José Roberto Kfoury Junior

Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular heme-dependent enzyme that catalyzes the initial oxidation of L-tryptophan into the kynurenine pathway, thereby linking tryptophan metabolism to immune regulation. IDO1 expression is mainly induced by interferon-γ during immune activation and inflammation, and its activity helps control immune responses through tryptophan depletion and the generation of immunomodulatory metabolites. Because of its central role in immunometabolism, IDO1 has been widely investigated as a therapeutic target, and several strategies have been developed to inhibit its enzymatic activity or reduce its functional contribution to immune suppression. However, increasing evidence indicates that IDO1 inhibition may not completely interrupt tryptophan catabolism or downstream immunoregulatory signaling. Instead, IDO1 blockade can be accompanied by compensatory mechanisms that preserve metabolic and immune regulatory outputs. These mechanisms may include activity or upregulation of alternative tryptophan-catabolizing enzymes such as TDO2, IDO2, and IL4I1; metabolic diversion toward serotonin and melatonin pathways; microbiota-derived indole production; and cell-type-specific metabolic rewiring. Therefore, understanding these adaptive responses is essential for interpreting the limited efficacy of IDO1-targeted approaches and for improving therapeutic strategies directed at tryptophan metabolism. This review discusses the main compensatory pathways that may emerge under IDO1 inhibition and their relevance to developing more effective immunometabolic interventions.

The tongue is a highly specialized organ whose structural organization reflects functional adaptations related to feeding, grooming, and sensory perception. Although the morphology of the adult domestic cat tongue is well documented, information concerning its prenatal development remains scarce. This study aimed to characterize the macroscopic, microscopic, and ultrastructural development of the lingual epithelium in domestic cat fetuses ( Felis catus , Linnaeus, 1758) at different gestational stages. Materials and Methods: Fifteen male fetuses were allocated into three gestational groups: early (31–39 days), intermediate (40–50 days), and late (≥ 51 days). Gestational age was determined by crown–rump length measurement. Tongue samples were analyzed using light microscopy, scanning electron microscopy, and transmission electron microscopy to assess epithelial differentiation, papillae formation, and extracellular matrix organization throughout development. In the early stage, the epithelium exhibited initial organization, with a basal layer, a poorly stratified superficial layer, and early papillary primordia, accompanied by sparse and disorganized collagen fibers. The intermediate stage demonstrated marked epithelial stratification, with defined basal, spinous, and granular layers and focal stratum corneum formation, associated with increased collagen density and structural organization. In the late stage, the tongue exhibited a keratinized stratified squamous epithelium, fully differentiated filiform, fungiform, foliate, and circumvallate papillae, and a dense, organized collagen network. Ultrastructurally, well-developed desmosomal junctions indicated strong epithelial cohesion. The domestic cat tongue develops progressively and coordinately during gestation, reaching structural maturity prenatally, thereby ensuring immediate functional competence at birth.

Purpose: To characterize histologically and stereologically the hepatic steatosis in obese Zucker (fat, n = 6, with a mutation in the leptin receptor – Leprfa) and control Zucker (lean, n = 6) rats, analyzing macroscopic and microscopic differences to understand the influence of obesity on hepatic pathology.

O diagnóstico e o tratamento de patologias hepáticas em cães e gatos são cruciais, considerando o papel vital do fígado no metabolismo, na detoxificação e na síntese de proteínas indispensáveis. Este estudo busca avaliar a relevância do diagnóstico e manejo das patologias hepáticas nesses animais, identificando os métodos diagnósticos mais precisos, avaliando as opções terapêuticas existentes e sua eficiência, e explorando o impacto dessas intervenções na qualidade de vida e prognóstico dos pets. A metodologia de revisão bibliográfica adotada envolve a localização, análise e compilação sistemática de publicações pertinentes sobre o tema, com o intuito de alcançar um entendimento detalhado e crítico do estado atual dos conhecimentos na área. Este trabalho enfatiza a necessidade de uma abordagem integrada e abrangente no diagnóstico e tratamento das doenças hepáticas em cães e gatos. A combinação de inovações diagnósticas com tratamentos interdisciplinares é essencial para otimizar os resultados clínicos. Além disso, a pesquisa contínua e a implementação prática das descobertas são fundamentais para o desenvolvimento sustentável neste campo crucial da medicina veterinária. Com a evolução das técnicas e a melhoria dos tratamentos, espera-se não apenas prolongar a vida desses animais, mas também melhorar significativamente sua qualidade de vida.

Extrinsic thoracic limb muscles are a muscular group that supports the thoracic limb in mammals without the clavicle and serve to move the scapula and shoulder joint. However, there are few evolutionary studies of these muscles in Felis catus, which should take into account the topology and innervation of the muscles to hypothesize the muscle derivation from a common ancestor. The main objective of this study was to check the extrinsic thoracic limb muscles in ten cadavers. Intra‐ and interspecific anatomical variants were found with that formerly described and other felids. Based on the topology and innervation found in this study, the evolutionary derivation was hypothesized. Therefore, the omotransversarius and rhomboideus muscles are derived from the serratus ventralis cervicis muscle. The cleidobrachialis muscle is derived mainly from the m. deltoideus and accessorily from the supracoracoid muscular group. The pectoantebrachialis and pectoralis abdominalis muscles are derived from the pectoralis descendens and cutaneus trunci muscles, respectively. In conclusion, most extrinsic thoracic limb muscles of F. catus may have evolutionary derivations from the last common ancestor of mammals, while some of them are from the last common ancestor of carnivorans or within the family Felidae.

In the tumor microenvironment, the function of T cells is a fate-changer for tumor progression. In the meantime, CD28 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are vital role players in the controlling activity of T cells as an activator and deactivator, respectively. In T cells in comparison to CD28, the molecular mechanism of CTLA-4 is unclear. In addition, despite the fact that most tumor cell types express CTLA-4, its role in tumor cells is not well understood and only few studies focused on the role of CTLA-4 signaling in tumor cells. It is illustrated that CTLA-4 signaling causes PD-L1 expression in tumor cells. However, numerous characteristics of CTLA-4 signaling in tumor cells are ambiguous and require to be described. In this article, we proposed that the CTLA-4 signaling during immunotherapy with anti-CTLA-4 antibodies may cause poor responses by patients. In addition, we attract attention to several fundamental questions regarding CTLA-4 signaling in tumor cells. Overall, the CTLA-4 signaling function and the related gaps about its role in tumor cells in the present review are challenged.

This study aimed to evaluate the CD4⁺ and CD8⁺ T lymphocytes counts and CD4⁺: CD8⁺ ratio in a colony of cats with chronic gingivostomatitis (CGS). We used forty domestic short-haired cats inhabiting the same colony. Ten cats with CGS were immunodeficiency virus-positive (group IV), and ten with CGS were immunodeficiency virus-negative (group III). As a control, twenty cats without CGS were used: ten cats were immunodeficiency virus-positive and (group II) and ten cats were immunodeficiency virus-negative (group I). We employed flow cytometry to count CD4⁺ and CD8⁺ T lymphocytes. In FIV-infected cats, the presence of CD4⁺ lymphocytes were lower both for animals with and without CGS. Conversely, non-FIV-infected cats with CGS had a higher amount of CD4⁺ when compared to seronegative animals without CGS. The counts of CD8⁺ T lymphocytes showed no significant difference among cats with CGS, whether infected with FIV or not. The CD4⁺: CD8⁺ ratio was only different for group III, which was higher than any other group. No difference was observed for total lymphocyte number and CD8⁺ among groups. By contrast, mean CD4⁺ levels were different, with cats from groups III and IV showing higher levels than those from groups I and II. The flow cytometry could be a useful tool for the diagnosis and prognosis of cats with CGS infected by the immunodeficiency virus.

En la fisiología de los peces triploides, falta información sobre sus respuestas moleculares bajo estrés y cómo cuantificar los niveles o la intensidad del estrés. Por lo tanto, los objetivos de este ensayo fueron evaluar el patrón de HSP70 en las branquias, el corazón y los músculos de truchas arco iris diploides y triploides no estresadas, y en las células sanguíneas después de la exposición al estrés por calor para evaluar sus niveles de estrés. Se observó una detección inmunohistoquímica de HSP70 similar en las muestras de branquias, corazón y músculos en ambas ploidías. Sin embargo, la expresión de HSP70 en sangre varió entre ploidías durante el tiempo experimental. Las truchas diploides de control y estresadas mostraron niveles análogos de HSP70, pero las truchas triploides estresadas por calor mostraron niveles más bajos de HSP70 durante todo el experimento con diferencias observadas después de 12 h y 24 h. Se esperaba una mayor expresión de HSP70 en ambas ploidías una vez que esta proteína protege a las células contra una amplia gama de agentes perturbadores. Evidencias recientes mostraron que los peces triploides tienen una menor expresión génica y este hecho debe ser explorado en futuras investigaciones en truchas arcoíris. En conclusión, las comparaciones a lo largo del tiempo entre los niveles diploides y triploides de HSP70 en truchas podrían usarse en la evaluación del estrés y de bienestar.