Current Medicinal Chemistry - Volume 31, Issue 41, 2024

Parasitic diseases are a public health problem despite the existence of drugs for their treatment. These treatments have variable efficacy and, in some cases, serious adverse effects. There has been interest in the enzyme carbonic anhydrase (CA) in the last two decades since it is essential in the life cycle of various parasites due to its important participation in processes such as pyrimidine synthesis, HCO3^- transport across cell membranes, and the maintenance of intracellular pH and ion transport (Na⁺, K⁺, and H⁺), among others.

In this review, CA was analyzed as a pharmacological target in etiological agents of malaria, American trypanosomiasis, leishmaniasis, amoebiasis, and trichomoniasis. The CA inhibitors´ design, binding mode, and structure-activity relationship are also discussed.

According to this review, advances in discovering compounds with potent inhibitory activity suggest that CA is a candidate for developing new antiprotozoal agents.

Propolis and its major phenolic compound, caffeic acid phenethyl ester (CAPE), have garnered considerable scientific interest due to their anti-inflammatory properties and potential therapeutic applications.

This narrative review explores the potential utility of CAPE in cancer treatment.

We comprehensively reviewed relevant studies from scientific databases (PubMed and Web of Science) from 2000 to 2022. Our search focused on keywords such as cancer, natural drugs, caffeic acid phenethyl ester, CAPE, cancer cell lines, antitumor effects, and propolis.

CAPE exhibits diverse biological benefits, including antimicrobial, antioxidant, antiviral, anti-inflammatory, cytotoxic, and potentially anti-carcinogenic properties. Numerous studies have demonstrated its wide-ranging antitumor effects on various cancer cell lines, including growth inhibition, apoptosis induction, tumor invasiveness prevention, malignancy suppression, and anti-angiogenic activity.

Following comprehensive preclinical toxicity assessments, further evaluation of CAPE's efficacy and safety through clinical trials is highly recommended to elucidate its potential health benefits in diverse forms of human cancer.

To explore the diagnostic biomarkers for diagnosing endometriosis.

Endometriosis is a benign, progressive, estrogen-dependent gynecological disorder that has highly variant prevalence. Therefore, it is essential to develop reliable diagnostic biomarkers for endometriosis diagnosis.

To explore the diagnostic biomarkers for endometriosis diagnosis.

Based on transcriptome data from GSE145701, we identified potential therapeutic targets through the intersection of endometriosis-related genes from weighted gene correlation network analysis (WGCNA) and differential expression analysis. Aprotein-protein interaction (PPI) was constructed. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for functional enrichment analysis. The intersection of hub genes from topological analysis and module genes from module-based network analysis were selected as core targets, which were used for diagnostic model construction. Its robustness was validated using GSE7305 and GSE134056. Associations of core targets with immune characteristics and pathways were further evaluated. Molecular docking was employed to evaluate the docking affinity between core targets and drugs. Additionally, western blot and quantitative real-time polymerase chain reaction were also carried out to validate molecular docking results.

A diagnostic model was constructed using 7 core targets, which had a high diagnostic ability for endometriosis. CTSK was positively correlated with immune scores, while CDH2 was negatively correlated with immune scores. CTSK, HGF, and EPCAM were positively correlated with energy metabolism and inflammation-related pathways, while RUNX2, FN1, NCAM1, and CDH2 were positively correlated with epithelial-to-mesenchymal transition (EMT) and unfolded protein response (UPR). Moreover, FN1 had good docking affinity with Elagolix, Esmya, and Proellex. NCAM1 might be a promising target modulated by Elagolix. In vitro experiment revealed that the expression of FN1 in human normal endometrial cell lines (hEEC) gradually decreased with the increase of Esmya concentration, indicating that FN1 was a target for Esmya.

These results may facilitate the in-depth understanding of the development of endometriosis, and guide early diagnostic as well as clinical treatments for patients with endometriosis.

Systemic multi-organ dysfunction resulting from dysregulated immune responses in the host triggered by microbial infection or other factors is a major cause of death in sepsis, and secretory pathways play an important role in it.

GSE57065, GSE65682, GSE145227, and GSE54514 from Gene Expression Omnibus (GEO) were derived for this study. Secretory pathways single sample gene set enrichment analysis (ssGSEA) scores in sepsis and normal samples were exposed. Gene modules associated with secretory pathways were selected by weighted gene co-expression network analysis (WGCNA) for Protein-Protein Interaction Networks (PPI) assessment, and crossover genes in both were evaluated by eXtreme Gradient Boosting (XGBoost) model in feature selection to identify hub genes in sepsis. In addition, we explored the immune cells and signaling pathways regulated by hub genes.

Remarkable dysregulation of secretory pathways was demonstrated in sepsis. The secretory pathways-associated gene modules were intimately involved in cytokine and immune responses in infection. Four crossover genes (CD163, FCER1G, C3AR1, ARG1) were present in WGCNA and PPI, and training in the XGBoost model revealed the best diagnostic performance of these 4 genes, meaning that these genes were the hub genes for sepsis. The 4-hub genes showed a significant negative correlation with T cell activity and a significant positive correlation with inflammatory immune cells. In addition, we found that the 4-hub genes markedly positively regulated INFLAMMATORY RESPONSE, IL6 JAK STAT3 SIGNALING.

Based on WGCNA, PPI, and XGBoost models, we identified hub genes that play an important regulatory role in sepsis. We also developed novel molecular models for the diagnosis of sepsis.

Due to the confounding heterogeneity, the therapeutic strategy for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) remains to be defined.

We report a 38-year-old man with recurrent swelling of the eyelids and lower limbs, undergoing rituximab combined with steroid and tacrolimus treatment, who achieved an improved renal outcome. Underlying solid malignant tumours were excluded from the diagnosis.

We treated patients with rituximab along with steroids and tacrolimus. Improvements in proteinuria and renal function were observed. We also reviewed the current literature to assess the efficacy of rituximab in the treatment of PGNMID.

However, a larger pool of patients and a longer follow-up period are required to establish the role of rituximab and steroids in the treatment of PGNMID.