PROPIEDADES BIOLÓGICAS DE PÉPTIDOS DERIVADOS DEL COLÁGENO DE ORGANISMOS MARINOS

Las especies marinas, así como los subproductos generados a partir de su industrialización representan una valiosa fuente de proteínas, entre las que se encuentra el colágeno. Típicamente, el colágeno se utiliza para la elaboración de gelatina, alimentos funcionales, películas para fotografía, empaques biodegradables, productos de cosmetología, entre otros. Sin embargo, otra forma de aprovechamiento poco explorada y novedosa de este material es la obtención de péptidos con actividad biológica (PABs). Los PABs derivados del colágeno y gelatina a partir de especies marinas tienen un enorme potencial, debido a que poseen excelentes propiedades biológicas, tales como antioxidantes, antihipertensivas, anticancerígenas, antimicrobianas, neuroprotectoras, así como inducir el crecimiento de tejido óseo y retardar el envejecimiento de la piel, propiedades que se han asociado frecuentemente a la presencia de aminoácidos prolina e hidroxiprolina en la secuencia del péptido y ciertas características estructurales. El presente trabajo recopila los hallazgos más recientes sobre los efectos benéficos de los PABs derivados de colágeno y gelatina de especies marinas, con énfasis en las características estructurales que definen sus propiedades antioxidantes, antihipertensivas, anticancerígenas y antimicrobianas

SERS study of thiocarbonyl compounds adsorbed on metal nanoparticles

Thiocarbonyl compounds have been reported to exhibit interesting biological and pharmacological properties but they are many often characterized by their toxicological effects. However the chemistry of thiobenzoic acid (TBA) and thiobenzamide (TB) has not been fully studied yet. Some of the biological studies of TBA are related to the tautomerism of thiocarboxylic acids and the important role that the -C(=O)-S and -C(=S)-O functional groups play in the catalytic activities of enzymes such as cysteine or serine proteases.1 On the other hand, TB and derivatives are well known hepatotoxins and have been used as inhibitor in enzymatic reactions and in pharmacy due to their microbial activity.2 From a chemical point of view, thiocarboxylates are an interesting type of molecules having two different donor atoms, a soft sulfur donor atom and a hard oxygen donor one. The presence of these unlike groups can lead to the bonding with metal surfaces. Likewise the interaction of thiobenzamide and their derivatives with metals is of great interest because both the sulfur and nitrogen atoms are also able to coordinate with the surface. Therefore the high affinity of these molecules for metal surfaces makes them suitable SERS target adsorbates. Taking advantage of the fact that SERS spectroscopy is both surface selective and highly sensitive we have attempted to determine the molecular structure of TBA and TB once they are adsorbed on the metal. The main objective of this work is focussed on discussing the observed vibrational wavenumber shifts of TBA and TB upon adsorption on silver nanoparticles. In this work the SERS substrates have been prepared by using different colloidal silver solutions according to the method described by Creighton et al.3 and Leopold and Lendl.4 The analysis of the vibrational wavenumbers shifts of the Raman and SERS spectra allow us to know the adsorption process (Figure 1). In the case of TBA, the wavenumber of the SERS band assigned to (C=O) vibrational mode shows an important blue shift up to 40 cm-1 with respect to the Raman whereas the (C-S) band undergoes a red shift up to 40 cm-1. These results suggest a unidentate coordination of TBA to the silver surface through the sulfur atom. On the other hand, the SERS band assigned in the case of TB to Amide III (mainly (CN)) exhibits a significant blueshift up to 41 cm-1, and the SERS band assigned to Amide I (mainly (CS)) shows a red shift up to 11 cm-1. These wavenumber shifts indicate that TB interacts to the silver surface through the sulfur atom. Interestingly, in previous SERS studies of pyridinecarboxamides and benzamide we have observed that some SERS bands assigned to 1;ring, Amide I (mainly (C=O)) and Amide III (mainly C-N)) show wavenumber shifts of +50, -50 and +10 cm-1, respectively, which were attributed to the deprotonation of carboxamide group.5,6 Finally, in order to verify experimental results DFT calculations have been carried out for different silver complexes of TBA and TB concluding that the unidentate coordination is the most likely interaction of both of them.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Proteomics and gene expression analyses of squalene-supplemented mice identify microsomal thioredoxin domain-containing protein 5 changes associated with hepatic steatosis

Squalene is an abundant hydrocarbon present in virgin olive oil. Previous studies showed that its administration decreased atherosclerosis and steatosis in male apoE-knock-out mice. To study its effects on microsomal proteins, 1 g/kg/day of squalene was administered to those mice. After 10 weeks, hepatic fat content was assessed and protein extracts of microsomal enriched fractions from control and squalene-treated animals were analyzed by 2D-DIGE. Spots exhibiting significant differences were identified by peptide fingerprinting and MSMS analysis. Squalene administration modified the expression of thirty-one proteins involved in different metabolic functions and increased the levels of those involved in vesicle transport, protein folding and redox status. Only mRNA levels of 9 genes (Arg1, Atp5b, Cat, Hyou1, Nipsnap1, Pcca, Pcx, Pyroxd2, and Txndc5) paralleled these findings. No such mRNA changes were observed in wild-type mice receiving squalene. Thioredoxin domain-containing protein 5 (TXNDC5) protein and mRNA levels were significantly associated with hepatic fat content in apoE-ko mice. These results suggest that squalene action may be executed through a complex regulation of microsomal proteins, both at the mRNA and post-transcriptional levels and the presence of apoE may change the outcome. Txndc5 reflects the anti-steatotic properties of squalene and the sensitivity to lipid accumulation

High Sensitivity C Reactive Protein in Patients with Rheumatoid Arthritis Treated with Antibodies against IL-6 or Jak Inhibitors: A Clinical and Ultrasonographic Study

Background: We examined whether high-sensitivity CRP (hsCRP) reflected the inflammatory disease status evaluated by clinical and ultrasound (US) parameters in RA patients receiving IL-6 receptor antibodies (anti-IL-6R) or JAK inhibitors (JAKi). Methods: We conducted a cross-sectional study of patients with established RA receiving anti-IL-6R (tocilizumab, sarilumab) or JAKi (tofacitinib, baricitinib). Serum hsCRP and US synovitis in both hands were measured. Associations between hsCRP and clinical inflammatory activity were evaluated using composite activity indices. The association between hsCRP and US synovitis was analyzed. Results: 63 (92% female) patients (42 anti- IL-6R and 21 JAKi) were included, and the median disease duration was 14.4 (0.2–37.5) years. Most patients were in remission or had low levels of disease. Overall hsCRP values were very low, and significantly lower in anti-IL-6R patients (median 0.04 mg/dL vs. 0.16 mg/dL). Anti-IL-6R (82.4%) patients and 48% of JAKi patients had very low hsCRP levels (≤0.1 mg/dL) (p = 0.002). In the anti-IL-6R group, hsCRP did not correlate with the composite activity index or US synovitis. In the JAKi group, hsCRP moderately correlated with US parameters (r = 0.5) but not clinical disease activity, and hsCRP levels were higher in patients with US synovitis (0.02 vs. 0.42 mg/dL) (p = 0.001). Conclusion: In anti-IL-6R RA-treated patients, hsCRP does not reflect the inflammatory disease state, but in those treated with JAKi, hsCRP was associated with US synovitis

Imaging Findings in Patients with Immune Checkpoint Inhibitor-Induced Arthritis

Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited. Methods: We conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and (18)F-FDG PET/CT)] between January 2017 and January 2022. Results: Nineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 (18)F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen. Conclusions: ICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings