Achilles tendon rupture in the dog is a common traumatic lesion. An accurate evaluation of etiology, grade of the lesion with or without loss of tendon substance, and time elapsed from the trauma can guide the surgeon in choosing the best surgical technique. Moreover, the healing process after a tendon injury is usually difficult and uncertain because the prognosis is influenced by extent of trauma, time elapsed between the trauma and its treatment and low tendon vascularization. However, the rapid development of tissue engineering and regenerative medicine could soon result in the development of scaffolds with bioactive proteins that can direct the healing process toward complete tendon regeneration without fibrotic tissue development.

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.

The objective of this study was to evaluate relative echogenicity of superficial and deep digital flexor tendons, the accessory ligament of the deep digital flexor tendon and interosseous muscle of the metacarpal region in foals ages 1 week to 4 months; and assess the association between echogenicity and sex or side/laterality. Seven Standardbred trotter foals were examined. Right and left metacarpal regions (palmar surface) were ultrasonographically investigated, and four regions of interest were assessed. A significant increase in echogenicity was seen in superficial and deep digital flexor tendons, accessory ligament of deep digital flexor tendon, and interosseous muscle during growth from 1 week to 4 months of age. Echogenicity of examined tendons and ligaments was not influenced by gender nor laterality. Reference values for tendon and ligament echogenicity could function as a tool to discriminate between physiological and abnormal conditions such as congenital contractural conditions.

Background DNA ligases are crucial for DNA repair and cell replication since they catalyze the final steps in which DNA breaks are joined. DNA Ligase III (LIG3) exerts a pivotal role in Alternative-Non-Homologous End Joining Repair (Alt-NHEJ), an error-prone DNA repair pathway often up-regulated in genomically unstable cancer, such as Multiple Myeloma (MM). Based on the three-dimensional (3D) LIG3 structure, we performed a computational screening to identify LIG3-targeting natural compounds as potential candidates to counteract Alt-NHEJ activity in MM. Methods Virtual screening was conducted by interrogating the Phenol Explorer database. Validation of binding to LIG3 recombinant protein was performed by Saturation Transfer Difference (STD)—nuclear magnetic resonance (NMR) experiments. Cell viability was analyzed by Cell Titer-Glo assay; apoptosis was evaluated by flow cytometric analysis following Annexin V-7AAD staining. Alt-NHEJ repair modulation was evaluated using plasmid re-joining assay and Cytoscan HD. DNA Damage Response protein levels were analyzed by Western blot of whole and fractionated protein extracts and immunofluorescence analysis. The mitochondrial DNA (mtDNA) copy number was determined by qPCR. In vivo activity was evaluated in NOD-SCID mice subcutaneously engrafted with MM cells. Results Here, we provide evidence that a natural flavonoid Rhamnetin (RHM), selected by a computational approach, counteracts LIG3 activity and killed Alt-NHEJ-dependent MM cells. Indeed, Nuclear Magnetic Resonance (NMR) showed binding of RHM to LIG3 protein and functional experiments revealed that RHM interferes with LIG3-driven nuclear and mitochondrial DNA repair, leading to significant anti-MM activity in vitro and in vivo. Conclusion Taken together, our findings provide proof of concept that RHM targets LIG3 addiction in MM and may represent therefore a novel promising anti-tumor natural agent to be investigated in an early clinical setting.