Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs

Plasmodium vivax circumsporozoite genotypes: a limited variation or new subspecies with major biological consequences?

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium vivax </it>circumsporozoite variants have been identified in several geographical areas. The real implication of the genetic variation in this region of the <it>P. vivax </it>genome has been questioned for a long time. Although previous studies have observed significant association between VK210 and the Duffy blood group, we present here that evidences of this variation are limited to the CSP central portion.</p> <p>Methods</p> <p>The phylogenetic analyses were accomplished starting from the amplification of conserved domains of <it>18 SSU RNAr </it>and <it>Cyt B</it>. The antibodies responses against the CSP peptides, MSP-1, AMA-1 and DBP were detected by ELISA, in plasma samples of individuals infected with two <it>P. vivax CS </it>genotypes: VK210 and <it>P. vivax</it>-like.</p> <p>Results</p> <p>These analyses of the two markers demonstrate high similarity among the <it>P. vivax CS </it>genotypes and surprisingly showed diversity equal to zero between VK210 and <it>P. vivax</it>-like, positioning these <it>CS </it>genotypes in the same clade. A high frequency IgG antibody against the N- and C-terminal regions of the <it>P. vivax </it>CSP was found as compared to the immune response to the R- and V- repetitive regions (<it>p </it>= 0.0005, Fisher's Exact test). This difference was more pronounced when the <it>P. vivax</it>-like variant was present in the infection (<it>p </it>= 0.003, Fisher's Exact test). A high frequency of antibody response against MSP-1 and AMA-1 peptides was observed for all <it>P. vivax CS </it>genotypes in comparison to the same frequency for DBP.</p> <p>Conclusions</p> <p>This results target that the differences among the <it>P. vivax CS </it>variants are restrict to the central repeated region of the protein, mostly nucleotide variation with important serological consequences.</p

Budd-Chiari syndrome in a 25-year-old woman with Behçet's disease: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The risk that patients with Behçet's disease will develop thrombotic complications has been previously described. Although it is distributed worldwide, Behçet's disease is rare in the Americas and Europe. Even though the pathogenic mechanisms of vascular complications of Budd-Chiari syndrome in patients with Behçet's disease are unknown, severe vascular complications of Budd-Chiari syndrome associated with Behçet's disease seem to affect mainly young men.</p> <p>Case presentation</p> <p>We report a case of Budd-Chiari syndrome, a severe vascular complication that developed in a 25-year-old Afro-Brazilian woman with Behçet's disease.</p> <p>Conclusion</p> <p>Severe vascular complications of Budd-Chiari syndrome in patients with Behçet's disease are much more common in young adult male patients; we present a rare case of Budd-Chiari syndrome in a young Afro-Brazilian woman with Behçet's disease.</p