Current Medicinal Chemistry - Volume 32, Issue 19, 2025

Periodontal disease is a highly prevalent oral pathology in the human population, which has a significant local and systemic impact. Currently, multi-omics analyses, including lipidomics, are fundamental to obtaining an in-depth molecular understanding of the individual. Lipidomics is dedicated to the study of lipid species and their interactions in various health contexts. This specific multi-omics analysis is important for understanding the alteration of metabolism and signaling in disease, identifying biochemical markers, and potential therapeutic targets.

This study aimed to carry out a systematic review of the existing scientific literature on lipidomics in periodontal disease and thus determine which molecules have already been analyzed and their potential in this specific disease.

This study followed the recommendations of the PRISMA 2020 methodology. The inclusion criteria used were articles published in indexed journals between 2000 and 2023, written in English, and establishing an exclusive relationship about lipidomics in human periodontal disease. The articles were searched in three different databases.

Considering the criteria defined, only six articles were selected and analyzed individually in detail. In four of the six studies, differences in the lipidome of individuals with periodontal disease were identified. Furthermore, phosphoethanolamine ceramide was found to have potential as a diagnostic biomarker. Finally, the therapeutic potential of a lipoxin A4 analogue was also identified.

These results reinforce the need for future research in this area so that the consequences of this disease on the lipidome can be identified.

While it has been demonstrated that delivery of cytotoxic chemotherapy using nanoparticles greatly improves patient drug tolerance and reduces toxicity when compared to the standard formulation, the crucial question of whether they also increase anticancer efficacy remains. The CRLX101 is a nanoparticle composed of cyclodextrin and 20(S)-camptothecin cytotoxic chemotherapy.

In order to compare the efficacy of the CRLX101 to its corresponding traditional formulation, we carried out this systematic literature search for randomized clinical and non-randomized trials.

Multiple electronic databases, including PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and clinicaltrials.gov, were used to conduct a thorough literature search. By employing a technique akin to a random-effects model, the median of the study-specific was taken into account as the pooled median estimate with a 95% confidence interval.

Finally, nine clinical studies were chosen for the meta-analysis. The treatment and control groups' overall survival were examined in five and three trials, respectively. Additionally, six out of nine trials and two out of nine trials, respectively, examined the treatment and control groups for progression-free survival (PFS). Meta-analysis revealed that the treatment group had a lower median overall survival (OS) but a greater median progression-free survival than the control group.

Our meta-analysis shows that CRLX101 outperforms camptothecin in PFS despite its inferior OS. Unresolved pharmacology limits carrier-mediated drug therapeutic application. Carrier-mediated dosages may differ from normal formulations because they are rarely studied.

Colorectal cancer (CRC) cases with advanced or distal metastases experience a survival rate of less than 20%, with the lack of spectral therapeutic targets and prognostic markers posing a significant challenge for CRC treatment. SLC4A4 may be a CRC-targeted therapy for which there is currently inadequate evidence.

In this report, we performed a comprehensive analysis of data on colorectal cancer (CRC) to elucidate the association among Solute Carrier Family 4 Member 4 (SLC4A4) and the abundance of immunological features and immune cell infiltration in CRC and to explore the impact of SLC4A4 on the CRC tumor microenvironment.

The objective of this study was to systematically reveal the characteristics of the tumor microenvironment created by SLC4A4.

We downloaded RNA sequencing files from the Cancer Genome Atlas (TCGA-COADREAD). The correlations of SLC4A4 with immune-related characteristics were analyzed. A Limma package was applied for selecting SLC4A4/immunity-related differentially expressed genes (DEGs). An assessment system for predicting CRC prognosis was constructed based on univariate COX and multivariate COX analyses. A nomogram was also designed to assess the survival risk status of CRC. Besides, we evaluated the potential association of SLC4A4 to immunotherapy through TIDE analysis.

We found that SLC4A4 expression was positively correlated with immune checkpoint expression (PD-L1). SLC4A4 promoted the infiltration of CD8 T cells, dendritic cells, macrophages, NK cells, and Th1 cells in CRC, shaping the inflammatory tumor microenvironment. Up-regulated SLC4A4 might improve drug response to anti-FGFR3 therapy, anti-PPARG therapy, nivolumab, and ipilimumab in CRC patients, and down-regulated SLC4A4 might promote drug response to anti-EGFR therapy and Aflibercept drug response. The constructed RiskScore model showed excellent predictive effect and robustness. RiskScore presented a trend of negative correlation with SLC4A4, which was consistent with the trend of the effect of SLC4A4 on CRC survival. TIDE analysis further disclosed that high-risk groups with high levels of SLC4A4 were possible for immune escape. Finally, the constructed nomogram also showed potential clinical value.

Overall, upregulation of SLC4A4 expression promoted an inflammatory tumor microenvironment in CRC, and RiskScore predicted therapeutic expectancy. SLC4A4 could be a potentially clinically valuable target for CRC therapy.

The aim of this study was to evaluate the combined and comparative efficacy of Caffeic acid phenethyl ester (CAPE) and curcumin in breast cancer.

CAPE and curcumin are a class of phenolics. While curcumin is obtained from turmeric, CAPE is found in Baccharis sarothroides and Populus deltoides. Both agents are reported to produce activities in some cancer types. The combined and comparative effects of the two agents in breast cancer have not yet reported.

We evaluated the potential of CAPE and curcumin in both in vitro and in vivo breast cancer models.

Human breast cancer cell lines, MDA-MB-231 and MCF-7, were exposed to CAPE and curcumin, followed by functional assays such as cell cytotoxicity, cell proliferation and colony formation, cell cycle, mitochondrial membrane potential, apoptosis, and monodansylcadaverine (MDC) staining for autophagy. Computational analyses and mouse models were also used.

Employing computational analyses, both agents were found to exhibit drug-like properties. Both molecules interacted with the key molecules of the NF-κB pathway. CAPE and curcumin inhibited cell proliferation, colony formation, and invasion, triggering apoptosis in breast cancer cells. CAPE was found to be more effective than curcumin. Two agents working together were more effective than each agent working alone. Both agents suppressed the expression of survivin, Bcl-xL and GLUT-1. The level of cleaved PARP was increased by both agents. Both phenolics observed an induction in ROS generation. Further, both molecules triggered a dissipation in mitochondrial membrane potential. In mice models implanted with Ehrlich-Lettre ascites carcinoma (EAC) cells, both drugs inhibited the growth of the tumour. The phenolics also modulated the metabolic parameters in tumour-bearing mice.

The observations suggest that the combination of curcumin plus CAPE may be better in comparison to individual molecules.

The study opens a window for analysing the efficacy of the combination of CAPE and curcumin in animal studies. This will provide a basis for examining the combined efficacy of two agents in a clinical trial.