Mass calibration and Relative Humidity compensation requirements for optical portable particulate matter monitors : the IMPASHS (Impact of smoke-free policies in EU Member States) WP2 preliminary results

Better knowledge of particulate matter (PM) concentrations needs portable, reliable, user friendly, low cost, real time mass analyzers of PM2.5 and PM10. Optical Particle Counters (OPC) measuring mass have manufacturer calibration specific gravity “K” factor referred to polystyrene latex particles which are completely different than those of the real world, therefore they require specific calibrations. Measurements are also subject to Relative Humidity (RH) heavy interference.Fundação para a Ciência e a Tecnologia (FCT

Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

AVAILABILITY OF DATA AND MATERIAL : The data that support the findings of this study are available from the corresponding author upon reasonable request.The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds ( IC50 ≤ 1 μM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.The Department of Science and Innovation (DSI) of South Africa, the University of Pretoria, the L’Oréal-UNESCO for Woman in Science and National Research Foundation of South Africa.https://link.springer.com/journal/13659am2024ChemistrySDG-03:Good heatlh and well-beingSDG-15:Life on lan

In vitro dual activity of Aloe marlothii roots and its chemical constituents against Plasmodium falciparum asexual and sexual stage parasites

Please abstract in the article.The Department of Science and Innovation (DSI) of South Africa; the South African Research Chairs Initiative of the DSI, administered through the South African National Research Foundation; the South African Medical Research Council; the University of Pretoria Postgraduate Research Support Bursary, South Africa and the L’Oréal-UNESCO for Woman in Science grant.https://www.elsevier.com/locate/jethpharm2023-07-19hj2023BiochemistryChemistryGeneticsMicrobiology and Plant PathologySchool of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery

AVAILABILITY OF DATA : The data that support the findings of this study are available from the corresponding author upon reasonable request.The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of ‘legacy’ antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.The Department of Science and Innovation (DSI) of South Africa; the South African Medical Research Council, the University of Pretoria, the L’Oréal-UNESCO for Woman in Science and the National Research Foundation of South Africa.https://link.springer.com/journal/13659am2024ChemistrySDG-03:Good heatlh and well-beingSDG-15:Life on lan

Optimizing extraction of pelargonium sidoides roots : impact of ethanol concentration on biological activity of extracts

Pelargonium sidoides DC. (Geraniaceae) is an important indigenous medicinal plant in South Africa, historically employed by various ethnic groups to treat respiratory and gastrointestinal ailments. The proprietary herbal tincture, Umckaloabo , utilizes an ethanolic extract (EPs 7630) from the roots of P. sidoides, and has demonstrated effectiveness in alleviating symptoms of respiratory infections. P. sidoides roots contain numerous highly oxygenated coumarins and phenolic metabolites, notably the marker compound umckalin. While Umckaloabo is prepared using 11 % ethanol extraction, the South African commercial market predominantly employs 60 % ethanol extraction due to its consistent umckalin yield and antimicrobial activity. The effects of these extraction methods on chemical composition and in vitro pharmacological activity remain poorly understood. This study confirmed superior antibacterial and antifungal activity in the 60 % ethanol extracts prepared from six root samples compared to the 11 % ethanol extracts. MIC values for both Gram-negative and Gram-positive bacteria ranged from 0.078 to 2.5 mg/mL in the 60 % extracts. Remarkably, two of the root extracts exhibited excellent to very good activity against C. albicans and C. neoformans with MIC values of 0.039 and 0.078 mg/mL, respectively. A positive correlation was identified between total minimum inhibitory concentration (MIC) levels and polyphenol content, rather than umckalin levels. The influence of these extracts on the pro-inflammatory cytokine IL-6 was assessed. Both 60 % and 11 % root extracts of P. sidoides at 100 mg/mL significantly reduced IL-6 production, with the 60 % extracts demonstrating a more pronounced effect (p = 0.008). Statistical analysis revealed significant differences between 11 % and 60 % ethanol extractions in terms of average MIC overall, average Gram-negative MIC, average Gram-positive MIC, fungal MIC, and IL-6 levels. Extracts with higher polyphenol values exhibited superior antimicrobial activity and antioxidant potential, suggesting that polyphenol content may serve as a more reliable indicator of antimicrobial activity than umckalin levels. Additionally, polyphenol levels in the roots may vary with altitude and other environmental factors, warranting further research.The National Research Foundation and Nativa (Pty) Ltd, South Africa.http://www.elsevier.com/locate/sajbam2024ChemistryParaclinical SciencesNon

Use of hyphenated analytical techniques to identify the bioactive constituents of Gunnera perpensa L., a South African medicinal plant, which potently inhibit SARS-CoV-2 spike glycoprotein-host ACE2 binding

Please read abstract in the article.The DSI (Department of Science and Innovation Agency of South Africa); the NRF (National Research Foundation); the Wistar Science Discovery Fund; the Commonwealth of Pennsylvania; the Canadian Institutes for Health Research; the Robert I. Jacobs Fund of the Philadelphia Foundation and the Herbert Kean, M.D., Family Professorship.https://link.springer.com/journal/216hj2023Chemistr

An in vitro study to elucidate the effects of product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors

CORRIGENDUM : An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors. Front. Pharmacol. 15:1401376. doi: 10.3389/fphar.2024.1401376.DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.Please read abstract in the article.The University of KwaZulu-Natal; the Polio Research Foundation (PRF); he South African Medical Research Council through its Division of Research Capacity Development under the Bongani Mayosi National Health Scholars Programme from funding received from the Public Health Enhancement Fund/South African National Department of Health; the National Research Foundation (NRF); the Department of Science and Innovation; he South African Medical Research Council with funds received from the South African Department of Science and Innovation.http://www.frontiersin.org/Pharmacologyhj2024ChemistrySDG-03:Good heatlh and well-bein

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

[EN] Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non- invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlightedJ.M.B. received EASL Registry Awards 2016 and 2019 (European CCA Registry, ENS-CCA). J.M.B. and M.J.P. were supported by: the Spanish Ministry of Economy and Competitiveness (J.M.B.: FIS PI12/00380, FIS PI15/01132, FIS PI18/01075 and Miguel Servet Programme CON14/00129; M.J.P.: FIS PI14/00399, FIS PI17/00022 and Ramon y Cajal Programme RYC-2015-17755, co-financed by “Fondo Europeo de Desarrollo Regional” (FEDER)); ISCIII CIBERehd; “Diputación Foral de Gipuzkoa” (J.M.B: DFG15/010, DFG16/004), and BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD); the Department of Health of the Basque Country (M.J.P.: 2015111100; J.M.B.: 2017111010), and “Fundación Científica de la Asociación Española Contra el Cancer” (AECC Scientific Foundation) (J.M.B.). J.M.B. and J.W.V. were supported by the European Commission Horizon 2020 programme (ESCALON project 825510). The laboratory of J.B.A. is supported by competitive grants from the Danish Medical Research Council, the Danish Cancer Society, and the Novo Nordisk and A.P. Møller Foundations. J.J.G.M. and R.I.R.M. were supported by the Carlos III Institute of Health, Spain (PI16/00598 and PI18/00428) and were co-financed by the European Regional Development Fund. J.M.B. and J.J.G.M. were supported by the Ministry of Science and Innovation, Spain (SAF2016-75197-R), and the “Asociación Española Contra el Cancer”, Spain (AECC-2017). R.I.R.M. was supported by the “Centro Internacional sobre el Envejecimiento”, Spain (OLD-HEPAMARKER, 0348-CIE-6-E). A.L. received funding from the Christie Charity. M.M. was supported by the Università Politecnica delle Marche, Ancona, Italy (040020_R.SCIENT.A_2018_MARZIONI_M_STRATEGICO_2017). M.S. was supported by the Yale Liver Center Clinical and Translational Core and the Cellular and Molecular Core (DK034989 Silvio O. Conte Digestive Diseases Research Center). C.C. is supported by grants from INSERM, Université de Rennes, INCa, and ITMO Cancer AVIESAN dans le cadre du Plan Cancer (Non-coding RNA in Cancerology: Fundamental to Translational), Ligue Contre le Cancer and Région Bretagne. J.Bruix was supported by grants from Instituto de Salud Carlos III (PI18/00763), AECC (PI044031) and WCR (AICR) 16-0026. A.F. was supported by grants from ISCIII (PI13/01229 and PI18/00542). CIBERehd is funded by the Instituto de Salud Carlos III. V.C., D.M., J. Bridgewater and P.I. are members of the European Reference Network - Hepatological Diseases (ERN RARE-LIVER). J.M.B. is a collaborator of the ERN RARE-LIVER

HPLC-based purification and isolation of potent anti-HIV and latency reversing Daphnane Diterpenes from the medicinal plant Gnidia sericocephala (Thymelaeaceae)

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The “shock and kill” therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 g/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 M without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.SUPPLEMENTARY MATERIAL : TABLE S1: Anti-HIV replication activity of the positive control efavirenz using the in vitro deCIPhR assay: TABLE S2: Anti-HIV replication activity of G. sericocephala root extracts using the in vitro deCIPhR assay: TABLE S3: Cytotoxicity of G. sericocephala root extracts using the in vitro deCIPhR assay; FIGURE S1: 1H NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S2: 13C NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S3: The DEBT NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3).Funding was provided by the South African Department of Science and Innovation (DST/CON 0031/2019), Canadian Institutes for Health Research (CIHR PJT-153057) (I.T.) and the New Frontiers in Research Fund—Explorations (NFRFE-2018-01386) (I.T.). This work was also supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) (I.T.; N.G.), a DELTAs African Initiative [grant # DEL-15-006]. The DELTA African Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Welcome Trust [grant # 107752/Z/15/Z] and the UK government. This work was also supported by grants to L.J.M.: Beyond Antiretroviral Treatment (BEAT)-HIV Delaney Collaboratory Grants UM1AI126620 and UM1AI64570. It was also supported by the Robert I. Jacobs Fund of the Philadelphia Foundation; Penn Center for AIDS Research Grant P30 AI 045880; and the Herbert Kean. The APC was funded by University of Pretoria and Deaprtment of Science and Innovation.https://www.mdpi.com/journal/virusesam2023Chemistr

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC