Current Medicinal Chemistry[JOURNAL]
Sun
200 papers
Construction and Evaluation of a Prognostic Model Based on Efferocytosis-related Genes for Idiopathic Pulmonary Fibrosis.
Sun Y, Sun Z
Curr Med Chem · 2026 May · PMID 42152668 · Publisher ↗
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal interstitial lung disease with limited treatment options. Impaired efferocytosis, the clearance of apoptotic cells, is implicat...
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal interstitial lung disease with limited treatment options. Impaired efferocytosis, the clearance of apoptotic cells, is implicated in IPF pathogenesis. This study aimed to identify prognostic efferocytosis-related genes (ECRGs) and construct a predictive gene signature for IPF. METHODS: Differentially expressed ECRGs (DEECRGs) were identified by intersecting DEGs between IPF and healthy samples with known ECRGs. A risk model was built using univariate Cox and LASSO regression analyses, and its performance was evaluated via Kaplan-Meier and ROC curves. Multivariate Cox analysis, nomogram construction, GSVA, and immune infiltration analysis were conducted. Validation was performed using datasets GSE70866 (training) and GSE10667. RESULTS: A five-gene prognostic signature (CXCR4, ODC1, AXL, DOCK5, MERTK) was established. High-risk patients had significantly poorer survival. The model showed strong predictive accuracy with AUCs >0.78 for 1-3-year survival. GSVA revealed enrichment of pathways like TNFSF11 signaling and ECM-receptor interaction in high- -risk patients. Immune infiltration analysis showed distinct profiles, notably in mast cells and macrophages. Results were consistent in validation cohorts. DISCUSSION: The efferocytosis-related gene signature robustly predicts IPF prognosis and provides insights into underlying immunological and fibrotic mechanisms. CONCLUSION: This novel gene signature offers a potential tool for risk stratification and personalized treatment planning in IPF patients.
Recent Perspectives on the Physiological and Therapeutic Benefits of Placental Extracts in Chronic Noninfectious Diseases and Aging.
Xinliang Z, Dudnik EN, Gavrikov LK … +5 more , Liye A, Hui Z, Potapova OV, Kryzhanovskaya SY, Glazachev OS
Curr Med Chem · 2026 May · PMID 42136313 · Publisher ↗
INTRODUCTION: Non-communicable diseases (NCDs), including metabolic disorders, cardiovascular diseases, liver pathologies, and age-related syndromes, are a major global health challenge. Human placental extract (HPE) and...
INTRODUCTION: Non-communicable diseases (NCDs), including metabolic disorders, cardiovascular diseases, liver pathologies, and age-related syndromes, are a major global health challenge. Human placental extract (HPE) and related formulations, such as Laennec and porcine-derived extracts, have been investigated as cell-free therapeutic agents capable of modulating physiological and immunological pathways. METHODS: A systematic literature review was conducted using PubMed, MEDLINE, Scopus, Google Scholar, and the National Library of Medicine databases. Only original English-language research articles were included. Data were extracted on the biochemical composition, mechanisms of action, and therapeutic outcomes of placental extracts in preclinical and clinical studies. RESULTS: HPE was shown to enhance liver function by reducing oxidative stress, promoting hepatocyte regeneration, and regulating apoptosis and autophagy. In metabolic disorders and cachexia, it preserved muscle and adipose tissue and alleviated symptoms of cirrhosis and metabolic dysfunction- associated steatohepatitis. Laennec and porcine extracts improved iron metabolism, reduced hepatic fibrosis, and enhanced glucose regulation in type 2 diabetes and non-alcoholic fatty liver disease. Additional reported effects included anti-aging properties, relief in chronic fatigue syndrome, and dermatological benefits, such as reduced hair loss and improved allergic contact dermatitis. DISCUSSION: Placental extracts, such as HPE, Laennec, and porcine formulations, show promise for treating NCDs, including metabolic disorders, liver pathologies, and age-related syndromes. Preclinical and clinical studies highlight their mechanisms, which involve reducing oxidative stress, promoting hepatocyte regeneration, regulating apoptosis/autophagy, and improving iron metabolism and glucose control. Benefits include alleviating cirrhosis, type 2 diabetes, cachexia, chronic fatigue, and dermatological issues like hair loss. While the evidence is encouraging, largescale trials are needed to confirm their efficacy and the underlying molecular pathways. CONCLUSION: Placental extracts exhibited diverse therapeutic effects across multiple NCDs, mediated by immunomodulatory, antioxidative, and metabolic regulatory mechanisms. While current evidence from preclinical and clinical studies is promising, large-scale, rigorously designed trials are needed to validate efficacy and clarify molecular pathways.
Repositioning Mefloquine as an Anticancer Drug: An Evidence-Based Review.
Zafar E, Maqbool MF, Maqsood K … +3 more , Khan M, Maqbool HH, Bashir S
Curr Med Chem · 2026 May · PMID 42136312 · Publisher ↗
Drug repurposing has gained significant attention in recent years, particularly in cancer research, due to its potential to develop innovative therapeutics. This approach offers cost-effective strategies while bypassing...
Drug repurposing has gained significant attention in recent years, particularly in cancer research, due to its potential to develop innovative therapeutics. This approach offers cost-effective strategies while bypassing some of the stringent regulatory hurdles imposed by the Food and Drug Administration (FDA). Mefloquine has been extensively investigated since 1960 and was approved by the FDA in 1989 for the treatment of malaria. Recently, Mefloquine has been rediscovered for its anticancer effects. Collective data from a plethora of research reports show that Mefloquine exhibits anticancer activity in preclinical models against a wide range of human malignancies, including gastric and colorectal cancer, prostate cancer, cervical cancer, breast cancer, glioblastoma and neuroblastoma, acute and chronic myeloid leukemia, esophageal and oral squamous carcinoma through different molecular mechanisms in both in vitro and in vivo study models. In addition to apoptosis, it has been shown to set the cancer cells on the road to ruin via induction of autophagy and ferroptosis, making it a promising drug for killing apoptosis-resistant cancer cells. Apart from its anticancer effects as a single agent, mefloquine has been shown to improve the efficacy of clinical cancer drugs in various study models when used in combination therapy. Keeping in view the aforesaid research findings, Mefloquine may warrant further investigation for potential repurposing in cancer therapy, either as monotherapy or in combination with other clinically practiced chemotherapeutics.
Prognostic Value, Immune Landscape, and Drug Response of HOGA1 in Clear Cell Renal Cell Carcinoma.
Zhang H, Wen X, Wu X … +4 more , Li S, Lei X, Wang S, Long C
Curr Med Chem · 2026 May · PMID 42136311 · Publisher ↗
INTRODUCTION: HOGA1 is expressed mainly in the liver and kidney, and mutations of this gene were reported to be the cause of primary hyperoxaluria type III. In malignant tumors, HOGA1 has been reported to function as a s...
INTRODUCTION: HOGA1 is expressed mainly in the liver and kidney, and mutations of this gene were reported to be the cause of primary hyperoxaluria type III. In malignant tumors, HOGA1 has been reported to function as a suppressor in pancreatic cancer. But its role in renal cell carcinoma remained undetermined. This study aims to explore the expression, prognostic value, immune landscape, and drug response associations of HOGA1 in clear cell renal cell carcinoma(ccRCC). METHODS: The Immunohistochemistry (IHC) was carried out to illuminate the protein expression of HOGA1 in ccRCC and normal renal tissues. Several publicly available databases and bioinformatics analyses were performed to detect the role of HOGA1 in ccRCC. RESULTS: Bioinformatics analysis and IHC indicated that HOGA1 expression was obviously reduced in ccRCCs compared with normal renal tissues. And Multivariate analysis clarified that HOGA1 mRNA expression was an independent prognostic factor in ccRCC. Patients with lower HOGA1 expression levels had a worse prognosis. Additionally, Enrichment analysis showed that HOGA1-associated genes were mainly enriched in drug metabolism in ccRCC. HOGA1 showed weak but statistically significant negative correlations with the IC50 value of Afatinib, Erlotinib, Rapamycin, and Sorafenib. In addition, HOGA1 expression was found to be correlated with immune infiltration and immune evasion. DISCUSSION: Clear cell renal cell carcinoma (ccRCC) remains a significant clinical challenge due to its aggressive nature and limited therapeutic options. Our analysis highlights HOGA1 as a potential tumor suppressor in ccRCC, with its reduced expression associated with poorer prognosis. Using bioinformatics tools, we revealed that lower HOGA1 expression correlates with increased immune evasion and metabolic dysregulation within the tumor microenvironment (TME), contributing to ccRCC progression. Specifically, we found that HOGA1 loss may enhance the recruitment of macrophages, myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs), which play key roles in immune suppression and tumor survival. Moreover, HOGA1 expression was positively correlated with improved sensitivity to several chemotherapy drugs, suggesting its potential as a therapeutic target. These findings underscore the importance of HOGA1 in regulating both metabolic and immune landscapes in ccRCC and highlight its role as a novel prognostic biomarker. However, further validation through independent clinical cohorts and mechanistic studies, including in vitro and in vivo experiments, is needed to confirm these observations and explore the therapeutic potential of restoring HOGA1 function in ccRCC treatment. CONCLUSION: Overall, HOGA1 may serve as a suppressor in ccRCC. Downregulation of HOGA1 may facilitate the malignant progression of ccRCC by regulating TME and disrupting the metabolic balance. Consequently, HOGA1 may serve as a potential biomarker in ccRCC, though its therapeutic implications remain to be validated.
Identification and Experimental Validation of PLAC8 as a Biomarker for Follicular Lymphoma.
Zhang T, He L, Zhu Y
Curr Med Chem · 2026 May · PMID 42136310 · Publisher ↗
INTRODUCTION: Follicular lymphoma (FL) is the second most common lymphoma type. However, the molecular mechanisms underlying its pathogenesis remain poorly understood. This study aimed to identify and validate potential...
INTRODUCTION: Follicular lymphoma (FL) is the second most common lymphoma type. However, the molecular mechanisms underlying its pathogenesis remain poorly understood. This study aimed to identify and validate potential FL biomarkers using a combination of microarray analysis, machine learning, and experimental validation. METHODS: Differential expression analysis was performed to identify differentially expressed genes (DEGs) between FL patients and matched controls using microarray datasets. Multiple machine learning algorithms were used to identify the hub genes for FL. The predictive performance was further evaluated using the receiver operating characteristic curves for all datasets. Functional analyses were performed to explore the underlying mechanisms. The expression of the biomarker was validated in clinical FL samples. Additionally, gene knockdown and overexpression experiments were conducted to assess the effects of the biomarker on biological functions, such as cell proliferation, apoptosis, and migration in FL cells. RESULTS: A total of 144 DEGs were identified between the FL and control samples. Machine learning algorithms refined the four FL hub genes. Following comprehensive evaluations across all datasets, placenta-associated 8 (PLAC8) was identified as the most significant gene with area under the curve values exceeding 0.879 for all datasets. Functional analyses suggested a correlation between PLAC8 and immune-related pathways in FL. In clinical samples, PLAC8 expression was significantly lower in patients with FL than in controls. Experimental validation revealed that reduced PLAC8 expression enhanced FL cell proliferation and migration while, inhibiting apoptosis, whereas increased PLAC8 expression suppressed proliferation, activated apoptotic pathways, and reduced migration in vitro. DISCUSSION: The combination of microarray analysis and machine learning enables the identification of key variables and complex relationships within the data, offering insights that might be overlooked by traditional methods. Our findings were further supported by experimental validation, underscoring the potential clinical relevance. This integrated approach provides a robust framework for the discovery of biomarkers of complex diseases. CONCLUSION: This study identified and validated PLAC8 as a promising biomarker for FL. Functional experiments further demonstrated that PLAC8 plays a regulatory role in FL cell behavior in vitro. These findings provide insights into the molecular mechanisms underlying this disease.
3D-QSAR, Molecular Docking, Molecular Dynamics Simulation, and Pharmacokinetic Prediction of 1H-Pyrazolo[3,4-d]pyrimidine Derivatives as PI3Kδ Inhibitors.
Liu H, Meng X, Ma Y … +2 more , Wang ZY, Chen XT
Curr Med Chem · 2026 May · PMID 42136309 · Publisher ↗
INTRODUCTION: The inhibition of cellular inflammatory factor secretion by phosphatidylinositol- 3-kinase δ (PI3Kδ) makes it a novel target for acute lung injury therapy. This study aimed to elucidate the structure-activi...
INTRODUCTION: The inhibition of cellular inflammatory factor secretion by phosphatidylinositol- 3-kinase δ (PI3Kδ) makes it a novel target for acute lung injury therapy. This study aimed to elucidate the structure-activity relationship of 1H pyrazolo [3, 4-d] pyrimidine derivatives as PI3Kδ inhibitors for novel drug design. METHODS: In this study, a three-dimensional quantitative conformational relationship (3DQSAR) model was constructed using COMFA and CoMSIA techniques with Sybyl X-2.0 software. In-silico ADME and toxicity predictions were also evaluated using SwissADME and pkCSM tools. Molecular docking and molecular dynamics (MD) simulations (100 ns) were conducted to confirm the interaction of the compounds with the target protein using the GROMACS 2021 software package. RESULTS: Good predictability was assessed using the CoMFA model (Qcv² = 0.547; Rncv² = 0.991; Rpred² = 0.996) and the best CoMSIA model (Qcv² = 0.58; Rncv² = 0.992; Rpred² = 0.994). The A, B, and C rings were the basic skeleton for the potency of the inhibitors. The hydrogen bond acceptor field, electrostatic field, and hydrophobic field significantly influenced activity. The newly designed T03 showed stable RMSD/RMSF during 100 ns MD simulations and low predicted toxicity (LD50: 1579.4 mg/kg). Molecular docking revealed that T03 formed six hydrogen bonds with PI3Kδ, exhibiting a high binding affinity of -11.6 kcal/mol. DISCUSSION: The structural features of 1H pyrazolo [3, 4-d] pyrimidine derivatives through 3D-QSAR modelling established a relationship between functional groups and their biological activity. Based on the constructed 3D-QSAR model, five novel 1H pyrazolo [3, 4- d] pyrimidine derivatives targeting PI3Kδ were designed with improved predicted activities. Furthermore, molecular docking and MD simulations demonstrated stability and revealed ligand-receptor interactions. These novel potent inhibitors were assessed for their ADMET properties. CONCLUSION: The 3D-QSAR model exhibits great reliability and predictive power through ADMET, molecular docking, and molecular dynamic approaches. These results would provide a valuable insight into lead optimization for new drug discovery.
Zeolite-iron Oxide Hybrid on an Interdigitated Microelectrode to Auxiliary Monitoring Abdominal Aortic Aneurysms by Aptamerantibody Sandwich.
Wang H, Dai R, Xia H … +4 more , Ding S, Gopinath SCB, Subramaniam S, Zhao L
Curr Med Chem · 2026 May · PMID 42136308 · Publisher ↗
INTRODUCTION: An abdominal aortic aneurysm (AAA) is a bulge/enlargement in an artery that expands over time and is more likely to rupture. Imaging techniques such as Magnetic resonance imaging and computed tomography sca...
INTRODUCTION: An abdominal aortic aneurysm (AAA) is a bulge/enlargement in an artery that expands over time and is more likely to rupture. Imaging techniques such as Magnetic resonance imaging and computed tomography scans are commonly used to investigate the condition of AAA. However, these techniques are expensive due to their complicated procedure. METHODS: This research developed a highly sensitive zeolite-Fe-based interdigitated microelectrode (IDM) sensor to quantify osteopontin, a well-known biomarker for AAA. To quantify the osteopontin, an aptamer and antibody sandwich pattern was designed on the IDM. Aptamer was bonded to the IDM by zeolite-Fe modification with an amine. Osteopontin was allowed to interact with the aptamer and then sandwiched by an anti-osteopontin antibody. RESULTS: This sandwich biosensor detected the osteopontin at as low as 100 pM, following a linear regression model (y = 4.8929x - 2.7467, R2 = 0.9909) over a concentration range of 100 to 3200 pM. Further, the detection with osteopontin-spiked serum was demonstrated by sandwich assay without any interferences, indicating the selective detection of osteopontin. In addition, control performances with complementary aptamer sequence and control proteins failed to increase the current flow, proving the specific detection of osteopontin. CONCLUSION: This highly sensitive zeolite-Fe modified IDM sensor detects osteopontin with an expanded surface area, which elevates the sensing performance compared to the existing sensors and helps to diagnose the severity of AAA.
The Enigma of Protein Succinylation in Diabetes.
Ma J, Li C, Di X … +4 more , Chen J, Zhu Q, Liu L, Li X
Curr Med Chem · 2026 May · PMID 42136307 · Publisher ↗
Lysine succinylation is a dynamic post-translational modification that alters protein structure and function by adding a succinyl group to lysine residues. This review first presents current evidence on the discovery of...
Lysine succinylation is a dynamic post-translational modification that alters protein structure and function by adding a succinyl group to lysine residues. This review first presents current evidence on the discovery of lysine succinylation and its regulatory enzymes, and then focuses on its roles in diabetes and its complications. We summarize that succinylation is potentially governed by writers (HAT1), erasers (SIRT5), and readers (GAS41), linking metabolic state to signaling and epigenetic regulation. Dysregulation of succinylation is associated with mitochondrial dysfunction, oxidative stress, and insulin resistance in key metabolic tissues, including the pancreas, liver, kidney, and heart. However, most studies remain correlative, and mechanistic insights into site-specific modifications are limited. The identities of bona fide succinyltransferases and dedicated reader domains are still uncertain, and tissue-specific regulatory networks in diabetes require further exploration. By synthesizing these findings, this review aims to inspire scientists to explore the succinylome to deepen our understanding of diabetic pathophysiology and identify novel therapeutic strategies.
Addressing Carbapenem Beta-Lactam Resistance by Nanotechnology.
Ghosh M, Banik BK
Curr Med Chem · 2026 May · PMID 42136306 · Publisher ↗
INTRODUCTION: A class of beta-lactam antibiotics known as carbapenems is used as a last option to treat serious bacterial infections that are resistant to multiple drugs. However, the fast rise of Carbapenem-Resistant Or...
INTRODUCTION: A class of beta-lactam antibiotics known as carbapenems is used as a last option to treat serious bacterial infections that are resistant to multiple drugs. However, the fast rise of Carbapenem-Resistant Organisms (CROs), a serious threat to world health, is a result of the overuse and misuse of these antibiotics. Acinetobacter baumannii and Pseudomonas aeruginosa have been linked to treatment failure rates of about 40-60% in severe infections, with fatality rates as high as 60% in carbapenem- resistant A. baumannii (CRAB)-associated pneumonia. METHODS: This review systematically analyzes recent literature (2010-2024) on the application of carbapenem, the development of different carbapenem resistances, the mechanism of action, and evaluates nanotechnology-based strategies to solve the carbapenem resistance problem. RESULTS: Nanotechnology-based techniques could offer a solution to this global problem. Nanoparticle-antibiotic combinations have higher antibacterial activity than free antibiotics alone. Significant decreases in MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values, improved bactericidal kinetics, a wider zone of inhibition, and strong synergistic interactions were found. Nanocarriers efficiently shielded carbapenems from enzymatic degradation, increased intracellular delivery, and damaged bacterial membranes via a variety of processes, including reactive oxygen species (ROS) formation. DISCUSSION: This systematic review attempts to provide an in-depth analysis of carbapenem resistance with the most recent data in order to assess the role and effect of this combined drug-nanostructure to combat carbapenem resistance. Additionally, it examines and emphasizes preclinical research that treats Multidrug-Resistant (MDR) bacterial infections by combining nanomaterials with antibiotics. By highlighting the benefits of the enhanced antibacterial and antibiofilm qualities and offering a workable plan for combating carbapenem-resistant bacteria, this review significantly contributes to a new understanding of biomedical research. CONCLUSION: Nanotechnology-based carbapenem delivery systems are a potent and diverse technique for combating carbapenem resistance. Preclinical investigations have found that employing nanotechnology to treat carbapenem beta-lactam resistance is particularly beneficial. Nanomaterial-based techniques provide unique and effective solutions to the growing antibiotic resistance dilemma by utilizing multi-modal mechanisms of action that bypass standard bacterial defense routes. Drug-nanoparticle conjugation improves antibacterial activity, lowers resistance development, and provides a realistic method to extend the therapeutic life of carbapenem antibiotics.
Efficacy of SGLT2i and GLP-1RA in Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.
Zhao H, Liu F, Zhang J … +9 more , Liu Y, Tan Z, Zhang J, Yu P, Zhang D, Liu X, Fu T, Huang J, Liu X
Curr Med Chem · 2026 May · PMID 42099143 · Publisher ↗
INTRODUCTION: The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in acute myocardial infarction (AMI) remains uncertain. We aimed to investigate the...
INTRODUCTION: The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in acute myocardial infarction (AMI) remains uncertain. We aimed to investigate the effectiveness of SGLT2i and GLP-1RA in patients with AMI. METHODS: We conducted a comprehensive search on PubMed, the Cochrane Library, Embase, and ClinicalTrials.gov databases to identify relevant randomized controlled trials (RCTs) up to January 2025. The primary outcomes included all-cause mortality and left ventricular ejection fraction (LVEF). RESULTS: Six RCTs assessed SGLT2i (SGLT2i: n=5,660; placebo: n=5,651) and five assessed GLP-1RA (GLP-1RA: n=300; placebo: n=333). Compared with placebo, SGLT2i improved LVEF (mean difference = 1.58, p = 0.01, high certainty) and reduced heart failure hospitalization (HHF) (odds ratio = 0.78, p = 0.023, moderate certainty) in AMI patients. No significant benefit was observed in all-cause mortality with SGLT2i, and no significant benefits of GLP-1RA were observed in all-cause mortality, cardiac death, myocardial infarction relapse, infarct size, LVEF, left ventricular end-diastolic volume, or left ventricular end-systolic volume. TSA indicated potential false positives for the LVEF and HHF findings with SGLT2i. DISCUSSION: Several limitations of the included studies include a small number of studies, heterogeneity in experimental design, and reliance on alternative endpoints. CONCLUSION: SGLT2i improved LVEF and reduced HHF in patients with AMI but did not significantly improve all-cause mortality. GLP-1RA did not significantly improve LVEF or major clinical endpoints. Further large-scale RCTs are needed to verify these results and provide more robust evidence.
CCNJL as a Prognostic Biomarker and Therapeutic Target in Cholangiocarcinoma.
Li D, Lyu G
Curr Med Chem · 2026 May · PMID 42099142 · Publisher ↗
INTRODUCTION: Cholangiocarcinoma (CHOL) is a highly aggressive and lethal malignancy whose global incidence is increasing. This increase has been attributed to various factors, including an aging population and changes i...
INTRODUCTION: Cholangiocarcinoma (CHOL) is a highly aggressive and lethal malignancy whose global incidence is increasing. This increase has been attributed to various factors, including an aging population and changes in environmental exposure. Therefore, the identification of reliable biomarkers for prognosis and treatment is crucial because of its poor survival rates and limited therapeutic options. This research examines the expression patterns and clinical relevance of Cyclin J Like (CCNJL) in CHOL, evaluating its potential as a candidate prognostic marker and immunotherapy target. METHODS: We analyzed CCNJL expression in CHOL tissues compared with normal tissues using data from The Cancer Genome Atlas (TCGA) and the GSE31370 dataset. We performed differential expression analysis, Kaplan-Meier survival analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) to elucidate relationships among CCNJL expression, clinical outcomes, immune infiltration, and drug sensitivity. CCNJL expression levels were validated in CHOL cell lines by quantitative real-time PCR (qRT-PCR). RESULTS: CCNJL expression is significantly higher in CHOL tissues than in controls (mean ± SD: 1.714 ± 0.201 vs 0.165 ± 0.027; p < 0.001; AUC = 0.946). High CCNJL expression independently predicts worse overall survival (HR = 2.84, 95% CI = 1.01-7.95, p = 0.047) and disease-specific survival (HR = 3.40, 95% CI = 1.09-10.55, p = 0.035). GSEA linked high CCNJL expression to cytokine-cytokine receptor interaction, chemokine signaling, CAMs, and antigen processing. High CCNJL expression correlated inversely with CD8+ T-cell infiltration (p < 0.001) and with reduced sensitivity to elesclomol, tanespimycin, and selumetinib (all p < 0.05). qRT-PCR confirmed significant CCNJL up-regulation in CHOL cell lines. DISCUSSION: CCNJL emerges as a novel, independent prognostic biomarker and a candidate immunotherapy target in CHOL. Its association with immune evasion and drug resistance suggests that therapeutic targeting of CCNJL could enhance antitumor immunity and restore drug sensitivity. Limitations include a modest sample size and a lack of functional validation; prospective multicenter studies and mechanistic investigations are warranted. CONCLUSION: CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.
Exploring the Anticancer Potential of Launaea mucronata: Biological Assessment, Molecular Docking, and Molecular Dynamics Simulations.
Al-Karmalawy AA, Alabdali AYM, El-Amier YA … +8 more , Al Khatib AO, Alnajjar R, Khalifa MM, Farouk F, Saadeldin AA, Almujri SS, Abdullah Alzahrani AY, Taher RF
Curr Med Chem · 2026 May · PMID 42099141 · Publisher ↗
BACKGROUND: Launaea mucronata has garnered the interest of chemists, particularly in the field of oncology. While not traditionally used for cancer treatment, studies have shown that its methanolic extract exhibits cytot...
BACKGROUND: Launaea mucronata has garnered the interest of chemists, particularly in the field of oncology. While not traditionally used for cancer treatment, studies have shown that its methanolic extract exhibits cytotoxic effects against human cancer cell lines. METHODS: Herein, thirty-three metabolites were spotted in the aqueous extract of Launaea mucronata via UPLC-MS/MS, primarily flavonoids, hydroxycinnamic acid derivatives, and carboxylic acid derivatives. The extract's antiproliferative activity was tested on HCT-116 (colon), MCF7 (breast), and HePG2 (liver) cancer cells, showing notable potency. A molecular docking study assessed the extract's bioactive compounds for their binding to human DNA-Topo II enzyme complexes. Molecular dynamics simulations (200 ns) were performed on the top-scoring complexes (dicaffeoyl-succinoylquinic acid 7, tricaffeoyl quinic acid 10, feruloyl-O-p-coumaroyl- O-caffeoylshikimic acid 12, and kaempferol-rutinoside 23) using Schrödinger's Desmond package. Binding stability was further validated by MM-GBSA energy calculations via Schrödinger's thermal_mmgbsa.py script. RESULTS: The IC50 values were 5.35 ± 0.09 μg/mL in the HePG2 cell line versus 48.99 ± 21.51 μg/mL for doxorubicin. Similarly, for the MCF7 cells, the recorded IC50 of the extract was found to be 5.60 ± 1.15 μg/mL versus 4.97 ± 0.35 μg/mL for doxorubicin. DISCUSSION: A total of 33 metabolites of Launaea mucronata identified via UPLC-MS/MS were identified as promising anticancer candidates against both HePG2 and MCF7 cell lines. Additionally, their mechanisms of action involve DNA intercalation and inhibition of topoisomerase II (Topo II) through molecular docking, molecular dynamics, and MM-GBSA calculations. CONCLUSION: These findings highlight Launaea mucronata's promising anticancer potential, supported by both experimental and computational evidence.
Innovative Applications of Cutting-Edge Nanomaterials in Diabetic Wound Healing.
Wang J, Zhu M, Tong Y … +1 more , Yang Y
Curr Med Chem · 2026 May · PMID 42099140 · Publisher ↗
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Diabetic wound healing faces severe challenges, such as low treatment efficiency and susceptibility to infection due to its complex patholo...
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Diabetic wound healing faces severe challenges, such as low treatment efficiency and susceptibility to infection due to its complex pathological microenvironment. Conventional treatments like antimicrobial dressings and debridement are limited by issues such as low drug bioavailability and poor tissue penetration. In recent years, nanomaterials have demonstrated significant potential in diabetic wound management by leveraging their unique physicochemical properties and multifunctional integration capabilities. They enable precise intervention in the wound microenvironment through targeted delivery, controlled release, and synergistic multi-mechanistic actions involving antibacterial, antioxidant, immunomodulatory, and pro-angiogenic aspects. This review systematically summarizes innovative applications of various cutting-edge nanomaterials in diabetic wound repair, including metal nanomaterials (e.g., Ag, Au), metal-organic frameworks (MOFs), polymeric nanomaterials (e.g., chitosan), ceramic nanomaterials, carbon- based nanomaterials (e.g., graphene, carbon quantum dots), lipid nanoparticles (LNPs), and exosomes. For instance, silver-loaded Prussian blue-chitosan nanocomposite (Ag@Chi-PB NPs) under near-infrared (NIR) laser activation achieved eradication rates of 65% and 60% against Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) biofilms, respectively. Trisulfide lipid nanoparticles (TS LNPs) loaded with Interleukin-4 (IL4)-mRNA in diabetic mouse models reduced reactive oxygen species levels by 7-fold and increased M2 macrophage proportion to 53%. Moreover, a graphene-based composite hydrogel achieved nearly 99.7% wound closure within 14 days, demonstrating excellent conductivity and promoting re-epithelialization. This review focuses on the latest mechanistic insights and application advances of nanomaterials in chronic diabetic wound therapy, aiming to provide systematic and forward- looking academic references for researchers and clinicians and to promote their clinical translation.
Unveiling the Anti-cancer Potential of Vulpinic Acid: A Selective Therapeutic Agent Against Oral Squamous Cell Carcinoma.
Şengüm DN, Alkan AH, Bozkurt FZ … +2 more , Mutlu P, Cansaran-Duman D
Curr Med Chem · 2026 May · PMID 42099139 · Publisher ↗
INTRODUCTION: Lip and oral cavity cancers are among the most common types of cancer worldwide and remain a major health problem due to poor prognosis and treatment- related side effects. Therefore, identifying new natura...
INTRODUCTION: Lip and oral cavity cancers are among the most common types of cancer worldwide and remain a major health problem due to poor prognosis and treatment- related side effects. Therefore, identifying new naturally derived compounds with selective cytotoxic effects on oral cancer cells is essential. Vulpinic acid, a lichenderived secondary metabolite, has shown antioxidant and anticancer activities in various cancer types. However, its effects on oral cancer cells have not yet been clarified. This study aims to investigate the cytotoxic and apoptotic effects of vulpinic acid on oral cancer cells and to explore its possible molecular mechanisms. METHODS: The cytotoxic effect of vulpinic acid on OSC-19 oral cancer and MRC-5 normal fibroblast cells was assessed using xCELLigence analysis. The impact of vulpinic acid on cell cycle progression, apoptotic mechanisms, colony formation, wound healing, and molecular-level effects was analyzed using flow cytometry, mitochondrial membrane potential assay, and qRT-PCR. The effect of vulpinic acid on BIRC5 protein levels was further confirmed by western blot analysis. RESULTS: The results showed that the IC50 value of vulpinic acid was 59 μM in OSC-19 cells and 114 μM in MRC-5 cells, demonstrating its selective cytotoxic effect on oral cancer cells. Vulpinic acid treatment suppressed colony formation by 55.5% and reduced cell migration by 71.2-fold at 96 h. Cell cycle analysis revealed that vulpinic acid induced G1 phase arrest, while apoptosis analysis showed a decrease in mitochondrial membrane potential. qRT-PCR analysis revealed an upregulation of pro-apoptotic genes (BID, CASP4, CASP7, BAK1, BCL2L2) and downregulation of the anti-apoptotic gene survivin (BIRC5). According to western blot analysis, BIRC5 protein expression decreased 2.39-fold following vulpinic acid treatment. DISCUSSION: These findings indicate that vulpinic acid has the potential to be considered as an anti-cancer agent. CONCLUSION: Further in vivo and clinical studies are required to validate its therapeutic efficacy and safety profile.
Phytochemical Exploration and Anti-asthmatic Activity of Crude Methanol Extract and Derived Fractions of Sonchus asper (L.) Hill.
Ahmad K, Abdullah, Khan M … +1 more , Ahmad S
Curr Med Chem · 2026 Apr · PMID 42083961 · Publisher ↗
INTRODUCTION: Asthma is a chronic inflammatory airway disease with limited curative therapies. Sonchus asper, traditionally used in Pakistan for asthma, was investigated for its phytochemical profile and in vivo anti-ast...
INTRODUCTION: Asthma is a chronic inflammatory airway disease with limited curative therapies. Sonchus asper, traditionally used in Pakistan for asthma, was investigated for its phytochemical profile and in vivo anti-asthmatic potential. METHODS: The whole plant was extracted with 80% methanol, fractionated, followed by phytochemical screening, HPLC analysis, and total phenolic and flavonoid quantification. Anti-asthmatic activity was evaluated using an ovalbumin-induced asthma model following oral administration of extracts and fractions. Bronchoalveolar lavage fluid analysis, total and differential leukocyte counts, and lung histopathology were performed. The most active fraction (chloroform) was subjected to column chromatography and GC-MS analysis. RESULTS: Alkaloids, flavonoids, saponins, tannins, and phenolics were detected, with the chloroform fraction exhibiting the highest phenolic and flavonoid contents. HPLC analysis identified quercetin, catechin, and rutin. The chloroform fraction displayed the most potent anti-asthmatic activity, significantly reducing total inflammatory cells by 73.2% (p ˂ 0.001), 63% (p ˂ 0.01) and 57.7% (p < 0.01) at 300, 150 and 75 mg/kg respectively, with marked suppression of eosinophils, neutrophils, lymphocytes and macrophages, and improved histopathology, while the ethyl acetate fraction produced comparable reductions (72.61%, 61.90%, 56.54%) across the same dose range. GC-MS identified caryophyllenyl alcohol and phytol. DISCUSSION: The significant anti-asthmatic activity of Sonchus asper, particularly the chloroform and ethyl acetate fractions, supports existing evidence on flavonoid and phenolic-rich medicinal plants, although the lack of cytokine profiling and molecular mechanistic validation remains a limitation. CONCLUSION: These findings support the traditional use of Sonchus asper in asthma and identify it as a promising source of anti-inflammatory agents.
Predictive Analyses of Tumor Relapse-free Survival Prognosis Related to Consistency between Different Cancer Tissues and Adjacent Normal Tissues in Drug Repurposing for Solid Tumor via Connectivity Map.
Hao M, Li D, Qiao Y … +3 more , Xiong M, Li J, Ma W
Curr Med Chem · 2026 Apr · PMID 42083960 · Publisher ↗
INTRODUCTION: Traditional drug discovery faces challenges, including high costs, time-intensive processes, and inherent risks. The disease-specific signature-based Connectivity Map (CMap) approach is widely utilized. How...
INTRODUCTION: Traditional drug discovery faces challenges, including high costs, time-intensive processes, and inherent risks. The disease-specific signature-based Connectivity Map (CMap) approach is widely utilized. However, the commonly employed method for constructing disease-specific signatures, known as Differentially Expressed Genes (DEGs), suffers from inconsistencies between dysregulated genes and their prognostic implications in tumor tissue, as well as discrepancies in prognosis genes between tumor and normal tissues. In this study, we present predictive analyses of CMap-based drug repurposing for solid tumors that account for discrepancies in gene activity between tumor and adjacent normal tissues. METHODS: We propose a predictive approach, Prognosis Consistency Scoring (PCS), designed to address these inconsistencies by analyzing six types of solid tumors: BRCA, HNSC, LIHC, LUAD, LUSC, and THCA. PCS measures the consistency of gene prognosis between tumor and normal tissues by integrating the Recurrence- Free Survival (RFS) prognostic power of genes in both contexts. Disease-specific signatures are then constructed based on PCS, and drug repurposing is performed using the CMap and Lincs Unified Environment (CLUE). The predicted drugs were validated using data from DrugBank, ClinicalTrials, CancerDrugs_DB, Re- DO_Trials_DB, GDSC2, CTRPv2, and PRISM. Biological enrichment analysis was conducted via the Metascape platform. RESULTS: Our findings reveal that these inconsistencies are pervasive. Compared to signatures based on DEGs, PCS-based signatures exhibit superior performance, identifying more drugs with higher prediction accuracy, as confirmed by DrugBank annotations. Notably, a significant proportion of predicted drugs without corresponding indications were subsequently validated in the ClinicalTrials database. For instance, three trials support the efficacy of gemcitabine in LIHC, and two trials support the use of dasatinib for the treatment of LUAD and LUSC. The prediction accuracy of PCS is higher than that of DEGs (20/31 vs. 1/31, Fisher's exact test, p-value < 0.001). In the CancerDrugs_DB and ReDO_Trials_DB databases, the performance of PCS was also influenced by DEGs. In the three in vitro tumor cell line drug response databases, including GDSC2, CTRPv2, and PRISM, PCS outperformed DEGs. Comparative analysis between PCS and Tumor Prognosis Score (TPS) indicates that, although TPS is a component of PCS, the performance of PCS is still influenced by TPS. Additionally, PCS-based signatures demonstrated elevated disease specificity and association with Drug-Related Genes (DRGs). DISCUSSION: New drug discovery is time-consuming and risky. To address this, we proposed PCS, a method that improves drug repurposing accuracy by considering consistency between gene dysregulation and prognosis in tumor and normal tissues. PCS outperformed DEG-based approaches in predicting drugs and showed higher validation in DrugBank and ClinicalTrials. It also demonstrated disease specificity and supported rational combination therapies. PCS offers a more precise alternative and holds promise for further refinement. CONCLUSION: PCS outperformed DEGs in drug repurposing predictions and exhibited higher disease specificity. The availability of tumor-normal paired samples with RFS was limited. Our method lacked comparisons with alternative approaches. PCS exhibited limited predictive utility in certain tumor types, suggesting its potential unsuitability for all solid tumors. PCS had a notable flaw, as positive scores also enriched some treatment drugs.
Apatinib and Adebrelimab Exhibit Synergistic Antitumor effects in Small Cell Lung Cancer: An In Vitro Study.
Zhu Y, Cheng X, Wu L … +2 more , Wang Y, Huang L
Curr Med Chem · 2026 Apr · PMID 42083959 · Publisher ↗
BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive malignancy. This study investigated whether Apatinib (Apa) combined with Adebrelimab (Ade) exerted synergistic effects against SCLC. METHODS: Half-maximal...
BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive malignancy. This study investigated whether Apatinib (Apa) combined with Adebrelimab (Ade) exerted synergistic effects against SCLC. METHODS: Half-maximal inhibitory concentration (IC50) value of Apa and Ade, administered alone or in combination, was determined in H446 and H1436 cells using cell counting kit-8 (CCK-8) assays. Synergistic effects were quantified by calculating fractional inhibitory concentration (FIC) indices. Cell proliferation, migration, and invasion were assessed by CCK-8, wound healing, and Transwell assays, respectively. After co-culture with CD8+ T cells, PD-L1 expression and CD8+ IFN-γ+ T cell proportion were measured by flow cytometry. TGF-β secretion and LDH release were detected using ELISA and LDH assay, respectively; the protein level of VEGFR2 and STAT3 was analyzed by western blot. RESULTS: Apa alone exhibited IC50 values of 20.03 μM (H446) and 35.50 μM (H1436), while Ade alone exhibited 5.789 μM and 6.959 μM, respectively. The sum FIC values were 0.681 for H446 cells and 0.973 for H1436 cells. Compared with either monotherapy, combined treatment more effectively reduced cell viability, migration, and invasion. In co-culture experiments, the combination further suppressed PD-L1 expression and TGF-β secretion, increased CD8+ IFN-γ+ T cells and LDH release, and downregulated VEGFR2, p-STAT3, and PD-L1 protein levels. DISCUSSION: This study demonstrated that the combination of Apa and Ade exerted synergistic anti-tumor effects against SCLC in vitro. Further investigation, including animal studies and clinical trials, is warranted to evaluate the efficacy and long-term safety of this combination therapy. CONCLUSION: In summary, the combination of Apa and Ade represented a promising innovative therapeutic strategy for SCLC.
Global Research Progress of Sepsis and Mitochondria: Bibliometrics and Visualized Analysis.
Shang L, Cai Y, Wang S … +6 more , Li J, Zhou F, Zhang M, Wang Y, Huang J, Yang S
Curr Med Chem · 2026 Apr · PMID 42083958 · Publisher ↗
OBJECTIVE: Many studies have demonstrated a significant association between mitochondria and sepsis. As research on mitochondria continues to deepen, substantial advancements have been achieved in elucidating the connect...
OBJECTIVE: Many studies have demonstrated a significant association between mitochondria and sepsis. As research on mitochondria continues to deepen, substantial advancements have been achieved in elucidating the connection between mitochondria and sepsis. Nevertheless, there has been no systematic bibliometric analysis or visualization of the related publications in this field. This study aims to visually present the knowledge system and research focus between mitochondria and sepsis through the method of bibliometrics. METHODS: An extensive review of existing literature was conducted using the Web of Science Core Collection (WoSCC) database to identify publications investigating the relationship between mitochondria and sepsis. Subsequent bibliometric analysis was conducted using R software (version 4.4.0) with the Bibliometrix package (version 4.2.3), complemented by visualization and network analysis through VOSviewer (version 1.6.20) and CiteSpace (version 6.1.6). RESULTS: From 1997 to 2025, the Web of Science Core Collection retrieved a total of 1993 relevant publications. The number of publications related to mitochondria and sepsis has continued to increase throughout this period. China, along with the United States and the United Kingdom, plays a central role in advancing research in this field. Leading institutions contributing to this area include the University of Pennsylvania, Harvard University, and the University of London. SINGER M and ZHANG Y are the top authors in this research field. The keyword analysis reveals that the high-frequency terms include sepsis, mitochondrial dysfunction, oxidative stress, and inflammation. We summarized the pathogenesis of sepsis related to mitochondria, as well as the existing and potential therapeutic drugs for sepsis that are associated with these mechanisms. DISCUSSION: As the comprehensive bibliometric analysis in this field, our study visually presents key research trends and hotspots linking mitochondria to sepsis, emphasizing the significance of mitochondrial dysfunction and other factors in the pathogenesis of sepsis, offering a valuable framework for future scientific and clinical advancements. CONCLUSION: The field of mitochondrial research in sepsis has experienced steady growth over the past two decades, with substantial contributions from China, the United States, and the United Kingdom. Emerging evidence suggests that future investigations are likely to center on key pathological mechanisms such as mitochondrial dysfunction and oxidative stress.
Identification and Validation of Diagnostic Biomarkers for Osteoarthritis Coexisting with IVDD and LFH via Bioinformatics and Machine Learning.
Han W, Deng Z, Lin Z … +2 more , Luo J, Xu J
Curr Med Chem · 2026 Apr · PMID 42083957 · Publisher ↗
INTRODUCTION: Osteoarthritis (OA), intervertebral disc degeneration (IVDD), and ligamentum flavum hypertrophy (LFH) frequently manifest concurrently in the aging population. This study aims to identify potential diagnost...
INTRODUCTION: Osteoarthritis (OA), intervertebral disc degeneration (IVDD), and ligamentum flavum hypertrophy (LFH) frequently manifest concurrently in the aging population. This study aims to identify potential diagnostic genes associated with these three interconnected conditions. METHODS: Utilizing datasets from the Gene Expression Omnibus (GEO) database, we applied Limma and weighted gene co-expression network analysis (WGCNA) to discern pivotal genes. Subsequent enrichment analyses shed light on the functional implications of these identified genes. The utilization of three distinct machine learning algorithms facilitated the identification of hub genes. Evaluation of the predictive capacity of these hub genes was conducted through nomograms and receiver operating characteristic (ROC) curves. Additionally, predictions pertaining to transcription factors, microRNAs, and potential therapeutic drugs were made. Furthermore, the study delved into the exploration of immune cell infiltration in OA. RESULTS: An integrated bioinformatics analysis of OA datasets identified 246 key genes enriched in inflammatory pathways, including MAPK signaling and interleukin signaling. Comparison across OA, IVDD, and LFH datasets identified 9 common differentially expressed genes. Machine learning algorithms subsequently identified ANKH and GADD45B as central hub genes. A diagnostic nomogram constructed using these genes demonstrated strong predictive performance, particularly for OA. Further analyses predicted SREBF1 as a potential co-regulator and quercetin as a drug candidate targeting both hub genes. Immune infiltration analysis revealed altered levels of resting memory CD4 T cells and activated mast cells in OA, correlating with hub gene expression. Finally, RT-qPCR validation in clinical samples confirmed the differential expression patterns of ANKH and GADD45B, supporting their relevance. DISCUSSION: The identification of ANKH and GADD45B as common hub genes offers novel insights into the shared molecular mechanisms underlying co-occurring OA, IVDD, and LFH. The strong predictive performance of the nomogram using these genes underscores their potential as diagnostic biomarkers for OA. The predicted interaction of quercetin with both hub genes, alongside SREBF1 as a co-regulator, suggests new therapeutic targets for these genes. Moreover, the findings on altered activated mast cell levels in OA correlating with hub gene expression highlight their potential role in OA pathogenesis and as therapeutic targets. These findings, supported by initial RT-qPCR validation, provide a foundation for further experimental studies to confirm their clinical utility. CONCLUSION: This study identifies ANKH and GADD45B as promising diagnostic genes for distinguishing OA co-occurring with IVDD and LFH. Furthermore, our findings underscore the significance of MCs in the context of OA, providing insights into their potential role in the pathogenesis of the condition.
Identification of PPIA, DPP4, and ITK as Potential Targets of Pterostilbene in Abdominal Aortic Aneurysm: A Network Pharmacology and Molecular Docking Study.
Li W, Xiao X, Yang J … +2 more , Liu D, Sun Z
Curr Med Chem · 2026 Apr · PMID 42083956 · Publisher ↗
BACKGROUND: Pterostilbene is a polyphenolic compound with antioxidant and anti-inflammatory properties. This study aims to explore its potential therapeutic effects on Abdominal Aortic Aneurysm (AAA). METHODS: The Gene E...
BACKGROUND: Pterostilbene is a polyphenolic compound with antioxidant and anti-inflammatory properties. This study aims to explore its potential therapeutic effects on Abdominal Aortic Aneurysm (AAA). METHODS: The Gene Expression Omnibus (GEO) database was accessed to obtain single- cell sequencing data and transcriptome datasets to identify Differentially Expressed Genes (DEGs) in AAA. The DEGs were further intersected with predicted targets of pterostilbene to identify common genes, which were considered core genes for functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Molecular docking and 100 ns Molecular Dynamics (MD) simulations were then performed to evaluate binding affinity and stability. RESULTS: PPIA, DPP4, and ITK were identified as overlapping genes associated with both pterostilbene and AAA. A single-cell atlas revealed their specific expression patterns across different cell types. The three genes were also correlated with IL6/JAK/STAT3, inflammatory response, and immune-related pathways. Molecular docking showed binding affinities ranging from -5.66 to -7.11 kcal/mol, and 100 ns MD simulations revealed stable binding conformations for all three targets. DISCUSSION: The present multi-omics analysis suggests that pterostilbene may exert therapeutic effects on AAA by modulating inflammation- and immune-related pathways, providing a hypothesis-generating basis for further investigation. CONCLUSION: This hypothesis-generating study proposes that pterostilbene may exert therapeutic effects on AAA by targeting PPIA, DPP4, and ITK and modulating inflammation- and immune-related pathways. However, these computational findings require further experimental validation.
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