Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an ...early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.
Summary
Background and Objective
The aim was assessing a short training for healthcare providers on patient‐focused counselling to treat childhood obesity in primary care, along with dietitian‐led ...workshops and educational materials.
Methods
Randomized clustered trial conducted with paediatrician‐nurse pairs (Basic Care Units BCU) in primary care centres from Tarragona (Spain). BCUs were randomized to intervention (MI) (motivational interview, dietitian‐led education, and educational materials) or control group (SC, standard care). Participants were 8–14‐year‐old children with obesity, undergoing 1–11 monthly treatment visits during 1 year at primary care centres. The primary outcome was BMI z‐score reduction.
Results
The study included 44 clusters (23 MI). Out of 303 allocated children, 201 (n = 106 MI) completed baseline, final visits, and at least one treatment visit and were included in the analysis. BMI z‐score reduction was −0.27 (±0.31) in SC, versus −0.36 (±0.35) in MI (p = 0.036).
Mixed models with centres as random effects showed greater reductions in BMI in MI than SC; differences were B = −0.11 (95% CI: −0.20, −0.01, p = 0.025) for BMI z‐score, and B = −2.06 (95% CI: −3.89, −0.23, p = 0.028) for BMI %. No severe adverse events related to the study were notified.
Conclusion
Training primary care professionals on motivational interviewing supported by dietitians and educational materials, enhanced the efficacy of childhood obesity therapy.
BACKGROUNDStandard patch test series must be updated using objective data on allergen sensitization. The Spanish standard series was last updated in 2016 and the European series in 2019, and the ...inclusion of several emerging allergens needs to be evaluated. MATERIAL AND METHODSWe conducted a prospective, observational, multicenter study of consecutive patients from the registry of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) who were patch tested in 2019 and 2020 with linalool hydroperoxide, limonene hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, octylisothiazolinone, textile dye mix (TDM), sodium metabisulfite, propolis, bronopol, Compositae mix II, diazolidinyl urea, imidazolidinyl urea, decyl glucoside, and lauryl glucoside. RESULTSWe analyzed data for 4654 patients tested with diazolidinyl urea, imidazolidinyl urea, and bronopol, and 1890 tested with the other allergens. The values for the MOAHLFA index components were 30% for male, 18% for occupational dermatitis, 15% for atopic dermatitis, 29% for hand, 6.5% for leg, 23% for face, and 68% for age > 40 years. Sensitization rates above 1% were observed for 7 allergens: linalool hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, limonene hydroperoxide, TDM, sodium metabisulfite, and propolis. Three allergens had a current relevance rate of over 1%: linalool hydroperoxide, 2-hydroxyethyl-methacrylat, and limonene hydroperoxide. Benzisothiazolinone and TDM had a relevance rate of between 0.9% and 1%. CONCLUSIONSOur results indicate that 7 new allergens should be considered when extending the Spanish standard patch test series. The data from our series could be helpful for guiding the next extension of the European baseline series.
Standard patch test series must be updated using objective data on allergen sensitization. The Spanish standard series was last updated in 2016 and the European series in 2019, and the inclusion of ...several emerging allergens needs to be evaluated.
We conducted a prospective, observational, multicenter study of consecutive patients from the registry of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) who were patch tested in 2019 and 2020 with linalool hydroperoxide, limonene hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, octylisothiazolinone, textile dye mix (TDM), sodium metabisulfite, propolis, bronopol, Compositae mix II, diazolidinyl urea, imidazolidinyl urea, decyl glucoside, and lauryl glucoside.
We analyzed data for 4,654 patients tested with diazolidinyl urea, imidazolidinyl urea, and bronopol, and 1,890 tested with the other allergens. The values for the MOAHLFA index components were 30% for male, 18% for occupational dermatitis, 15% for atopic dermatitis, 29% for hand, 6.5% for leg, 23% for face, and 68% for age > 40 years. Sensitization rates above 1% were observed for 7 allergens: linalool hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, limonene hydroperoxide, TDM, sodium metabisulfite, and propolis. Three allergens had a current relevance rate of over 1%: linalool hydroperoxide, 2-hydroxyethyl-methacrylat, and limonene hydroperoxide. Benzisothiazolinone and TDM had a relevance rate of between 0.9% and 1%.
Our results indicate that 7 new allergens should be considered when extending the Spanish standard patch test series. The data from our series could be helpful for guiding the next extension of the European baseline series.
La actualización de las series estándar de pruebas epicutáneas debe basarse en datos objetivos de frecuencia de sensibilización de los alérgenos que componen cada batería. La última renovación de la batería estándar española se realizó en 2016 y de la europea en 2019, quedando pendiente valorar la inclusión de alérgenos emergentes.
Desarrollamos un estudio observacional, prospectivo y multicéntrico de los pacientes consecutivos del registro del Grupo Español de Investigación en Dermatitis y Alergia Cutánea sometidos a pruebas epicutáneas con hidroperóxido de linalool, hidroperóxido de limoneno, 2-hidroxi-etil-metacrilato, benzisotiazolinona, octilisotiazolinona, mezcla textil, metabisulfito sódico, propóleo, bronopol, mezcla de compuestas II, diazolidinil urea, imidazolidinil urea, decil glucósido y lauril glucósido, durante los años 2019 y 2020.
Se analizó una muestra de 4.654 pacientes estudiados con diazolidinil urea, imidazolidinil urea y bronopol, y de 1.890 pacientes con el resto de los alérgenos. El índice MOAHLFA fue: M 30%, O 18%, A 15%, H 29%, L 6,5%, F 23%, A 68%. Siete alérgenos mostraron una frecuencia de sensibilización mayor del 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato, benzisotiazolinona, hidroperóxido de limoneno, mezcla textil, metabisulfito sódico y propóleo. Tres alérgenos mostraron una frecuencia de relevancia presente superior al 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato e hidroperóxido de limoneno; para benzisotiazolinona y mezcla textil, esta frecuencia fue de entre el 0,9 y el 1%.
Nuestros resultados indican que debería valorarse la inclusión de siete nuevos alérgenos en la batería estándar española. Estos resultados podrían contribuir a la próxima actualización de la batería basal europea.
Tryptophan–threonine-rich antigen (TryThrA) is a
Plasmodium falciparum homologue of
Plasmodium yoelii-infected erythrocyte membrane pypAg-1 antigen. pypAg-1 binds to the surface of uninfected mouse ...erythrocytes and has been used successfully in vaccine studies. The two antigens are characterized by an unusual tryptophan-rich domain, suggesting similar biological properties. Using synthetic peptides spanning the TryThrA sequence and human erythrocyte we have done binding assays to identify possible TryThrA functional regions. We describe four peptides outside the tryptophan-rich domain having high activity binding to normal human erythrocytes. The peptides termed HABPs (high activity binding peptides) are 30884 (
61LKEKKKKVLEFFENLVLNKKY
80) located at the N-terminal and 30901 (
401RKSLEQQFGDNMDKMNKLKKY
420), 30902 (
421KKILKFFPLFNYKSDLESIM
440) and 30913 (
641DLESTAEQKAEKKGGKAKAKY
660) located at the C-terminal. Studies with polyclonal goat antiserum against synthetic peptides chosen to represent the whole length of the protein showed that TryThrA has fluorescence pattern similar to PypAg-1 of
P. yoelii. All HABPs inhibited merozoite in vitro invasion, suggesting that TryThrA protein may be participating in merozoite–erythrocyte interaction during invasion.
Virulence and immunity are still poorly understood in Mycobacterium tuberculosis. The H37Rv M. tuberculosis laboratory strain genome has been completely sequenced, and this along with proteomic ...technology represent powerful tools contributing toward studying the biology of target cell interaction with a facultative bacillus and designing new strategies for controlling tuberculosis. Rv2004c is a putative M. tuberculosis protein that could have specific mycobacterial functions. This study has revealed that the encoding gene is present in all mycobacterium species belonging to the M. tuberculosis complex. Rv2004c gene transcription was observed in all of this complex's strains except Mycobacterium bovis and Mycobacterium microti. Rv2004c protein expression was confirmed by using antibodies able to recognize a 54‐kDa molecule by immunoblotting, and its location was detected on the M. tuberculosis surface by transmission electron microscopy, suggesting that it is a mycobacterial surface protein. Binding assays led to recognizing high activity binding peptides (HABP); five HABPs specifically bound to U937 cells, and six specifically bound to A549 cells. HABP circular dichroism suggested that they had an α‐helical structure. HABP–target cell interaction was determined to be specific and saturable; some of them also displayed greater affinity for A549 cells than U937 cells. The critical amino acids directly involved in their interaction with U937 cells were also determined. Two probable receptor molecules were found on U937 cells and five on A549 for the two HABPs analyzed. These observations have important biological significance for studying bacillus–target cell interactions and implications for developing strategies for controlling this disease.
Plasmodium falciparum reticulocyte binding protein RBP-2 homologues a and b (
PfRBP-2-Ha and -Hb) have been described as being high molecular weight proteins, expressed at the
P. falciparum merozoite ...apical extreme, belonging to a family of proteins found in other
Plasmodium involved in the search for erythrocyte populations before being invaded by merozoites. 185, 20-mer-long non-overlapping peptides, spanning the entire
PfRBP-2-Ha and -Hb sequences, were synthesised, radiolabelled and tested in erythrocyte binding assays. Fifteen
PfRBP-2-Ha and -Hb high binding activity peptides (HBAPs) specifically binding to erythrocytes with high affinity were identified. Dissociation constants were between 70 and 300 nM and Hill coefficients were 1 approximately. HBAPs residues critical for binding to erythrocytes were determined. Cross-linking was performed allowing possible receptors for
PfRBP-2-Ha and -Hb to be identified on the surface of the erythrocytes. Some of the HABPs showed merozoite invasion inhibition greater than 90% in in vitro assays.
Receptor–ligand interactions between synthetic peptides and normal human erythrocytes were studied to determine Plasmodium falciparum merozoite surface protein‐3 (MSP‐3) FC27 strain regions that ...specifically bind to membrane surface receptors on human erythrocytes. Three MSP‐3 protein high activity binding peptides (HABPs) were identified; their binding to erythrocytes became saturable, had nanomolar affinity constants, and became sensitive on being treated with neuraminidase and trypsin but were resistant to chymotrypsin treatment. All of them specifically recognized 45‐, 55‐, and 72‐kDa erythrocyte membrane proteins. They all presented α‐helix structural elements. All HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by ∼55%–85%, suggesting that MSP‐3 protein's role in the invasion process probably functions by using mechanisms similar to those described for other MSP family antigens.
Background
/
Aims
: Identify hepatitis C virus (HCV) sequences in E1 and E2 protein binding to HepG2.
Methods
: Synthetic 20-mer long, ten-residue overlapped peptides, from E1 and E2 proteins, were ...tested in HepG2 or Raji cell-binding assays. Affinity constants, binding site number per cell and Hill coefficients were determined by saturation assay for high activity binding peptides (HABPs). Receptors for HepG2 cell were determined by cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.
Results
: Twelve HABPs were found in HCV genotype 1a, allowing six hepatocyte-binding sequences (HBSs) to be defined: two peptide-binding regions in E1 HABPs 4913 (
YQVRNSTGLYHVTNDCPNSS) and 4918 (
MTPTVATRDGKLPATQLRRHY). Four hepatocyte-binding regions were defined in E2: region-I, peptide 4931 (
ETHVTGGSAGHTVSGFVSLLY); region-II, 4937–4939 (
HHKFNSSGCP
ERLASCRPLTDFDQGWGPI
SYANGSGPDQR
); region-III, 4943–4945 (
PVYCFTPSP
VVVGTTDRSGAPTYSWGEND
TDVFVLNNTR
) and region-IV, 4949–4952 (
CGAPPCVIG
GAGNNTLHCPTDCFRKHPDATYSRCGSGPWI
TPRCLVDYPY
). The underlined sequences are most relevant in the binding process. HABPs 4913 and 4938 also bind to CD81 positive Raji cells. Region-II 4938 HABPs bind to 50 and 60
kDa HepG2 cell membrane surface proteins.
Conclusions
: Six HVRs to the HepG2 were identified. Some HABPs have been previously found to be antigenic and immunogenic. HABPs, 4918 (from E1), 4938, 4949, 4950, 4951 and 4952 (from E2) have not been previously recognised. These HABPs could be relevant to HCV invasion of hepatocytes.
PDF
