Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 25, Issue 6, 2025

Bioinformatic analysis is a valuable tool that allows us to collect, archive, analyze, and disseminate biological data for further interpretation. Analysis of the IL-23/IL-17A axis and its receptors will provide us with essential information about their functions, interactions, and relationships with various diseases. This review aims to identify the central genes co-expressed in the IL-23/IL-17A axis and their receptors and to understand their ontology and modifying factors.

We used several databases, including COXPRESdb to obtain the co-expressed genes, ShinyGO and ToppGene platforms to explore gene functional enrichment, and the NetworkAnalyst 3.0 platform for gene expression profiling.

We found that genes encoding IL-23/IL-17A axis proteins and their receptors mainly respond to microbial components, participate in the inflammatory response, and are primarily associated with inflammatory and autoimmune diseases. In addition, we observed an association of the IL-23/IL-17 axis with Behcet's disease, Graft-versus-host disease, and Hodgkin's disease, although there is no direct evidence of their interaction.

The IL-23/IL-17A axis is associated with several inflammatory and autoimmune pathologies. Therefore, we suggest further research to confirm its role in these pathologies and, if possible, use it as a therapeutic target.

Obesity is becoming a global pandemic with pandemic proportions. According to the WHO estimates, there were over 1.9 billion overweight individuals and over 650 million obese adults in the globe in 2016. In recent years, scientists have encountered difficulties in choosing acceptable animal models, leading to a multitude of contradicting aspects and incorrect outcomes. This review comprehensively evaluates different screening models of obesity and obesity-associated comorbidities to reveal the advantages and disadvantages/limitations of each model while also mentioning the time duration each model requires to induce obesity.

For this review, the authors have gone through a vast number of article sources from different scientific databases, such as Google Scholar, Web of Science, Medline, and PubMed.

In-vivo models used to represent a variety of obesity-inducing processes, such as diet-induced, drug-induced, surgical, chemical, stress-induced, and genetic models, are discussed. Animal cell models are examined with an emphasis on their use in understanding the molecular causes of obesity, for which we discussed in depth the important cell lines, including 3T3-L1, OP9, 3T3-F442A, and C3H10T1/2. Screening models of obesity-associated co-morbidities like diabetes, asthma, cardiovascular disorders, cancer, and polycystic ovarian syndrome (PCOS) were discussed, which provided light on the complex interactions between obesity and numerous health problems.

Mimicking obesity in an animal model reflects multifactorial aspects is a matter of challenge. Future studies could address the ethical issues surrounding the use of animals in obesity research as well as investigate newly developed models, such as non-mammalian models. In conclusion, improving our knowledge and management of obesity and related health problems will require ongoing assessment and improvement of study models.

The objective of this study was to examine the impact of “Tianyu” Pairing on oxidative stress in the development of Rheumatoid arthritis (RA) and approach its potential mechanism using cell experiments.

A cell model of RA was developed by stimulating rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumor necrosis factor-α (TNF-α). This model aimed to assess the impact of serum containing Rhodiola rosea-Euonymus alatus drug pair (TYP) on inflammation and oxidative stress in the development of RA, specifically through the Keap1/Nrf2/HO-1 pathway.

The findings from the in vitro experiment demonstrated that the presence of TYP in the serum effectively suppressed the proliferation of RA-FLS induced by TNF-α. Additionally, TYP facilitated the apoptosis of afflicted cells, attenuated the migratory and invasive capabilities of diseased cells, and decreased the levels of Kelch ECH associating protein 1 (Keap1), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) (p < 0.01). The influence of inflammation and oxidative stress in RA-FLS cells was reduced by increasing the nuclear-cytoplasmic ratio of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and levels of phosphorylated Nrf2, Heme Oxygenase 1 (HO-1), and Superoxide Dismutase (SOD) (p < 0.01).

TYP can regulate inflammation and oxidative stress in RA-FLS cells by activating the Keap1/Nrf2/HO-1 pathway.

This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression.

Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented.

In this work, we aimed to examine the molecular mechanisms of a novel m6A-modified circRNA, hsa_circ_0131922, in PTC progression.

Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments.

The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 in vivo and in vitro.

The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.

We present an unusual case of a 28-year-old rheumatologic male patient who developed eosinophilia while he was on etanercept therapy previously and then on golimumab.

Although eosinophilia is rarely reported in the literature as a side-effect of various Tumor Necrosis Factor-alpha (TNF-alpha) antagonists, it represents a riddle about the future treatments of these patients since the persistence of therapy might lead to the onset of dermatologic or visceral eosinophilic complications in such patients.

Furthermore, the pathogenesis of eosinophilia is still unknown, and all the proposed hypotheses do not explain the eosinophilic proliferation in certain subjects.