HUMN

In this report we provide a summary of the presentations and discussion of the latest knowledge regarding the buccal micronucleus (MN) cytome assay. This information was presented at the HUMN workshop held in Malaga, Spain, in connection with the 2023 European, Environmental Mutagenesis and Genomics conference. The presentations covered the most salient topics relevant to the buccal MN cytome assay including (i) the biology of the buccal mucosa, (ii) its application in human studies relating to DNA damage caused by environmental exposure to genotoxins, (iii) the association of buccal MN with cancer and a wide range of reproductive, metabolic, immunological, neurodegenerative and other age-related diseases, (iv) the impact of nutrition and lifestyle on buccal MN cytome assay biomarkers; (v) its potential for application to studies of DNA damage in children and obesity, and (vi) the growing prospects of enhancing the clinical utility by automated scoring of the buccal MN cytome assay biomarkers by image recognition software developed using artificial intelligence...

A new protocol for the direct synthesis of 2-aminothiazole has been developed from oxime acetate and readily available sodium thiocyanate using a copper catalyst. The present transformation has good functional group tolerance. Various thiazoles were smoothly synthesized in good to excellent yields. The applicability of the present method has been extended to the formal synthesis of the non-steroidal and anti-inflammatory drug, fentiazac via the Sandmeyer reaction and Suzuki coupling.

Facial bone osteomas are uncommon, with only a few cases reported in the literature. Osteomas are benign neoplasms that are composed of well-differentiated, mature bones. There are three types of osteomas: central osteomas that develop from the endosteum, peripheral osteomas (PO) that develop from the periosteum, and extra-skeletal soft tissue osteomas that develop from the muscle. Both central and peripheral osteomas of the facial bones have been described. Peripheral osteomas have been reported in the frontal, ethmoid, and maxillary sinuses, but they are uncommon in the jawbone...

A direct oxidation of the bromo-derived Fischer-Borsche oxo-ring leading to carbazolequinone has been developed by using molecular iodine. This unprecedented transformation has been used for the modular synthesis of the anti-cardiotonic agent murrayaquinone. Furthermore, the present method has been generalized to a broad range of functional groups, with good to excellent yield.

Endophytic fungi are microorganisms capable of colonizing the interior of plant tissues without causing damage to them. The study of the secondary metabolites produced by their vast biodiversity fungal is relevant for the discovery of new products for biotechnological and agrochemical applications. In addition, extract of the endophytic fungus Aspergillus sp., isolated from the almonds of Bertholletia excelsa Humn & Bonlp collected in the Brazilian Amazon, oviposition deterrent, and larvicidal activity of against Aedes aegypti...

The "Micronuclei and Disease" workshop was organized by the HUMN Project consortium and hosted by the European Environmental Mutagen and Genomics Society at their annual meeting in Rennes, France, on 23 May 2019. The program of the workshop focused on addressing the emerging evidence linking micronucleus (MN) frequency to human disease. The first objective was to review what has been published and evaluate the level and quality of evidence for the connection between MN frequency and various diseases through all life stages...

A novel, efficient and regioselective transition-metal-free one-pot synthesis of aryl sulfones via the reactive quinone imine ketal intermediate is demonstrated using easily accessible bench-stable sulfinate salts. A broad range of functionality on p-anisidine substrates as well as sulfinate salts was tolerated under the mild reaction condition to provide the corresponding aryl sulfones in good to excellent yields.

Chromosomal aberrations, such as micronuclei (MN), have served as biomarkers of genotoxic exposure and cancer risk. Guidelines for the process of scoring MN have been presented by the HUman MicroNucleus (HUMN) project. However, these guidelines were developed for assay performance but do not address how to statistically analyze the data generated by the assay. This has led to the application of various statistical methods that may render different interpretations and conclusions. By combining MN with data from other high-throughput genomic technologies such as gene expression microarray data, we may elucidate molecular features involved in micronucleation...

Human serum albumin (HSA) has been investigated as a serum half-life extender of therapeutic proteins thanks to its unusually long serum half-life. However, in mice, the serum half-life of a HSA-conjugated protein was much shorter than that of HSA in humans, likely due to the species-dependent nature of albumin-FcRn interactions. Herein, we investigated species-dependent albumin-FcRn interactions using species-matched albumin (mouse serum albumin) and species-mismatched albumin (HSA) in non-transgenic mice...

The Beckmann rearrangement of ketoximes, mediated by ammonium persulfate-dimethyl sulfoxide as a reagent, has been achieved under neutral conditions. Based on the radical trapping and (18)O-labeling experiments, the transformation follows a mechanism involving a radical pathway. The scope and generality of the developed protocol has been demonstrated by 19 examples. The developed protocol and Pd-catalyzed intramolecular double C-H activation were used as key steps in the formal total synthesis of antimalarial natural product isocryptolepine...

Adenosine receptors (A1, A2a, A2b and A3) have several physiological and pathological roles in cancer cell lines. The present study was carried out to evaluate the mRNA and protein expression profile and functional role of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 ovarian cancer cell lines. The levels of mRNA and protein expression of A1, A2a, A2b and A3 adenosine receptors in the ovarian cancer cell lines were measured by Real-time PCR and western blotting. The functional roles of adenosine receptors were investigated through measurement of cAMP levels after agonist treatment...

An efficient regioselective iodination of the Fischer-Borsche ring has been achieved using molecular iodine, in a one-pot synthesis. The acid-, metal-, and oxidant-free conditions of the present method are highly convenient and practical. Furthermore, the one-pot direct iodination process is extended to the concise synthesis of glycozoline, 3-formyl-6-methoxy-carbazole, and 6-methoxy-carbazole-3-methylcarboxylate natural alkaloids. This method has been proven to be tolerant to a broad range of functional groups, with good to excellent yields...

A new protocol for the aromatization of tetrahydrocarbazoles has been achieved using a catalytic amount of iodine, giving high yields. The role of iodine in the aromatization has been explained by DFT, and its wide scope is extended to the total synthesis of glycozoline and murrayafoline A. This method has proven to be tolerant of a broad range of functional groups.

BACKGROUND & OBJECTIVES: During 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation. METHODS: Transcriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays...

The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies...

The use of micronucleus (MN) assays in in vitro genetic toxicology testing, radiation biodosimetry and population biomonitoring to study the genotoxic impacts of environment gene-interactions has steadily increased over the past two decades. As a consequence there has been a strong interest in developing automated systems to score micronuclei, a biomarker of chromosome breakage or loss, in mammalian and human cells. This paper summarises the outcomes of a workshop on this topic, organised by the HUMN project, at the 6th International Conference on Environmental Mutagenesis in Human Populations at Doha, Qatar, 2012...

The human buccal micronucleus cytome assay (BMCyt) is one of the most widely used techniques to measure genetic damage in human population studies. Reducing protocol variability, assessing the role of confounders, and estimating a range of reference values are research priorities that will be addressed by the HUMN(XL) collaborative study. The HUMN(XL) project evaluates the impact of host factors, occupation, life-style, disease status, and protocol features on the occurrence of MN in exfoliated buccal cells...

The International Human Micronucleus (HUMN) Project (www.humn.org) was founded in 1997 to coordinate worldwide research efforts aimed at using micronucleus (MN) assays to study DNA damage in human populations. The central aims were to (i) collect databases on baseline MN frequencies and associated methodological, demographic, genetic and exposure variables, (ii) determine those variables that affect MN frequency, (iii) establish standardised protocols for performing assays so that data comparisons can be made more reliably across laboratories and countries and (iv) evaluate the association of MN frequency with disease outcomes both cross-sectionally and prospectively...

Children may be more susceptible to the effects of the environmental exposure and medical treatments than adults; however, limited information is available about the differences in genotoxic effects in children by age, sex and health status. Micronucleus (MN) assay is a well established method of monitoring genotoxicity, and this approach is thoroughly validated for adult lymphocytes by the Human Micronucleus Biomonitoring project (HUMN.org). Similar international undertaking is in progress for exfoliated buccal cells...

BACKGROUND: Immunosuppressive therapy is essential for patients after renal transplantation, but it may have mutagenic side effects. The frequency of micronuclei (MN) assessed by the cytokinesis block assay is well established in the diagnosis of DNA damage. METHODS: We examined 79 patients before and after renal transplantation with the cytokinesis block assay. For MN evaluation, the criteria of the Human Micron Nucleus (HUMN) project were used. RESULTS: Age and sex had no influence on the number of MN before transplantation...