структуру асортименту зареєстрованих м’яких лікарських засобів, що сприяють загоєнню ран, за фазами ранового процесу, фармакологічною дією, допоміжними речовинами та досліджено їх використання в педіатрії. Виявлено, що в досліджуваному асортименті ринку дерматологічних засобів на 1 фазі ранового процесу частка лікарських засобів (ЛЗ) із протимікробною, анальгезуючою, репаративною та протизапальною діями становить 16,1 %; на 1–2 фазах – 55,6 %, на 2–3 фазах – 42,9 %. Аналіз препаратів групи D03 за типом основи підтвердив перевагу м’яких лікарських засобів (МЛЗ) на емульсійній основі (70 % ЛЗ), у групі D06 – на гідрофільній 33 % та гідрофобній основах – 29 % ЛЗ, у групі D08 – на емульсійній – 40 % та гідрофільній основах – 30 % ЛЗ. Із 54 найменувань, згідно з інструкцією для медичного застосування, у педіатрії рекомендовано застосовувати 72,2 % ЛЗ, 20,4 % протипоказані дітям, а у 7,4 % препаратів безпека та ефективність використання дітям не встановлені.

Висновки. Для українського фармацевтичного ринку на сьогодні актуальне розширення асортименту м’яких лікарських засобів, що сприяють загоєнню ран, комплексної дії, виготовлених на основах із різною осмотичною активністю та безпечних для використання в педіатрії.
ВПЛИВ КОНЦЕНТРАЦІЇ ЕТАНОЛУ В ЕКСТРАГЕНТІ НА ФЛАВОНОЇДНИЙ ПРОФІЛЬ ВИТЯГУ ІЗ ЛИСТЯ ШОВКОВИЦІ БІЛОЇ І ЙОГО ЦУКРОЗНИЖУВАЛЬНУ ДІЮ
Authors: Vronska L. V. , Dub A. I. , Demyd A. Ye. , Hroshovyi T. A. , Klishch I. M.
Published: April 2020

Мета роботи. Вивчення флавоноїдного профіля спиртових витягів і цукрознижувальної дії сухого екстракту листя шовковиці білої  залежно від концентрації етанолу в екстрагенті. Матеріали і методи. Матеріал дослідження – рідкі витяги, отримані методом дробної мацерації з листя шовковиці білої за допомогою спиртових розчинів із вмістом етанолу 10–95 % (об/об), співвідношення сировини до екстрагенту 1:10, кратність екстрагування – 5, тривалість одного екстрагування – 24 год; витяги згущували в ротаційному випарювачі і висушували при температурі 45–50 °С. Вивчення флавоноїдного профіля здійснювали хроматографічними методами, кількісний вміст флавоноїдів визначали спектрофотометрично, вміст сухого залишку – гравіметрично. Вивчення цукрознижувальної дії екстрактів проводили на білих щурах (модель «глюкозного навантаження»). Результати й обговорення. Якісні дослідження спиртових витягів листя шовковиці білої, здійснені методами ТШХ і ВЕРХ, дозволили ідентифікувати рутин, ізокверцитрин, кемпферол-3-О-глюкозид і кверцитрин (мала кількість). Якісний склад є практично незмінним, що пов’язано із розчинністю глікозидів флавоноїдів у широкому інтервалі концентрацій етанолу. Встановлено, що зростання вмісту етанолу в екстрагенті від 40 до 80 % (об/об), приводить до підвищення екстракції флавоноїдів. Екстрагенти із вмістом етанолу 40–80 % (об/об) дозволяють отримувати рідкі витяги з практично однаковим сухим залишком (2 %). Екстрагенти із вмістом етанолу 70–80 % (об/об) забезпечують найвище вилучення флавоноїдів за інших однакових умов (1,17–1,24 мг/мл у перерахунку на рутин, спектрофотометрично). Сухі екстракти, отримані за допомогою екстрагентів із вмістом етанолу 60–90 % (об/об), показали здатність істотно знижувати рівень глюкози в крові тварин під час «глюкозного навантаження». Висновки. Хроматографічний профіль спиртових витягів із листя шовковиці білої містить рутин, ізокверцитрин, кемпферол-3-О-глюкозид і кверцитрин. З підвищенням концентрації етанолу в екстрагенті зростає вміст флавоноїдів, а екстрагенти із вмістом етанолу 70–80 % (об/об) є найбільш ефективними для вилучення флавоноїдів. Сухі екстракти, отримані на основі досліджуваних витягів, істотно знижують рівень глюкози в крові тварин в експерименті на моделі «глюкозного навантаження».
Excessive EP4 Signaling in Smooth Muscle Cells Induces Abdominal Aortic Aneurysm by Amplifying Inflammation
Authors: Hiromi Taro , Yokoyama Utako , Kurotaki Daisuke , Mamun Al , Ishiwata Ryo , Ichikawa Yasuhiro , Nishihara Hiroshi , Umemura Masanari , Fujita Takayuki , Yasuda Shota , Minami Tomoyuki , Goda Motohiko , Uchida Keiji , Suzuki Shinichi , Takeuchi Ichiro , Masuda Munetaka , Breyer Richard M. , Tamura Tomohiko , Ishikawa Yoshihiro
Published: April 2020

Objective:

Excessive prostaglandin E
2
production is a hallmark of abdominal aortic aneurysm (AAA). Enhanced expression of prostaglandin E
2
receptor EP4 (prostaglandin E receptor 4) in vascular smooth muscle cells (VSMCs) has been demonstrated in human AAAs. Although moderate expression of EP4 contributes to vascular homeostasis, the roles of excessive EP4 in vascular pathology remain uncertain. We aimed to investigate whether EP4 overexpression in VSMCs exacerbates AAAs.

Approach and Results:

We constructed mice with EP4 overexpressed selectively in VSMCs under an SM22α promoter (EP4-Tg). Most EP4-Tg mice died within 2 weeks of Ang II (angiotensin II) infusion due to AAA, while nontransgenic mice given Ang II displayed no overt phenotype. EP4-Tg developed much larger AAAs than nontransgenic mice after periaortic CaCl
2
application. In contrast, EP4
fl/+
;SM22-Cre;ApoE
−/
−
and EP4
fl/+
;SM22-Cre mice, which are EP4 heterozygous knockout in VSMCs, rarely exhibited AAA after Ang II or CaCl
2
treatment, respectively. In Ang II–infused EP4-Tg aorta, Ly6C
hi
inflammatory monocyte/macrophage infiltration and MMP-9 (matrix metalloprotease-9) activation were enhanced. An unbiased analysis revealed that EP4 stimulation positively regulated the genes binding cytokine receptors in VSMCs, in which IL (interleukin)-6 was the most strongly upregulated. In VSMCs of EP4-Tg and human AAAs, EP4 stimulation caused marked IL-6 production via TAK1 (transforming growth factor-β–activated kinase 1), NF-κB (nuclear factor-kappa B), JNK (c-Jun N-terminal kinase), and p38. Inhibition of IL-6 prevented Ang II–induced AAA formation in EP4-Tg. In addition, EP4 stimulation decreased elastin/collagen cross-linking protein LOX (lysyl oxidase) in both human and mouse VSMCs.

Conclusions:

Dysregulated EP4 overexpression in VSMCs promotes inflammatory monocyte/macrophage infiltration and attenuates elastin/collagen fiber formation, leading to AAA exacerbation.
Noncoding RNAs in Vascular Diseases
Authors: Jaé Nicolas , Dimmeler Stefanie
Published: April 2020

The advent of deep sequencing technologies led to the identification of a considerable amount of noncoding RNA transcripts, which are increasingly recognized for their functions in controlling cardiovascular diseases. MicroRNAs have already been studied for a decade, leading to the identification of several vasculoprotective and detrimental species, which might be considered for therapeutic targeting. Other noncoding RNAs such as circular RNAs, YRNAs, or long noncoding RNAs are currently gaining increasing attention, and first studies provide insights into their functions as mediators or antagonists of vascular diseases in vivo. The present review article will provide an overview of the different types of noncoding RNAs controlling the vasculature and focus on the developing field of long noncoding RNAs.
Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease
Authors: Abbate Antonio , Toldo Stefano , Marchetti Carlo , Kron Jordana , Van Tassell Benjamin W. , Dinarello Charles A.
Published: April 2020

The intracellular sensing protein termed NLRP3 (for NACHT, LRR, and PYD domains-containing protein 3) forms a macromolecular structure called the NLRP3 inflammasome. The NLRP3 inflammasome plays a major role in inflammation, particularly in the production of IL (interleukin)-1β. IL-1β is the most studied of the IL-1 family of cytokines, including 11 members, among which are IL-1α and IL-18. Here, we summarize preclinical and clinical findings supporting the key pathogenetic role of the NLRP3 inflammasome and IL-1 cytokines in the formation, progression, and complications of atherosclerosis, in ischemic (acute myocardial infarction), and nonischemic injury to the myocardium (myocarditis) and the progression to heart failure. We also review the clinically available IL-1 inhibitors, although not currently approved for cardiovascular indications, and discuss other IL-1 inhibitors, not currently approved, as well as oral NLRP3 inflammasome inhibitors currently in clinical development. Canakinumab, IL-1β antibody, prevented the recurrence of ischemic events in patients with prior acute myocardial infarction in a large phase III clinical trial, including 10 061 patients world-wide. Phase II clinical trials show promising data with anakinra, recombinant IL-1 receptor antagonist, in patients with ST-segment–elevation acute myocardial infarction or heart failure with reduced ejection fraction. Anakinra also improved outcomes in patients with pericarditis, and it is now considered standard of care as second-line treatment for patients with recurrent/refractory pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing IL-1α and IL-1β, has also shown promising results in a phase II study in recurrent/refractory pericarditis. In conclusion, there is overwhelming evidence linking the NLRP3 inflammasome and the IL-1 cytokines with the pathogenesis of cardiovascular diseases. The future will likely include targeted inhibitors to block the IL-1 isoforms, and possibly oral NLRP3 inflammasome inhibitors, across a wide spectrum of cardiovascular diseases.
Vaccination Strategies and Immune Modulation of Atherosclerosis
Authors: Nilsson Jan , Hansson Göran K.
Published: April 2020

Adaptive as well as innate immune responses contribute to the development of atherosclerosis. Studies performed in experimental animals have revealed that some of these immune responses are protective while others contribute to the progression of disease. These observations suggest that it may be possible to develop novel therapies for cardiovascular disease by selectively modulating such atheroprotective and proatherogenic immunity. Recent advances in cancer treatment using immune check inhibitors and CAR (chimeric antigen receptor) T-cell therapy serve as excellent examples of the possibilities of targeting the immune system to combat disease. LDL (low-density lipoprotein) that has accumulated in the artery wall is a key autoantigen in atherosclerosis, and activation of antigen-specific T helper 1–type T cells is thought to fuel plaque inflammation. Studies aiming to prove this concept by immunizing experimental animals with oxidized LDL particles unexpectedly resulted in activation of atheroprotective immunity involving regulatory T cells. This prompted several research groups to try to develop vaccines against atherosclerosis. In this review, we will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk. We will also summarize ongoing clinical studies and discuss the challenges associated with developing an effective and safe atherosclerosis vaccine.
Dobzhansky and Dreyfus’s Group: The Introduction of Natural Population Genetics Studies in Brazil (1943–1960)
Authors: Monte Sião José Franco , Pereira Martins Lilian Al-Chueyr
Published: April 2020

An important center in which genetic research started and was carried out in Brazil during the 20thcentury was situated at the Faculty of Philosophy, Sciences and Linguistics of the University of São Paulo, led by André Dreyfus (1897–1952). Beginning in 1943, the Ukrainian geneticist Theodosius Dobzhansky (1900–1975) visited Dreyfus’s group four times. This paper evaluates the impact of Dobzhansky’s visits on the studies of genetics and evolution developed by the members of Dreyfus’s group during the 1940s and the 1950s. The study leads to the conclusion that Dobzhansky’s visits had an impact, not only in quantitative terms (the number of individual and joint publications), but also in qualitative terms. However, we also detect a decrease in the number of individual and joint publications related to the subject of the project during certain periods. The adoption of new experimental organisms by some members of the group; the involvement with subjects not related to the initial project, such as botany; Dobzhansky’s and his wife’s health problems during the third visit; and scientific disagreements between Dobzhansky and Brazilian researchers may have contributed to the decrease in publications.
What Do the Inconsolable See?
Authors: Baker Robert
Published: April 2020

Wisdom is often is often said to begin with a meditation on death or, at the deepest level, with our attempt to cope with the death of another: with our passage through loss, grief, mourning, the risk of despair. Stories of loss and renewal help us to work again, love again, and walk with a lighter step again. Stories of inconsolable grief remind us that there is something absolute in loss: that we are never the same after certain losses, no matter what we tell ourselves. What do the inconsolable see? This essay takes up this question through readings of the story of Orpheus in Virgil and Rilke and the story of Ruth in Marilynne Robinson’s Housekeeping. These stories acknowledge the absolute quality of loss while at the same time disclosing a further clearing, a clearing beyond the ordinary course of things, the kind of clearing we call spiritual.
Loofah Activated Carbon Sodium Alginate Hydrogel Microspheres with High Efficiency Cyclic Adsorption for Antibiotic Contaminants
Authors: Wang Zhe , Li Wenyao , Zhang Kenan , Jiang Haishun , Ji Tao , Li Jiaojiao , Liu Jingjing , Han Weihua
Published: April 2020

The global abuse of antibiotics has led to many environment problems such as water pollution and drug-resistant bacteria. In this study, pure natural loofah was used as raw material to form powdered loofah activated carbon (LAC) after high temperature carbonization annealing, and sodium
alginate (SA) with gel ability was combined to prepare loofah activated carbon sodium alginate (LAC-SA) hydrogel sphere by external emulsification method. This work showed that the adsorption mechanisms of LAC-SA microspheres for the three antibiotics of ofloxacin (OFO), tetracycline (TC)
and norfloxacin (NFO) were in line by the psedosecond-order and the formula of Langmuir. The ofloxacin (OFO) antibiotic solution was used as a sample for cyclic adsorption experiment for 10 times and the cumulative adsorption amount exceeded 700 mg g–1.
Two Functional Nanofibers of Polyaniline with Application in Supercapacitor and Photosensor
Authors: Tao Yulun , Zhang Ying , Yao Shun , Zhu Jinbo , Wang Chengjun , Liu Yanbin , Yang Jinian
Published: April 2020

A series of nanosheets and nanofibers polyaniline was prepared via controlled polymerization. The optimum acid doping amount of polyaniline was obtained (acetic acid:aniline = 7:9; hydrochloric acid:aniline = 2.5:5; citric acid:aniline = 3:5), in which the specific capacitance can reach
162.5 F/g, 271.25 F/g, 240.99 F/g, respectively. The C–V curve indicating the nanorods polyaniline photosensitive sensor chip exhibits excellent sensitivity to green light and blue light. The photocurrent of the sample doped with hydrochloric acid is closest to the 10–6
A. It can be concluded that the PANI has an immense potential in photosensitive sensors and supercapacitors.
NiCo2S4 Nanosheet Arrays on Carbon Cloth for Asymmetric Supercapacitors
Authors: Li Xiaojuan , Qu Guangmeng , Bu Hongxia , Xu Xijin
Published: April 2020

NiCo2S4 nanosheet arrays have been successfully grown on carbon cloth via an easy hydrothermal way, which were then used to assemble asymmetric supercapacitors. The microstructures, the crystal structures and the electrochemical properties were carefully studied,
and the NiCo2S4 nanosheet arrays exhibited impressive specific capacitance (SC) of 184.2 mAh/g at 1 A/g. The asymmetric supercapacitors (ASCs) with NiCo2S4 nanosheets as positive electrode demonstrated the energy density of 55.6 Wh/kg at 1.6 kW/kg.
Furthermore, good cycle stability (93.72% after 5000 cycles) can be also possessed.
Summer High Temperature Extremes over China Linked to the Pacific Meridional Mode
Authors: Luo Ming , Lau Ngar-Cheung , Zhang Wei , Zhang Qiang , Liu Zhen
Published: April 2020

This study investigates the association between summer high temperature extremes (HTEs) over China and the Pacific meridional mode (PMM) that is characterized by an anomalous north–south sea surface temperature gradient and an anomalous surface circulation over the northeastern subtropical Pacific. It is found that the HTE activities over most parts of southern China (particularly eastern China) are prominently intensified during the positive PMM phase and weakened during the negative phase. Further examinations suggest that the PMM is linked with HTEs in China through processes that entail both eastward and westward development of signals emanating from the PMM site. The westward development is associated with the formation of an anomalous low-level cyclone over the western North Pacific (WNP), which may be viewed as a Matsuno–Gill-type response to the off-equatorial heating in the eastern Pacific. This circulation change is accompanied by anomalous ascent over WNP and northern China, and subsidence over eastern China. On the other hand, the eastward development process is linked to the PMM-induced displacement of the East Asian jet stream and the generation of a midlatitude Rossby wave train. In the positive PMM phase, the above circulation changes are accompanied by anomalous air subsidence and enhanced adiabatic heating, reduced precipitation, anomalous lower-level anticyclone, and rising surface pressure over the eastern part of China. Moreover, the land surface of that region receives more solar radiation. Opposite changes are discernible over northern China. These changes are favorable for the occurrence and persistence of HTEs over eastern China and tend to suppress HTEs over northern China.
Role of Tropical Variability in Driving Decadal Shifts in the Southern Hemisphere Summertime Eddy-Driven Jet
Authors: Yang Dongxia , Arblaster Julie M. , Meehl Gerald A. , England Matthew H. , Lim Eun-Pa , Bates Susan , Rosenbloom Nan
Published: April 2020

The Southern Hemisphere summertime eddy-driven jet and storm tracks have shifted poleward over the recent few decades. In previous studies, explanations have mainly stressed the influence of external forcing in driving this trend. Here we examine the role of internal tropical SST variability in controlling the austral summer jet’s poleward migration, with a focus on interdecadal time scales. The role of external forcing and internal variability are isolated by using a hierarchy of Community Earth System Model version 1 (CESM1) simulations, including the pre-industrial control, large ensemble, and pacemaker runs. Model simulations suggest that in the early twenty-first century, both external forcing and internal tropical Pacific SST variability are important in driving a positive southern annular mode (SAM) phase and a poleward migration of the eddy-driven jet. Tropical Pacific SST variability, associated with the negative phase of the interdecadal Pacific oscillation (IPO), acts to shift the jet poleward over the southern Indian and southwestern Pacific Oceans and intensify the jet in the southeastern Pacific basin, while external forcing drives a significant poleward jet shift in the South Atlantic basin. In response to both external forcing and decadal Pacific SST variability, the transient eddy momentum flux convergence belt in the middle latitudes experiences a poleward migration due to the enhanced meridional temperature gradient, leading to a zonally symmetric southward migration of the eddy-driven jet. This mechanism distinguishes the influence of the IPO on the midlatitude circulation from the dynamical impact of ENSO, with the latter mainly promoting the subtropical wave-breaking critical latitude poleward and pushing the midlatitude jet to higher latitudes.
Impact of Mass–Size Parameterizations of Frozen Hydrometeors on Microphysical Retrievals: Evaluation by Matching Radar to In Situ Observations from GCPEx and OLYMPEx
Authors: Sy Ousmane O. , Tanelli Simone , Durden Stephen L. , Heymsfield Andrew , Bansemer Aaron , Kuo Kwo-Sen , Niamsuwan Noppasin , Beauchamp Robert M. , Chandrasekar V. , Vega Manuel , Johnson Michael P.
Published: April 2020

This article illustrates how multifrequency radar observations can refine the mass–size parameterization of frozen hydrometeors in scattering models and improve the correlation between the radar observations and in situ measurements of microphysical properties of ice and snow. The data presented in this article were collected during the GPM Cold Season Precipitation Experiment (GCPEx) (2012) and Olympic Mountain Experiment (OLYMPEx) (2015) field campaigns, where the true mass–size relationship was not measured. Starting from size and shape distributions of ice particles measured in situ, scattering models are used to simulate an ensemble of reflectivity factors for various assumed mass–size parameterizations (MSP) of the power-law type. This ensemble is then collocated to airborne and ground-based radar observations, and the MSPs are refined by retaining only those that reproduce the radar observations to a prescribed level of accuracy. A versatile “retrieval dashboard” is built to jointly analyze the optimal MSPs and associated retrievals. The analysis shows that the optimality of an MSP depends on the physical assumptions made in the scattering simulators. This work confirms also the existence of a relationship between parameters of the optimal MSPs. Through the MSP optimization, the retrievals of ice water contentMand mean diameterDmseem robust to the change in meteorological regime (between GCPEx and OLYMPEx); whereas the retrieval of the diameter spreadSmseems more campaign dependent.