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1.
Biochem Genet ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816671

RESUMO

MicroRNAs (miRNAs) are short, endogenously encoded small RNAs, 18-26 nucleotides in length, which can posttranscriptionally regulate gene expression through translation inhibition or endonucleolytic cleavage. The muskmelon is one of the most widely cultivated fruits in the Cucurbitaceae family. Despite its significance, only 120 miRNAs from different families have been reported in muskmelon. In this study, we aimed to expand this knowledge base by predicting 40 new miRNAs in muskmelon using a spectrum of genomic-based tools. Precursor and mature sequences were obtained from microRNA registry database as reference and analyzed via the basic local alignment search tool (Blastn) for ESTs identification. After removing the non-coding sequences, the remaining candidate sequences were analyzed using MFOLD to generate secondary structures for the newly predicted miRNAs. Additionally, the predicted muskmelon miRNAs were validated using a set of five randomly chosen primers and RT-PCR. Through gene ontology (GO) analysis, we identified 89 targets associated with newly predicted muskmelon miRNAs. Transcription factor-coding genes play a crucial role in plant growth and development. Additionally, the miR4249 has been found to have the same targets in muskmelon that have been linked to cell signaling and transcription factors. The identified targets are integral for diverse biological processes including plant growth, development, metabolism, aging, disease resistance, and resistance to environmental stresses, such as salt, cold, and oxidative stress. As a result, the outcomes of this study demonstrate that this mechanism not only contributes to the production of a higher quality crop but also enhances overall production.

2.
Microb Pathog ; 177: 106046, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36842515

RESUMO

In this study, we collected feces of Tibetan piglets from Nyingchi area for isolation, culture, identification, virulence gene analysis and drug resistance analysis of Escherichia Coli. The results demonstrated a 41.3% isolation rate of Diarrheagenic Escherichia Coli from Tibetan pigs with the main phylogenetic groups: group A (68.6%) and group B2 (15.7%). Typical E.coli accounted for 76.5%. The highest detection rates of porcine virulence genes were E.coli heat-resistant enterotoxin STb (58.82%) and F107 fimbrial subunit (23.53%). The highest detection rates of virulence genes from Tibetan pigs were fimC (80.39%) and ompA (76.47%). A drug sensitivity test showed that Diarrheagenic Escherichia Coli from Tibetan pigs had high drug resistance rates to mezlocillin, doxycycline and gentamicin. This study comprehensively analyzed the species composition, virulence and drug resistance of Diarrheagenic Escherichia Coli from Tibetan pigs, which provided a clearer and more targeted idea for the prevention and treatment of yellow and white dysentery in Tibetan pigs in the future.


Assuntos
Infecções por Escherichia coli , Animais , Suínos , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/tratamento farmacológico , Virulência , Tibet , Filogenia , Diarreia/veterinária , Escherichia coli , Resistência a Medicamentos
3.
Environ Sci Technol ; 57(48): 20380-20391, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37965815

RESUMO

Molecular separations involving solvents and organic impurities represent great challenges for environmental and water-intensive industries. Novel materials with intrinsic nanoscale pores offer a great choice for improvement in terms of energy efficiency and capital costs. Particularly, in applications where gradient and ordered separation of organic contaminants remain elusive, smart materials with switchable pores can offer efficient solutions. Here, we report a hierarchically networked porous organic cage membrane with dynamic control over pores, elucidating stable solvent permeance and tunable dye rejection over different molecular weights. The engineered cage membrane can spontaneously modulate its geometry and pore size from water to methanol and DMF in a reversible manner. The cage membrane exhibits ≥585.59 g mol-1 molecular weight cutoff preferentially in water and is impeded by methanol (799.8 g mol-1) and DMF (≈1017 g mol-1), reflecting 36 and 73% change in rejection due to self-regulation and the flexible network, respectively. Grazing incidence X-ray diffraction illustrates a clear peak downshift, suggesting an intrinsic structural change when the cage membranes were immersed in methanol or DMF. We have observed reversible structural changes that can also be tuned by preparing a methanol/DMF mixture and adjusting their ratio, thereby enabling gradient molecular filtration. We anticipate that such cage membranes with dynamic selectivity could be promising particularly for industrial separations and wastewater treatment.


Assuntos
Metanol , Água , Solventes , Porosidade , Cromatografia Líquida
4.
Molecules ; 28(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36677762

RESUMO

Allenes with two carbon-carbon double bonds belong to a unique class of unsaturated hydrocarbons. The central carbon atom of allene is sp hybridized and forms two σ-bonds and two π-bonds with two terminal sp2 hybridized carbon atoms. The chemistry of allenes has been well documented over the last decades. They are more reactive than alkenes due to higher strain and exhibit significant axial chirality, thus playing a vital role in asymmetric synthesis. Over a variety of organic transformations, allenes specifically undergo classical metal catalyzed cycloaddition reactions to obtain chemo-, regio- and stereoselective cycloadducts. This review briefly describes different types of annulations including [2+2], [2+2+1], [3+2], [2+2+2], [4+2], [5+2], [6+2] cycloadditions using titanium, cobalt, rhodium, nickel, palladium, platinum, gold and phosphine catalyzed reactions along with a mechanistic study of some highlighted protocols. The synthetic applications of these reactions towards the synthesis of natural products such as aristeromycin, ent-[3]-ladderanol, waihoensene(-)-vindoline and (+)-4-epi-vindoline have also been described.

5.
Clin Transplant ; 36(6): e14627, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35279872

RESUMO

BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Transplante de Fígado , Bilirrubina , Glucose , Deficiência de Glucosefosfato Desidrogenase/cirurgia , Hepatectomia , Humanos , Fígado/cirurgia , Doadores Vivos , Fosfatos , Estudos Prospectivos
6.
Mol Biol Rep ; 49(6): 5521-5534, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35553343

RESUMO

BACKGROUND: To supply high-quality cotton fibre for the textile industry, the development of long, strong and fine fibre cotton varieties is imperative. An interlinked approach was used to comprehend the role of fibre genes by analyzing interspecific progenies of cotton species. Wild Gossypium species and races are rich source of genetic polymorphism due to environmental dispersal and continuous natural selection. These genetic resources hold mass of outclass genes that can be used in cotton improvement breeding programs to exploit possible traits such as fibre quality, abiotic stress tolerance, and disease and insect resistance. Therefore, use of new molecular techniques such as genomics, transcriptomics and bioinformatics is very important to utilize the genetic potential of wild species in cotton improvement programs. METHODS: Interspecific lines and Gossypium species used in the study were grown at Central Cotton Research Institute (CCRI), Multan. After retrieving DNA sequence of the genes from NCBI, the primers for gene expression and full-length gene sequence were designed. Expression profiling of Expansin A4, BURP Domain protein RD22-like and E6-like fibre genes was performed through Real Time PCR. BLAST and DNA sequence alignment was conducted for sequence comparison of interspecific lines and Gossypium species. Different in silico analysis were used for characterization of fibre genes and identification of cis acting promoter elements in promoter region. RESULTS: Variable expression of genes related to fibre development was observed at different stages. BLAST and DNA sequence alignment demonstrated resemblance of interspecific lines with G. hirsutum. In silico analysis on the sequence data also confirmed the role of Expansin A4, BURP Domain protein RD22-like and E6-like fibre genes in fibre development. Genetic engineering is also recommended by transferring E6-like, Expansin A4 and BURP Domain RD22-like genes in local cotton cultivars. Similarly, several stress tolerant and light responsive cis acting elements were identified through promotor analysis, which may contribute for fibre development in the breeding programs. CONCLUSION: Expansin A4, BURP Domain RD22-like and E6-like have positive role in fibre development with variable expression at fiber length and strength associated stages.


Assuntos
Gossypium , Melhoramento Vegetal , Fibra de Algodão , DNA/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Gossypium/metabolismo , Estresse Fisiológico
7.
Global Health ; 18(1): 106, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564847

RESUMO

BACKGROUND: The vast investments that have been made in recent decades in new medicines, vaccines, and technologies will only lead to improvements in health if there are appropriate and well-functioning health systems to make use of them. However, despite the growing acceptance by major global donors of the importance of health systems, there is an enthusiasm gap when it comes to disbursing funds needed to understand the intricacies of how, why and when these systems deliver effective interventions. To understand the reasons behind this, we open up the black box of donor decision-making vis-à-vis Health Policy and Systems Research (HPSR) financing: what are the organizational processes behind the support for HPSR, and what are the barriers to increasing engagement? METHODS: We conducted 27 semi-structured interviews with staff of major global health funders, asking them about four key issues: motivations for HPSR financing; priorities in HPSR financing; barriers for increasing HPSR allocations; and challenges or opportunities for the future. We transcribed the interviews and manually coded responses. RESULTS: Our findings point to the growing appreciation that funders have of HPSR, even though it is often still seen as an 'afterthought' to larger programmatic interventions. In identifying barriers to funding HPSR, our informants emphasised the perceived lack of mandate and capacities of their organizations. For most funding organisations, a major barrier was that their leadership often voiced scepticism about HPSR's long time horizons and limited ability to quantify results. CONCLUSION: Meeting contemporary health challenges requires strong and effective health systems. By allocating more resources to HPSR, global donors can improve the quality of their interventions, and also contribute to building up a stock of knowledge that domestic policymakers and other funders can draw on to develop better targeted programmes and policies.


Assuntos
Administração Financeira , Política de Saúde , Humanos , Pesquisa sobre Serviços de Saúde , Programas Governamentais , Investimentos em Saúde
8.
Health Res Policy Syst ; 20(1): 101, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127696

RESUMO

BACKGROUND: Recent estimates report that 2.4 billion people with health conditions globally could benefit from rehabilitation. While the benefits of rehabilitation for individuals and society have been described in the literature, many individuals, especially in low- and middle-income countries do not have access to quality rehabilitation. As the need for rehabilitation continues to increase, it is crucial that health systems are adequately prepared to meet this need. Practice- and policy-relevant evidence plays an important role in health systems strengthening efforts. The aim of this paper is to report on the outcome of a global consultative process to advance the development of a research framework to stimulate health policy and systems research (HPSR) for rehabilitation, in order to generate evidence needed by key stakeholders. METHODS: A multi-stakeholder participatory technical consultation was convened by WHO to develop a research framework. This meeting included participants from selected Member States, rehabilitation experts, HPSR experts, public health researchers, civil society and other stakeholders from around the world. The meeting focused on introducing systems approaches to stakeholders and deliberating on priority rehabilitation issues in health systems. Participants were allocated to one of four multi-stakeholder groups with a facilitator to guide the structured technical consultations. Qualitative data in the form of written responses to guiding questions were collected during the structured technical consultations. A technical working group was then established to analyse the data and extract its emerging themes. This informed the development of the HPSR framework for rehabilitation and a selection of preliminary research questions that exemplify how the framework might be used. RESULTS: A total of 123 individuals participated in the multi-stakeholder technical consultations. The elaborated framework is informed by an ecological model and puts forth elements of the six WHO traditional building blocks of the health system, while emphasizing additional components pertinent to rehabilitation, such as political priority, engagement and participatory approaches, and considerations regarding demand and access. Importantly, the framework highlights the multilevel interactions needed across health systems in order to strengthen rehabilitation. Additionally, an initial set of research questions was proposed as a primer for how the framework might be used. CONCLUSIONS: Strengthening health systems to meet the increasing need for rehabilitation will require undertaking more HPSR to inform the integration of rehabilitation into health systems globally. We anticipate that the proposed framework and the emerging research questions will support countries in their quest to increase access to rehabilitation for their populations.


Assuntos
Programas Governamentais , Política de Saúde , Humanos , Saúde Pública
9.
Health Res Policy Syst ; 19(1): 31, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676521

RESUMO

For the renewed global impetus on primary health care (PHC) to translate into action at a country level, it will be important to strengthen existing ways of understanding and assessing country PHC systems. The architecture and performance of primary care systems are widely acknowledged to be crucial determinants of the health of populations in high-income countries as well as in low- and middle-income countries. There is no one-size-fits-all model of a country-level PHC system, and countries have implemented diverse models, adapted to and conditioned by their respective social, economic and political contexts. This paper applies advances in the field of health policy and systems research (HPSR) to propose an approach to the assessment of country PHC systems, using a compendium of 70 elements of enquiry requiring mixed quantitative and qualitative assessment. The approach and elements of enquiry were developed based on a review of policy and guidance documents and literature on PHC and HPSR and were finalized as part of a consultation of experts on PHC. Key features of the approach include sensitivity to context, flexibility in allowing for in-depth enquiry where necessary, systems thinking, a learning emphasis, and complementarity with existing frameworks and efforts. Implemented in 20 countries to date, the approach is anticipated to have further utility in a single country as well as in comparative assessments of PHC systems.


Assuntos
Atenção à Saúde , Países em Desenvolvimento , Programas Governamentais , Política de Saúde , Humanos , Atenção Primária à Saúde
10.
Physiol Mol Biol Plants ; 27(5): 1073-1087, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34092951

RESUMO

The present study involved two pot experiments to investigate the response of mung bean to the individual or combined SO4 2- and selenate application under drought stress. A marked increment in biomass and NPK accumulation was recorded in mung bean seedlings fertilized with various SO4 2- sources, except for CuSO4. Compared to other SO4 2- fertilizers, ZnSO4 application resulted in the highest increase in growth attributes and shoot nutrient content. Further, the combined S and Se application (S + Se) significantly enhanced relative water content (16%), SPAD value (72%), photosynthetic rate (80%) and activities of catalase (79%), guaiacol peroxidase (53%) and superoxide dismutase (58%) in the leaves of water-stressed mung bean plants. Consequently, the grain yield of mung bean was markedly increased by 105% under water stress conditions. Furthermore, S + Se application considerably increased the concentrations of P (47%), K (75%), S (80%), Zn (160%), and Fe (15%) in mung bean seeds under drought stress conditions. These findings indicate that S + Se application potentially increases the nutritional quality of grain legumes by stimulating photosynthetic apparatus and antioxidative machinery under water deficit conditions. Our results could provide the basis for further experiments on cross-talk between S and Se regulatory pathways to improve the nutritional quality of food crops. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00992-6.

11.
Global Health ; 16(1): 15, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32079530

RESUMO

In 2015, the United Nations' (UN) Member States adopted a bold and holistic agenda of the Sustainable Development Goals (SDGs), integrating a vision of peace and prosperity for people and planet. Extensive work within, between, across sectors is required for this bold and holistic agenda to be implemented. It is in this context that this special article collection showcases multisectoral approaches to achieving SDG 3-Good Health and Well-Being-which, though focused explicitly on health, is connected to almost all other goals. A confluence of social and health inequities, within a context of widespread environmental degradation demands systems thinking and intersectoral action. Articles in this issue focus on the SDGs as a stimulus for renewed multisectoral action: processes, policies, and programs primarily outside the health sector, that have health implications through social, commercial, economic, environmental, and political determinants of health. Case studies offer critical lessons on effectively engaging other sectors to enhance their health outputs, identifying co-benefits and 'win-wins' that enhance human health.


Assuntos
Colaboração Intersetorial , Desenvolvimento Sustentável/tendências , Humanos , Nações Unidas/organização & administração , Nações Unidas/tendências
12.
Global Health ; 16(1): 5, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918730

RESUMO

BACKGROUND: Given the paradigmatic shift represented by the Sustainable Development Goals (SDGs) as compared to the Millennium Development Goals - in particular their broad and interconnected nature - a new set of health policy and systems research (HPSR) priorities are needed to inform strategies to address these interconnected goals. OBJECTIVES: To identify high priority HPSR questions linked to the achievement of the Sustainable Development Goals. METHODS: We focused on three themes that we considered to be central to achieving the health related SDGs: (i) Protecting and promoting access to health services through systems of social protection (ii) Strengthening multisectoral collaborations for health and (iii) Developing more participatory and accountable institutions. We conducted 54 semi-structured interviews and two focus group discussions to investigate policy-maker perspectives on evidence needs. We also conducted an overview of literature reviews in each theme. Information from these sub-studies was extracted into a matrix of possible research questions and developed into three domain-specific lists of 30-36 potential priority questions. Topic experts from the global research community then refined and ranked the proposed questions through an online platform. A final webinar on each theme sought feedback on findings. RESULTS: Policy-makers continue to demand HPSR for many well-established issues such as health financing, human resources for health, and service delivery. In terms of service delivery, policy-makers wanted to know how best to strengthen primary health care and community-based systems. In the themes of social protection and multisectoral collaboration, prioritized questions had a strong emphasis on issues of practical implementation. For participatory and accountable institutions, the two priority questions focused on political factors affecting the adoption of accountability measures, as well as health worker reactions to such measures. CONCLUSIONS: To achieve the SDGs, there is a continuing need for research in some already well established areas of HPSR as well as key areas highlighted by decision-makers. Identifying appropriate conceptual frameworks as well as typologies of examples may be a prerequisite for answering some of the substantive policymaker questions. In addition, implementation research engaging non-traditional stakeholders outside of the health sector will be critical.


Assuntos
Política de Saúde , Pesquisa sobre Serviços de Saúde , Desenvolvimento Sustentável , Pessoal Administrativo/psicologia , Grupos Focais , Acessibilidade aos Serviços de Saúde , Humanos , Política Pública , Pesquisa , Responsabilidade Social
13.
Health Res Policy Syst ; 18(1): 78, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646439

RESUMO

BACKGROUND: Evidence-based decision-making is crucial to leadership in the health sector to identify country-level priorities and generate solutions supported by rigorous research. Barriers and enablers have been explored, but limited evidence about what works to strengthening capacity at individual and institutional levels within countries has been reported, and inconsistent use of evidence to inform policy-making is a persistent challenge and concern. METHODS: We conducted a framework analysis comparing experiences of nine purposively selected countries (Chile, Ethiopia, Ghana, Kyrgyzstan, Lebanon, Mozambique, Rwanda, South Africa and Sri Lanka). We utilised qualitative case studies developed by in-country teams to explore enablers and barriers described across components of a predefined theory of change and then identified six cross-cutting themes and recommendations for relevant stakeholders associated with each theme. RESULTS: The cross-cutting themes included (1) leadership and political will, (2) incentives and resources, (3) infrastructure and access to health data, (4) designated structures and processes, (5) interaction and relationships, and (6) capacity strengthening and engagement. While each case country's context and experience was different, common enablers and barriers surfaced across each of these themes, with Ministries of Health and other government agencies having strong roles to play, but also recognising the need for other stakeholders, including researchers, donors and civil society, to serve as essential collaborators in order to strengthen evidence uptake. Substantial and sustained investment in research capacities, able leaders and stronger engagement of civil servants are needed to further this progress and strengthen processes of health decision-making. CONCLUSIONS: All countries represented in this study have made commendable progress in increasing evidence uptake and strengthening supportive systems. Establishing and strengthening necessary structures and the relationships that underpin them takes time as well as resources. Going forward, the findings from this study can help guide and support advocacy to increase domestic funding for health research, especially health policy and systems research, and ensure that civil servants as well as researchers have the capacity and support to collaborate and continue to bolster evidence uptake.


Assuntos
Fortalecimento Institucional , Etiópia , Gana , Humanos , Líbano , Moçambique , Ruanda , África do Sul
14.
Health Res Policy Syst ; 18(1): 59, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503569

RESUMO

BACKGROUND: Scientific journals play a critical role in research validation and dissemination and are increasingly vocal about the identification of research priorities and the targeting of research results to key audiences. No new journals specialising in health policy and systems research (HPSR) and focusing in the developing world or in a specific developing world region have been established since the early 1980s. This paper compares the growth of publications on HPSR across Latin America and the world and explores the potential, feasibility and challenges of innovative publication strategies. METHODS: A bibliometric analysis was undertaken using HPSR MeSH terms with journals indexed in Medline. A survey was undertaken among 2500 authors publishing on HPSR in Latin America (LA) through an online survey, with a 13.1% response rate. Aggregate indicators were constructed and validated, and two-way ANOVA tests were performed on key variables. RESULTS: HPSR publications on LA observed an average annual growth of 27.5% from the years 2000 to 2018, as against 11.4% worldwide and yet a lag on papers published per capita. A total of 48 journals with an Impact Factor publish HPSR on LA, of which 5 non-specialised journals are published in the region and are ranked in the bottom quintile of Impact Factor. While the majority of HPSR papers worldwide is published in specialised HPSR journals, in LA this is the minority. Very few researchers from LA sit in the Editorial Board of international journals. Researchers highly support strengthening quality HPSR publications through publishing in open access, on-line journals with a focus on the LA region and with peer reviewers specialized on the region. Researchers would support a new open access journal specializing in the LA region and in HPSR, publishing in English. Open access up-front costs and disincentives while waiting for an Impact Factor can be overcome. CONCLUSION: Researchers publishing on HPSR in LA widely support the launching of a new specialised journal for the region with a vigorous editorial policy focusing on regional and country priorities. Strategies should be in place to support English-language publishing and to develop a community of practice around the publication process. In the first years, special issues should be promoted through a priority-setting process to attract prominent authors, develop the audience and attain an Impact Factor.


Assuntos
Política de Saúde , Pesquisa sobre Serviços de Saúde , Editoração , Bibliometria , Políticas Editoriais , América Latina
15.
Pak J Pharm Sci ; 33(5(Supplementary)): 2317-2322, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33832906

RESUMO

Hepatitis C virus (HCV) has major role in spreading of liver diseases worldwide. The HCV nonstructural NS5B is a polymerase (RdRp) that is present at the carboxylic-end of the polyprotein chain. It is essential and most important for the replication cycle. In current study, the potential of 100 phytochemicals against HCV NS5B polymerase was determined. Phytochemical structures were retrieved from PubChem database. The phytochemicals were docked with the NS5B active site amino acids, in order to discover their attractions as inhibitors. After docking, molecules with top five conformations were selected from 100 molecules by docking scores and RMSD values. The results demonstrated strong interactions of phytochemicals with the NS5B. The selected compounds with best docking scores and RMSD were found to be glycitein, ferulic acid, eugenol, 1-octanol and sebacic acid. These were further evaluated through Lipinski's rule of five to explore their molecular properties and drug-likeliness characteristics and all five selected phytochemicals were found to have drug-likeliness characteristics. Further, according to ADME analysis, the ferulic acid, 1-octanol and eugenol were found to be nontoxic, non-carcinogenic and have the ability to cross the blood brain barriers. Therefore, these phytochemicals could be strong drug candidates for HCV NS5B.


Assuntos
Antivirais/farmacologia , Desenvolvimento de Medicamentos , Inibidores Enzimáticos/farmacologia , Hepacivirus/efeitos dos fármacos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Absorção Fisiológica , Antivirais/química , Antivirais/farmacocinética , Domínio Catalítico , Vias de Eliminação de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Hepacivirus/enzimologia , Humanos , Modelos Biológicos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacocinética , Ligação Proteica , Distribuição Tecidual , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
16.
Pak J Pharm Sci ; 33(5): 2171-2178, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33824126

RESUMO

Hepatitis C virus (HCV) is a primary cause of chronic liver disease along with various complications like liver cirrhosis and malignancy which leads to death. It has infected more than 185 million people worldwide. There is no congruence established for the treatment of various genotypes of HCV infection owing to diversity in prevalence globally. Assessment of affected individuals with HCV by polymerase chain reaction (PCR), viral load of HCV and liver enzyme levels (i.e., ALT and AST) are the foundation to evaluate the safety and efficacy of HCV therapies. The antiviral efficacy has been greatly improved and sustained viral response (SVR) rates increased from 6% with interferon monotherapy to 50-80% with PEG-interferon/ribavirin combination therapy to >95% after the approval of all interferon free oral direct acting antiviral agents. The main objective of this review article is to compile data from reference sources regarding the old and current therapeutic strategies used to manage HCV infection. It is accepted that chronic HCV infection increases patient's thrombocytopenia and neutropenia risk and complications increased in co-morbid disorders like in tuberculosis, HIV, diabetes etc. In past treatment associated side effects were the major consequences and many patients have to stop the treatment. But after the approval of direct acting antiviral drugs create a revolution in the treatment of HCV infection. So, it could be concluded that current combination therapies are a promising hope to eradicate and to control HCV but some safety concerns required more considerations Therefore, this review focus on the available latest combination therapies and their effectiveness to eradicate HCV infection.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Quimioterapia Combinada , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
17.
Pak J Pharm Sci ; 33(1(Supplementary)): 355-360, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122868

RESUMO

Current outbreak of dengue has shown serious health concerns in Pakistan. The present study reports the anti-dengue potential of Carica papaya natural compounds. The leaves of C. papaya have previously shown promising results in cure of Dengue fever. The aim of this project is to find specific bioactive compounds by computational screening and biological activities of C. papaya against serine NS2B, NS3 and NS5 proteases of dengue virus. Docking study resulted in the screening of nine bioactive compounds having highest docking scores. However, three compounds namely epigallocatchin, catechin and protocatechuric acid had the strongest binding affinity with the active residues i.e., Ser135, His51 and Asp75 of dengue virus serine proteases. Results also indicated that the extract of C. papaya was a strong antimicrobial and antioxidant agent. It is concluded that the C. papaya compounds can be commercially applied for medical formulations against dengue virus.


Assuntos
Carica , Vírus da Dengue/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Inibidores de Proteases/farmacologia , Serina Endopeptidases , Proteínas não Estruturais Virais/antagonistas & inibidores , Dengue/tratamento farmacológico , Vírus da Dengue/enzimologia , Humanos , Simulação de Acoplamento Molecular/métodos , Compostos Fitoquímicos/uso terapêutico , Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/uso terapêutico , Serina Endopeptidases/metabolismo , Proteínas não Estruturais Virais/metabolismo
18.
Environ Sci Technol ; 53(17): 10398-10407, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31389235

RESUMO

Graphene-based stable pH-responsive membranes (GPMs) were developed by alternative deposition of graphene oxide (GO) with polyethylenimine (PEI) in a layer-by-layer manner. Different from the conventional pore-blocking pH-responsive membranes, the size of the gaps among the GO sheets were first designed to respond to the surrounding pH. Atomic force microscopy was used to dynamically explore the internal structure alteration of GPM in the pH range from 3 to 11. It was found that the PEI molecules not only cross-linked the GO sheets through amide bonds to ensure the membrane stability but also reversibly altered the gate size of GPM in a certain extent according to the surrounding pH. In filtration, the gates of GPM were widened with the decreasing pH of the feed and vice versa. As a result, the permeate flux of GPM increased with the decreasing feed pH. More importantly, the molecular weight cutoff of GPM could be continuously regulated by the feed pH in a certain range; during the filtration of the polyvinylpyrrolidone (PVP) and polyethylene oxide (PEO) mixed solution, only PVP (58 kDa) could penetrate GPM at pH 11, while the left PEO (600 kDa) would penetrate GPM at pH 3. The controlled penetration through GPM led to a complete separation and recovery of the molecules in different sizes, which is highly desirable for advanced molecular separation in environmental applications.


Assuntos
Grafite , Filtração , Concentração de Íons de Hidrogênio , Óxidos , Polietilenoimina
19.
Global Health ; 15(1): 64, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31847852

RESUMO

The WHO Eastern Mediterranean Region is endowed with deep intellectual tradition, interesting cultural diversity, and a strong societal fabric; components of a vibrant platform for promoting health and wellbeing. Health has a central place in the Sustainable Development Goals (SDGs) for at least three reasons: Firstly, health is shaped by factors outside of the health sector. Secondly, health can be singled out among several SDGs as it provides a clear lens for examining the progress of the entire development process. Thirdly, in addition to being an outcome, health is also a contributor to achieving sustainable development. Realizing this central role of health in SDGs and the significance of collaboration among diverse sectors, the WHO is taking action. In its most recent General Program of Work 2019-2023 (GPW 13), the WHO has set a target of promoting the health of one billion more people by addressing social and other determinants of health through multi-sectoral collaboration. The WHO Regional Office for the Eastern Mediterranean Region, through Vision 2023, aims at addressing these determinants by adopting an equity-driven, leaving no one behind approach. Advocating for Health in All Policies, multi-sectoral action, community engagement, and strategic partnerships are the cornerstone for this approach. The focus areas include addressing the social and economic determinants of health across the life course, especially maternal and child health, communicable diseases, non-communicable diseases, and injuries. The aspirations are noteworthy - however, recent work in progress in countries has also highlighted some areas for improvement. Joint work among different ministries and departments at country level is essential to achieve the agenda of sustainable development. For collaboration, not only the ministries and departments need to be engaged, but the partnerships with other stakeholders such as civil society and private sector are a necessity and not a choice to effectively pursue achievement of SDGs.


Assuntos
Equidade em Saúde/organização & administração , Desenvolvimento Sustentável , Organização Mundial da Saúde/organização & administração , Humanos , Região do Mediterrâneo
20.
Health Res Policy Syst ; 17(1): 51, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101060

RESUMO

BACKGROUND: Pakistan has one of the highest infant and child mortality rates in the world, half of these occurring due to vaccine-preventable diseases. The country started its Expanded Programme on immunisation (EPI) in 1978. However, the programme's performance is often questioned, as the Immunisation rates have been chronically low and on-time vaccination unsatisfactory. We explored the programme's insights about its structural and implementation arrangements within the larger governance system, and the ensuing challenges as well as opportunities. METHODS: We carried out a qualitative case study comprised of semi-structured, in-depth interviews with 34 purposively selected key informants from various tiers of immunisation policy and programme implementation. The interviews revolved around WHO's six building blocks of a health system, their interactions with EPI counterparts, and with the outer ecological factors. Interviews were transcribed and content analysed for emergent themes. RESULTS: The EPI faces several challenges in delivering routine immunisation (RI) to children, including lack of clarity on whether to provide vaccination through fixed centres or mobile teams, scarcity of human resource at various levels, lack of accurate population data, on-ground logistic issues, lack of a separate budget line for EPI, global pressure for polio, less priority to prevention by the policy, security risks for community-based activities, and community misconceptions about vaccines. CONCLUSIONS: The fulcrum for most of the challenges lies where EPI service delivery interacts with components of the broader health system. The activities for polio eradication have had implications for RI. Socio-political issues from the national and global environment also impact this system. The interplay of these factors, while posing challenges to effective implementation of RI, also brings opportunities for improvement. Collective effort from local, national and global stakeholders is required for improving the immunisation status of Pakistani children, global health security and the sustainable development goals.


Assuntos
Saúde da Criança , Atenção à Saúde/normas , Programas Governamentais/normas , Programas de Imunização/normas , Avaliação de Programas e Projetos de Saúde , Vacinação , Doenças Preveníveis por Vacina/prevenção & controle , Criança , Mortalidade da Criança , Participação da Comunidade , Tomada de Decisões , Atenção à Saúde/métodos , Países em Desenvolvimento , Saúde Global , Conhecimentos, Atitudes e Prática em Saúde , Política de Saúde , Humanos , Imunização , Lactente , Mortalidade Infantil , Paquistão/epidemiologia , Poliomielite/prevenção & controle , Pesquisa Qualitativa , Melhoria de Qualidade , Doenças Preveníveis por Vacina/epidemiologia , Vacinas
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