Endocrine, Metabolic & Immune Disorders-Drug Targets - Current Issue

Childhood acute lymphoblastic leukemia (cALL), the most common pediatric hematologic malignancy, arises primarily from B-cell origin and is strongly associated with immune dysfunction. This article integrated single-cell and bulk transcriptomic data to identify key B-cell subsets and cALL-related molecules as biomarkers.

Single-cell RNA sequencing (scRNA-seq) Data from 2 pre-B high hyperdiploid (HHD) ALL patients and 3 healthy pediatric bone marrow samples (GSE132509) were utilized for cell clustering using the Seurat package. Functional enrichment, pseudo-time trajectory, and cell-cell communication analyses were performed using clusterProfiler, Monocle2, and CellChat R packages, respectively. Bulk RNA-seq data of 511 cALL samples in the TARGET-ALL-P2 cohort were used to construct a prognostic model via Cox and LASSO regression. Immune infiltration differences between different risk groups were analyzed using ESTIMATE, MCP-counter, and CIBERSORT algorithms.

The scRNA-seq analysis identified five cell subpopulations, with B cells demonstrating significant enrichment in cALL samples. Notably, the C2 subset was associated with cell proliferation. Ligand-receptor analysis revealed key interactions involving B cell C2. Four marker genes (CENPF, IGLL1, ANP32E, and PSMA2) were identified to build a risk model. Low-risk patients showed better survival, while high-risk patients had higher ESTIMATE scores.

This study examined the key role of B cells in cALL, constructed a risk model with strong prognostic predictive ability applying multi-omics analysis, and primarily explored its potential mechanism in immune regulation.

This study revealed the critical role of B cells in cALL, and the prognostic model showed a high prediction accuracy, providing a potential target for individualized treatment of cALL.

Hyperuricemia Nephropathy (HN) is an emerging metabolic disorder that predisposes individuals to Chronic Kidney Disease (CKD), yet effective treatments remain limited. Inflammation plays a pivotal role in HN-induced kidney injury, with the NLRP3 inflammasome serving as a central mediator of this process. This study investigates the therapeutic effects of Yipishen Xiezhuo Jiedu Decoction (YPSXZJDD), a traditional Chinese medicine, on HN-induced kidney injury through the miR-223/NLRP3/Caspase-1 pathway.

The key active components of YPSXZJDD were screened using UHPLC-Q Exactive Orbitrap-MS, and a Protein-Protein Interaction (PPI) network diagram was constructed to explore potential mechanisms of action. The identified components were then utilized to intervene in both cellular and animal models of hyperuricemic nephropathy, evaluating their therapeutic effects and underlying mechanisms.

Catalpol and Tanshinone IIA were identified as the key active components of YPSXZJDD. These compounds significantly mitigated renal epithelial cell apoptosis and inflammation by upregulating miR-223, which in turn inhibited the NLRP3/Caspase-1 pathway. The upregulation of miR-223 led to a marked reduction in NLRP3 activity and inflammatory responses, thereby alleviating HN-induced kidney damage.

The findings of this study underscore the critical role of miR-223 in regulating the NLRP3 inflammasome and highlight its potential as a therapeutic target for HN. The inhibition of the NLRP3/Caspase-1 pathway by miR-223 significantly reduces inflammation and renal injury, demonstrating the therapeutic efficacy of YPSXZJDD. These results offer a novel perspective on the application of traditional Chinese medicine in treating HN, highlighting the importance of miR-223 in regulating inflammation.

This study demonstrates that YPSXZJDD alleviates HN-induced kidney injury by upregulating miR-223 and inhibiting the NLRP3/Caspase-1 pathway. The therapeutic potential of YPSXZJDD is supported by its ability to mitigate inflammation and renal damage, offering a promising approach for HN treatment. Further research into the broader role of miR-223 in kidney disease and related conditions is warranted to expand the understanding of its therapeutic applications.

This study aims to investigate the relationship between steroid use, adrenal suppression, and frequent emergency department (ED) visits in patients with Chronic Obstructive Pulmonary Disease (COPD).

Systemic glucocorticoids are commonly prescribed in the management of COPD exacerbations; however, prolonged or repeated steroid use may lead to adrenal suppression. Although the standard steroid regimen for COPD exacerbations is short-term, frequent ED visits may result in cumulative steroid exposure, raising concerns about adrenal insufficiency and its clinical consequences.

This study investigates the potential association between steroid-induced adrenal suppression and frequent ED visits among COPD patients. It further examines the impact of steroid administration on cortisol and Adrenocorticotropic hormone (ACTH) levels.

This prospective, cross-sectional, observational study was conducted in a university-based ED. Patients with COPD, with dyspnea and who presented to the ED between 06:00-08:00 were included. Demographics, previous presentations to the ED, medications used, hormone levels, and other laboratory results were recorded.

Fifty patients (82% were male) included. Sputum symptoms along with incidences of heart failure were higher in patients who received steroids in the ED. Ronchi was higher, crackles and pretibial edema were lower in the patients who received steroids in the ED. Among the patients with low cortisol levels, the frequency of patients who received steroids in the ED was higher than those who did not.

Primary healthcare clinicians should monitor COPD patients for potential adrenal insufficiency. Careful regulation of steroid dosages during exacerbation treatment and minimizing polypharmacy are essential to mitigate the long-term effects of prolonged steroid use.

The objective of this study was to evaluate the demographic, clinical, laboratory, and ultrasonographic characteristics of patients diagnosed with subclinical hypothyroidism, with a particular emphasis on the anti-thyroid peroxidase (anti-TPO) antibody and inflammatory biomarkers.

The study included 157 patients diagnosed with subclinical hypothyroidism, categorised into anti-TPO-positive and anti-TPO-negative groups. A retrospective comprehensive evaluation comprising demographic data, thyroid medication status, ultrasonographic characteristics, and laboratory parameters was conducted and statistically analysed between the groups.

Of 157 patients, 48.4% were anti-TPO positive. This group was significantly associated with increased levothyroxine (LT4) use and sonographic parenchymal heterogeneity. However, there were no significant differences in nodule presence, number, size, or structure. A positive correlation was found between anti-TPO and ferritin levels. In addition, a positive correlation was observed between the thyroid-stimulating hormone (TSH)/free T4 ratio and the solidity of nodules, as well as between TSH and the neutrophil-to-lymphocyte ratio (NLR). Surprisingly, a negative correlation was found between anti-TPO levels and the number of nodules, as well as the cystic characterisation of the nodules.

In our study, higher levels of anti-TPO and TSH were associated with inflammatory markers such as ferritin and NLR, suggesting a possible link with systemic inflammation. Furthermore, anti-TPO and the TSH/T4 ratio also showed associations with specific sonographic features of the thyroid gland.

TSH and anti-TPO levels might be associated with systemic inflammation and thyroid sonographic findings in patients with subclinical hypothyroidism. More studies on larger patient populations should confirm the same results to suggest their clinical significance.