Current Topics in Medicinal Chemistry - Online First

Prostate cancer is among the most prominent malignant tumors in the male population, characterized by growing morbidity, a high fatality rate, and currently limited therapeutic options, necessitating the urgent development of novel clinical medications. The objective of the current study was to examine the therapeutic potential of zingerone in prostate cancer cells.

In this study, we investigated the underlying mechanism by which zingerone exerts its anticancer effects in prostate cancer cells. We conducted various in vitro and in silico experiments to determine the therapeutic efficacy and mechanism of action of zingerone.

Cytotoxicity analysis of zingerone revealed its substantial cytotoxic impact and ability to elevate lactose dehydrogenase levels in DU145 cells. Using the MTT assay, we determined that a concentration of 24.84 μM zingerone in DU145 cells grown for 24 h resulted in an IC50 value. Zingerone effectively induced apoptosis by increasing the levels of cytochrome c and caspase in DU145 cells. Regarding the identification of signs of ferroptosis, evidence has been shown for the presence of heightened mitochondrial ROS, disrupted mitochondrial membrane potential, increased levels of glutathione (GSH) and malondialdehyde (MDA), and reduced expression of SCL7A11 and GPX4.

Importantly, our study confirms that zingerone triggered both apoptosis and ferroptosis in DU145 cells by downregulating SLC7A11 and GPX4 expression.

This study provides evidence that makes zingerone a potent therapeutic agent for prostate cancer.

This study aimed to explore the mechanisms by which interleukin-10 (IL-10) influences tumorigenesis through T regulatory cells (Treg) regulation.

Environmental factors, such as IL-10, significantly shape the immune microenvironment and tumor progression, yet the regulatory pathways remain unclear.

1) To elucidate the regulatory mechanism of IL-10 on Treg cells through in vitro assays; 2) To elaborate whether Nrp-1/PDX1 knockout affects tumorigenesis via in vivo assays.

CD4+ T cells were isolated from the healthy mice's spleen and induced to differentiate into Treg cells. Then, after being treated with IL-10 and mouse melanoma cell supernatant (CM), the expression levels of Nrp-1 and FoxP3 in Treg cells were examined via qRT-PCR and Western blotting. The ratio of Treg cells was measured by flow cytometry. The interaction between Nrp-1 and PDX1 proteins was detected through GST pull-down assay, Co-IP, Western blotting and immunofluorescence staining. STAT3 luciferase activity was detected, and the expression levels of JAK1 and STAT1 proteins were detected by Western blotting. Furthermore, the B16-bearing melanoma mice and Nrp-1/PDX1 knockout mice model were established to verify the effects of Nrp-1 and PDX1 on Treg formation and tumor development.

The results demonstrated that IL-10 promoted Nrp-1 expression in Treg cells via the JAK-STAT3 signaling pathway. Nrp-1 could combine with PDX1 to form a complex, facilitating PDX1-mediated activation of FoxP3 and Treg production. In melanoma xenograft models, targeting Nrp-1 and PDX1 using shRNAs or antibodies significantly reduced Treg levels and inhibited tumor growth. Collectively, IL-10 promotes Treg formation and tumorigenesis via regulating Nrp-1/PDX1/FoxP3 axis.

This study was the first to identify the interaction between Nrp-1 and PDX1, leading to PDX1 ubiquitination, which enhanced FoxP3 expression and Treg function in the tumor microenvironment. These novel insights highlighted the Nrp-1/PDX1/FoxP3 axis as a critical regulator of Treg-mediated tumorigenesis, offering potential targets for cancer therapy.

These findings highlight the interplay between environmental influences and immune regulation, providing novel insights into Treg-mediated tumorigenesis and suggesting potential strategies for targeted therapy.

Schizophrenia is a heterogeneous chronic brain disorder driven by multiple pathophysiological processes. While dopaminergic theories dominate current therapies, emerging evidence highlights glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDAR) hypofunction, as a key mechanism alongside dopaminergic, serotonergic, and neurodevelopmental pathways. This article synthesizes mechanistic insights, focusing on neurotransmitter disruptions, oxidative stress, neuroinflammation, and Wnt signaling, to elucidate the clinical diversity of schizophrenia and identify biomarkers for precise diagnostics and therapeutics.

A comprehensive literature search was conducted using Web of Science, Scopus, Google Scholar, and PubMed, with keywords including “schizophrenia,” “psychosis,” “pathophysiology,” “mechanism,” and “biomarker.” Studies were selected to explore NMDAR hypofunction, glutamatergic dysregulation, and associated signaling pathways, integrating preclinical and human data to map circuit-based interactions and biomarker profiles.

We present a novel circuit-based model of schizophrenia pathophysiology, centered on NMDAR hypofunction and glutamatergic dysregulation, integrating dopaminergic, GABAergic, and inflammatory pathways. Key biomarkers, including inflammatory (e.g., high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), neurochemical (e.g., brain-derived neurotrophic factor [BDNF]), and functional (e.g., mismatch negativity [MMN]), are categorized by symptomatic domains and clinical stages, providing diagnostic and prognostic insights.

The findings underscore NMDAR hypofunction’s role in driving schizophrenia’s symptomatic spectrum, though its interplay with other pathways highlights the disorder’s complexity. Neuronal loss, although not universal, is context-specific (e.g., hippocampal interneurons), complementing functional biomarkers such as MMN. Limitations include the need for robust human validation of biomarkers and broader exploration of non-glutamatergic mechanisms.

Considering the multifaceted nature of the disorder, our emphasis on the NMDAR hypofunction model can help explain many of the synergies involved among the seemingly independent dysregulated events.

Zika virus (ZIKV), a flavivirus primarily transmitted by Aedes aegypti, became a major global health concern during the 2015–2016 outbreak, particularly in Brazil. Its association with congenital malformations and neurological disorders underscores the urgent need for effective therapeutic interventions. This review explores molecular targets for ZIKV treatment within the Brazilian context.

A systematic search was conducted using PubMed, ScienceDirect, and Scopus for studies published between 2004 and 2024. Inclusion criteria focused on studies identifying druggable molecular targets related to viral replication, immune evasion, or host-virus interactions. Key search terms included “Zika virus,” “molecular targets,” “Brazil,” “antiviral,” and “drug discovery.”

The review identified several critical viral proteins, NS1, NS3, NS5, and the envelope protein, as potential drug targets. Host cellular factors essential for viral survival were also highlighted. Technologies such as high-throughput screening, molecular docking, and structural genomics contributed significantly to the identification and validation of these targets.

Although promising targets have been identified, therapeutic development is hindered by the genetic variability of ZIKV and its antigenic similarity to other flaviviruses, notably the dengue virus. These challenges complicate the specificity and efficacy of drugs. Nevertheless, Brazil has made strides in research infrastructure and collaborations to tackle these obstacles.

This review synthesizes current knowledge on ZIKV molecular targets and ongoing drug discovery efforts. The findings support the strategic development of antivirals and emphasize the necessity for sustained investment in research to mitigate future ZIKV outbreaks in Brazil and globally.

Obesity, a widespread health condition marked by excessive body fat, markedly elevates the risk of chronic diseases and has emerged as a major global health issue. Chrysin, a flavonoid with promising health benefits, exhibits potent antioxidant and anti-inflammatory properties. This study seeks to examine the impact of chitosan chrysin nanoparticles (Chrysin-CSNPS) on obesity induced by a high-fat diet (HFD) in male rats.

Rats were fed a high-fat diet for 4 weeks to induce obesity, followed by a 4-week treatment period. Thirty rats were allocated into five groups (six rats per group): control (dist. water, orally), HFD control (dist. water, orally), HFD + chrysin (500 mg/kg, orally), HFD + chitosan-NP (60 mg/kg, orally), and HFD + Chrysin-CSNPS (60 mg/kg, orally).

In silico studies revealed that chrysin has a binding energy value of −8.8 kcal/mol to fat mass and obesity-associated (FTO) protein. Also, Chrysin is identified as an inhibitor of several cytochrome P450 enzymes, specifically CYP1A2, CYP2D6, and CYP3A4. Albumin, high-density lipoprotein cholesterol, glutathione, and nitric oxide levels rose, whereas glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, total cholesterol, triglycerides, malondialdehyde, and nitric oxide levels fell upon Chrysin-CSNPS treatment. The histological examination revealed a significant enhancement in the structures of the liver and kidneys.

These findings suggest that chrysin could potentially inhibit FTO activity, thereby contributing to a reduction in obesity-related phenotypes. The compound that satisfied Lipinski’s criteria was selected for toxicity prediction.

Chrysin-CSNPS have hypolipidemic properties and an antioxidant role, reducing HFD consequences in the liver and kidney.

This study aims to elucidate the mechanisms underlying Dementia using bioinformatics analysis and machine learning algorithms, to identify novel therapeutic targets for its clinical management.

Gene expression datasets related to dementia were sourced from the GEO database. Differentially expressed genes (DEGs) were identified using R, and key module genes were determined through the Weighted Gene Co-expression Network Analysis (WGCNA) method. Oligodendrocyte (OL) related targets were retrieved from the GeneCards database. The intersecting genes from DEGs, WGCNA, and OL were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Subsequently, three machine learning algorithms were employed to pinpoint core genes associated with OL in dementia. The CIBERSORT algorithm was used to evaluate the abundance of 22 immune cell types and their correlation with Dementia-related immune infiltration. Validation was carried out via quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Through bioinformatics and machine learning techniques, six core OL genes associated with Dementia were identified, notably C1QA, CD163, and TGFB2, which showed elevated expression in Dementia. Immune cell infiltration analysis indicated that several immune cell types may contribute to Dementia's pathogenesis, and RT-qPCR results corroborated the bioinformatics findings.

The discovered genes may contribute to dementia pathogenesis through oligodendrocyte dysfunction and neuroimmune interactions. Notably, TGFB2 and complement-related genes (C1QA, CD163) suggest involvement in both myelination defects and neuroinflammation, highlighting their therapeutic potential.

The six feature genes: TGFB2, C1QA, CD163, ACTG1, WIF1, and OPALIN are significantly linked to Dementia.

Colorectal cancer (CRC) remains a significant global health challenge due to its high incidence and mortality rates. The disease's complexity and heterogeneity impede early diagnosis and effective treatment. The study aims to investigate the role of Tetraspanin 11 (TSPAN11) in CRC, exploring its potential as a prognostic biomarker and immunotherapy target through bioinformatics analysis and experimental validation.

Pan-cancer patient data were obtained from The Cancer Genome Atlas (TCGA) and the GSE71187 dataset, including 672 CRC tissues and 51 adjacent normal tissues. Differential expression analysis, Kaplan-Meier survival analysis, gene set enrichment analysis (GSEA), and immune infiltration assessment were performed. TSPAN11 expression was validated in CRC cell lines using quantitative reverse transcription PCR (qRT-PCR).

TSPAN11 was significantly downregulated in CRC tissues compared to normal tissues (p < 0.001), with lower expression associated with poorer overall survival (OS; p = 0.011) and disease-specific survival (DSS; p = 0.038). Multivariate analysis identified TSPAN11 as an independent prognostic factor (p = 0.045). TSPAN11 expression was linked to key pathways such as ECM receptor interaction and TGF-β signaling, and correlated with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity.

The findings suggest that TSPAN11 may influence CRC progression through multiple biological pathways and immune-related mechanisms. Its downregulation is associated with poorer prognosis and immune evasion, highlighting its potential as a biomarker and therapeutic target. However, validation in larger cohorts and elucidation of underlying mechanisms are needed to confirm these results and translate them into clinical practice.

TSPAN11 may serve as a promising prognostic biomarker and immunotherapy target in CRC. Its associations with clinical outcomes, immune features, and drug sensitivity underscore its potential for improving CRC diagnosis and treatment strategies.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting 70-75% of women. This condition is frequently linked with large and dysfunctional ovaries, high levels of androgens, and insulin resistance. A variety of conventional treatments, including metformin, oral contraceptives, and anti-androgen agents, have been used to treat PCOS and its complications, but they have been linked to several negative side effects, including hyperkalemia, weight gain, cardiovascular and hepatic toxicity, vitamin B12 and folic acid deficiency. As a result, there is growing interest in natural methods as complementary or alternative approaches to mitigate these side effects. According to several studies, traditionally used Natural oils (NOs) from various sources have been utilized to identify their ameliorating characteristics against PCOS. The paper aims to study pre-clinical investigations and clinical studies of NOs from different sources against PCOS and gives a comprehensive overview of controlling PCOS. Also, it highlights and tabulates the prominent bioactive phytoconstituents from the reported NOs and their mechanism of action.

For this review purpose, the authors have gone through a vast number of scientific literature from different scientific databases like Google Scholar, ScienceDirect, Web of Science, and PubMed.

Mentha spicata L., Foeniculum vulgare Mill., Linum usitatissimum L., Nigella sativa L., Bambusa bambos (L.) Voss, Thuja occidentalis L., Syzygium aromaticum L., Pimpinella anisum L., Rosa canina L., Cocos nucifera L., Oenothera biennis L., Corylus avellana L., and fish oil have been reported to have anti-PCOS activity by maintaining body weight, testosterone, LH, FSH levels, and improving ovarian cysts.

NOs derived from plant and animal sources show promise in treating PCOS by balancing hormone levels, enhancing ovarian morphology, and alleviating metabolic symptoms. However, significant clinical trials and molecular research are required to evaluate their therapeutic potential, identify suitable dosages, investigate their precise mechanisms of action, and ensure long-term safety and efficacy in PCOS management.

Further research is needed to understand the molecular mechanisms of NOs responsible for anti-PCOS activity. Studies are needed to concentrate on their mechanisms of action, routes of impact, safe dosage, and potential side effects to ensure their efficacy and safety in treating PCOS.

Current trends in peptide synthesis protocols have emerged as the most attractive domain in the field of pharma and medicine. Since most of the peptide/peptidomimetic-based molecules serve as potential candidates for many diseases, as they are bioavailable molecules.

We present the synthesis of bioactive peptides through TAGGING approach with the help of TAG-OH as a linker to the N^α-protected amino acid.

FRDEHKK and NKDRG are two peptides that possess antioxidant and antiproliferative activity, and their in-silico investigations reveal that they exhibit anticancer properties when bound to the AXL kinase and EGFR proteins.

This TAG method enables the easy isolation of peptides at each step as solids, and all the impurities were washed off by simple filtration. The method allows a bulk-scale preparation of the peptides without any difficulty, and hence the protocol is highly efficient for the production of peptides of therapeutic importance.

The two peptides FRDEHKK and NKDRG were isolated as fine solids with 82% and 85% yield and were characterized by NMR and MASS spectroscopy. In-silico studies reveal FRDEHKK and NKDRG peptides exhibit good affinity towards EGFR and AXL kinase.

Skin cutaneous melanoma (SKCM) is a life-threatening malignancy, and pyroptosis-mediated inflammatory response is associated with SKCM progression. We aimed to uncover the underlying pathogenesis of SKCM based on pyroptosis features.

The single-cell and bulk RNA-seq data and clinical information of SKCM patients were downloaded from the TCGA and GEO databases, and the REACTOME_PYROPTOSIS.v2024.1.Hs.gmt from the MSigDB database was used for Gene Set Enrichment Analysis (GSEA). Differentially expressed gene (DEG) analysis was performed utilizing the “limma” R package, and the “GSVA” R package was used for the analysis of pyroptosis pathway activation. In addition, scRNA-seq analysis and cell communication analysis were carried out by employing the “Seurat” R package and “CellChat” R package, respectively. Gene expression was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR), while cell counting kit-8 (CCK-8), wound healing, and Transwell assays were carried out to assess cell proliferation, migration, and invasion, respectively.

DEGs analysis detected no significant pyroptosis-related DEGs. Analysis of the expression of two representative pyroptosis genes (GZMA and GSDMB) revealed that GZMA was significantly upregulated in the SKCM tissues, but the expression of GSDMB was downregulated. The pyroptosis pathway was not activated in the tumor group. In addition, we observed that high expression of GZMA and GSDMB was closely associated with a favorable outcome in SKCM. The two genes were downregulated in SKCM cells, while the overexpression of GZMA significantly impaired the proliferation, migration, and invasion ability of SKCM cells. Nine main cell subpopulations were identified, and GZMA was specifically overexpressed in CD8+ T cells. Gene function analysis revealed that specific genes of CD8+ T cells were enriched in cell death-related and inflammation activation pathways. Cell communication demonstrated that CD8+ T cells interacted with melanocytes through the CD99-CD99 and HLA-C-KIR2DL3 ligand-receptor pairs.

Based on the pyroptosis features in SKCM, this study found that blocking GZMA protein in CD8+ T cells within melanocytes may be the potential underlying pathogenesis for tumor immune escape in cancer.

CAs serve as crucial enzymes involved in a variety of physiological processes, including brain metabolism and cognitive function. hCA VII, a brain-associated isoform, plays an important role in modulating cerebral metabolism. Activating hCA VII may provide therapeutic benefits in Alzheimer's disease and other neurodegenerative or age-related illnesses. This study proposes to add to the growing interest in CAAs by developing innovative drugs with selective activation characteristics that target brain-associated CA isoforms.

A series of 4-arylazo-3,5-diamino-1H-pyrazoles have been produced by reacting aniline and aniline derivatives with a malononitrile solution at 0-5 °C, resulting in compounds 1(a-m). Then, arylazo malononitrile compounds were added with hydrazine monohydrate to obtain 4-arylazo-3,5-diamino-1H-pyrazole derivatives 2(a-m). The activity of the synthesized compounds was examined on human CA isoforms I, II, IV, and VII to determine activation potency and selectivity.

The synthesized compounds demonstrated a wide spectrum of strong micromolar activation on human CA isoforms, with particularly encouraging results for hCA VII. The discovered activators showed a high selectivity profile for the brain-associated hCA VII isoform, indicating their potential use in neurological methods of therapy.

Among the most compelling findings of this study is the unprecedented potency of several synthesized derivatives, particularly 2i and 2m, in selectively activating hCA VII far beyond the benchmark histamine, positioning them as promising pharmacological candidates for addressing CA-related neurological disorders.

The research successfully discovered potent and selective CAAs with specific activity against hCA VII, a key enzyme in brain metabolism. These outcomes offer novel possibilities for developing medicinal products for neurological disorders and provide critical molecules for further study into CAAs. Furthermore, the study advances our understanding of enzyme activation kinetics and gives significant insights into the future of enzyme-based treatment research.

During cerebral ischemia, brain tissue is damaged in two successive stages: ischemia and reperfusion (I/R). In the ischemic phase, brain tissue undergoes energy failure due to an impaired circulatory system (cerebrovascular), resulting in oxygen and glucose deprivation and consequent brain damage.

The study aimed to determine the effect of a two-week administration of naringin on caspase-3, IL-17, and NF-κB levels in cerebellar tissue in experimental focal brain ischemia-reperfusion in rats.

The research was conducted on 10- to 12-week-old Wistar-type rats obtained from the Selcuk University Experimental Animals Research and Application Center. Experimental brain ischemia-reperfusion in rats was performed under general anesthesia (carotid arteries were exposed to ischemia for 30 minutes). Experimental groups were formed as follows. 1) Control group, 2) Sham, 3) Sham + vehicle, 4) Ischemia-reperfusion, 5) Ischemia-reperfusion + Naringin supplemented group for two weeks (100mg/kg). At the end of the experiments, the levels of IL-17, caspase-3, and NF-κB were determined in the cerebellum tissue of the animals under general anesthesia. First of all, blood was drawn from the heart, and the animals were killed by cervical dislocation.

Experimental brain ischemia-reperfusion significantly increased caspase-3, IL-17, and NF-κB levels in the brain tissue of rats. In contrast, naringin supplementation for 2 weeks significantly suppressed the ischemia-reperfusion-induced inflammatory process.

The findings obtained from our research generally showed that, as a result of focal brain ischemia-reperfusion in rats, the levels of NF-κB, a key molecule involved in inflammatory pathways, as well as the pro-inflammatory cytokine IL-17 and caspase-3, an indicator of apoptosis, increased significantly in cerebellar tissue. However, intragastric naringin supplementation for two weeks following ischemia-reperfusion led to significant improvements in the adverse effects caused by the ischemic injury.

The study's results demonstrate that naringin treatment effectively mitigates inflammatory activation in the cerebellum following brain ischemia-reperfusion in rats.

Polysaccharide-derived biomaterials have emerged as promising candidates for wound healing applications due to their biocompatibility, biodegradability, and ability to mimic the extracellular matrix. These materials play a crucial role in maintaining a moist wound environment, promoting cell proliferation, and exhibiting anti-microbial properties, making them suitable alternatives to traditional wound dressings.

A systematic literature review was conducted using reputable databases including ScienceDirect, PubMed, Scopus, and Google Scholar. Relevant studies were identified, screened, and analyzed to ensure comprehensive coverage of the topic.

Wound healing is aided by essential polysaccharides such as chitosan, alginate, cellulose, and carrageenan, which help to retain moisture, promote cell proliferation, and prevent infections.

Polysaccharide-derived biomaterials, including chitosan, alginate, and cellulose, facilitate wound healing by maintaining moisture, promoting cell migration, and exhibiting anti-microbial properties. However, challenges such as weak mechanical strength and rapid degradation limit their clinical use. Recent advancements in composite hydrogels, nanomaterials, and 3D-printed scaffolds have improved stability, drug release, and anti-microbial efficacy. Further research is required to enhance their mechanical properties and long-term applicability for clinical wound care solutions.

Biomaterials developed from polysaccharides have the potential to revolutionize wound healing by providing biocompatible, adaptable solutions that promote enhanced tissue regeneration and infection control.

The goal of this study is to provide a comprehensive review of physicochemical and pharmacological properties, including pharmacokinetics and pharmacodynamics parameters, with an overview of preclinical and clinical trial data, chemistry, and multiple routes of synthesis, bioanalytical methods, and patents of the API: Vadadustat

A review was conducted by compiling data from Science Direct, PubMed, Drug Bank, WIPO patent, Clinicaltrialgov, Wolters Kluwer, and many others to enhance understanding of the topic

The FDA approved Vadadustat on March 27, 2024, for treating anemia in adults with CKD on dialysis. Vadadustat effectively increased hemoglobin levels in both non-dialysis and dialysis-dependent CKD patients. It showed comparable efficacy to traditional erythropoiesis-stimulating agents (ESAs) like darbepoetin alfa. Multiple clinical trials, including Phase 2 and Phase 3 studies, demonstrated Vadadustat’s potential as an effective treatment for anemia in CKD patients.

Vadadustat, as an oral HIF-PH inhibitor, offers significant advantages in the treatment of anemia in CKD. Its oral route of administration improves patient compliance, and its efficacy is comparable to ESAs. Clinical and preclinical data support its safety and therapeutic potential, although long-term cardiovascular effects remain under observation.

This review examines therapeutic, pharmacological, analytical, and regulatory aspects related to Vadadustat.

The limitations of conventional drug delivery methods, such as systemic side effects and poor absorption, highlight the need for safer and more effective alternatives. Polysaccharides, due to their biocompatible, biodegradable, and mucoadhesive properties, have shown promise in formulations for the oral cavity, particularly in localized delivery systems and tissue regeneration. This study aims to conduct a bibliometric analysis to characterize the scientific output on the use of polysaccharides in the oral cavity, identifying trends, international collaborations, and research gaps.

A Web of Science search was conducted in January 2025 using keywords related to polysaccharides and mucosal adhesion. The analysis included original articles published in English between 2015 and 2024. Bibliometric data and study characteristics were extracted and analyzed, focusing on study types, formulation types, and international collaborations.

The analysis included 66 articles with 1144 citations. In vitro studies were predominant, while clinical trials were lacking. Chitosan and alginate emerged as the most commonly used polysaccharides, with gels and hydrogels being the most prevalent formulations. International collaborations involved 28 countries, with China, Brazil, and Italy standing out in terms of scientific production.

The results highlight important advancements in the use of polysaccharides for oral cavity formulations, particularly in gels and hydrogels. However, the predominance of in vitro studies and the lack of clinical trials suggest limitations for translating these findings into clinical practice. The strong performance of countries such as China, Brazil, Italy, Spain, and Norway underscores the relevance of international collaborations and the global potential of this topic.

The increasing scientific output reflects the growing interest in the use of polysaccharides for oral health applications. Despite these advancements, critical gaps remain, such as the lack of clinical studies. Future research should prioritize translational studies, personalized therapies, and the sustainable development of biomaterials.