bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence, Awareness, Management and Control of Hypertension in Men and Women in Benin, West Africa: the TAHES study.
Authors: Desormais Ileana , Amidou Salimanou Ariyoh , Houehanou Yessito Corine , Houinato Stephan Dismand , Gbagouidi Gwladys Nadia , Preux Pierre Marie , Aboyans Victor , Lacroix Philippe
Published: September 2019

Background Sub-Saharan Africa is facing a growing burden of non-communicable diseases, including cardiovascular diseases (CVDs), due to epidemiological transitions. Among their risk factors, hypertension is a major determinant of CVDs, but the prevalence and level of awareness and management of this condition are poorly studied in African populations. The aim of this study was to determine the prevalence of hypertension and identify its associated risk factors as well as the awareness and management of this condition in a community-dwelling cohort in Benin. Methods A cross-sectional door-to-door study was conducted in the population over the age of 25 years in Tanve, a rural setting in Benin. The questionnaire and anthropometric measurements of the World Health Organization STEPWISE survey were used. Blood pressure was measured using standard procedures. Results The sample included 1777 subjects (60.9% females, mean age was 42.5±16.5 years). The prevalence of hypertension was 32.9%, similar in men (32.8%) and women (33.0%, p=0.9342). Age and obesity were significantly associated with hypertension. Less than half (42%) of hypertensive people were aware about their condition and only 46.3% of them were treated. Awareness ratios differed between men and women (respectively 32.9% vs. 47.5%; p= 0.0039) and was not influenced by age, education, occupation, marital status or income. Female sex was the only factor associated with better controlled HTN, independent of socio-economic parameters. Conclusion This large population-based study confirms the high prevalence, low awareness, and low control of hypertension in men and women in sub-Saharan Africa. Only half of the populations with hypertension are aware of their hypertension, indicating a high burden of undiagnosed and un-controlled high blood pressure in these populations.
Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm
Authors: Miszczuk Milena , Müller Verena , Althoff Christian Ernst , Stroux Andrea , Widhalm Daniela , Dobberstein Andy , Greiner Andreas , Kuivaniemi Helena , Hinterseher Irene
Published: September 2019

Background: Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathophysiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA.

Methods: Two groups of patients (100/group), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis.

Results: SRC (73% vs. 57%; p<0.001) and CKD (31% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA.

Conclusions: Knowledge about pathophysiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.
Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy
Authors: O'Toole Sharon , Spillane Cathy , Huang Yanmei , Fitzgerald Marie , Ffrench Brendan , Mohamed Bashir , Ward Mark , Gallagher Michael , Kelly Tanya , O'Brien Cathal , Ruttle Carmel , Bogdanska Anna , Martin Cara , Mullen Dorinda , Connolly Elizabeth , McGarrigle Sarah A , Kennedy John , O'Leary John J
Published: September 2019

Background: Detection and enumeration of Circulating Tumour Cells (CTCs) has been evaluated in many cancers such as breast cancer. However, the full prognostic and predictive power of CTCs for cancer cannot currently be harnessed, and the association between pathological complete response in patients receiving neoadjuvant chemotherapy for breast cancer and CTCs is still not clear. The aim of this study was to assess if CTCs could be used to predict pathological response to neoadjuvant chemotherapy in breast cancer patients.
Methods: 26 patients were recruited, and blood samples taken pre- and post-neoadjuvant chemotherapy. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets clusters/microemboli. Counts were then correlated to the pathological response as measured by the Miller-Payne grading system. The associations between CTCs and clusters and pathological variables were evaluated with χ2 or ANOVA tests performed in the SPSS 24.0 statistics software.
Results: 89% of the patients had invasive ductal carcinoma and 11% invasive lobular carcinoma. At baseline 85% of patients had CTCs present and only 4 patients were CTC negative. Median baseline CTC count was 7 (0-161) CTCs per 3mls of whole blood. Post chemotherapy, 58% of the patients had an increase in CTCs. This change in CTC count did not correlate with the Miller Payne grade of response to chemotherapy. No significant association was identified between the number of CTCs and clinical characteristics, including patient age, receptor status, tumour grade, disease type, lymph node metastasis, lymphovascular space invasion, radiological response or clinical or pathological stage. However, we did observe a correlation between pre-treatment CTC counts and body mass index, p<0.05.
Conclusions: There was no correlation between the pre- and post-chemotherapy total number of CTCs/clusters and the Miller Payne grade. It is not enough to evaluate pathological response for neoadjuvant chemotherapy for breast cancer patients utilising CTCs identified by Giemsa staining alone. Additional characterisation is needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in breast cancer patients undergoing neoadjuvant chemotherapy.
Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma
Authors: Kang Da Hyun , Yeo Min-Kyung , Lee Da Hye , Yoo Geon , Cho Sang Yeon , Oh In-Jae , Kim Ju-Ock , Park Hee Sun , Chung Chaeuk , Lee Jeong Eun
Published: September 2019

Background
The resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the most important problems in lung cancer field. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR) and studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical studies showed that lung cancer patients with high expression of Mig-6 are associated with a poor prognosis. Recent study showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function in lung cancer and EGFR-TKI resistance.
Methods
We compared the expression and phosphorylation status of Mig6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We checked the function of Mig6 by knock down and overexpression in those cells and evaluated the efficacy of combination of Mig6 knock down and EGFR-TKI in PC9/GR. The correlation between Mig6 expression and the prognosis of lung adenocarcinoma were examined by The Cancer Genome Atlas (TCGA) data and clinical samples.
Results
Our results showed that the expression of Mig-6 was significantly increased PC9/GR cells compared to PC9 cells. And most of Mig-6 was phosphorylated in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions are correlated with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma.
Conclusion
Our work supports that Mig-6 is an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.
Studies on Seed Germination and Micropropagation of Clinopodium nepeta: A Medicinal and Aromatic Plant
Authors: Vlachou Georgia , Papafotiou Maria , Bertsouklis Konstantinos F.
Published: September 2019

Seed ecophysiology and micropropagation of Clinopodium nepeta, an aromatic Mediterranean plant with pharmaceutical and horticultural uses was investigated. The optimum germination temperature of seeds stored at room temperature for 0, 6, or 12 months was 15 to 20 °C (100% germination completed in 10 to14 days) and cardinal temperatures were defined at 10 and 30 °C (80% to 82% and 62% to 76% germination, respectively). Six or 12 months of storage did not seem to affect germination, although 12-month-old seeds germinated at higher percentage and completed germination earlier at 15 °C than at 20 °C. Concerning micropropagation, shoot multiplication at subcultures of both adult plant- and seedling-origin nodal explants was tested on Murashige and Skoog (MS) medium supplemented with various cytokinin types, i.e., zeatin (ZEA), 6-benzyladenine (BA), kinetin (KIN), and 6-γ-γ-(dimethylallylamino)-purine (2IP), at various concentrations from 0.0 to 8.0 mg·L−1. Both explant types presented a rather similar response during in vitro culture. Increasing concentration of all cytokinin types resulted in an increase in shoot number per responding explant (1.1–5.3) and in most cases a decrease in shoot length (0.6–3.4 cm). Increasing cytokinin concentration induced hyperhydricity to a number of shoots (0.1–6.5) per explant, mostly when ZEA and BA were used. Supplementing the MS medium with 8.0 mg·L−1 BA combined with 0.1 mg·L−1 1-naphthaleneacetic acid (NAA) led to almost elimination of hyperhydricity and very satisfactory shoot production (80%/88% explant response and 6.5/7.5 shoot number per responding explant for seedling- / adult-origin explants, respectively). Alternatively, increasing the agar concentration to 12.0 g·L−1 and supplementing the medium with 8.0 mg·L−1 BA only, resulted in the same effect on eliminating hyperhydricity, such as the addition of NAA, and in the best shoot multiplication response achieved in this study (100% explant response, 9.4/9.9 shoots per explant for seedling-/adult-origin explants, respectively). Microshoots rooted abundantly (92% to 100%) on half-strength MS medium, either Hf or supplemented with 0.5 mg·L−1 to 4.0 mg·L−1 indole-3-butyric acid (IBA). The addition of IBA to the rooting medium, regardless of its concentration, affected only the root length by increasing it 2- to 3-fold. Microshoot clusters produced on multiplication media rooted at 96% when cultured on Hf half-strength MS medium. Rooted microshoots and shoot clusters survived at 80% to 100%, respectively, after ex vitro acclimatization in peat:perlite 1:1 (v/v).
Estudo comparativo entre equipamentos visando à redução do vandalismo nos pontos de entrega voluntária de recicláveis
Authors: Papa Amanda Patrícia Oliveira , Silva Janine Souza da , Santana Salomão José de
Published: September 2019

Há muitos anos são estudadas formas de minimização no impacto ambiental, onde o lixo urbano das grandes cidades é causador de desastres ambientais por ser descartado em locais inadequados. No Município de Salvador existe o programa de coleta seletiva que conta com Pontos de Entrega Voluntária (PEV), que são equipamentos disponibilizados em pontos estratégicos espalhados pela cidade para que o cidadão deposite seus dejetos corretamente. Porém, estes equipamentos sofrem diversos tipos de ataques degradantes, desde o descarte incorreto de resíduos à destruição total. O presente artigo tem por objetivo comparar os tipos de equipamentos disponíveis, analisando de forma técnica a opção mais adequada para a minimização dos impactos e redução da incidência do vandalismo, que traz tantos prejuízos para o programa e para a sociedade. Os conceitos utilizados abordam temas como hábitos da sociedade e utilização dos PEV's. Através de entrevistas com os representantes dos equipamentos e responsáveis pelo programa de coleta, foram coletados dados indispensáveis para realização da análise. O artigo propõe uma opção de equipamento que inviabilize ao máximo as ações de degradação dos equipamentos.
New occurrences of dragonflies in the Atlantic Forest fragments of Santa Teresa, Espírito Santo, Brazil
Authors: Storari Arianny P. , Pereira Diego , Furieri Karina S.
Published: September 2019

One of the greatest obstacles to biodiversity conservation is the lack of information to prioritize efforts on practical actions. This lack of information comes mainly from absence of inventories in many areas where few groups have reasonably complete databases. The distribution of the dragonfly fauna of Brazil is little known - only 29% of the Brazilian territory presents data about the richness of Odonata. In this contribution, a database of Odonata species of Santa Teresa Municipality was built, Espírito Santo State, Brazil. The database has 627 specimens registered, 77 species distributed in eight families and thirty-eight genera, forty of these species are common, one endemic of the State of Espírito Santo, and nineteen endemic of Brazil. In relation to the measure of conservation, four species are present in the category Insufficient Data (DD), one present in the Nearly Endangered (NT) category, three species in the Vulnerable category (VU) and one in the category In Danger (EN). Twenty-five species are considered new occurrences for the city. These results suggest that the fauna of the studied region deserves attention and points to the interest in implanting future conservation units in the region of Santa Teresa municipality.
A importância da construção, aplicação e ponderação dos sistemas de indicadores de sustentabilidade de forma participativa
Authors: Lacerda Cícero Sousa , Carmona Raquel de Lourdes de Miranda e Silva , Sousa Hercílio de Medeiros , Rocha Josemary M. Freire Rodrigues de C. , Lima Érika Marques de Almeida , Lima Patrícia Tavares de , Nascimento Jaíze Costa do , Carvalho Luciano Honório de , Miranda e Silva João Carlos de , Miranda Natália Marques de Almeida Lima
Published: September 2019

Para analisar a eficácia das ações propostas pelo modelo de desenvolvimento sustentável, posto como uma alternativa para um crescimento harmonioso entre o meio ambiente e a sociedade humana, surgem os modelos de indicadores de sustentabilidade. Estes modelos de indicadores apresentam diagnósticos da realidade atual e traçam perspectivas e estados desejados para o futuro, levando em conta os princípios da sustentabilidade. Neste sentido o objetivo deste artigo foi apresentar a importância dos sistemas de indicadores de sustentabilidade serem elaborados, aplicados e ponderados a partir da participação dos atores sociais locais. Para tanto utilizou-se o método da pesquisa bibliográfica por meio da leitura de artigos, dissertações e teses. Segundo a literatura pesquisada, observou-se que a utilização de sistemas de indicadores elaborados, aplicados e ponderados com a inclusão da sociedade local em todo o processo, os resultados terão mais confiabilidade, visto que a população local possui todos os conhecimentos com propriedade. Para tanto a utilização desses resultados participativos norteará melhor as tomadas de decisões o planejamento e o desenvolvimento local de forma sustentável.
Contribuições da história indígena da Paraíba para uma ética de preservação ambiental
Authors: Carmona Raquel de Lourdes de Miranda e Silva , Silva Cassiano Augusto Oliveira da , Cavalcanti Carlos André Macêdo , Miranda e Silva João Carlos de , Lacerda Cícero Sousa , Lima Érika Marques de Almeida , Rocha Josemary M. Freire Rodrigues de C. , Lima Patrícia Tavares de , Sousa Hercílio de Medeiros , Carvalho Luciano Honório de , Miranda Natália Marques de Almeida Lima
Published: September 2019

Este artigo vem se somar ao entendimento de que é necessária uma reflexão mais apurada acerca do papel das reservas indígenas paraibanas, no sentido do seu contingente populacional que preserva, ainda que de maneira muito restrita os saberes tradicionais, trazendo assim, uma sensível contribuição para uma fundamental ética de preservação ambiental. Trata-se de um breve estudo que vai apresentar um panorama histórico e um olhar antropológico acerca do aspecto preservacionista do patrimônio natural presente no litoral paraibano, nomeadamente nas terras indígenas Tabajara, no litoral sul da Paraíba que vem se consolidando como espaço de ressignificação para um povo que enfrenta cotidianamente os desafios de preservar um legado ancestral, corroborando com a preservação ambiental.
Reflexões socioambientais para um estudo geo histórico do Assentamento Nova Vivência, Município de Sapé, Estado da Paraíba, Nordeste do Brasils
Authors: Luna Emmanuel Paulino , Carmona Raquel de Lourdes de Miranda e Silva , Cavalcanti Carlos André Macêdo , Miranda e Silva João Carlos de , Lacerda Cícero Sousa , Sousa Hercílio de Medeiros , Lima Érika Marques de Almeida , Rocha Josemary M. Freire Rodrigues de C. , Lima Patrícia Tavares de , Carvalho Luciano Honório de , Miranda Natália Marques de Almeida Lima
Published: September 2019

Este artigo tem como proposta, apresentar uma abordagem geo-histórica, tendo como bojo principal o socioambientalismo, tomando como exemplo o Assentamento Nova Vivência, localizado na zona rural de Sapé, na Paraíba. Trata-se, portanto, de uma perspectiva histórica e social, que vai considerar uma comunidade de assentados como um grupo que representa uma forma de luta contra a opressão do capital latifundiário, que retirou o homem do campo do seu meio. Assim, é uma luta ressignificada, nos modelos dos levantes indígenas ocorridos no Brasil colonial, ou ainda, nas formações dos quilombos que legitimavam a liberdade do homem, associando-o à terra. Assim, nos tempos hodiernos, os assentamentos rurais são frutos de uma extensa luta pela terra no Brasil, portanto, núcleos capazes de contribuir de maneira eficaz para oferta de alimento de qualidade a população como toda, tendo em conta sempre o uso consciente do meio ambiente, numa interação harmoniosa com os ecossistemas.
Importância da implantação do plano de gerenciamento de resíduos da construção civil e de demolição no Município de João Pessoa (Estado da Paraíba, Nordeste do Brasil)
Authors: Miranda Natália Marques de Almeida Lima , Lima Virgínia Falcão de Oliveira , Rocha Josemary M. Freire Rodrigues de C. , Carmona Raquel de Lourdes de Miranda e Silva , Lacerda Cícero Sousa , Lima Érika Marques de Almeida , Lima Patrícia Tavares de , Sousa Hercílio de Medeiros , Nascimento Jaíze Costa do , Miranda e Silva João Carlos de
Published: September 2019

O presente artigo trata sobre a importância do manejo, que inclui o descarte dos resíduos sólidos da construção civil e demolição (RCD). Além de deixar evidente a necessidade da Educação Ambiental para a compreensão da multifatorialidade que envolve esse contexto. Assim, tornou-se necessário abordar a legislação brasileira, as normativas pertinentes à defesa do meio ambiente, no que diz respeito ao tratamento dado aos RCD's de maneira geral e o que aponta a Prefeitura Municipal de João Pessoa, capital paraibana. Para dar corpo a este estudo, partiu-se em busca de uma investigação qualitativa de natureza bibliográfica que, dentre outras questões, elencou o processo de tratamento dado ao descarte proveniente deste setor no contexto local.
Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine As A Cannabinoid Receptor 1 Agonist
Authors: Russo Silvana , de Azevedo Walter Filgueira
Published: September 2019

Background:

Cannabinoid receptor 1 has its crystallographic structure available in
complex with agonists and inverse agonists, which paved the way to establish an understanding
of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities
and is widely used in some countries. Recently some evidence of a dipyrone metabolite
acting over the Cannabinoid Receptor 1has been shown.

Objective:

Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid
Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural
basis for its interaction with the Cannabinoid Receptor 1.

Method:

We reviewed here recent functional studies related to the dipyrone metabolite focusing
on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions
for this complex obtained through docking simulations against the crystallographic structure
of the Cannabinoid Receptor 1.

Results:

Analysis of the crystallographic structure and docking simulations revealed that most
of the interactions present in the docked pose were also present in the crystallographic structure
of Cannabinoid Receptor 1 and agonist.

Conclusion:

Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed
the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val
196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis
and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine
interacts with the Cannabinoid Receptor 1.
Hydroxyapatite-alginate Based Matrices for Drug Delivery
Authors: Nayak Amit K. , Hasnain Md. Saquib , Nanda Sitansu S. , Yi Dong K.
Published: September 2019

Background:

Hydroxyapatite (HAp) is a biocompatible bioceramic compound by nature and widely utilized in a broad range of biomedical applications, especially in drug delivery, tissue engineering, orthopedics, dentistry, etc. To intensify its usage, HAp is being reinforced with different biopolymer(s). In these bioceramicbiopolymeric systems, HAp crystallites have been well inviolate with the alginate molecules. The objective of this review article is to present a comprehensive discussion of different recently researched drug-releasing potential by HAp-alginate based matrices.

Methods:

During past few years, HAp particles (both synthesized and naturally derived) have been reinforced within different alginate-based systems to load a variety of drug candidates. Most of the reported drug-releasing HAp-alginate based matrices were prepared by the methodology of ionic-gelation of sodium alginate followed by air-drying/spray drying process.

Results:

HAp-alginate systems have already been proved as useful for loading a variety of drugs and also resulting sustained drug delivery with minimizing the drawbacks of pure alginate matrices (such as burst drug-releasing and low mechanical property in the alkaline pH).

Conclusion:

HAp-alginate composites loaded with different kinds of drugs have already been reported to exhibit sustained releasing of loaded drugs over a longer period.
Plant Antifungal Lectins: Mechanism of Action and Targets on Human Pathogenic Fungi
Authors: Del Rio Marianela , de la Canal Laura , Regente Mariana
Published: September 2019

Lectins are proteins characterized by their ability to specifically bind different carbohydrate motifs. This feature is associated with their endogenous biological function as well as with multiple applications. Plants are important natural sources of these proteins; however, only a reduced group was shown to display antifungal activity. Although it is hypothesized that the target of lectins is the fungal cell wall, the mechanism through which they exert the antifungal action is poorly understood. This topic is relevant to improve treatment against pathogens of importance for human health. In this context, mechanisms pointing to essential attributes for virulence instead of the viability of the pathogen emerge as a promising approach. This review provides the current knowledge on the action mechanism of plant antifungal lectins and their putative use for the development of novel active principles against fungal infections.
Breakpoint: Cell Wall and Glycoproteins and their Crucial Role in the Phytopathogenic Fungi Infection
Authors: Plaza Verónica , Silva-Moreno Evelyn , Castillo Luis
Published: September 2019

The cell wall that surrounds fungal cells is essential for their survival, provides protection against physical and chemical stresses, and plays relevant roles during infection. In general, the fungal cell wall is composed of an outer layer of glycoprotein and an inner skeletal layer of β-glucans or α- glucans and chitin. Chitin synthase genes have been shown to be important for septum formation, cell division and virulence. In the same way, chitin can act as a potent elicitor to activate defense response in several plant species; however, the fungi can convert chitin to chitosan during plant infection to evade plant defense mechanisms. Moreover, α-1,3-Glucan, a non-degradable polysaccharide in plants, represents a key feature in fungal cell walls formed in plants and plays a protective role for this fungus against plant lytic enzymes. A similar case is with β-1,3- and β-1,6-glucan which are essential for infection, structure rigidity and pathogenicity during fungal infection. Cell wall glycoproteins are also vital to fungi. They have been associated with conidial separation, the increase of chitin in conidial cell walls, germination, appressorium formation, as well as osmotic and cell wall stress and virulence; however, the specific roles of glycoproteins in filamentous fungi remain unknown. Fungi that can respond to environmental stimuli distinguish these signals and relay them through intracellular signaling pathways to change the cell wall composition. They play a crucial role in appressorium formation and penetration, and release cell wall degrading enzymes, which determine the outcome of the interaction with the host. In this review, we highlight the interaction of phypatophogen cell wall and signaling pathways with its host and their contribution to fungal pathogenesis.
Computational Approaches for Elucidating Protein-Protein Interactions in Cation Channel Signaling
Authors: Hu Baichun , Zheng Xiaoming , Wang Ying , Wang Jian , Zhang Fengjiao
Published: September 2019

Background:

The lipid bilayer of the plasma membrane is impermeable to ions, yet
changes in the flux of ions across the cell membrane are critical regulatory events in cells. Because of
their regulatory roles in a range of physiological processes, such as electrical signaling in muscles and
neurons, to name a few, these proteins are one of the most important drug targets.

Objective:

This review mainly focused on the computational approaches for elucidating proteinprotein
interactions in cation channel signaling.

Discussion:

Due to continuously advanced facilities and technologies in computer sciences, the physical
contacts of macromolecules of channel structures have been virtually visualized. Indeed, techniques
like protein-protein docking, homology modeling, and molecular dynamics simulation are
valuable tools for predicting the protein complex and refining channels with unreleased structures.
Undoubtedly, these approaches will greatly expand the cation channel signaling research, thereby
speeding up structure-based drug design and discovery.

Conclusion:

We introduced a series of valuable computational tools for elucidating protein-protein
interactions in cation channel signaling, including molecular graphics, protein-protein docking, homology
modeling, and molecular dynamics simulation.
Hyaluronan Fragmentation During Inflammatory Pathologies: A Signal that Empowers Tissue Damage
Authors: Avenoso Angela , Bruschetta Giuseppe , D`Ascola Angela , Scuruchi Michele , Mandraffino Giuseppe , Saitta Antonino , Campo Salvatore , Campo Giuseppe M.
Published: September 2019

:

The mechanisms that modulate the response to tissue injury are not fully understood. Abnormalities
in the repair response are associated with a variety of chronic disease states characterized
by inflammation, followed subsequently by excessive ECM deposition. As cell-matrix interactions are
able to regulate cellular homeostasis, modification of ECM integrity appears to be an unspecific factor
in promoting the onset and progression of inflammatory diseases. Evidence is emerging to show that
endogenous ECM molecules supply signals to damage tissues and cells in order to promote further
ECM degradation and inflammation progression. Several investigations have been confirmed that HA
fragments of different molecular sizes exhibit different biological effects and responses. In fact, the increased
deposition of HA into the ECM is a strong hallmark of inflammation processes. In the context
of inflammatory pathologies, highly polymerized HA is broken down into small components, which
are able to exacerbate the inflammatory response by inducing the release of various detrimental mediators
such as reactive oxygen species, cytokines, chemokines and destructive enzymes and by facilitating
the recruitment of leukocytes. However, strategies involving the modulation of the HA fragment
with specific receptors on cell surface could represent different promising effects for therapeutic scope.

:

This review will focus on the inflammation action of small HA fragments in recent years obtained by
in vivo reports.
Identification of Inhibitors against Botulinum Neurotoxins: 8-Hydroxyquinolines Hold Promise
Authors: Chauhan Ritika , Chauhan Vinita , Sonkar Priyanka , Dhaked Ram Kumar
Published: September 2019

Botulinum neurotoxins (BoNTs) are the most toxic category A biological warfare agents. There is no therapeutics available for BoNT intoxication yet, necessitating the development of a medical countermeasure against these neurotoxins. The discovery of small molecule-based drugs has revolutionized in the last two decades resulting in the identification of several small molecule inhibitors of BoNTs. However, none progressed to clinical trials. 8-Hydroxyquinolines scaffold-based molecules are important ‘privileged structures’ that can be exploited as inhibitors of a diverse range of targets. In this review, our study of recent reports suggests the development of 8-hydroxyquinoline derived molecules as a potential drug may be on the horizon.
MiR-34a Inhibits Spinal Cord Injury and Blocks Spinal Cord Neuron Apoptosis by Activating Phatidylinositol 3-kinase (PI3K)/AKT Pathway Through Targeting CD47
Authors: Qi Liao , Jiang-Hua Ming , Ge-Liang Hu , Qing Chen , Ya-Ming Li
Published: September 2019

Objective:

Dysregulation of miR-34a has been reported for its implication in neuronal
development. This study aims to explore the effect and possible mechanism of miR-34a on neuron
apoptosis induced by Spinal Cord Injury (SCI).

Materials and Methods:

SCI model was established using Allen's weight-drop method and rats in
the sham group were performed with laminectomy without weight-drop injury. Basso Bcattie
Bresnahan (BBB) rating scale was applied to evaluate the locomotor function of rats. Pathological
changes of spinal cord tissues in SCI rats were observed after hematoxylin and eosin (HE) staining.
Rats were separately injected with miR-34a agomir, miR-34a agomir NC, si-CD47 and si-
CD47 NC before their spinal cord tissues were collected for terminal-deoxynucleoitidyl Transferase
Mediated nick end labeling (TUNEL) staining. Expressions of miR-34a, si-CD47, apoptosis
related proteins and AKT pathway related proteins were measured by quantitative reverse transcription-
polymerase chain reaction (qRT-PCR) and western blot.

Results:

SCI rat models were successfully established evidenced by decreased BBB scores and HE
staining. Injection of miR-34a agomir and/or si-CD47 could suppress neuron cell apoptosis, with
deceased apoptotic index (AI) and pro-apoptotic protein (cleaved caspase-3 and Bax) levels, and
increased expressions of anti-apoptotic proteins (Bcl-2 and Mcl-1). Phosphorylated levels of phatidylinositol
3-kinase (PI3K) and AKT were further increased in rats injected with miR-34a agomir
and si-CD47, compared with miR-34a agomir or si-CD47 injection alone.

Conclusion:

MiR-34a can downregulate CD47 expression to activate PI3K/AKT signal pathway,
and thus inhibit SCI induced spinal neuron apoptosis.
Prognostic Value of Cystatin C in Acute Ischemic Stroke Patients with Intravenous Thrombolysis
Authors: Shi Jijun , Zhang Chunyuan , Cao Yongjun , Qu Xinyuan , Liu Huihui , You Shoujiang
Published: September 2019

Background:

Less is known about the prognostic value of serum cystatin C in acute
ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). The aim of the present
study was to examine the association between serum cystatin C levels and prognosis of AIS patients
after IVT.

Methods:

Serum cystatin C was measured within 24 hours after recombinant tissue plasminogen
activator (rt-PA) treatment in 280 consecutively recruited patients with AIS. The main outcomes
included combination of death and major disability, death, major disability (modified Rankin Scale
score 3-5) and vascular events at 3-month follow-up.

Results:

During the 3-month follow-up, 94 patients (33.6%) experienced death or major disability
(28 deaths and 66 major disability) and 49 patients (17.5%) experienced vascular events. After
multivariate adjustment, serum cystatin C was significantly associated with an increased risk of the
combined outcome of death and major disability (OR=4.51, P = 0.006). Adding serum cystatin C
quartiles to a model containing conventional risk factors improved the predictive power for the
combined outcome of death and major disability (continuous net reclassification index 43.88%, P
< 0.001; categorical net reclassification index 9.15%, P = 0.013; integrated discrimination improvement
2.31%, P = 0.025). Similar phenomena were also observed in major disability and vascular
events.

Conclusions:

Higher levels of serum cystatin C in AIS patients after IVT were independently associated
with increased risks of poor functional outcomes and vascular events, especially combining
conventional risk factors, suggesting that serum cystatin C might improve risk prediction for poor
prognosis in AIS patients receiving rt-PA treatment.
MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)
Authors: Liu Qishuai , Wang Li , Yan Guizhen , Zhang Weifa , Huan Zhigang , Li Jianyuan
Published: September 2019

Background:

MicroRNAs (miRNA) are known to play a key role in the etiology and
treatment of epilepsy through controlling the expression of gene. However, miR-125a-5p in the
epilepsy is little known. Epilepsy in rat models was induced by Pentylenetetrazol (PTZ) and miR-
125a-5p profiles in the hippocampus were investigated in our experiment. Also, the relationship
between miR-125a-5p and calmodulin-dependent protein kinase IV (CAMK4) was identified and
the related mechanism was also illustrated.

Methods:

The miR-125a-5p mRNA expression levels were evaluated by quantitative real time polymerase
chain reaction (qRT-PCR). Western Blot (WB) was used to analyze the CAMK4 protein
expression levels. Seizure score, latency and duration were determined based on a Racine scale.
The enzyme-linked immunosorbent assay (ELISA) was used to analyze the inflammatory factor
expression. The relationship between miR-125a-5p and CAMK4 was detected through dual luciferase
assay.

Results:

Downregulation of miR-125a-5p was observed in the hippocampus of PTZ-induced epilepsy
rats. The overexpression of miR-125a-5p attenuated seizure and decreased inflammatory factor
level in the hippocampus of PTZ-induced rats. The miR-125a-5p alleviated epileptic seizure
and inflammation in PTZ-induced rats by suppressing its target gene, CAMK4.

Conclusion:

miR-125a-5p may represent a novel therapeutic treatment for PTZ-induced epilepsy
by preventing the activation of CAMK4.
Gender Differences in Characteristics and Outcome in Primary Intraventricular Hemorrhage
Authors: Guo Rui , Yin Lu , Chen Ruiqi , Zhou Liang , You Chao , Ma Lu , Li Hao
Published: September 2019

Background:

Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral
Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences
in patients' characteristics, management and outcome at discharge and 90 days after
PIVH.

Methods:

Consecutive patients with PIVH from a single center in China were enrolled over a 7-
year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and
outcomes were examined. The logistic regression models were used in the study to identify the
predictors of poor outcome.

Results:

In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with
PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p =
0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were
fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001),
harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission
compared with men. There were no differences between female and male patients regarding
the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI,
0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment,
the gender specific independent predictors for unfavorable outcome were higher with a
Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women,
and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus
(OR = 0.17; 95% CI, 0.03-0.86) in men.

Conclusions:

Women with PIVH exhibit some distinctive baseline features compared with men.
The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors
of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus
in men.
MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1
Authors: Xiong Jun , Wang Huijun , Mu Feng , Liu Zhanxue , Bao Yin , Sun Yongxing
Published: September 2019

Purpose:

Research has shown that exposure to anesthesia might increase the risks of
cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced
hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments
remains unclear.

Methods:

Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected
by the Morris water maze (MWM) test. The hippocampus was observed by HE staining.
The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The
interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase
reporter assay. The mRNA and expression levels of related genes and mRNA were examined
by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western
blot.

Result:

Sevoflurane induced the cognitive dysfunction presenting with longer latency time and
few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both
sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease
in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in
rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore
the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p
inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased
the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water
maze test. At the same time, the expression of LIMK1 was dramatically increased.

Conclusion:

Altogether, these findings suggested that miR-125b-5p inhibitor could protect against
the sevoflurane-induced cognitive impairments by targeting LIMK1.
Antiviral Activity of Fecal Water Samples from HIV-1 Infected Subjects Treated with a Specific Probiotic Formulation
Authors: Falasca Francesca , Cavallari Eugenio Nelson , Innocenti Giuseppe Pietro , Scagnolari Carolina , Mezzaroma Ivano , Santinelli Letizia , Ceccarelli Giancarlo , Vullo Vincenzo , Turriziani Ombretta , d'Ettorre Gabriella
Published: September 2019

Objectives:

The aim of the study was to investigate if the supplementation with multistrain
probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate
the anti-HIV activity of probiotic by studying fecal water (FW) samples.

Methods:

Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined
antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx
®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti-
HIV activity of FW samples was evaluated in vitro.

Results:

CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers
(CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an
increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction;
FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction).

Discussion:

Our data suggest that the administration of the specific probiotic formulation improves
the antiviral status of people living with HIV-1 under cART, also modulating T cell response.

Conclusion:

Anti-HIV activity of FW may have several public health and social implications for
sexually transmitted diseases that need to be further explored.
Serum Levels of Fibroblast Growth Factor 23 in People Living with HIV
Authors: Yoshino Yusuke , Seo Kazunori , Kitazawa Takatoshi , Ota Yasuo
Published: September 2019

Background:

Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone
produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels
are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the
risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of
risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports
related to FGF23 in PLWH have been published.

Methods:

Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital,
Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled
in the study. In addition to serum FGF23 measurements, the clinical factors assessed included
age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis
were performed to determine factors significantly associated with FGF23.

Results:

In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the
median CD4 count was 529 cells/μL, and the median serum FGF23 level was 36.0 pg/mL. Based on
correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with
HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P
= 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704).

Conclusions:

Factors significantly associated with elevated serum FGF23 levels included poor virologic
control and ABC/3TC use.
In Silico Design of Chimeric and Immunogenic Protein-Containing IpaB and IpaD as a Vaccine Candidate against Shigella dysenteriae
Authors: Arianzad Seyed Akbar , Zeinoddini Mehdi , Haddadi Azam , Nazarian Shahram , Sajedi Reza Hasan
Published: September 2019

Background:

S. dysenteriaeis the causative agent of shigellosis, a severe form of bacillary
dysentery and this infectious disease is still a health problem worldwide, especially in children. The most
important proteins of the Shigellatype III secretion system are IpaB and IpaD, which attach to the
intestinal epithelial cells and provide the possibility of invasion and disease. These two proteins with
immunogenic properties can be a suitable target to design and manufacture subunit recombinant vaccines.

Objective:

The aim of this study is to design an immunogenic chimeric protein against IpaB and IpaD
as a subunit vaccine candidate through an in silicostudy.

Methods:

Firstly, the immunogenic epitopes of amino acid sequences, physico-chemical parameters,
and the allergenicity of the chimeric protein were determined. Then the tertiary structure and the
potential ability of the chimeric protein were predicted and evaluated in terms of inducing B cells’
immune responses with effective epitopes. Finally, the optimization of the chimeric protein was
examined as the index affecting the protein expression.

Results:

Data showed an instability index of 37.18 and a well-established predicted third structure for
the chimeric protein, with a z-score of -6.11. Also, more than 99% of its amino acids were in the
optimal range. Minimum energy for mRNA structure increased to -317.9 and the Codon Adaptive
Index (CAI) rose to 88%. The designed protein had no IgE specific B cell epitopes.

Conclusion:

Overall, the results of this study show that the designed protein can be considered as an
immunogen vaccine candidate against S. dysenteriae.
Platelet-Derived Growth Factors (PDGFs) are Key Players in the Stimulation of Airway Smooth Muscle Cells (ASMCs) Alteration in Asthma and Chronic Obstructive Pulmonary Disease (COPD) with Multifarious Inhibitors at an Early Stage of Development
Authors: Shi Xiaodong , Appiah-Kubi Kwaku
Published: September 2019

Background:

Alterations in airway smooth muscle cells cause an increase in their mass and
result in a significant impact on airway remodeling diseases such as asthma and chronic obstructive
pulmonary disease. Several studies have used platelet-derived growth factors to stimulate the
alterations of airway smooth muscle cells.

Objective:

This review discusses the platelet-derived growth factor-stimulated alterations of airway
smooth muscle cells, diversity of inhibitors and inhibitory actions against these alterations and their
related mechanisms, and how this diversity presents an avenue for the development of multifarious
therapeutic targets for airway remodeling diseases especially asthma and chronic obstructive pulmonary
disease.

Methods:

A comprehensive search of PubMed and Medscape database for studies that investigated
the stimulation of the alterations of airway smooth muscle cells in asthma and chronic obstructive
pulmonary disease by platelet-derived growth factors and inhibitions of these alterations.

Results:

Marked platelet-derived growth factor-stimulated alterations of airway smooth muscle cells
are proliferation, migration and proliferative phenotype with diverse inhibitors and inhibitory actions
against these alterations. Inhibitory actions are the result of the activation of protein kinase,
overexpression of Tripartite motif protein, human transporter sub-family ABCA1 protein and
miRNAs, knockdown of an isoform of reticulon 4 and follistatin protein, exogenous applications of
recombinant proteins, supplements and active metabolite of retinoic acid, flavonoid extracts and
polysaccharides extract.

Conclusion:

The multifarious inhibitors and inhibitory actions with varied mechanisms in
platelet-derived growth factors-stimulated alterations of airway smooth muscle cells present a potential
for diverse therapeutic targets for the treatment of airway remodeling diseases.