Current Medicinal Chemistry[JOURNAL]
Sun
200 papers
Uncovering Cancer-Associated Adipocytes: An Emerging Force Reshaping the Immunotherapy Landscape for Breast Cancer.
Qian K, Xu S, Zhang K … +1 more , Zhang H
Curr Med Chem · 2026 Apr · PMID 42083955 · Publisher ↗
The progression of breast cancer is intricately linked to the dynamic crosstalk between tumor cells and stromal cells. Within this complex interplay, Cancer-Associated Adipocytes (CAAs) have emerged as pivotal stromal co...
The progression of breast cancer is intricately linked to the dynamic crosstalk between tumor cells and stromal cells. Within this complex interplay, Cancer-Associated Adipocytes (CAAs) have emerged as pivotal stromal components driving breast cancer malignancy by establishing a unique "adipose-immune" interface-one that integrates adipose-derived metabolic cues with immune cell dynamics to create a niche that accelerates tumor invasion, angiogenesis, and treatment resistance. This review systematically analyzes the roles of CAAs in breast cancer pathogenesis, focusing on how CAAs regulate the Tumor Immune Microenvironment (TIME) and the Adipose Tissue Microenvironment (ATME) individually and how they influence therapeutic responses through their interplay. A particular emphasis is placed on the functional heterogeneity of CAAs across different breast cancer subtypes and metabolic contexts, and its implications for shaping immunosuppressive niches and immunotherapy resistance. Specific mechanisms include: reshaping adipokine and inflammatory cytokine profiles to foster a pro-tumorigenic secretory landscape; inducing metabolic reprogramming in tumor cells to sustain aggressive growth; mediating intercellular signaling via exosomes to propagate malignant traits; altering immune cell functional states to shift toward an immunosuppressive phenotype; and promoting the establishment of immune escape pathways. Based on these mechanisms, the review synthesizes CAA-targeted therapeutic strategies for breast cancer, including: disrupting key adipokine-mediated signaling cascades to interrupt tumor-stroma communication, modulating CAA-secreted factors to reorient immune cell activities toward anti-tumor functions, and rewiring lipid metabolic pathways in the TIME to enhance therapeutic sensitivity. In-depth dissection of CAA functional networks is crucial for elucidating their pathogenic significance in breast cancer and fueling precision immunotherapy innovation, as such insights may open avenues for rebalancing TIME immune interactions and boosting immunotherapeutic efficacy.
Antimalarial Effects of Dobinin K against Chloroquine-resistant Plasmodium falciparum Through Disruption of the Parasite's Redox System.
He LF, Sun H, Cang LQ … +4 more , Wang JD, Xiao CJ, Jiang B, Shen L
Curr Med Chem · 2026 Apr · PMID 42083535 · Publisher ↗
OBJECTIVE: The current study was designed to systematically evaluate the antiplasmodial ability of Dobinin K against the chloroquine-resistant strain of Plasmodium falciparum (P. falciparum) Dd2 and investigate its poten...
OBJECTIVE: The current study was designed to systematically evaluate the antiplasmodial ability of Dobinin K against the chloroquine-resistant strain of Plasmodium falciparum (P. falciparum) Dd2 and investigate its potential mechanism of action. METHODS: The effects of Dobinin K against Dd2 were assessed by both SYBR Green I fluorescence assay and Giemsa staining assay. Transcriptomic analysis was performed to examine global gene expression changes in P. falciparum following Dobinin K treatment. To explore the acting mechanism of Dobinin K on Dd2, contents of redox substrates and metabolites, as well as the activities of enzymes, were examined using the corresponding kit. Ultrastructural analysis was performed using transmission electron microscopy. The mitochondrial membrane potential (ΔΨm) was assessed based on JC-1 fluorescence intensity. The mRNA expression levels were analyzed through qRT-PCR. DNA fragmentation during apoptosis was evaluated using the TUNEL assay. RESULTS: Dobinin K exhibited antiplasmodial activity against Dd2 that was both concentration- and time-dependent, affecting all developmental stages of the parasite. Transcriptomic analysis suggested that the mechanism of action of Dobinin K refers to the disruption of the redox system in the parasite. Dobinin K increased the levels of oxidative products, elevated the GSSG / GSH ratio, inhibited the activities of antioxidant enzymes, including PfGR, PfTrxR, and PfSOD, decreased the NADP+ / NADPH ratio, disruptedΔΨm, upregulated mRNA expression of most essential apicoplast metabolic enzymes, and ultimately induced apoptosis in Dd2. DISCUSSION: Artemisinin-based combination therapies for chloroquine-resistant malaria face tremendous challenges due to the occurrence of artemisinin resistance. Our findings suggested that Dobinin K exerted its antimalarial effects by disrupting the parasite's redox homeostasis, a mechanism that differs from artemisinin. This further supports redox system targeting as an effective strategy against chloroquine-resistant P. falciparum. CONCLUSION: Dobinin K disrupts the redox system of P. falciparum, subsequently disturbing mitochondrial and apicoplast functions and triggering apoptosis in Dd2.
Prognostic and Immunoinfiltration Analysis of Transcription Factor BTF3 in Pan-cancer.
Liu X, Zhang X, Sun R … +1 more , Du H
Curr Med Chem · 2026 Apr · PMID 42083534 · Publisher ↗
INTRODUCTION: BTF3, also known as BETA-NAC, BTF3b, BTF3a, and NACB, is a transcription factor originally isolated from HeLa cell extracts. It forms stable complexes with RNA polymerase II and plays a critical role in tra...
INTRODUCTION: BTF3, also known as BETA-NAC, BTF3b, BTF3a, and NACB, is a transcription factor originally isolated from HeLa cell extracts. It forms stable complexes with RNA polymerase II and plays a critical role in transcription initiation. Although aberrant BTF3 expression has been reported in certain malignancies, its overall role across diverse tumor types remains poorly defined. This study aimed to elucidate the functional implications of BTF3 across various cancers. METHODS: BTF3 expression was analyzed using datasets from The Cancer Genome Atlas (TCGA), including TCGA_GTEx, TCGA unpaired, and TCGA paired samples. The prognostic significance of BTF3 across 33 tumor types was evaluated using Kaplan-Meier survival and univariate Cox regression analyses. In cancers where BTF3 expression showed prognostic value, additional clinical correlation analyses were performed. Clear cell renal carcinoma (sample size >500) was selected for nomogram construction to illustrate BTF3's prognostic relevance. The association between BTF3 expression and immune cell infiltration was also examined, alongside functional enrichment analysis to explore involved signaling pathways. RESULTS: BTF3 displayed variable expression across tumor types and was significantly correlated with several clinical parameters. Survival and regression analyses identified BTF3 as a prognostic marker in specific cancers. The nomogram model for clear cell renal carcinoma further supported its predictive value. BTF3 expression was also associated with features of the tumor immune microenvironment. Functional enrichment analysis implicated signaling pathways, including the tuberous sclerosis complex/mechanistic target of rapamycin (TSC/mTOR), phosphoinositide 3-kinase/AKT (PI3K/AKT), and rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) in BTF3-associated tumorigenesis. DISCUSSION: These findings underscore the heterogeneous expression of BTF3 across malignancies and highlight its potential involvement in modulating the tumor immune landscape and oncogenic signaling pathways. The results expand our understanding of BTF3's role in cancer biology and suggest mechanistic links to well-characterized tumorigenic processes. However, further experimental validation is necessary to substantiate these associations. CONCLUSION: BTF3 may serve as a promising prognostic biomarker and a potential target for immunotherapeutic intervention across multiple cancer types.
Identifying Key Pathogenic Mechanisms in Recurrent Glioblastoma Through Bioinformatics Analysis.
Rong X, Han M, Bao L … +5 more , Wang Z, Pavlov V, Gareev I, Wu J, Dong X
Curr Med Chem · 2026 Apr · PMID 42083533 · Publisher ↗
INTRODUCTION: Despite aggressive surgery and adjuvant therapy, glioblastoma commonly recurs within months. We aimed to identify key genes and microRNAs (miRNAs)- mRNA regulatory networks associated with recurrent gliobla...
INTRODUCTION: Despite aggressive surgery and adjuvant therapy, glioblastoma commonly recurs within months. We aimed to identify key genes and microRNAs (miRNAs)- mRNA regulatory networks associated with recurrent glioblastoma and to nominate candidate repurposable drugs. METHODS: Two mRNA expression datasets (GSE58399 and GSE42669) from GEO were analyzed to identify differentially expressed genes (DEGs) between recurrent and primary tumors. Functional enrichment (Gene Ontology, KEGG) characterized implicated processes and pathways. A protein-protein interaction network (STRING and Cytoscape) identified hub genes. miRWalk 3.0, integrating TargetScan, miRDB, and miRTarBase, predicted miRNAs targeting hub genes and defined miRNA-mRNA interactions. The Connectivity Map (CMap) was used to prioritize small molecules predicted to reverse the DEGs signature. Kaplan-Meier survival analyses assessed associations between candidate genes and patient outcomes. RESULTS: We identified 201 DEGs and constructed a PPI network comprising 180 nodes and 337 edges. Ten hub genes were prioritized. CMap nominated five top candidate compounds- levamisole, chlorzoxazone, ranitidine, atovaquone, and chrysin-as potential therapeutics for glioblastoma recurrence. Synaptotagmin 1 (SYT1) emerged among hub genes and was predicted to be regulated by 12 miRNAs. Elevated SYT1 expression correlated with poorer overall and progression-free survival in recurrent glioblastoma patients. DISCUSSION: This integrative analysis highlights SYT1 and its upstream miRNAs as candidate biomarkers and potential therapeutic targets in recurrent glioblastoma and proposes several repurposable compounds for experimental validation. Further functional studies and clinical validation are required prior to translation. CONCLUSION: Collectively, this study offers valuable insights into the regulatory landscape of recurrent glioblastoma and lays the groundwork for more targeted and personalized therapeutic approaches.
Quantum Consciousness: A Molecular Perspective Involving Glycoprotein-Tunnelling Hypothesis (GPTH).
Atta-Ur-Rahman
Curr Med Chem · 2026 Apr · PMID 42083532 · Publisher ↗
Long-term memory exhibits a remarkable problem: it is extraordinarily stable over decades, yet it supports rapid, flexible cognition, logic, and conscious awareness. Classical neuroscience has largely attributed memory t...
Long-term memory exhibits a remarkable problem: it is extraordinarily stable over decades, yet it supports rapid, flexible cognition, logic, and conscious awareness. Classical neuroscience has largely attributed memory to synaptic plasticity and networklevel dynamics; however, these mechanisms alone do not adequately explain the molecular durability of memory traces in the face of continuous protein turnover. A hypothesis advanced by the author proposes that memory is encoded in stable, folded glycoprotein patterns, particularly within synaptic and peri-synaptic environments. This review examines how such structurally persistent molecular architectures could support dynamic information processing through quantum-enabled chemical mechanisms. Considering recent advances in glycobiology, enzymology, quantum biology, and medicinal chemistry, it is suggested that proton and electron tunnelling provide a plausible and experimentally grounded mechanism for reading out stable glycoprotein-encoded information without requiring large-scale molecular rearrangement or long-lived macroscopic quantum coherence. Such an approach reconciles molecular stability with cognitive flexibility and yields testable predictions that are relevant to neurodegenerative disease and drug discovery.
Ginsenoside Re Suppresses Tumorigenesis in NSCLC through PERK-Mediated Endoplasmic Reticulum Stress and the Mitochondrial Apoptosis Pathway.
Zhao J, Liu X, Sun K … +9 more , Tan R, Liu Z, Zu S, Li A, Feng L, Li G, Chen C, Jin X, Wan X
Curr Med Chem · 2026 Apr · PMID 42083370 · Publisher ↗
INTRODUCTION: To investigate the antitumor effects of ginsenoside Re on human non-small cell lung cancer cells, specifically the NCI-H460 and 95D cell lines. METHODS: This study investigated the effects of ginsenoside Re...
INTRODUCTION: To investigate the antitumor effects of ginsenoside Re on human non-small cell lung cancer cells, specifically the NCI-H460 and 95D cell lines. METHODS: This study investigated the effects of ginsenoside Re on the proliferation of two cell lines using the CCK-8 assay; observed changes in cell morphology using DAPI and AO/EB staining; analyzed cell cycle and apoptosis rate using flow cytometry; and evaluated cell migration and invasion ability using Transwell and wound healing assays. Western blotting and qPCR results indicated that ginsenoside Re induces apoptosis in NCI-H460 and 95D cells by regulating the expression of genes and proteins, including Bax, BIP, CHOP, eIF-2α, Bcl-2, and β-actin. RESULTS: Ginsenoside Re inhibited the proliferation of two cell types in a time- and dosedependent manner. Cell cycle analysis revealed that ginsenoside Re induced G2 phase arrest in NCI-H460 cells and G1/S phase arrest in 95D cells, and that the morphology of apoptosis could be visualized by DAPI and AO/EB fluorescence staining. Cell scratchhealing and invasion assays confirmed that ginsenoside Re inhibited the invasion and migration of NCI-H460 and 95D cells, and the coverage of 95D cells decreased from 73.17±0.26% to 33.02±0.40%. DISCUSSION: Ginsenoside Re significantly inhibited NSCLC 95D and NCI-H460 cells by suppressing proliferation, cell cycle progression, migration, invasion, and inducing apoptosis. CONCLUSION: Ginsenoside Re can effectively induce tumor cell apoptosis by regulating the endoplasmic reticulum apoptosis pathway and thereby exert anti-tumor effects. The experiment provides a reliable basis for establishing a mechanistic framework explaining the role of ginsenoside Re in non-small cell lung cancer.
Studies on Oxidative Stability of Vegetable Oil During Frying.
Roy A, Maiti DK, Banik BK
Curr Med Chem · 2026 Apr · PMID 42083369 · Publisher ↗
BACKGROUND: To study various reactions during frying with vegetable oil is an interesting topic because people have been using this process daily. Despite the widespread daily use of deep frying, the high temperatures in...
BACKGROUND: To study various reactions during frying with vegetable oil is an interesting topic because people have been using this process daily. Despite the widespread daily use of deep frying, the high temperatures involved lead to chemical degradation of vegetable oils, including hydrolysis, oxidation, and polymerization, which not only reduce their oxidative stability but also diminish nutritional quality and may generate harmful compounds such as 4-HNE. While antioxidant additives and oil blending are potential strategies to mitigate these effects, limited research exists on how specific blends of mustard and sesame oil, with added antioxidants, perform under high-temperature frying conditions. This study addresses this gap by systematically evaluating the oxidative stability of such a blend during deep frying, using multiple chemical indices to track degradation. OBJECTIVE: This study focused on various chemical measures to assess the degradation and oxidation of the oil (a combination of sesame and mustard oil with additional antioxidants), including 4-HNE value, conjugated diene, peroxide value, para-anisidine value, acid value, iodine value, and conjugated triene values. An experimental model is created to evaluate the oxidative stability of mustard and sesame oil when fried at high temperatures. METHODS: Peeled potatoes are deep-fried with blended oil, and numerous chemical reactions are followed during this process. RESULTS: Vegetable oil undergoes hydrolysis, oxidation, and polymerization during deep frying, which reduces its oxidative stability and causes a decline in its nutritional benefits. Blending prevents oxidation in oil. DISCUSSION: Blending prevents oxidation in oil as well as prevents hydrolysis, oxidation, and polymerization during deep frying, and thus it protects oxidative stability and nutritional benefits. CONCLUSION: Oils undergo a number of reactions during deep-frying, including hydrolysis, catalytic oxidation, and thermal alteration. These processes produce a variety of compounds, some of which create health problems. But blended oil prevents oxidation than single-use oil.
Research Trends and Future Prospects on Solid Lipid Nanoparticles in the Early 21st Century - A Bibliometric Analysis.
Hu Q, Meng F, Jia S … +4 more , Wang Y, Jin X, Wang D, Wang Z
Curr Med Chem · 2026 Apr · PMID 42083368 · Publisher ↗
BACKGROUND: Research on Solid Lipid Nanoparticles has increased significantly due to their ability to improve drug delivery and control drug release from lipids. This bibliometric study illustrated SLN's evolution, co-au...
BACKGROUND: Research on Solid Lipid Nanoparticles has increased significantly due to their ability to improve drug delivery and control drug release from lipids. This bibliometric study illustrated SLN's evolution, co-authored networks between researchers, and research trends. METHODS: We analyzed 5,063 'Article' type publications obtained from the Web of Science Core Collection using the multi-tools VOSviewer, CiteSpace, and HistCite. RESULTS: Solid Lipid Nanoparticles' journal growth for publications and citations highlighted continued scientific interest in this area. India was the most productive country (1,003 publications). At the same time, the Free University of Berlin was the most productive institution, and the most productive authors, Souto, Eliana B. (98 publications, 16 collaborative links), and Mueller, R.H. (82 publications, 7 collaborative links), formed the core of the co-authorship network. Keywords associated and emerging frontiers indicated an innovative field evolving from formulation studies to one focused on application data. DISCUSSION: We traced the trajectory from the lowest-hanging fruit to use cases in grand challenges, but coverage of database bias remains a concern. CONCLUSION: The past twenty years have witnessed an increase in publications and citations, as evidenced by active contributions from numerous countries, institutions, and authors. Keyword analysis and emerging frontiers marked their hot topics and research directions.
Poria Cocos Polysaccharide Triggers Mitochondrial-mediated Apoptosis in Hepatocellular Carcinoma Cells through P53 and Bioenergetic Collapse.
Zhao J, Yang X, Liu X … +9 more , Wu X, Liu Z, Zu S, Li A, Feng L, Jin X, Li G, Chen C, Wan X
Curr Med Chem · 2026 Apr · PMID 42083367 · Publisher ↗
INTRODUCTION: This study aimed to investigate the inhibitory effect of Poria cocos polysaccharide (PCP) on hepatocellular carcinoma cells SMMC-7721 and its potential mechanism. METHODS: We performed a series of in vitro...
INTRODUCTION: This study aimed to investigate the inhibitory effect of Poria cocos polysaccharide (PCP) on hepatocellular carcinoma cells SMMC-7721 and its potential mechanism. METHODS: We performed a series of in vitro experiments to evaluate the effects of PCP on hepatocellular carcinoma cells SMMC-7721. The effects of PCP on SMMC-7721 cell proliferation, apoptosis, migration, invasion, and related protein expression were evaluated by CCK-8 assay, AO/EB and DAPI fluorescent staining, cell scratch healing assay, Transwell assay, and protein immunoblotting assay. in vivo experiments in mice were performed to illustrate the effects of PCP on hepatocellular carcinoma in mice. RESULTS: PCP demonstrated significant efficacy against hepatocellular carcinoma in vitro and in vivo, suppressing SMMC-7721 cells' proliferation, migration, and invasion, and inducing mitochondrial apoptosis via concomitant upregulation of P53, Bax, Caspase-3, Caspase-9, and Cytochrome c, and downregulation of Bcl-2, MMP-2, and MMP-9. DISCUSSION: Hepatocellular carcinoma cells (SMMC-7721) proliferation, migration, and invasion were markedly suppressed, and apoptosis was extensively induced, through modulation of the mitochondrial apoptotic pathway by PCP, thereby conferring significant antitumor activity. CONCLUSION: This study provides an experimental basis for the application of PCP in the treatment of hepatocellular carcinoma.
Antiviral Potential of 3,4-Dimethoxychalcone Against SARS-CoV-2: A Promising Candidate.
Kleber Rodrigues Lima W, Monteiro Ferreira G, Zeneida Gomes Parente Alves Lima C … +15 more , Willian de Alencar Pereira E, Mendonça Munhoz Dati L, Galvão Lopes V, Kleber Gomes Parente Alves Lima V, Sousa Ferreira L, Quintino da Rocha C, Portes Ureshino R, Lemes R, Sessa Stilhano R, Nicoliche T, Máximo Prado C, Hiromi Okuda L, Bonjour K, Hiroyuki Hirata M, Gonçalves Lima-Neto L
Curr Med Chem · 2026 Apr · PMID 42083366 · Publisher ↗
INTRODUCTION: This study aimed to investigate the potential of LQPN-05, a compound derived from Fridericia platyphylla flowers, as a novel antiviral agent against SARS-CoV-2. METHODS: Molecular modeling and dynamics simu...
INTRODUCTION: This study aimed to investigate the potential of LQPN-05, a compound derived from Fridericia platyphylla flowers, as a novel antiviral agent against SARS-CoV-2. METHODS: Molecular modeling and dynamics simulations were used to analyze the interaction between LQPN-05 and the SARS-CoV-2 spike protein. In vitro assays assessed spike protein thermal stability and antiviral activity in infected cells. Cytotoxicity was evaluated in cell lines, and efficacy was further tested in an animal model of SARS-CoV- -2 infection. RESULTS: Simulations revealed favorable binding of LQPN-05 to the spike protein, particularly protomer C. In vitro, LQPN-05 modified the spike protein's melting temperature and inhibited viral replication. The compound showed minimal cytotoxicity and, in vivo, helped maintain animal weight and cellular lung organization per fractal analysis. DISCUSSION: The results signify LQPN-05's potential as a spike protein inhibitor from a natural source. Its efficacy amid concerns of drug resistance is notable. Study limitations include the preliminary nature of the in vivo findings. CONCLUSION: LQPN-05 demonstrates promising anti-SARS-CoV-2 activity, underscoring the value of exploring natural compounds for antiviral therapy against emerging pathogens.
IL-1β Blocker and Its Influence on Preserving Lung Tissues Sensitized by Echinococcus granulosus Sac Fluid by Regulating Macrophage Phenotypic Transformation.
Wang CS, Kulaixi X, Zhou JR … +4 more , Pu XL, Wang JL, Abulajiang X, Ye JR
Curr Med Chem · 2026 Apr · PMID 42059235 · Publisher ↗
INTRODUCTION: This study aimed to elucidate the molecular mechanisms underlying macrophage involvement in lung injury following sensitization to the cyst fluid induced by Echinococcus granulosus. METHODS: Eighteen C57/BL...
INTRODUCTION: This study aimed to elucidate the molecular mechanisms underlying macrophage involvement in lung injury following sensitization to the cyst fluid induced by Echinococcus granulosus. METHODS: Eighteen C57/BL6 mice were randomly divided into three groups, with six mice in each group. After mice were intraperitoneally injected with Echinococcus granulosus, they were raised for 3 months. In the control group (group A, n = 6), normal saline was injected into the abdominal cavity and airway. In the blocker group (group B, n=6), IL-1β blocker was injected through the tail vein, followed by intraperitoneal injection of 0.1 ml/g Echinococcus granulosus cyst fluid and airway injection of 0.05 ml/g Echinococcus granulosus cyst fluid. In the sensitized group (group C, n = 6), 0.1 ml/g Echinococcus granulosus cyst fluid was injected intraperitoneally, and 0.05 ml/g Echinococcus granulosus cyst fluid was injected into the airway. Changes in macrophages in lung tissue were detected by flow cytometry. The pathological sections of lung tissue were prepared, and immunohistochemical analysis was performed. At the same time, the lung tissues of the three groups of mice were analyzed by Western blot and RT-PCR. The protein and mRNA expression of PI3K/AKT/NF-κB and the levels of inflammatory factors IL-6 and TNF-α were detected. RESULTS: After the application of IL-1β blockers, the number of M2-type macrophages in the lungs increased significantly, the mRNA and protein expression levels of PI3K/AKT/ NF-κB and inflammatory factors IL-6 and TNF-α decreased, and the damage was significantly alleviated. DISCUSSION: The findings suggest that IL-1β drives lung injury in E. granulosus sensitization by skewing macrophages toward a pro-inflammatory phenotype and activating the PI3K/AKT/NF-κB pathway. The protective effect of IL-1β blockade highlights its potential as a therapeutic target to modulate macrophage polarization and mitigate inflammation in hydatid disease-related lung injury. CONCLUSION: IL-1β blockers exert a protective effect on lung injury caused by allergic reactions to the cystic fluid of Echinococcus granulosus by promoting an increase in the M2 phenotype of macrophages.
Artificial Intelligence in Medication Research and Development: The Pharmaceutical Industry's Future.
AlMatar M, Eker E, Balgouthi K … +2 more , Al-Reasi HA, Lakhal R
Curr Med Chem · 2026 Apr · PMID 42059234 · Publisher ↗
It is no wonder that AI is making a major impact in drug development. As AI tools continue to advance and improve, it is easy to understand why pharmaceutical companies are taking a keen interest in AI in drug developmen...
It is no wonder that AI is making a major impact in drug development. As AI tools continue to advance and improve, it is easy to understand why pharmaceutical companies are taking a keen interest in AI in drug development and its potential benefits for saving time and money. AI is helping drug development become faster, more accurate, and cost-effective, all while benefiting the bottom line. When machine learning and deep learning come into play in this scenario, the potential for AI and its benefits in drug development is endless. It has already been proven in areas such as predicting drug properties, identifying and validating new targets, developing small molecule drugs, and even speeding up clinical trials through drug repurposing, drug development, and drug outcome predictions. Of course, as in all things in life, there are obstacles and hurdles that need to be addressed and overcome. This includes better data-sharing practices, better standards for algorithms, and even the potential for bringing biology and computer science closer together in order to bring lab work and modeling closer.
Key Toxic Genes and Mechanisms of Di(2-ethylhexyl) Phthalate-Induced Non-Alcoholic Fatty Liver Disease: A Multi-Omics Study.
Zhao X, Gu Z, Yan J
Curr Med Chem · 2026 Apr · PMID 42051095 · Publisher ↗
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease, with di(2-ethylhexyl) phthalate (DEHP) potentially exacerbating its progression. The toxicological mechanis...
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease, with di(2-ethylhexyl) phthalate (DEHP) potentially exacerbating its progression. The toxicological mechanisms through which DEHP induces NAFLD remain elusive. This study aims to identify critical toxic genes involved in the development of DEHP-induced NAFLD. METHODS: The carcinogenic potential of DEHP was predicted based on its Simplified Molecular Input Line Entry System (SMILES) notation. Biomarkers were identified through differential expression analysis, and a nomogram was constructed and validated. The functional roles of these biomarkers were explored through enrichment analysis, immune cell infiltration, molecular docking, and molecular dynamics simulations. Single- cell analysis pinpointed the key cellular players in the process. RESULTS: The study identified activating transcription factor 3 (ATF3) and mitogen-activated protein kinase 8 (MAP3K8) as critical biomarkers. Pathways enriched by these biomarkers included "electron transfer from variant/mutation-inactivated PINK1 to complex I". Both ATF3 and MAP3K8 showed significant negative correlations with M2 macrophages and strong positive associations with activated mast cells. Binding affinities of ATF3 and MAP3K8 to DEHP were calculated at -5.9 kcal/mol and -7.7 kcal/mol. Hepatic stellate cells were ultimately identified as pivotal in the disease mechanism. DISCUSSION: Compared to traditional research approaches, this study employs network toxicology and molecular docking techniques, integrating single-cell sequencing and spatial transcriptomics to provide a comprehensive framework for investigating the potential toxic effects of di(2-ethylhexyl) phthalate (DEHP) in non-alcoholic fatty liver disease (NAFLD). CONCLUSION: This study provides valuable insights into the molecular processes underlying DEHP-induced NAFLD.
Augmented Anti-leukemic Efficacy of Selenium-Fermented Ferulic Acid Derived from Macrotyloma uniflorum: Insights into in vitro and in vivo Models.
Rizwan A, Shaikh H, Farooqi H
Curr Med Chem · 2026 Apr · PMID 42003100 · Publisher ↗
INTRODUCTION: Conventional leukemia therapies often damage healthy cells, creating significant public health challenges. Ferulic acid, extracted from Macrotyloma uniflorum (horse gram), has demonstrated antileukemic prop...
INTRODUCTION: Conventional leukemia therapies often damage healthy cells, creating significant public health challenges. Ferulic acid, extracted from Macrotyloma uniflorum (horse gram), has demonstrated antileukemic properties. Fermentation is known to enhance the bioavailability of active compounds, and selenium offers additional health benefits. This study investigated whether selenium supplementation during fermentation improves the yield and antileukemic potency of ferulic acid compared with non-fermented and selenium-free conditions. MATERIALS AND METHODS: Ferulic acid was extracted under three conditions: non-fermented, fermented, and selenium-supplemented fermentation. Yield quantification was performed for each extract. Antileukemic efficacy was evaluated in HL-60 human leukemia cells. in vivo effects were assessed in female Balb/c mice, including blood cell counts and histopathological changes in the liver, spleen, and bone marrow. RESULTS: Fermentation increased ferulic acid yield by more than 50%, and selenium supplementation further enhanced it by more than 70%. All extracts exhibited antileukemic activity, with the selenium-enriched fermented extract showing the highest efficacy. It induced apoptosis more effectively than vinblastine and significantly reduced HL-60 cell viability. in vivo, the extract selectively decreased leukemic blast cells, red and white blood cells, lymphocytes, neutrophils, and monocytes, while sparing basophils and eosinophils. Histopathological analysis revealed protection of the liver, spleen, and bone marrow from ENU-induced damage. DISCUSSION: Selenium-supplemented fermentation significantly enhanced both the yield and antileukemic activity of ferulic acid. The enriched extract demonstrated selective induction of apoptosis in leukemia cells and protective effects on normal tissues, underscoring its biological relevance and therapeutic potential. CONCLUSION: Ferulic acid derived from selenium-supplemented fermented Macrotyloma uniflorum exhibited significantly greater antileukemic potency and therapeutic efficacy than ferulic acid from fermented or non-fermented conditions, highlighting its promise as a natural, effective antileukemic agent.
Multi-Omics Analysis Reveals DNASE1L3 in Hepatocellular Carcinoma Prognosis, Immune Microenvironment, and Immunotherapy Response.
Tang X, Xue J, Li X … +2 more , Zhang J, Zhou J
Curr Med Chem · 2026 Apr · PMID 42003099 · Publisher ↗
INTRODUCTION: Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer, characterized by its poor prognosis. Deoxyribonuclease 1-like 3 (DNASE1L3), a member of the deoxyribonuclease 1 family, has been im...
INTRODUCTION: Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer, characterized by its poor prognosis. Deoxyribonuclease 1-like 3 (DNASE1L3), a member of the deoxyribonuclease 1 family, has been implicated in various human cancers, but its specific role in HCC remains unclear. METHODS: By integrating transcriptomic and proteomic datasets, DNASE1L3 was identified as significantly associated with HCC through WGCNA and Lasso regression analysis. Subsequently, the clinical diagnostic significance of DNASE1L3 was confirmed using data from TCGA. Additionally, we evaluated immune treatment responsiveness by analyzing Tumor Mutation Burden (TMB) values, Tumor Immune Dysfunction and Exclusion (TIDE) scores, and the expression of immune checkpoint genes. Furthermore, DNASE1L3 expression in HCC was examined through single-cell RNA sequencing (scRNA-seq) analysis using the TISCH 2.0 database. RESULTS: DNASE1L3 expression was significantly reduced in HCC and associated with a poor prognosis. The DNASE1L3low group exhibited higher TMB values and expression of immune checkpoint genes, along with a lower TIDE score, suggesting a greater likelihood of successful immunotherapy. Moreover, scRNA-seq analysis revealed that DNASE1L3 was predominantly expressed in HCC endothelial cells, myeloid cells, and innate lymphoid cells. DISCUSSION: Our findings indicate that DNASE1L3 may be a potential biomarker for both predicting prognosis and assessing the effectiveness of immunotherapy, thus providing significant information for forecasting clinical results and responses to immunotherapy in HCC. CONCLUSION: The findings of this research could facilitate early detection and propose possible therapeutic targets for HCC.
Identification of Drug-resistant Cell Subpopulations in Colorectal Cancer Through Single-cell Analysis and Exploration of Potential Therapeutic Strategies.
Chen Y, Wang D
Curr Med Chem · 2026 Apr · PMID 42003098 · Publisher ↗
INTRODUCTION: The therapeutic efficacy of Colorectal Cancer (CRC) is often compromised by resistance to the standard chemotherapy agent oxaliplatin. METHODS: This study obtained single-cell RNA sequencing (scRNA-seq) dat...
INTRODUCTION: The therapeutic efficacy of Colorectal Cancer (CRC) is often compromised by resistance to the standard chemotherapy agent oxaliplatin. METHODS: This study obtained single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) between resistant and sensitive epithelial subpopulations were identified, followed by enrichment analysis. Pseudotemporal trajectory and cell-cell communication were analyzed using Monocle2 and CellChat, respectively. The candidate drug was predicted by Connectivity Map (cMAP) analysis. External validation included assessment of the EpC2 signature in an oxaliplatin-resistant cell line dataset (GSE76092), survival analysis using The Cancer Genome Atlas (TCGA) cohorts, and re-analysis of the GSE179784 dataset to assess the reproducibility of EpC2-like subpopulations and their DNA Damage Repair (DDR) scores. RESULTS: Cell subpopulations were divided into 10 clusters. Among them, epithelial cells comprised 5 subpopulations, with EPC2 identified as a potential oxaliplatin-resistant subset. DEGs were enriched in the TNF and IL-17 pathways. External validation confirmed the enrichment of EpC2 in resistant cell lines and its association with poor survival. Pseudotemporal trajectory revealed that epithelial cells underwent state transitions, forming two distinct branches. The resistant group exhibited enrichment in RNA splicing and NF-κB pathways. Cell-cell communication analysis revealed interactions involving MDK- NCL and PPIA-BSG. Dasatinib was predicted as a candidate drug. DISCUSSION: We identified an oxaliplatin-resistant subpopulation of Epithelial Cells (EpC2) in CRC, elucidated its multi-layered resistance mechanisms, and integrated multi- omics and cMAP database analyses to predict a potential intervention drug. CONCLUSION: This study provided potential therapeutic possibilities for oxaliplatin resistance, contributing to CRC treatment.
Determination of the 95% Effective Dose of Remifentanil for Moderate Sedation During Gastroscopy in Obese Patients.
Ran R, Chen Q, Zhu Q … +4 more , Ma Z, Zhang J, Tian Y, Shu S
Curr Med Chem · 2026 Apr · PMID 42003097 · Publisher ↗
INTRODUCTION: Obesity increases the risk of hypoxemia during gastroscopy. The optimal remifentanil dose for effective and safe conscious sedation in this population remained unclear. Applying the biased coin design up-an...
INTRODUCTION: Obesity increases the risk of hypoxemia during gastroscopy. The optimal remifentanil dose for effective and safe conscious sedation in this population remained unclear. Applying the biased coin design up-and-down sequential method, we aimed to determine the 95% Effective Dose (ED95) of remifentanil required for gastroscopy in obese patients. MATERIALS AND METHODS: In this prospective interventional dose-finding study, patients aged 18-65 years with a BMI ≥ 30 kg/m2 (ASA class I-III) undergoing elective gastroscopy received remifentanil via target-controlled infusion. Patients with opioid allergy were excluded. A biased coin design-up-and-down method was used to determine the dosage, and the ED95 was estimated using isotonic regression. Ramsay sedation scores, Visual Analog Scale (VAS) pain scores, vital signs, and satisfaction ratings were recorded. RESULTS: Forty-two patients were enrolled. Sedation was successful in 83.3% (35/42) of patients. The estimated ED95 of remifentanil was 0.915 μg/kg (95% CI: 0.790-0.989). The mean procedure time was 5.85 minutes. Hypoxemia occurred in 4.8% (n = 2, lowest SpO2 88%) and sinus bradycardia in 7.1% (n = 3). Patient and endoscopist satisfaction scores were 7.12 ± 1.42 and 6.75 ± 1.62, respectively. DISCUSSION: This study found that remifentanil monotherapy can serve as an effective and safe strategy for conscious sedation in obese patients undergoing gastroscopy. We determined the effective dose ED95 to be 0.915 μg/kg (95% CI, 0.790-0.989), providing a potential evidence-based starting point for clinical practice. The favorable safety profile, characterized by a low incidence of hypoxemia, addressed a critical need for sedation strategies that minimize respiratory depression in this high-risk population. Future research should explore combinations with non-opioid adjuvants to further reduce opioid- related adverse effects and incorporate objective respiratory monitoring, such as capnography, to enhance safety assessment. CONCLUSION: Remifentanil monotherapy provided effective conscious sedation for gastroscopy in obese patients, showing a high success rate and low incidence of hypoxemia. The ED95 was determined to be 0.915 μg/kg.
Bridging Clinical and Chemical Research in Occupational Asthma.
Yuan XM
Curr Med Chem · 2026 Apr · PMID 42003096 · Publisher ↗
Occupational Asthma (OA) accounts for a significant portion of adult asthma cases and is driven by diverse mechanisms linked to high- and low-molecular-weight workplace exposures. Despite extensive clinical and epidemiol...
Occupational Asthma (OA) accounts for a significant portion of adult asthma cases and is driven by diverse mechanisms linked to high- and low-molecular-weight workplace exposures. Despite extensive clinical and epidemiological studies, the molecular basis and medicinal chemistry approaches for diagnosing and managing OA remain underexplored. Here, I review the current literature identifying key occupational exposures, emphasizing the paucity of medicinal chemistry research targeting OA-related exposures. I advocate for translational research that integrates innovations in medicinal chemistry with clinical insights, leveraging exposomics to develop personalized exposure assessments and targeted therapeutics. The interdisciplinary approach involving chemical exposomes holds promise for improved OA prevention, diagnosis, and management tailored to specific occupational exposures and patient needs.
Metabolites and Polycystic Ovarian Syndrome: A Mendelian Randomization Study.
Aru N, Chen Y, Li T … +1 more , Liu J
Curr Med Chem · 2026 Apr · PMID 42003095 · Publisher ↗
INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. Nevertheless, the causal relationship between metabolites and PCOS remains undeter...
INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. Nevertheless, the causal relationship between metabolites and PCOS remains undetermined. METHODS: We utilized a comprehensive two-sample Mendelian randomization (MR) analysis, a genetic epidemiological approach that uses genetic variants as instrumental variables to assess causal relationships between exposures and outcomes, to examine the causal link between 1352 metabolites and PCOS. We employed complementary MR methods, such as the inverse-variance weighted (IVW) method, and conducted sensitivity analyses to evaluate the reliability of the outcomes. Reverse MR analysis was performed to evaluate the possibility of reverse causation. RESULTS: Five metabolites were identified to be significantly associated with PCOS risk: Methionine sulfoxide levels (IVW: OR [95%]: 1.549[1.274 to 1.883], p = 1.154E-5), Theophylline levels (IVW: OR [95%]: 0.725[0.589 to 0.890], p = 0.002), 4-hydroxycoumarin levels (IVW: OR [95%]: 0.786[0.658 to 0.940], p = 0.008), Tyramine O-sulfate levels (IVW: OR [95%]: 0.699[0.568 to 0.862], p = 0.0008), and Sulfate of piperine metabolite C16H19NO3 (3) levels (IVW: OR [95%]: 1.296[1.064 to 1.579], p = 0.009). We found PCOS was significantly associated with decreased Tyramine O-sulfate levels using the IVW method (OR [95%]: 0.953[0.917 to 0.991], p = 0.015) in the reverse MR analysis. The results of the sensitivity analyses were consistent with the main findings. DISCUSSION: This study establishes causal relationships between specific metabolites and PCOS, highlighting the significant roles of oxidative stress (methionine sulfoxide), dietary components (theophylline, piperine metabolite), and gut microbiome-derived metabolites. These findings provide novel insights into PCOS pathogenesis and identify potential targets for prevention and treatment. However, the study's limitation to European populations necessitates further validation in diverse ethnic groups. CONCLUSION: Our MR analysis provides strong evidence supporting a causal association between metabolites and the susceptibility of PCOS.
An In-Vitro Laboratory Exploration Revealed the Antitumor Effects of Melittin on Osteosarcoma CVCells.
Li Y, Xie X, Zhu H … +2 more , Chen D, Fan T
Curr Med Chem · 2026 Apr · PMID 42003094 · Publisher ↗
INTRODUCTION: Melittin, a 26-amino acid polypeptide with various pharmacological effects, possesses potential anti-tumor properties. The present study examined the possible mechanisms of action on Osteosarcoma (OS) cells...
INTRODUCTION: Melittin, a 26-amino acid polypeptide with various pharmacological effects, possesses potential anti-tumor properties. The present study examined the possible mechanisms of action on Osteosarcoma (OS) cells. MATERIALS AND METHODS: A series of in-vitro tests was implemented to investigate the effects of melittin on the survival, apoptosis, migration, and invasion of OS cells (143-B and MG63). An immunoblotting assay was applied to quantify the protein expression of potential mediators. Further, the mechanisms of action of melittin on OS cells were validated through rescue assays. RESULTS: In OS cells 143-B and MG63, melittin treatment evidently reduced the cell viability, migration, and invasion and elevated apoptosis, with downregulated Bcl-2 and upregulated Bax and cleaved caspase-3. Moreover, the phosphorylation of PI3K/AKT/m- TOR was diminished following melittin treatment. In contrast, the rescue assay demonstrated that the anti-OS effects of melittin in vitro were negated by the 740 Y-P (a known PI3K activator). This was evidenced by altered viability, migration, and invasion, reduced apoptosis in OS cells, and the expression of apoptosis-related mediators. DISCUSSION: Utilizing an in-vitro OS cell model, the current study discovered that melittin can suppress the growth, migration, and invasion of OS cells yet promote apoptosis, potentially via targeting PI3K/AKT/mTOR pathway, providing a novel mechanism underlying the effect of melittin on OS cells. CONCLUSION: The research demonstrated the anti-OS effects of melittin and its possible relationship with the PI3K/AKT/mTOR pathway.
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