Glycine is a non-essential amino acid with many functions and effects. Glycine can bind to specific receptors and transporters that are expressed in many types of cells throughout an organism to exert its effects. There have been many studies focused on the anti-inflammatory effects of glycine, including its abilities to decrease pro-inflammatory cytokines and the concentration of free fatty acids, to improve the insulin response, and to mediate other changes. However, the mechanism through which glycine acts is not clear. In this review, we emphasize that glycine exerts its anti-inflammatory effects throughout the modulation of the expression of nuclear factor kappa B (NF-κB) in many cells. Although glycine is a non-essential amino acid, we highlight how dietary glycine supplementation is important in avoiding the development of chronic inflammation.

Background: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells. The 3T3-L1 cells were stimulated with TNF-α (5 ng/mL) for 60 min as an inflammatory model. Gene expression was measured by RT-qPCR. Results: We showed that the inflammatory stimulus of TNF-α in adipocytes decreased the expression of the orphan receptors GPR21, GPR26, GPR39, GPR82 and GPR6, which are related to low-grade inflammation. Conclusions: Our results suggest that GPR21 and GPR82 are modulated by glycine, it shows a possible protective role in the presence of an inflammatory environment in adipocytes, and they could be a therapeutic target to decrease the inflammation in some diseases related to low-grade inflammation such as diabetes, obesity and metabolic syndrome.

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT₁R blockade has anti-inflammatory effects. The use of an AT₁ receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT₁ receptor gene silencing on the modulation of cytokines (e.g., IL-1β, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. Materials and Methods: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT₁R, NF-κB, and cytokines (IL-1β, TNF-α, and IL-10) were measured by RT-qPCR. Results: We observed that silencing of the AT₁ receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1β and TNF-α), NF-κB, and PPAR-γ. Conclusions: We conclude that AT₁R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1β via NF-κB in macrophages and having high blood pressure decrease.

Diabetes mellitus is a metabolic disease that can produce different alterations such as endothelial dysfunction, which is defined as a decrease in the vasodilator responses of the mechanisms involved such as the nitric oxide (NO) pathway. The overexpression of PDE5A has been reported in diabetes, which causes an increase in the hydrolysis of cGMP and a decrease in the NO pathway. For this reason, the aim of this study was to evaluate whether siRNAs targeting PDE5A can reduce the endothelial dysfunction associated with diabetes. We used male Wistar rats (200–250 g) that were administered streptozotocin (STZ) (60 mg/kg i.p) to induce diabetes. Two weeks after STZ administration, the siRNAs or vehicle were administered and then, at 4 weeks, dose–response curves to acetylcholine were performed and PDE5A mRNA levels were measured by RT-PCR. siRNAs were designed by the bioinformatic analysis of human–rat FASTA sequences and synthesised in the Mermade-8 equipment. Our results showed that 4 weeks of diabetes produces a decrease in the vasodilator responses to acetylcholine and an increase in the expression of PDE5A mRNA, while the administration of siRNAs partially restores the vasodilator response and decreases PDE5A expression. We conclude that the administration of siRNAs targeting PDE5A partially reverts the endothelial impairment associated with diabetes.

Zoapatle, a native plant utilized for centuries in traditional Mexican medicine, is abundantly found in Mesoamerica and northern South America. Pleiotropic effects of this genus have been recognized, primarily inducing alterations in smooth muscle contractility in animal models. The aim of this study was to evaluate the effect of Zoapatle on the hypertrophy index and the gene expression of TNF-α, IL-1β, NF-κB, STAT5, and the PRLR in the brain, left ventricle, and renal cortex of rats with isoproterenol-induced cardiac hypertrophy. Three groups were studied, the control group (n = 4), hypertrophy group (n = 4) and hypertrophy group treated with Zoapatle (n = 4). A ventricular hypertrophy model was developed with 150 mg/kg/day of isoproterenol intraperitoneally administered over two days with a 24 h interval between applications. Zoapatle was administered for 28 consecutive days (25 mg/kg). Gene expression was determined with RT-qPCR. Subsequently, a principal component analysis (PCA) was performed using the RNA expression variables. A notably reduced left ventricle mass index was observed in the Zoapatle group. Additionally, Zoapatle administration in cardiac hypertrophy demonstrated a significant decrease in the gene expression of TNF-α, IL-1B, STAT 5, and the PRLR. TNF-α and the transcription factor STAT5 exhibited a similar trend in both the left ventricle and renal cortex, suggesting a correlation with the inflammatory state in these tissues due to ventricular hypertrophy. The findings suggest that Zoapatle reverses the hypertrophy index in a hypertrophy model, concurrently reducing several proinflammatory mediators associated with the hypertrophy index.

Background: Conventional omics analysis often treats outliers as noise, yet they may harbor critical biological insights. Objetive: This study proposes a paradigm shift: actively investigating outliers to discover biologically relevant subtypes within metabolic–inflammatory syndromes. Methods: We applied a comprehensive analytical framework for outlier detection based on a multi-algorithm consensus (IQR, MAD, Isolation Forest) to a clinical cohort of diabetic neuropathy (n = 93) and an in vitro 3T3-L1 adipocyte model (n = 39). The identified outliers were characterized using robust PCA, co-expression networks, unsupervised clustering, and Random Forest predictive modeling. Results: In the clinical cohort, an outlier subgroup (47.3%) exhibited an extreme immune–metabolic phenotype characterized by hyperactivation of Th1/Th17 pathways (elevated T-bet and IL-17; p < 0.001), hypertriglyceridemia, and network reconfiguration (TGFβ and STAT4 hubs). In the cellular model, outlier samples (12.8%) showed autonomous pro-inflammatory behavior characterized by IL-6 overproduction (p = 0.002) and IL-10 suppression. Conclusions: Multivariate analysis confirmed spatial segregation of these profiles. Systematic outlier investigation revealed discrete pathophysiological subtypes invisible to mean-focused analyses, demonstrating that extreme values encapsulate potent biological signals. This framework offers a generalizable approach for uncovering clinical heterogeneity and identifying therapeutic targets in complex diseases.