Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns.

Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB.

Relative Tumour Volume in Canine Oral Melanoma Staging and Prognosis.

Melanoma is one of the most common canine oral malignant tumours and is highly aggressive and metastatic, even at the early stages of development. Surgery relies on wide excision of the primary tumour and regional lymphadenectomy, with or without adjuvant therapy. Tumour location and size are important when considering staging, which ultimately affects the curative intent of surgery. Nevertheless, absolute tumour volume (TV) is not related to the vast phenotypic variability within canine breeds. This study aimed to determine the cutoff values of two ratios-tumour-to-head volume (THR) and tumour-to-body volume (TBR)-and assess whether they could be associated with the odds of finding metastasis at presentation and/or the likelihood of achieving tumour-free excision margins. A retrospective case series involving 51 dogs was used to evaluate the preoperative head/neck and chest computed tomography and histopathology of the primary mass and excised lymph nodes. Higher TV, THR% and TBR% values were associated with bone lysis and mitotic count (MC). The Ki67 index was significantly associated with local and distant metastases at presentation, whereas MC was associated with local metastasis alone. Tumour-infiltrated surgical margins were associated with caudally located tumours, regardless of the tumour size. Dogs with lymph node metastasis at presentation were seven times more prone to have local relapse. TV, THR% and TBR% values were positively associated with local lymph node metastasis at presentation. Cutoff values for both TV and TBR% were proposed to predict lymph node metastasis at presentation (TV = 6.423 cm3 and TBR% = 0.043), being supported by post-surgical survival analysis.

SARS-CoV-2 variants induce distinct disease and impact in the bone marrow and thymus of mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model to study how differences in the course of infection by SARS-CoV-2 variants alpha, delta, and omicron relate to tissue pathology and the immune response triggered. We documented a variant-specific pattern of infection severity, inducing discrete lung and blood immune responses and differentially impacting primary lymphoid organs. Infections with variants alpha and delta promoted bone marrow (BM) emergency myelopoiesis, with blood and lung neutrophilia. The defects in the BM hematopoietic compartment extended to the thymus, with the infection by the alpha variant provoking a marked thymic atrophy. Importantly, the changes in the immune responses correlated with the severity of infection. Our study provides a comprehensive platform to investigate the modulation of disease by SARS-CoV-2 variants and underscores the impact of this infection on the function of primary lymphoid organs.

The functionalization of natural polymer-coated gold nanoparticles to carry bFGF to promote tissue regeneration.

Gold nanoparticles (AuNPs) enable the treatment and real-time monitoring of several diseases, providing an exciting and advantageous nanomedicine strategy. These NPs have therefore been adequately functionalized to enable them to carry growth factors (GF), namely basic fibroblastic (bF) GF, which play an essential role in different and important cellular processes including cellular proliferation, survival, migration and differentiation. The AuNPs were coated with natural polymers, chitosan and heparin, to enhance their physicochemical properties such as suspension stability. The polyelectrolyte coating was monitored using a quartz crystal microbalance with dissipation, size and zeta-potential analysis. The natural polymer-coated AuNPs have a spherical shape and a positive surface charge due to chitosan amino groups, enabling their biofunctionalization with monoclonal antibodies to target specific biomolecules. Additionally, cellular assays with the chondrocyte cell line ATDC5 show that the NPs are cytocompatible at relevant concentrations. As a proof of concept of their potential application in tissue regeneration, the natural polymer-coated AuNPs were further functionalized with an antibody to selectively bind the desired GF. The bFGF concentration reached in the NPs without compromising the cytocompatibility demonstrates the potential of this carrier for tissue regeneration.

The influence of patterned nanofiber meshes on human mesenchymal stem cell osteogenesis.

A specially designed electroconductive collector enables the electrospinning of P-NFM composed of areas of parallel/uniaxially aligned fibers and areas of random/orthogonal nanofiber distribution. The biological relevance of P-NFM is demonstrated using hBMSCs as an autologous cell source. The structures induce cell orientation along the uniaxially aligned fibers, mainly during earlier culturing periods under basal and osteogenic differentiation conditions. The microtopography of the P-NFM also controls the deposition of mineralized extracellular matrix along the pre-defined fiber direction. Genotypic characterization confirms the successful differentiation into the osteogenic lineage.