Curr. Med. Chem. [JOURNAL]
Sun
200 papers
Maternal Exposure to Organochlorine Pesticides and Epigenetic Alterations in Unexplained Recurrent Miscarriage.
Faramarz S, Asadikaram G, Abbasi-Jorjandi M … +4 more , Abolhassani M, Nematollahi MH, Norouzmahani ME, Pourghadamyari H
Curr Med Chem · 2026 Apr · PMID 41935366 · Publisher ↗
INTRODUCTION: Organochlorine Pesticides (OClPs) are environmental pollutants that can affect reproductive health. Unexplained Recurrent Miscarriage (URM) has not been fully clarified, but some evidence suggests that the...
INTRODUCTION: Organochlorine Pesticides (OClPs) are environmental pollutants that can affect reproductive health. Unexplained Recurrent Miscarriage (URM) has not been fully clarified, but some evidence suggests that the epigenome of fetal and placental tissues could be the cause. This study aimed to establish the correlation between OClP exposure and methylation of the TSHR and ATM promoters in these tissues. METHODS: Blood, fetal, and placental tissues were sampled in this cross-sectional case-- control study involving 73 women with URM and 30 controls. Gas chromatography was used to determine serum levels of OClPs (4,4-DDE, α-HCH, 2,4-DDE, γ-HCH, 4,4-DDT, β-HCH, and 2,4-DDT), and the determination of ATM and TSHR promoters' methylation in placental and fetal samples was assessed using Methylation-specific PCR. Logistic regression analysis was also used to test associations between OClP exposure and DNA methylation of the selected genes. RESULTS: 4,4-DDE, 2,4-DDE, β-HCH, α-HCH, and total OClPs (Ʃ7OClP, Ʃ2DDT, Ʃ2DDE, and Ʃ3HCH) were significantly higher in URM cases compared to controls. There were no significant differences in TSHR promoter methylation between the groups. On the other hand, ATM promoter hypomethylation was observed in URM placental tissues (45.8%) compared with controls (83.3%, p = 0.015) and was significantly associated with increased levels of 2,4-DDT and Ʃ2DDE. DISCUSSION: Exposure to OClPs, particularly 2,4-DDT and Ʃ2DDE, has the potential to interfere with placental DNA repair processes by hypomethylating the ATM promoter and thus potentially contribute to the pathogenesis of URM. Furthermore, these results emphasize the tissue-specific characteristics of epigenetic changes and highlight the complex interactions between environmental exposures and reproductive health outcomes. CONCLUSION: This study demonstrates the critical role of OClP-induced epigenetic alterations in the placental DNA repair mechanisms and their possible contribution to the pathophysiology of unexplained recurrent miscarriage.
Focal Adhesion Related Gene Signature for Glioma: The Pivotal Role of RAP1B in Disease Progression.
Wang N, Zhou H, Wang T … +11 more , Wang Y, Wu W, Xiang J, Chen X, Zhang B, Wu P, Zhou M, Cao Y, Li X, Yu H, Bao G
Curr Med Chem · 2026 Mar · PMID 41926292 · Publisher ↗
INTRODUCTION: Gliomas are the most common malignant primary brain tumors in adults, with generally unfavorable outcomes. Although focal adhesion-related genes are implicated in glioma progression, their clinical applicab...
INTRODUCTION: Gliomas are the most common malignant primary brain tumors in adults, with generally unfavorable outcomes. Although focal adhesion-related genes are implicated in glioma progression, their clinical applicability remains limited. METHODS: mRNA expression profiles were analyzed in 938 glioma samples from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), with TCGA as the discovery cohort and CGGA as the validation cohort. Consensus clustering and LASSO Cox regression were used to construct a focal adhesion-related gene (FARG) signature. Survival analysis, pathway enrichment, immune infiltration, and drug response analyses were subsequently performed based on this signature. In vitro and in vivo assays were performed to investigate RAP1B, the gene with the highest coefficient in the FARG signature. RESULTS: A 9-gene FARG signature was identified and effectively stratified patients into high- and low-risk groups with significantly different outcomes. High-risk patients exhibited malignant molecular features, activation of oncogenic pathways, treatment resistance, and an immunosuppressive microenvironment. RAP1B contributed most to the risk score, was significantly upregulated in gliomas, and correlated with poor prognosis. Mechanistically, NFKB1 enhanced RAP1B transcription, promoting glioma proliferation, migration, and tumorigenesis. DISCUSSION: The FARG signature integrates molecular and immune characteristics of gliomas, offering a predictive model for patient prognosis. RAP1B, as a key molecular target, holds potential for improving patient survival. However, this study largely relies on public databases, and further validation in independent cohorts and functional models is required. CONCLUSION: This study establishes a FARG-based prognostic model and identifies RAP1B as a potential therapeutic target in glioma.
Biomimetic Nanoparticles: Novel Therapeutic Strategies for Autoimmune Diseases.
Ghorbani-Shemshadsara F, Aghayan SN, Foroutan A … +3 more , Rasouli Z, Demneh FA, Gheibihayat SM
Curr Med Chem · 2026 Mar · PMID 41926291 · Publisher ↗
Autoimmune Diseases (ADs) encompass a multifaceted spectrum of chronic disorders characterized by an aberrant immune response against host tissues. Notwithstanding substantial progress in immunological research, current...
Autoimmune Diseases (ADs) encompass a multifaceted spectrum of chronic disorders characterized by an aberrant immune response against host tissues. Notwithstanding substantial progress in immunological research, current therapeutic interventions remain largely palliative, relying on broad-spectrum immunosuppressants that are frequently associated with substantial adverse effects and compromised immune defense. Currently, biomimetic nanoparticles (BMNPs) stand out as a paradigm-shifting approach in precision medicine, facilitating targeted delivery, enhanced biocompatibility, and sophisticated immune modulation. This review critically examines the therapeutic applications of BMNPs in managing autoimmune disorders, including rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and celiac disease. By emulating cellular membranes, such as those of erythrocytes, platelets, and leukocytes, BMNPs acquire the ability to evade immune detection, prolong systemic circulation time, and deliver therapeutic payloads directly to inflamed or diseased tissues. The integration of BMNPs with pharmacological agents, immunomodulators, or advanced gene-editing systems like CRISPR/Cas9 has demonstrated enhanced specificity and attenuated systemic toxicity in preclinical models; notably, these platforms exhibit several- fold higher drug accumulation in inflamed tissues compared to conventional non-targeted nanoparticles. Furthermore, the utilization of BMNPs in diagnostic imaging, particularly MRI and PET, has facilitated superior disease monitoring and treatment evaluation. While challenges such as large-scale production, potential toxicity, and regulatory hurdles persist, overcoming these barriers requires establishing standardized manufacturing protocols and clear translational pathways. This article delineates the latest advancements, design strategies, and translational challenges of BMNPs, underlining their potential to reshape the landscape of autoimmune disease diagnosis and therapy.
Carbonyl-to-Sulfur Skeletal Editing: A Transformative Strategy for Drug Scaffold Diversification.
Zhang J
Curr Med Chem · 2026 Mar · PMID 41926290 · Publisher ↗
Sulfur-containing functional motifs are embedded in roughly 25% of all FDA-approved small-molecule drugs, yet direct and practical methods for converting abundant carbonyl compounds into their sulfur-bearing analogs have...
Sulfur-containing functional motifs are embedded in roughly 25% of all FDA-approved small-molecule drugs, yet direct and practical methods for converting abundant carbonyl compounds into their sulfur-bearing analogs have long been constrained by toxic reagents, lengthy multi-step procedures, and narrow functional group compatibility. A landmark recent breakthrough has established a concise two-step Carbonyl- to-Sulfur (CO-to-S) skeletal transformation that relies on sequential C-C bond cleavage driven by a Nitrogen-Assisted Homolytic Activation (NAHA) reagent, paired with a Tosyl Disulfide (Ts-S-Ts) mediator under mild radical conditions (Zhang and Dong, Science, 2025). This perspective offers an in-depth dissection of the mechanistic elegance underpinning this strategy, with a sharp focus on its transformative roles in late-stage derivatization of drug candidates, rapid diversification of molecular scaffolds, and precise optimization of metabolic profiles. By situating this approach within the broader landscape of sulfur-centered chemistry in modern drug design, we critically evaluate its distinct advantages over conventional thiolation methods, address current limitations in stereochemical control and substrate scope, and outline promising future directions for enantioselective variants and applications in bioconjugation chemistry.
Exploring the Effects of Empagliflozin Administration and Physical Training on Cognitive Functions in an Amyloid Beta-Induced Alzheimer's Rat Model.
Behrouzfar H, Mortazavi P, Hassani S … +1 more , Aghebat Bekheir S
Curr Med Chem · 2026 Mar · PMID 41918193 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a widely prevalent and neurodegenerative disorder that leads to dementia and mortality worldwide. Previous investigations have reported the beneficial effects of physical exercis...
INTRODUCTION: Alzheimer's disease (AD) is a widely prevalent and neurodegenerative disorder that leads to dementia and mortality worldwide. Previous investigations have reported the beneficial effects of physical exercise on brain function, linked to anti-inflammatory effects in the brain vasculature and elevated BDNF production. Empagliflozin, a conventional antidiabetic agent, has shown potential neuroprotective properties in the central nervous system, evidenced by its ability to elevate BDNF and mitigate oxidative stress and inflammation. MATERIALS AND METHODS: In the present investigation, AD was induced in control, exercise, empagliflozin (10 mg/kg BW, PO), and combined intervention groups using intrahippocampal injections of an amyloid-beta (Aβ) prepared solution via stereotaxic surgery. The therapeutic effects of each treatment, exercise alone, empagliflozin alone, and exercise plus empagliflozin, were studied. After 28 days, spatial memory tests were used to assess memory and learning. Furthermore, histopathological (H&E and Congo red) and immunohistochemical (GFAP) analyses were performed, and the ADP/ATP ratio in isolated brain mitochondria was measured by HPLC. RESULTS: Our results showed that the combined program of physical training and empagliflozin treatment in the Aβ-induced AD model drastically improved cognitive functions and neurological parameters, including target-finding time, traveled distance, time spent in the target quadrant, and ADP/ATP ratios in brain mitochondria. Additionally, it diminished necrotic cell death and reduced Aβ plaques but did not notably affect astrocyte activity. DISCUSSION: Exercise and empagliflozin, by affecting mitochondrial energy balance and reducing amyloid deposition, play key roles in mitigating AD pathophysiology. CONCLUSION: The combined effects of the treatments used in this experimental method yielded significant improvements in cognitive functions. These findings provide a basis for further clinical studies for the exploration of the synergistic impact of the aforementioned therapeutic methods.
Curcumin Analogs in Glioblastoma Therapy: A Narrative Review.
Moeinipour Y, Bakhshi A, Ghoflchi S … +3 more , Taghavi A, Hosseini H, Jalili-Nik M
Curr Med Chem · 2026 Mar · PMID 41918192 · Publisher ↗
Glioblastoma (GBM) is an aggressive and treatment-resistant primary brain tumor with a poor prognosis. Conventional therapies are limited by tumor heterogeneity, therapy resistance, and restricted Blood-Brain Barrier (BB...
Glioblastoma (GBM) is an aggressive and treatment-resistant primary brain tumor with a poor prognosis. Conventional therapies are limited by tumor heterogeneity, therapy resistance, and restricted Blood-Brain Barrier (BBB) penetration, highlighting the need for novel multi-targeted therapeutic strategies. This review assesses the therapeutic potential of curcumin analogs in GBM, with a focus on their molecular mechanisms, in silico predictions, preclinical efficacy, and potential synergistic strategies with standard treatments. A comprehensive search of published in vitro, in vivo, and computational studies on curcumin analogs was conducted. Mechanistic investigations included apoptosis induction, cell-cycle arrest, autophagy, ferroptosis, and inhibition of key oncogenic pathways such as STAT3, NF-κB, PI3K/Akt/mTOR, and EGFR. Pharmacokinetic optimization and BBB permeability were also assessed. Curcumin analogs demonstrate enhanced cytotoxicity in GBM cells, including temozolomide-resistant lines, through multi-target modulation of apoptosis, oxidative stress, oncogenic signaling, and glioma stem cell pathways. in silico docking and network pharmacology reveal strong binding to GBM-relevant targets, corroborating experimental efficacy. Preclinical studies show that analogs such as C-150, ALZ003, and DMC-BH suppress tumor growth, inhibit angiogenesis, and prolong survival in orthotopic and xenograft models. Combination with temozolomide, radiotherapy, or anti-angiogenic agents exhibits synergistic anti-tumor effects. Curcumin analogs are promising multi-targeted agents capable of overcoming GBM heterogeneity, therapy resistance, and invasiveness. Optimization of pharmacokinetics and targeted delivery, along with clinical evaluation, is necessary to translate preclinical findings into effective GBM therapies. Glioblastoma (GBM) is a highly aggressive type of brain cancer characterized by treatment resistance and a poor prognosis. The efficacy of conventional treatment approaches is limited by treatment resistance, heterogeneity, and inability to cross the Blood-Brain Barrier (BBB). Therefore, there is a need to develop new multi-targeting treatment approaches. This review aims to describe the therapeutic potential of curcumin analogs for GBM treatment, focusing on their molecular mechanisms, in silico studies, and their potential to act synergistically with conventional treatment approaches. A comprehensive literature review of published studies on curcumin analogs was conducted. Mechanistic studies of curcumin analogs included induction of apoptosis, cell cycle inhibition, induction of autophagy, and ferroptosis, as well as inhibition of key oncogenic pathways, including STAT3, NF-κB, PI3K/Akt/mTOR, and EGFR. In addition, studies aimed at improving their pharmacokinetics and permeability through the BBB were included. Evidence from various studies indicates that curcumin analogs exhibit superior cytotoxic effects against GBM cells, including temozolomide-resistant GBM cells, through multi-targeting approaches. In addition, in silico studies have demonstrated high binding affinities to key GBM-related targets. Preclinical studies have demonstrated the efficacy of curcumin analogs, including C-150, ALZ003, and DMC-BH, in inhibiting GBM growth, angiogenesis, and improving survival in orthotopic and xenograft mouse models. These compounds have demonstrated synergistic effects with temozolomide, radiotherapy, and anti-angiogenic therapy. Therefore, curcumin analogs have demonstrated significant therapeutic potential as multi-targeting agents to address heterogeneity, treatment resistance, and invasiveness of GBM. However, to realize this potential, there is a need to improve their pharmacokinetics and permeability through the BBB.
Biochemical Analysis of Inflammatory Markers and Oxidative Stress Biomarkers in Oral Squamous Cell Carcinoma: A Comprehensive Case-Control Study.
Fahad AH, Musa SQ, Al-Dahhan NAA … +1 more , Ibrahim SM
Curr Med Chem · 2026 Mar · PMID 41879451 · Publisher ↗
BACKGROUND: Oral squamous cell carcinoma (OSCC) represents a significant global health burden with complex pathophysiology involving chronic inflammation and oxidative stress. Systemic inflammatory markers, including neu...
BACKGROUND: Oral squamous cell carcinoma (OSCC) represents a significant global health burden with complex pathophysiology involving chronic inflammation and oxidative stress. Systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have emerged as potential prognostic indicators, while oxidative stress biomarkers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect DNA damage associated with carcinogenesis. OBJECTIVE: This study aimed to evaluate the diagnostic potential of NLR, PLR, and oxidative stress biomarkers in OSCC patients, investigating the relationship between systemic inflammation, oxidative DNA damage, and antioxidant status in the context of oral carcinogenesis. METHODS: A case-control study was conducted involving 138 participants (82 OSCC patients and 56 healthy controls) aged 28-48 years. Comprehensive hematological analysis was performed using automated analyzers, while serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), 8-OHdG, and vitamin C were quantified using enzyme- linked immunosorbent assay (ELISA) techniques. Statistical analysis included independent t-tests and Pearson correlation analysis. RESULTS: OSCC patients demonstrated significantly elevated levels of white blood cells (13.01±4.31 vs. 4.54±7.32 ×109/L), NLR (6.84±0.88 vs. 1.91±0.34), PLR (185.02±40.10 vs. 91.88±17.77), and inflammatory biomarkers, including IL-6 (142.31±5.24 vs. 38.32±6.32 pg/mL) and CRP (43.30±3.42 vs. 8.11±2.21 mg/L), compared to controls (all p<0.01). Oxidative stress marker 8-OHdG was markedly elevated (31.82±2.32 vs. 5.78±1.76 ng/dL, p<0.001), while vitamin C levels were significantly reduced (3.53±2.35 vs. 4.88±2.42 mg/dL, p<0.001). Strong positive correlations were observed between CRP and IL-6 (r=0.544, p<0.005) and 8-OHdG (r=0.386, p<0.007). DISCUSSION: The significant elevations in inflammatory and oxidative stress biomarkers, coupled with their strong correlations with tumor stage, suggest these markers reflect the complex interplay between chronic inflammation and oxidative damage in OSCC pathogenesis. The exceptional diagnostic accuracy of the combined biomarker panel (NLR + IL-6 + 8-OHdG; AUC = 0.995) demonstrates the potential clinical utility of integrating multiple pathophysiological pathways for improved OSCC detection and risk stratification. CONCLUSION: Elevated NLR and PLR values, combined with increased oxidative stress markers and diminished antioxidant capacity, reflect the complex interplay between chronic inflammation and oxidative damage in OSCC pathogenesis. These biomarkers may serve as valuable adjunctive tools for early detection and prognostic assessment in oral cancer management.
IDH1 Mutation Increases the Sensitivity of Glioma Organoids to Radiotherapy and Targeted Therapy.
Yang C, Li M, Wu D … +1 more , Xu B
Curr Med Chem · 2026 Mar · PMID 41863178 · Publisher ↗
INTRODUCTION: In gliomas, the Isocitrate Dehydrogenase (IDH1) mutation is a key molecular marker that can distinguish subtypes. IDH1-mutant gliomas grow more slowly, are sensitive to radiotherapy and chemotherapy, and ha...
INTRODUCTION: In gliomas, the Isocitrate Dehydrogenase (IDH1) mutation is a key molecular marker that can distinguish subtypes. IDH1-mutant gliomas grow more slowly, are sensitive to radiotherapy and chemotherapy, and have a better prognosis. However, there are still individual differences in treatment responses and prognosis among patients with this subtype, making traditional treatments difficult to adapt. Organoid models can simulate the characteristics of IDH1-mutant tumors and provide important support for research on their personalized treatment. MATERIALS AND METHODS: Glioma tissues were dissociated, and cells were resuspended in Matrigel before being seeded into culture dishes for IDH1-mutant organoid culture. Organoids at different culture stages were subjected to morphological observation and viability confirmation via live-dead staining. The growth curves of two-dimensional (2D) and three-dimensional (3D) cells were measured by adding CellTiter-Glo (CTG). Hematoxylin and Eosin (H&E) staining and immunohistochemistry were performed on cultured organoids and original tumor tissue sections to validate organoid phenotypes, while immunofluorescence assays confirmed the IDH1 mutation status. Drug sensitivity tests were conducted using temozolomide and vorasidenib on IDH1-mutant and IDHwildtype glioma organoids. Relative luminescence Units (RLU) were measured via CTG at various time points. Organoids were irradiated with 8 Gy γ-rays at day 0 and day 4, and cell viability was measured. RESULTS: Immunohistochemical (IHC) results of the constructed organoids were consistent with those of the original tumor tissues, and immunofluorescence confirmed the presence of IDH1 mutations in the organoids. No significant difference in sensitivity to temozolomide was observed between IDH1-mutant and wild-type organoids, whereas IDH1-mutant organoids showed significantly higher sensitivity to vorasidenib than IDH-wildtype organoids. After 4 days of γ-ray irradiation, the cell viability of IDH1-mutant glioma organoids decreased significantly, while no significant change was observed in IDH-wildtype organoids. DISCUSSION: This study generated patient-derived IDH1-mutant glioma organoids, validated their value as an individualized precision drug-testing platform by comparing drug sensitivity and radiotherapy responses with IDH-wildtype organoids, and found that IDH1-mutant organoids were more sensitive to radiotherapy and vorasidenib, advancing glioma precision treatment. CONCLUSION: By constructing an IDH1-mutated glioma organoid model and integrating accurate molecular diagnostic information, it is expected to improve treatment efficacy and promote the development of personalized glioma medicine.
AlphaFold3: A Transformer in Life Sciences.
Zhu R, Wen Z, Wang L … +4 more , Zhao P, Fan HS, Jathan D, Lee HJ
Curr Med Chem · 2026 Mar · PMID 41863177 · Publisher ↗
The development of AlphaFold2 (AF2) marked a revolutionary milestone in the field of life sciences, such as structural and computational biology, offering highly accurate atomic-level predictions of individual protein st...
The development of AlphaFold2 (AF2) marked a revolutionary milestone in the field of life sciences, such as structural and computational biology, offering highly accurate atomic-level predictions of individual protein structures using deep learning techniques. Its unprecedented performance has transformed structural biology by providing insights that were previously dependent on time-consuming experimental methods. However, despite its success, AF2 has notable limitations. It struggles with accurately modeling protein-protein interactions and fails to reliably predict the presence and positioning of non-protein components, such as nucleic acids, metal ions, ligands, and posttranslational modifications, which are critical for understanding full biological functionality. In response to these shortcomings, AlphaFold3 (AF3) has emerged as a more comprehensive solution by integrating sequence, structural, and chemical context to predict a broader range of biomolecular structures and their interactions. However, AF3 is not without limitations. It still struggles with intrinsically disordered regions, low-homology sequences, and RNA structures, particularly long or unvalidated ones. Moreover, antibody- antigen docking and flexible binding site modeling remain challenging. Addressing these gaps may require hybrid approaches that combine AF3 with experimental data, molecular dynamics simulations, or network-based models. This review explores the technical innovations underlying AF3, evaluates its current performance across different biological contexts, and presents its transformative potential in fields, such as antibodies and vaccine development for infectious diseases, cancer, and other diseases, as well as basic biological research. Finally, we highlight the remaining challenges and propose future research directions to further improve the prediction of protein complexes and other biomolecular structures.
Potential Role and Mechanisms of Epigallocatechin-3-Gallate in Colorectal Cancer.
Bao Y, Du Y, Wang D … +3 more , Li J, Yao F, Wu Q
Curr Med Chem · 2026 Mar · PMID 41863176 · Publisher ↗
Colorectal cancer (CRC), the second deadliest cancer worldwide, is characterized by high incidence and poor prognosis. Although current treatments can effectively relieve patient symptoms, numerous toxic side effects rem...
Colorectal cancer (CRC), the second deadliest cancer worldwide, is characterized by high incidence and poor prognosis. Although current treatments can effectively relieve patient symptoms, numerous toxic side effects remain unresolved. Therefore, treating CRC remains a substantial challenge, and novel approaches are urgently needed. Epigallocatechin-3-gallate (EGCG), a natural polyphenol and the most abundant component of green tea, exerts preventive and anticancer effects. Herein, we review previous literature and summarize the effects of EGCG on the prevention and treatment of CRC. EGCG has been shown to inhibit cell proliferation, growth, and invasion, trigger apoptosis, and enhance sensitivity to chemotherapy and radiotherapy in patients with CRC. EGCG inhibits tumorigenesis through several mechanisms, mainly involving modulation of signaling pathways, suppression of inflammation, and regulation of gut microbiota in preclinical studies. However, the instability and low bioavailability of EGCG limit its clinical applications, and developing novel EGCG nanoparticles is an important future research direction. In conclusion, EGCG has proven valuable in suppressing CRC progression both in vitro and in vivo. Furthermore, the safety and efficacy of EGCG for treating CRC in clinical practice need to be further explored. The data were gathered by searching relevant information in multiple databases, such as PubMed, ScienceDirect, and Google Scholar.
The Role of Antioxidants in Child Eye Health with a Focus on Myopia.
Didara Y, Semenova Y, Bjørklund G
Curr Med Chem · 2026 Mar · PMID 41863175 · Publisher ↗
The role of antioxidants in pediatric eye health remains an underexplored area, particularly in the prevention and management of refractive errors. According to the World Health Organization, refractive errors are the le...
The role of antioxidants in pediatric eye health remains an underexplored area, particularly in the prevention and management of refractive errors. According to the World Health Organization, refractive errors are the leading cause of visual impairment among children globally, with myopia being the most prevalent and significant contributor. Oxidative stress and ocular hypoxia are key factors in myopia development and progression. Vision impairment resulting from myopia and associated ocular diseases can have profound consequences, affecting educational performance, psychosocial development, and daily activities. Antioxidant supplementation has been proposed as a potential strategy to counteract the effects of reactive oxygen species and support ocular health. This literature review examines the therapeutic potential of antioxidants-vitamin A, vitamin D, lutein, crocetin, omega-3 fatty acids, zinc, copper, manganese, and selenium- in mitigating myopia progression. Despite their promising protective effects, the clinical impact of these supplements remains a subject of debate. While experimental studies have demonstrated beneficial outcomes, further large-scale randomized controlled trials are necessary to establish their efficacy and determine optimal dosing for clinical application.
Recent Advances in Flavonoids and Chronic Disease: Mechanisms, Therapeutic Applications, and Future Directions.
Zhao Y, Liu H, Li Y … +8 more , Liu Z, Bao L, Yang Y, Miao Y, Zhang X, Yan R, Li Y, Song S
Curr Med Chem · 2026 Mar · PMID 41863174 · Publisher ↗
Flavonoids are a diverse class of polyphenolic secondary metabolites found in fruits, vegetables, tea, and medicinal plants, known for their antioxidant, anti-inflammatory, neuroprotective, and anticancer properties. Thi...
Flavonoids are a diverse class of polyphenolic secondary metabolites found in fruits, vegetables, tea, and medicinal plants, known for their antioxidant, anti-inflammatory, neuroprotective, and anticancer properties. This review summarizes recent advances in flavonoid research, focusing on their roles in aging, neuroprotection, cardiovascular health, metabolic regulation, inflammation, and cancer therapy. Flavonoids exert their effects by modulating key signaling pathways, such as NF-κB, Nrf2, PI3K/Akt, MAPK, and Wnt/β-catenin. They mitigate oxidative stress, enhance mitochondrial function, regulate autophagy, and modulate immune responses, offering potential therapeutic benefits against chronic diseases. Additionally, flavonoids improve chemotherapy sensitivity, inhibit tumor metastasis, and suppress angiogenesis. However, their poor bioavailability and individual metabolic variability present challenges for clinical translation. Future research should focus on nanotechnology-based delivery systems, personalized medicine strategies, and large-scale clinical trials to optimize flavonoid efficacy and facilitate their application in functional foods and pharmaceuticals.
Ligand and Structure-Based Drug Design of Biphenyl 1,2,4-Triazole Derivatives as Dual Target Inhibitors of Aromatase and Steroidal Sulfatase as Anti-Breast Cancer Agents.
Vivekananthan G, Subramaniam VSS, Sruthi NJS … +7 more , Jayashree M, Dinesh BGH, Ganjipette S, Kuppusamy S, Suresh AJ, Jaikanth C, Radhakrishnan S
Curr Med Chem · 2026 Mar · PMID 41863173 · Publisher ↗
INTRODUCTION: Dual inhibitors of AROM and STS (DASIs), through their synergistic action, hold the potential to suppress estrogen biosynthesis at multiple points. It also overcomes limitations associated with single-enzym...
INTRODUCTION: Dual inhibitors of AROM and STS (DASIs), through their synergistic action, hold the potential to suppress estrogen biosynthesis at multiple points. It also overcomes limitations associated with single-enzyme inhibition and reduces the risk of resistance development. In order to potentially improve the clinical outcomes in hormone-dependent breast cancers, 1,2,4-triazole derivatives having similar structural characteristics to third-generation Aromatase Inhibitors (AIs), including exemestane, letrozole, and anastrozole, were subjected to ligand-based screening. This research study comparatively analyzes the drug candidates as DASIs that aim at the development of advanced therapeutic strategies for breast cancer treatment. MATERIALS AND METHODS: In this study, a set of 172 biphenyl 1,2,4-triazole derivatives with defined biological activity against AROM and STS enzymes was subjected to 3DQSAR modelling, followed by ADMET, molecular docking, and dynamics. RESULTS: Through 3D-QSAR, significant statistical parameters of aromatase (q2 = 0.8429, r2 = 0.8874, r2pred = 0.8252) and steroidal sulfatase (q2 = 0.8877, r2 = 0.9402, r2pred = 0.9376) indicated the accuracy and reliability, and the good prediction power of the model. The external validation set further demonstrated its predictive capability. Furthermore, molecular docking, along with molecular dynamics at a time period of 100 ns, elucidated the stability of the docked complexes and found that Compound 109 emerged as the most promising dual inhibitor, exhibiting high binding affinities of -9.94 kcal/mol for Aromatase (AROM) and -9.41 kcal/mol for Steroid Sulfatase (STS). These values reflect a strong potential for dual enzyme inhibition. DISCUSSION: The structural features of triazole derivatives through QSAR modelling established a statistical correlation, establishing a relationship between functional groups and their biological activity. They are found to have dual inhibition efficiency in a target-based approach, accelerating for synthetic accessibility. CONCLUSION: The study highlights the potential of triazole derivatives and provides a multi-targeted therapeutic avenue for hormone-dependent breast cancers. It shows strong reliability and predictive power through molecular docking and a dynamic approach. Compound 109 emerged as the lead candidate due to its strong binding affinities and stable dual interactions.
A Global Bibliometric and Visualized Analysis of Proteolysis Targeting Chimeras from 2015 to 2024.
Zhao J, Liao B, Gong Y … +1 more , Li Y
Curr Med Chem · 2026 Mar · PMID 41863172 · Publisher ↗
INTRODUCTION: Proteolysis-targeting chimeras (PROTACs) have emerged as groundbreaking therapeutic agents and experienced explosive growth over the past decade. This study aim to comprehensively demonstrate the evolution...
INTRODUCTION: Proteolysis-targeting chimeras (PROTACs) have emerged as groundbreaking therapeutic agents and experienced explosive growth over the past decade. This study aim to comprehensively demonstrate the evolution of PROTACs in drug development research over the past decade and to reveal future trends. METHODS: Original publications focusing on PROTACs from 2015 to 2024 were extracted from the WoSCC (Web of Science Core Collection) database and analyzed using the visualization tools VOSviewer and CiteSpace. RESULTS: A total of 2307 eligible publications were analyzed. Two distinct phases were found in the publication trends based on annual and cumulative publications: a slow growth phase (2015-2018) and a rapid expansion phase (2019-2024), which indicates that the PROTAC technology received tremendous attention in the recent five years and is likely to remain active and robust in the coming years. China and the USA are the most productive countries in this field of research. DISCUSSION: Three major themes were identified: the design and optimization of PROTACs for various diseases, especially cancer; the exploration of ligands for E3 ligases; and the mechanisms of action and resistance of PROTACs. The research hotspots have shifted from traditional PROTACs to novel PROTACs based on nanotechnology for precise, controlled degradation; degrader-antibody conjugates; and dual or multiple PROTAC degrader strategies. The future may focus on exploring clinical translation, combination therapeutic strategies and the toxicity and resistance of PROTAC. CONCLUSION: PROTACs have advanced rapidly in therapeutic research over the past decade, and future research may mainly focus on achieving clinical application across various diseases, overcoming resistance, and improving safety profiles.
The dysregulation of tetrahydrobiopterin biosynthesis exacerbates the progression of chronic liver disease by modulating choline metabolism pathways and inflammatory responses.
Jiang J, Hu Z, Li L
Curr Med Chem · 2026 Mar · PMID 41863171 · Publisher ↗
BACKGROUND: Tetrahydrobiopterin (BH4) is a crucial cofactor in several biosynthetic pathways. Dysregulation of BH4 biosynthesis, particularly via sepiapterin reductase (SPR), has been implicated in chronic liver disease...
BACKGROUND: Tetrahydrobiopterin (BH4) is a crucial cofactor in several biosynthetic pathways. Dysregulation of BH4 biosynthesis, particularly via sepiapterin reductase (SPR), has been implicated in chronic liver disease (CLD). This study investigates the role of SPR and BH4 in liver fibrosis progression. METHODS: Clinical cirrhotic liver tissues were analyzed using liquid chromatography-mass spectrometry (LC-MS) to assess metabolite levels. Mouse models of liver injury (DDC, MCD, CCL4) were used to explore the impact of BH4 dysregulation. SPRi3, a selective SPR inhibitor, was administered to assess the effect of BH4 inhibition. Transcriptomic and metabolic changes were evaluated through RNA-seq and non-targeted metabolomics. RESULTS: In cirrhotic liver tissues, BH4 levels were reduced, while sepiapterin was elevated, indicating dysregulated BH4 biosynthesis. In animal models, SPR expression was downregulated and correlated with worsening fibrosis. Inhibition of SPR using SPRi3 exacerbated liver injury, altered immune responses, and disrupted lipid metabolism. RNA-seq and metabolomics revealed changes in inflammation-related pathways, choline, and fatty acid metabolism. SPR-mediated dysregulation of BH4 biosynthesis contributes to liver injury and fibrosis progression in CLD. CONCLUSIONS: Disruption of lipid and choline metabolism, alongside immune modulation, suggests that targeting the SPR/BH4 pathway may offer therapeutic potential for managing chronic liver diseases.
Comprehensive Assessment of Overactive Bladder (OAB) Treatment: Balancing Efficacy, Side Effects, and Quality of Life.
Yadav T, Sahu R, Shukla S … +5 more , Gupta B, Peter L, Oleksak P, Gupta S, Kuca K
Curr Med Chem · 2026 Mar · PMID 41863170 · Publisher ↗
This review paper aims to comprehensively evaluate various treatment modalities for overactive bladder (OAB), focusing on their advantages, disadvantages, and impact on the quality of life (QoL) of individuals with OAB....
This review paper aims to comprehensively evaluate various treatment modalities for overactive bladder (OAB), focusing on their advantages, disadvantages, and impact on the quality of life (QoL) of individuals with OAB. OAB is a prevalent and often debilitating urological condition characterized by symptoms such as urgency, frequency, and urge incontinence, which significantly impair the well-being and daily activities of those affected. Treatment options for OAB are diverse, ranging from behavioral therapies, including pelvic floor exercises and bladder training, to pharmacological interventions with antimuscarinic agents and beta-3 adrenergic agonists. Additionally, advanced treatments such as neuromodulation techniques, surgical interventions, and emerging therapies like tissue engineering are explored. The review underscores the importance of personalized treatment approaches that consider patient preferences, symptom severity, and potential side effects to optimize outcomes and enhance the QoL of OAB patients. A collaborative approach between healthcare providers and patients can play an important role in discovering the most efficient treatment strategy whilst reducing the adverse effects and increasing the QoL, which shows the successful OAB management. Understanding the pros and cons of each approach is essential for informed decision-making by both patients and healthcare providers, ensuring a holistic management strategy that addresses the multifaceted nature of OAB.
Study on the Mechanism of Mongolian Medical Warm Acupuncture in Regulating Biological Clock Genes and Improving Sleep in Insomniac Rats.
Si L, Ba Y, Wu R … +4 more , Tian M, Gula A, Bao L, Runa A
Curr Med Chem · 2026 Mar · PMID 41863169 · Publisher ↗
OBJECTIVE: To observe the effects of Mongolian medical warm acupuncture on hypothalamic biological clock genes such as Clock, Bmal1, Per1, and Per2 in insomnia rats, and to explore the mechanism by which Mongolian medica...
OBJECTIVE: To observe the effects of Mongolian medical warm acupuncture on hypothalamic biological clock genes such as Clock, Bmal1, Per1, and Per2 in insomnia rats, and to explore the mechanism by which Mongolian medical warm acupuncture regulates biological rhythms in insomniac rats. METHODS: SPF-grade SD rats were divided into groups, and a PCPA-induced insomnia rat model was established. Mongolian medical warm acupuncture was applied to acupoints such as "Dinghui", "Heyi", and "Heart". General behavior, spontaneous activity, and pentobarbital-induced sleep tests were observed before and after treatment; Western blot and IHC were used to analyze the expression of Clock, Bmal1, Per1, and Per2 proteins in the hypothalamus; Realtime Quantitative PCR was used to analyze mRNA expression of Clock, Bmal1, Per1, and Per2 in the hypothalamus; HE staining was used to observe morphological changes in hypothalamic neurons. RESULTS: After intervention with Mongolian medical warm acupuncture, insomniac rats showed quiet behavior and reduced activity, with drinking, eating, and mental state gradually returning to normal; Western blot results showed that, compared to the blank group, Clock and Bmal1 protein expression in the hypothalamus of the model group rats was significantly decreased (p<0.05), while Per1 and Per2 expression was significantly increased (p<0.05). Compared to the model group, the warm acupuncture group showed significantly increased Clock and Bmal1 protein expression (p<0.05), and significantly decreased Per1 and Per2 protein expression (p<0.05). IHC results showed that Clock and Bmal1 positive expression in the model group was significantly reduced, while expression in the warm acupuncture group and drug group was significantly increased; PCR results showed that, compared to the blank group, Clock and Bmal1 expression in the hypothalamus of the model group rats was significantly decreased (p<0.05), while Per1 and Per2 expression was significantly increased (p<0.05). Compared to the model group, the warm acupuncture group showed significantly increased Clock and Bmal1 expression (p<0.05), and significantly decreased Per1 and Per2 expression (p<0.05). HE staining results showed that in the blank group, cell membranes were intact, nuclei were located centrally, and nucleoli were clearly visible; in the model group, cell numbers were significantly reduced, boundaries were unclear, cells were swollen, and many nuclei were displaced; in the warm acupuncture group and drug group, hypothalamic cells were densely and orderly arranged, structures were clear, and cell damage was significantly restored. DISCUSSION: The findings suggest that Mongolian medical warm acupuncture exerts a regulatory effect on hypothalamic biological clock gene expression, which may contribute to the restoration of circadian rhythm balance and reduction of hyperarousal in insomnia rats. CONCLUSION: Mongolian medical warm acupuncture significantly reduces excitability in insomniac rats. The sleep-promoting mechanism of Mongolian medical warm acupuncture is closely related to its regulation of hypothalamic expression of biological clock genes Clock, Bmal1, Per1, and Per2 in insomniac rats.
IRF1-TNS3 Axis in Renal Injury: Extending Insights from IRF1/IRF2 Antiviral Regulation to Kidney Stress Responses.
Huang CW, Wen CY, Hsu YJ … +1 more , Li CJ
Curr Med Chem · 2026 Mar · PMID 41863168 · Publisher ↗
Recent findings emphasize that IRF1 and IRF2 play distinct roles in gene regulation, particularly through chromatin remodeling during antiviral responses. Our current data extend this by revealing that IRF1 directly targ...
Recent findings emphasize that IRF1 and IRF2 play distinct roles in gene regulation, particularly through chromatin remodeling during antiviral responses. Our current data extend this by revealing that IRF1 directly targets TNS3, a key regulator of renal stress, fibrosis, and the aging process. We identify a mechanistic parallel between the IRF1-TLR3 and IRF1-TNS3 pathways, proposing that targeting the IRF1-mediated modulation of TNS3 could offer a fresh therapeutic approach for kidney injury.
Impact of Sarcopenia Index on Prognosis in Patients with Chronic Heart Failure.
Sun R, Liu X, Huang B … +4 more , Cao Z, Jiang Y, Wang J, Zhang Y
Curr Med Chem · 2026 Mar · PMID 41863167 · Publisher ↗
BACKGROUND: The sarcopenia index (SI) was recommended as a surrogate marker of sarcopenia based on the serum creatinine-to-cystatin C ratio, given its accessibility and effectiveness. However, the impact of SI on chronic...
BACKGROUND: The sarcopenia index (SI) was recommended as a surrogate marker of sarcopenia based on the serum creatinine-to-cystatin C ratio, given its accessibility and effectiveness. However, the impact of SI on chronic heart failure (HF) has not been addressed. METHODS: A total of 1209 chronic HF patients from a retrospective cohort study were included. Cox regression and inverse probability of treatment weighting (IPTW) were used to analyze the impact of the SI on all-cause death and hospitalization. The C-index, net reclassification improvement (NRI), and discrimination improvement (IDI) were used to assess the predictive ability for all-cause death after the addition of SI. RESULTS: By IPTW analysis, chronic HF patients with a high SI (SI> 62.5) demonstrated a decreasing trend of 28-day hospital death (HR=0.44, 95% CI = 0.06, 3.27, p=0.422), 3-month death (HR=0.45, 95% CI = 0.06, 3.42, p=0.441) and 6-month death (HR=0.44, 95% CI = 0.06, 3.27, p=0.422) compared with a low SI group (SI≤62.5). The subsequent meta-analysis revealed that a low SI was significantly associated with all-cause mortality (OR 0.42, 95% CI = 0.28, 0.62, I2 = 0, p < 0.0001) in patients with chronic HF. Finally, the SI significantly improved the predictive performance of 6-month allcause mortality in chronic HF patients via the integrated IDI (0.002, 95% CI= 0.00-0.120, p=0.033) but not the C-index (Z statistic=0.116) or NRI (0.114, 95% CI= -0.301--0.263). DISCUSSION: Heart failure and sarcopenia share common pathogenetic pathways, including hormonal changes, malnutrition, inflammation and oxidative stress. CONCLUSION: A low SI may indicate a poorer prognosis in patients with chronic heart failure. These findings should be validated in larger, prospective studies.
BCL-2 Mediated Apoptotic Pathway as Promising Target for Bio- Synthesized Silver Nanoparticles: A Review Article.
Moulavi P, Karbalaeiheidar H, Lalami ZA … +8 more , Yazdani R, Noroozi S, Ashrafi F, Moulavi P, Ahmadian M, Kamli HM, Farkhondeh T, Samarghandian S
Curr Med Chem · 2026 Mar · PMID 41863166 · Publisher ↗
Nanotechnology has made significant advances and is now widely used across various fields, including medicine. In cancer treatment, metal nanoparticles have been used to release drugs in a controlled manner. Silver nanop...
Nanotechnology has made significant advances and is now widely used across various fields, including medicine. In cancer treatment, metal nanoparticles have been used to release drugs in a controlled manner. Silver nanoparticles [Ag-NPs] are commonly used in various fields, including biomedical science, to impart antibacterial, antiviral, anti- inflammatory, and anticancer properties. Among the different routes of Ag-NP synthesis, biological approaches using bacteria, fungi, and plant extracts are promising for producing these NPs. Additionally, bio-synthesized Ag-NPs can induce different apoptotic pathways in cancer cells. However, owing to the lack of literature on the relationship between apoptosis induction via the BCL-2 family and biologically synthesized Ag-NPs, we reviewed previous studies on the apoptotic activity of biosynthesized Ag-NPs via the BCL-2 pathway. According to our findings, Ag-NPs synthesized using plants, algae, fungi, yeasts, and bacteria can upregulate the expression and activity of Bax, P53, Caspases family genes as well as downregulate BCL-2 and BCLXL expression levels in various types of cancer cells, including breast, cervical, lung, prostate, skin, gastric, hepatic, ovarian, colorectal, and bone marrow neuroblastoma. The impact of further biosynthesized nanostructures should be tapped in the near future to continue advancing our understanding of nanometric materials in medicine. The present review systematically evaluates the available evidence on biosynthesized silver nanoparticles [Ag-NPs] and their ability to modulate the BCL-2-mediated apoptotic pathway in cancer, emphasizing mechanistic insights, therapeutic implications, and potential challenges for clinical translation.
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