| 1. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 2. |
- Mohamed, Tarik A., et al.
(författare)
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Plant cell cultures : An enzymatic tool for polyphenolic and flavonoid transformations
- 2022
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Ingår i: Phytomedicine. - : Elsevier BV. - 0944-7113 .- 1618-095X. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the pharmaceutical sector, tissue culture techniques for large-scale production of natural chemicals can be a less expensive alternative to large-scale synthesis. Although recent biotransformation research have used plant cell cultures to target a wide range of bioactive compounds, more compiled information and synopses are needed to better understand metabolic pathways and improve biotransformation efficiencies.Purpose: This report reviews the biochemical transformation of phenolic natural products by plant cell cultures in order to identify potential novel biotechnological approaches for ensuring more homogeneous and stable phenolic production year-round under controlled environmental conditions.Methods: Articles on the use of plant cell culture for polyphenolic and flavonoid transformations (1988 - 2021) were retrieved from SciFinder, PubMed, Scopus, and Web of Science through electronic and manual search in English. Following that, the authors chose the required papers based on the criteria they defined. The following keywords were used for the online search: biotransformation, Plant cell cultures, flavonoids, phenolics, and pharmaceutical products.Results: The initial search found a total of 96 articles. However, only 70 of them were selected as they met the inclusion criteria defined by the authors. The analysis of these studies revealed that plant tissue culture is applicable for the large-scale production of plant secondary metabolites including the phenolics, which have high therapeutic value.Conclusion: Plant tissue cultures could be employed as an efficient technique for producing secondary metabolites including phenolics. Phenolics possess a wide range of therapeutic benefits, as anti-oxidant, anti-cancer, and antiinflammatory properties. Callus culture, suspension cultures, transformation, and other procedures have been used to improve the synthesis of phenolics. Their production on a large scale is now achievable. More breakthroughs will lead to newer insights and, without a doubt, to a new era of phenolics-based pharmacological agents for the treatment of a variety of infectious and degenerative disorders.
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| 3. |
- Ibrahim, Mahmoud A. A., et al.
(författare)
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In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M-pro) Inhibitors
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M-pro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as M-pro inhibitors with Delta G(binding) <= -40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M-pro than lopinavir over 100 ns with Delta G(binding) values of -51.9 vs. -33.6 kcal/mol, respectively. Protein-protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target-function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.
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| 4. |
- Ibrahim, Mahmoud A. A., et al.
(författare)
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Blue Biotechnology : Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition
- 2021
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397 .- 1660-3397. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (M-pro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target M-pro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 M-pro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as M-pro inhibitors with Delta G(binding) < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against M-pro than darunavir with Delta G(binding) values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.
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| 5. |
- Hegazy, Mohamed-Elamir F., et al.
(författare)
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Terpenoid bio-transformations and applications via cell/organ cultures : a systematic review
- 2020
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Ingår i: Critical reviews in biotechnology. - : Informa UK Limited. - 0738-8551 .- 1549-7801. ; 40:1, s. 64-82
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Forskningsöversikt (refereegranskat)abstract
- Structurally diverse natural products are valued for their targeted biological activity. The challenge of working with such metabolites is their low natural abundance and complex structure, often with multiple stereocenters, precludes large-scale or unsophisticated chemical synthesis. Since select plants contain the enzymatic machinery necessary to produce specialized compounds, tissue cultures can be used to achieve key transformations for large-scale chemical and/or pharmaceutical applications. In this context, plant tissue-culture bio-transformations have demonstrated great promise in the preparation of pharmaceutical products. This review describes the capacity of cultured plant cells to transform terpenoid natural products and the specific application of such transformations over the past three decades (1988-2019).
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| 6. |
- Ibrahim, Mahmoud A. A., et al.
(författare)
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In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors
- 2020
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Ingår i: Computers in Biology and Medicine. - : Elsevier BV. - 0010-4825 .- 1879-0534. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (MPrn), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as MPr inhibitors with binding energies of 9.7 and 9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to MPr 's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of 44.8, 34.2 and 34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.
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| 7. |
- Reda, Eman H., et al.
(författare)
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Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species : Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses
- 2021
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Ingår i: Antibiotics. - : MDPI AG. - 0066-4774 .- 2079-6382. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- The genus Centaurea is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five Centaurea species were analyzed including: C. scoparia, C. calcitrapa, C. glomerata, C. lipii and C. alexandrina. Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. GC/MS analysis identified 120 EOs including mostly terpenoid except from C. lipii and C. alexandrina in which nonterpenoids were the major constituents. Major terpenoids included spathulenol, caryophyllene oxide and alloaromadendrene oxide-2. To probe antibacterial activity, potential EO inhibitors of a bacterial type II DNA topoisomerase, DNA gyrase B were screened via an in silico molecular docking approach. Spathulenol and alloaromadendrene oxide-2 possessed the best binding affinity in the ATP- binding pocket of Gyrase B enzyme. Principal component analysis and agglomerative hierarchical clustering were used for sample classification and revealed that sesquiterpenes contributed the most for accessions classification. In vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Aspergillus niger for all EOs were also evaluated. EOs from C. lipii, C. glomerata and C. calcitrapa exhibited significant MIC against S. aureus with an MIC value of 31.25 µg/mL.
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| 8. |
- Elshamy, Abdelsamed I., et al.
(författare)
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Recent Advances in Kaempferia Phytochemistry and Biological Activity : A Comprehensive Review
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:10
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Forskningsöversikt (refereegranskat)abstract
- Background: Plants belonging to the genus Kaempferia (family: Zingiberaceae) are distributed in Asia, especially in the southeast region, and Thailand. They have been widely used in traditional medicines to cure metabolic disorders, inflammation, urinary tract infections, fevers, coughs, hypertension, erectile dysfunction, abdominal and gastrointestinal ailments, asthma, wounds, rheumatism, epilepsy, and skin diseases.Objective: Herein, we reported a comprehensive review, including the traditional applications, biological and pharmacological advances, and phytochemical constituents of Kaempheria species from 1972 up to early 2019.Materials and methods: All the information and reported studies concerning Kaempheria plants were summarized from library and digital databases (e.g., Google Scholar, Sci-finder, PubMed, Springer, Elsevier, MDPI, Web of Science, etc.). The correlation between the Kaempheria species was evaluated via principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), based on the main chemical classes of compounds.Results: Approximately 141 chemical constituents have been isolated and reported from Kaempferia species, such as isopimarane, abietane, labdane and clerodane diterpenoids, flavonoids, phenolic acids, phenyl-heptanoids, curcuminoids, tetrahydropyrano-phenolic, and steroids. A probable biosynthesis pathway for the isopimaradiene skeleton is illustrated. In addition, 15 main documented components of volatile oils of Kaempheria were summarized. Biological activities including anticancer, anti-inflammatory, antimicrobial, anticholinesterase, antioxidant, anti-obesity-induced dermatopathy, wound healing, neuroprotective, anti-allergenic, and anti-nociceptive were demonstrated.Conclusions: Up to date, significant advances in phytochemical and pharmacological studies of different Kaempheria species have been witnessed. So, the traditional uses of these plants have been clarified via modern in vitro and in vivo biological studies. In addition, these traditional uses and reported biological results could be correlated via the chemical characterization of these plants. All these data will support the biologists in the elucidation of the biological mechanisms of these plants.
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| 9. |
- Hussien, Taha A., et al.
(författare)
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Guaianolide Sesquiterpene Lactones from Centaurothamnus maximus
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3β-hydroxy-4α(acetoxy)-4β(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3β, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), and quercetagetin-3,6-dimethyl ether-4’-O-β-d-pyranoglucoside (9). Chemical structures were elucidated using spectroscopic techniques, including High Resolution Fast Atom Bombardment Mass Spectrometry (HR-FAB-MS), 1D NMR; 1H, 13C NMR, Distortionless Enhancement by Polarization Transfer (DEPT), and 2D NMR (1H-1H COSY, HMQC, HMBC) analyses. In addition, a biosynthetic pathway for compounds 1–9 is proposed. The chemotaxonomic significance of the reported sesquiterpenoids and flavonoids considering reports from other Centaurea species is examined.
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