The renin–angiotensin–aldosterone system (RAAS) plays a pivotal role in regulating cardiovascular function, fluid balance, and blood pressure. Recent research has revealed the RAAS’s influence extends beyond cardiovascular physiology, encompassing key roles in inflammation, fibrosis, immune regulation, cancer progression, and organ-specific disease mechanisms. This review provides a comprehensive overview of classical and alternative RAAS pathways, focusing on the dual roles of angiotensin II (Ang II) and angiotensin-(1–7) (Ang 1–7), mediated through AT1R, AT2R, MasR, and MrgD receptors. We discuss molecular signaling cascades, including mitochondrial, nuclear, and caveolae-mediated mechanisms, and explore the impact of RAAS modulation on hepatic fibrosis, vascular remodeling, and autoimmune inflammation. Genetic models and emerging pharmacologic strategies illustrate tissue-specific RAAS actions, emphasizing the therapeutic potential of enhancing the ACE2/Ang 1–7/Mas axis while inhibiting the deleterious ACE/Ang II/AT1R signaling. Furthermore, we highlight implications for veterinary medicine, particularly in canine chronic inflammatory enteropathies, where RAAS dysfunction may contribute to treatment resistance. Understanding RAAS complexity and inter-receptor crosstalk is essential for developing new therapeutic strategies targeting cardiovascular, hepatic, and inflammatory diseases in both human and veterinary contexts.

The gut microbiota plays a crucial role in several physiologic functions of the host. In humans and animals, manipulation of the intestinal microbiota by oral administration of probiotic lactic acid bacteria plays a significant role in modulating the immune system. The aim of this study was to evaluate the safety of the probiotic mixture Slab51^® and the capacity of this mixture to stimulate immune function in healthy dogs. Twenty dogs were divided in two groups and received a control diet or the same diet supplemented with a dose of 400 billion cfu of lyophilized bacteria for a period of 60 days. Body weight, food intake, body condition score (BCS), fecal score (FSS), fecal immunoglobulin IgA concentration, plasma IgG concentration, and fecal microbiota composition were monitored. Weight, food intake, BCS, FSS, and biochemical parameters remained unchanged during the treatment in both groups of animals. The fecal microbiota showed a significant decrease in the abundance of Clostridium perfringens and a significant increase in the abundance of beneficial Bifidobacterium and Lactobacillus organisms (p < 0.05). Fecal IgA and plasma IgG levels were significantly higher in the group receiving the probiotic compared to healthy controls. These data show that dietary supplementation with the probiotic mixture Slab51^® is safe and well-tolerated, modulating the composition of the intestinal microbiota, and enhancing specific immune functions in healthy dogs.

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. 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. 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. 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.

Chronic constipation (CC) and idiopathic megacolon (IMC) occur frequently in cats. The aim of the study was to investigate the effects of a multi-strain probiotic (SLAB51™) in constipated cats (n=7) and in patients with megacolon and constipation (n=3). Ten pet cats with a diagnosis of chronic constipation, non-responsive to medical management received orally 2×10¹¹bacteria daily for 90 days. For microbiota analysis, selected bacterial groups were analysed by qPCR. Histological samples in megacolons were evaluated for interstitial cells of Cajal (ICC), enteric neurons, and neuronal apoptosis. Biopsies were compared at baseline (T0) and after the end of treatment (T1), and with those obtained from healthy control tissues (archived material from five healthy cats). Constipated cats displayed significantly lower ICC, and cats with idiopathic megacolon had significantly more apoptotic enteric neurons than controls. After treatment with SLAB51™, significant decreases were observed for feline chronic enteropathy activity index (FCEAI) (P=0.006), faecal consistency score, and mucosal histology scores (P<0.001). In contrast, a significant increase of ICC was observed after probiotic therapy.Lactobacillusspp. andBacteroideteswere increased significantly after treatment (comparing constipated cats before and after treatment, and control healthy cats to constipated cats after treatment), but no other differences in microbiota were found between healthy controls and constipated cats. Treatment with SLAB51™ in cats with chronic constipation and idiopathic megacolon showed significant clinical improvement after treatment, and histological parameters suggest a potential anti-inflammatory effect of SLAB51™, associated with a reduction of mucosal infiltration, and restoration of the number of interstitial cells of Cajal.

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.