Characterisation of a novel bioactive complex polysaccharide from a marine invertebrate with potent anticancer and antimalarial activities

Considerable excitement has been generated by the discovery of active compounds from marine organisms. These compounds have a remarkable role in cancer treatment, with fewer side effects on general health. Sulphated glycosaminoglycan (GAGs) are present in all animals, vertebrate and invertebrate. They are of proven economic importance, not only in the food industry but also in the pharmaceutical field. The present study identifies the key structural differences between the GAGs isolated from whelk and mammalian GAG and investigates their biological activity in relation to cancer and malaria. Glycans from marine sources are unique in terms of their structure and function. They work as an alternative natural source to provide effective treatment for several types of cancer, especially triple negative breast cancer (TNBC), which is the most aggressive type of cancer with fewer available treatment options. In addition, marine GAGs have a proven influence on malaria, although their mechanisms of action are not fully understood. Several methods have been employed to achieve the aims of this study. The structure of whelk GAG was determined using several analytical techniques such as gel filtration chromatography, ion exchange chromatography, mass spectrometry and nuclei magnetic resonance spectroscopy. Enzymatic depolymerisation was also used to generate a library of fragments; each was then evaluated for its biological activity on cancer growth. Anti-proliferation activity on several cancer cells, including pulmonary adenocarcinoma A459, the MCF-7 ER-positive cell line, overexpression of protein HER2- SKBR3 cell line, the hepatoblastoma-derived cell line (Hep G2), chronic myelogenous leukaemia (K562), TNBC and mammosphere formation in breast cancer subtypes, and on malaria has been investigated in vitro using drug sustainable assays. Focusing on TNBC, the label-free quantitative proteomic approach has been used to gain overall insight into the mechanisms of action of whelk GAG on two TNBC cell lines: MDA-MB-468 and MDA-MB-231. The results from whelk GAG analysis suggest a complex fine structure with a high sulphation levels that is clearly distinct from mammalian GAG. Few impurities were detected within the whelk GAG structure, which exhibits enzymatic resistance; this generated structurally indeterminate fragments. These resistant fragments still have significant biological activity against cancer growth. In vitro assays demonstrated significant inhibition activity of whelk GAG toward all types of cancer cells, mammosphere formation from breast cancer cells and malaria. The mechanisms of action by which whelk GAG inhibits the growth of two TNBC cell lines appear to involve influencing the cell integrin signalling cascade, extracellular organisation pathways including the regulation of fibroblast growth factor FGF signalling and fibroblast growth factor receptors FGFR, cell adhesion and reduced glycolysis metabolism. In addition, whelk GAG affected the cell mitosis pathways by downregulating DNA replication proteins. To our knowledge, this is the first study to identify significant structural differences between whelk GAGs and mammalian GAGs, which helps to explain the structural-functional relationship of marine glycans in inhibiting cancer cell growth. It also examines the biological role of GAGs isolated from whelk as anti-proliferation agents toward a wide variety of cancer cell lines and mammosphere formation in breast cancer. Finally, this study is the first to highlight the unique activity of whelk GAG against malaria infection

Pesticide residues with hazard classifications relevant to non-target species including humans are omnipresent in the environment and farmer residences

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring “no data available” situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals

Assessment of Potentially Toxic Elements in the Urban Soil and Plants of Kirkuk City in Iraq

Kirkuk city is known for its industrial activities, especially oil and cement production, as well as its road traffic. The aim of this study was to assess potentially toxic elements (PTEs) in the soil and plants from urban areas by measuring pollution indices and estimating the effect that this pollution has on the environment. Leaf and soil samples were taken from 10 different locations in Kirkuk. These samples were pre-treated using the acid digestion method and concentrations of 12 elements were determined using inductively coupled plasma mass spectrometry (ICP-MS). The results indicate a high content of aluminum and magnesium (mg/kg) in the soil samples from all study sites. For leaf samples, the results showed a moderate to low amount of magnesium and aluminum. Based on our results, the PTE concentrations were found in the following order—Mg > Al > Ni > Cu > Cr > Pb > Co > As > Se > Cd > Hg > Ti—in leaf samples from all 10 study sites. However, in the soil samples, PTE concentrations were in the following order—Mg > Al > Cr > Ni > Cu > Pb > Co > As > Se > Ti > Cd > Hg—from all study sites. Pollution indices showed a moderate level of contamination of Pb, Cd, and Ni, and a high level of contamination of As and Hg in plant and soil samples from all study sites in Kirkuk city

A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses <subtitle>a proof of principle study</subtitle>

AimsArthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods.Methods99mTc-UBI29-41-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria.ResultsBacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria.ConclusionThe hybrid tracer 99mTc-UBI29-41-Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies.Cite this article: Bone Joint Res 2023;12(1):72–79