Glioblastoma remains one of the most lethal and therapeutically intractable primary brain malignancies, with a critical need for novel therapeutic discoveries. Phenanthrenes and dihydrophenanthrenes, gaining attention for their cytotoxic and antiproliferative activities, represent a promising yet underexplored chemical space for glioblastoma drug discovery. Phytochemical investigation of Vanda curvifolia, a species of phenanthrene-rich family Orchidaceae, afforded ten previously undescribed phenanthrene and dihydrophenanthrene constituents, designated vandafolins A–J (1−10), together with twelve known compounds. Structures were elucidated by NMR and HR-ESI-MS, with absolute configurations assigned by ECD spectroscopy and optical rotation measurements supported by TDDFT calculations. Vandafolins A, B, G, and H exhibited moderate cytotoxicity against U-87 MG glioblastoma cells, while vandafolins A, G, and H further demonstrated moderate antiproliferative activity. Vandafolin A induced G0/G1 cell cycle arrest, while vandafolins G and H induced apoptosis in U-87 MG glioblastoma cells, as determined by propidium iodide (PI) and Annexin V/PI staining flow cytometry, respectively. These results identified vandafolins A, G, and H as preliminary cytotoxic hits against glioblastoma cells, warranting further mechanistic and structural investigation.
Background Tenofovir disoproxil fumarate (TDF) is one of the first-line antiretroviral therapies in patients with HIV infection. It may be associated with renal impairment. This study aimed to evaluate risk factors for a rapid decline in estimated glomerular filtration rate (eGFR) in patients with HIV infection treated with a TDF-based regimen. Methods This was a retrospective cohort study conducted in adult patients with HIV infection who were aged 18 years or older, had a baseline eGFR of 90 ml/min/1.73m2, and were treated at an HIV clinic with TDF. The primary outcome of this study was a decline in eGFR of 5 or more ml/min/1.73m2 with stable or deteriorating eGFR in the following year. Predictors of rapid eGFR decline were calculated by logistic regression analysis. Results A total of 533 patients with HIV infection met the study criteria. Of those, 174 patients (32.65%) experienced an eGFR decline of 5 ml/min/1.73m2 or more after treatment with TDF. The average follow-up time was 7.94 years (SD 1.80). Four factors were identified in the predictive model for a decline in eGFR of 5 or more ml/min/1.73m2, including age, hepatitis B virus infection, urine albumin-to-creatinine ratio, and duration of TDF treatment. Only duration of TDF treatment was independently associated with a decline in eGFR of 5 or more ml/min/1.73m2, with an adjusted odds ratio of 1.188 (95% confidence interval: 1.063–1.328). Conclusion This long-term cohort study of patients with HIV infection treated with TDF showed that duration of TDF treatment may be associated with a rapid decline in eGFR. Annual monitoring of eGFR is warranted.
Lung cancer remains a leading cause of cancer mortality, and resistance to apoptosis limits the effectiveness of conventional and targeted therapies. This systematic review synthesized preclinical evidence on natural products that induce non-apoptotic regulated cell death in lung cancer, focusing on pyroptosis, cuproptosis, and necroptosis. Six databases were searched for original studies evaluating natural products, phytochemicals, plant extracts, or related bioactive compounds in lung cancer models. Overall, 25 studies met the inclusion criteria: 18 investigated pyroptosis, 5 investigated necroptosis, and 2 investigated cuproptosis. Because the included agents represented diverse chemical classes and most primary studies did not perform formal structure-activity relationship analyses, this review was designed as a mechanistic evidence map rather than a scaffold-optimization guide. Evidence was predominantly preclinical and focused on non-small cell lung cancer, especially A549-based models; 17 studies also included xenograft, allograft, or related animal experiments. Across chemically diverse agents, natural products were associated with reduced viability, proliferation, migration, invasion, colony formation, spheroid growth, metastasis, or tumor growth. Pyroptosis most frequently involved ROS/NF-κB/NLRP3/caspase-1/GSDMD signaling or caspase-3/GSDME activation. Cuproptosis studies highlighted copper accumulation, DLAT-associated mitochondrial stress, redox imbalance, and metabolic disruption, whereas necroptosis studies emphasized RIPK1/RIPK3-centered signaling with contributions from ROS, calcium flux, lysosomal injury, mitochondrial dysfunction, and autophagy. Overall, natural products show promise as multi-target modulators of non-apoptotic cell death in lung cancer, but the field remains clinically immature and requires further validation in standardized preclinical and clinical studies.
Malaria remains a major global health challenge, worsened by drug-resistant Plasmodium falciparum. Natural products remain key sources for novel therapeutics. Rhinacanthus nasutus, a Southeast Asian medicinal plant, produces rhinacanthins naphthoquinones with diverse pharmacological activities but limited exploration in malaria. This study evaluated the antimalarial activity, cytotoxicity, and mechanism of four rhinacanthins from R. nasutus against drug-sensitive and drug-resistant P. falciparum. Roots of R. nasutus were extracted to yield rhinacanthins B, C, D, and N. In vitro activity was assessed against P. falciparum 3D7 and atovaquone-resistant strains using SYBR Green I assay. Cytotoxicity was determined in Vero and KB cells via sulforhodamine B assays. Mechanistic insights were obtained through molecular docking and dynamics simulations targeting the mitochondrial cytochrome bc1 (cyt bc1) complex. All four rhinacanthins inhibited P. falciparum 3D7 proliferation with IC₅₀ values of 27–406 nM, with rhinacanthin C and N most potent. Activity was significantly reduced against two atovaquone-resistant strains harboring missense mutations in mitochondrial cytochrome b, implicating cyt bc1 as a primary target. Computational studies supported this, showing strong binding of rhinacanthins to cyt bc1, with rhinacanthin D exhibiting the most stable interaction. Potency correlated with lipophilicity (log D), indicating a physicochemical contribution. These findings identify rhinacanthin C and N as promising antimalarial candidates, distinguished by their high potency, with marginal toxicity profiles, and specific targeting of the cyt bc1. Their dual attributes of antimalarial potency support further investigation as potential leads for the development of novel therapies against drug-resistant P. falciparum.
Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal forms of liver cancer, for which sorafenib (SOR) is an established first systemic targeted therapy. However, its limited efficacy and resistance issues necessitate the development of improved analogs. In this study, a quantitative structure–activity relationship (QSAR) approach was employed to investigate the structural features governing the inhibitory activity of newly designed sorafenib derivatives (pIC₅₀). Several machine learning models, including multiple linear regression (MLR), random forest (RF), gradient boosting regression (GBR), and XGBoost, were constructed and compared. Among the evaluated models, the GBR model showed the best performance (R2 = 0.951) and the lowest error (RMSEtest = 0.150), indicating good internal performance across the dataset based on cross-validation. Based on the optimized model, eleven novel 1,2,3-triazole-based sorafenib analogs were designed, and their inhibitory activities were predicted. Subsequent synthesis and in vitro evaluation showed the high potency of these compounds against the HepG2 cell line. Notably, compound 10a demonstrated promising activity, with an IC₅₀ of 0.515 μM, almost 12-fold stronger than the parent sorafenib, while exhibiting a preliminary in vitro selectivity profile. Together, these findings highlight the effectiveness of combining QSAR modeling, synthesis, and biological activity evaluation in the rational design of sorafenib analogs, offering a useful approach for the design of sorafenib analogs with activity against HepG2 cells.
Cyanobacteria are an evolutionarily ancient group of oxygenic photosynthetic prokaryotes recognized as prolific producers of structurally diverse secondary metabolites. Among these metabolites, peptides and polyketides constitute two major and classes of chemicals known for a broad-spectrum biological activities, viz., antimicrobial, antiviral, anticancer, anti-inflammatory, enzyme inhibitory, and immunomodulatory effects. The chemical diversity of these compounds is primarily derived from non-ribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and hybrid NRPS–PKS biosynthetic pathways, which enable the incorporation of non-proteinogenic amino acids, extensive tailoring reactions, and macrocyclization. In addition, ribosomally synthesized and post-translationally modified peptides (RiPPs) further expand the structural and functional repertoire of cyanobacterial natural products. This review provides a critical overview of cyanobacterial peptides and polyketides, focusing on their biosynthetic basis, structural diversity, and biological activities relevant to phytomedicine. Major peptide and polyketide scaffolds are discussed in relation to their molecular mechanisms of action and structure–activity relationships, with particular emphasis on applications in inflammation, cancer, infectious diseases, and immune modulation. Key challenges limiting translational application, including toxicity, low natural abundance, and cryptic biosynthetic gene clusters (BGCs), are also highlighted alongside emerging biotechnological strategies.
Inflammatory sickness behaviors—characterized by reduced mobility, anhedonia, and social withdrawal—represent significant clinical manifestations of systemic inflammation and immune activation. This study evaluated the pharmacological effects and mechanism of action of dendrophenol, a bioactive compound from Dendrobium senile, in preclinical models of inflammatory disease. Male mice received dendrophenol (12.5, 25, 50 mg/kg, i.p.) in acute inflammation models (LPS-induced endotoxemia and formalin-induced inflammation). Pharmacological efficacy was assessed via behavioral phenotyping, inflammatory marker quantification, and CNS safety evaluation. Dendrophenol demonstrated dose-dependent attenuation of sickness behaviors in both LPS and formalin models. Mechanistic studies revealed that dendrophenol suppressed systemic and central pro-inflammatory mediators (TNF-α, IL-6, IL-1β, MCP-1) in vivo. Cellular mechanistic validation in LPS-stimulated macrophages and microglia demonstrated that dendrophenol inhibited inflammatory immune cell activation and cytokine release. Critically, dendrophenol produced no effects on locomotor activity and general behaviors, confirming CNS safety at all tested doses. These findings establish dendrophenol as a pharmacologically active anti-inflammatory compound with favorable safety characteristics, supporting preclinical validation for further drug development in inflammation-associated pathologies. The compound warrants advancement to dose-escalation and pharmacokinetic studies.
The most lethal diseases to have affected humankind are cardiovascular disorders. For decades, researchers have sought to elucidate the aetiology of heart disease, while clinicians have worked to prevent premature mortality. In recent years, substantial progress has been made in understanding cardiovascular conditions, accompanied by the development of systematic therapeutic strategies that extend patient survival.Advances in proteomics have enabled the analysis of clinical samples with far greater depth than was possible using traditional approaches. Immunoblotting, much like line fishing, is highly specific but inherently inefficient. Proteomics, by contrast, resembles the use of a net, allowing the comprehensive capture of molecular information from limited samples without sacrificing analytical precision. With appropriate methodologies, extensive proteomic information can be obtained through the identification of protein fragments.Studies involving a wide range of sample sources, from solid tissues to biofluids, were included in this review. Tissue samples represent the most informative material for investigating pathological processes at sites of vascular occlusion. However, tissues such as the heart and blood vessels are vital for physiological function and have limited regenerative capacity, rendering these samples rare yet highly valuable.In contrast, biofluid samples are readily accessible. Although they contain more contaminants, such as salts, and yield lower amounts of protein than tissue samples, they nonetheless provide meaningful insights into the circulatory system. Proteomic analyses have revealed that cytoskeletal organisation, extracellular matrix remodelling, immune activation, inflammation, and metabolic processes are involved in most cardiomyopathies, whereas mitochondrial dysfunction, fibrosis, and additional pathways are more prominent in other cardiovascular diseases.Comparative analyses of proteomic data across different cardiovascular conditions and patient cohorts have identified shared molecular pathways, highlighting the capacity of proteomics to uncover multiple dimensions of cardiovascular pathology. Moreover, proteomic profiling facilitates the discovery of candidate biomarkers—whether diagnostic, prognostic, or indicative of disease risk—as well as potential therapeutic targets. These putative biomarkers and targets, however, require validation in larger and more diverse cohorts.
Background Resistance to erlotinib remains a major challenge in the treatment of non-small cell lung cancer (NSCLC), often driven by persistent activation of STAT3-mediated pro-survival signaling. Compound 1, a monoterpenoid dihydrochalcone derivative isolated from Conamomum rubidum, has demonstrated cytotoxic potential; however, its ability to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has not yet been elucidated. Objective This study aimed to evaluate the anticancer effects of compound 1, its capacity to restore erlotinib sensitivity in NSCLC, and the underlying molecular mechanisms. Methods Cytotoxicity and combination drug assays were conducted in A549 and H1975 cells, while apoptosis was assessed using Annexin V-FITC/propidium iodide (PI) staining. Network pharmacology, molecular docking, and molecular dynamics simulations were performed to predict compound 1 targets and binding stability, followed by target validation through immunoblotting. The compound’s efficacy was further examined in erlotinib-resistant HCC827 cells. Results Compound 1 significantly reduced NSCLC cell viability and enhanced erlotinib-induced apoptosis by suppressing both phosphorylated activator of transcription 3 (p-STAT3) and acetylated STAT3 (a-STAT3), leading to downregulation of Bcl-2. Molecular docking and simulation analyses suggested favorable interactions of compound 1 in a region proximal to the STAT3 SH2 domain, supporting STAT3 as a potential target. Moreover, compound 1 resensitized erlotinib-resistant HCC827 variants to erlotinib-induced cell death. Conclusion Compound 1 exhibits potent cytotoxic and chemosensitizing effects by suppressing the STAT3/Bcl-2 signaling axis. These findings suggest that compound 1 may represent a promising therapeutic candidate for overcoming EGFR-TKI resistance in NSCLC.
Background: Chinahas recently introduced patent term buchang (PTB) for new drugs. This study presents a systematic profile for China’s PTB, European SPC, and the U.S. PTE for new drug protection. Methods: Drug Development Time Period (DDTP) index and Final Drug Patent Protection Term (FDPPT) were calculated using predefined equations. Results: Our study showed the average PTB, SPC, and PTE for new drugs were 3.56, 4.11, and 2.82 years, respectively. Consequently, the average FDPPTfor these regions reached 11.20, 14.32, and 13.19 years,respectively. Our results revealed that the average DDTP index for these new drugs was 9.79 years in Europe, 12.36 years in China, and 10.05 years in the US. For the same drugs, the SPC term in Europe was 1.55 years longer than the PTE in the United States. The FDPPT in Europe was an average of 0.54 years longer than that in the US. Conclusions: Our studycharacterizesChina’s PTBprofile for the first timeand proposes a novel methodology-the DDTP index concept and its quartile range method-for investigating patent extension protection. The study shows that for new drugs with a DDTP index between 6 and 10 years, patent protection in Europe is substantially longer than in China and the US. For those drugs with an index between 10 and 15 years, Europe still offers the longest protection period (Avg. 13.41 years), while China has the shortest (Avg. 11.86 years); the US falls in the middle (Avg. 12.83 years). However, for drugs with a DDTP index above 10 years, the relative advantage of patent term extension in Europe diminishes and eventually disappears as the index increases.
Background Impatiens balsamina Linn. is an annual plant traditionally used to treat several cutaneous fungal infections, including conditions often associated with Malassezia spp. However, its anti-Malassezia activity, biomarkers, and underlying mechanisms remain insufficiently defined. This study establishes a rapid at-line LC-ESI-QTOF-MS/MS screening platform coupled with a colorimetric antifungal assay to identify anti-Malassezia biomarkers and assess their modes of action. Methods An at-line LC-ESI-QTOF-MS/MS platform was used to screen I. balsamina extracts and identify bioactive constituents. The most active extract was subjected to preparative HPLC for isolation of biomarkers. The resazurin-based microdilution antifungal assays were performed against M. furfur. The mechanisms of action of the identified compounds were investigated by lipase assay and biofilm formation assay. Results The ethyl acetate extract exhibited the most potent antifungal activity. The LC-ESI-QTOF-MS/MS and bioactive chromatograms pinpointed 2-methoxy-1,4-naphthoquinone (2MN) as the only active compound. Purified 2MN showed MIC values of 6.510 ± 1.906 µg/mL and MFC values of 8.854 ± 4.543 µg/mL. The compound reduced extracellular lipase activity and effectively inhibited biofilm formation of M. furfur. Conclusions The at-line LC-ESI-QTOF-MS/MS platform successfully guided and reduced the time and sample scale for purification of the anti-Malassezia compound. 2MN from I. balsamina exerts a significant antifungal effect and reduces fungal biofilm. Our rapid targeting approach and findings here encourage the discovery of antifungal phytochemicals as a candidate for anti-Malassezia therapy.
Plumbagin, a bioactive naphthoquinone from Plumbago species, has emerged as a pleiotropic anticancer candidate with activity across major breast cancer subtypes. Preclinical evidence indicates that plumbagin suppresses tumour growth by converging on redox stress and survival circuitry, including mitochondrial apoptosis and NF-κB-linked pathways, with reported inhibitory effects in ER-positive, HER2-overexpressing, and triple-negative models and a signal of relative selectivity in normal breast cells. Beyond cytotoxicity, plumbagin can attenuate metastatic programs, notably by NF-κB-dependent repression of CXCR4, thereby reducing migration and invasion. However, its clinical plausibility is constrained by poor solubility, exposure instability, and a narrow therapeutic window driven by quinone-mediated off-target oxidative burden. Advanced nanocarriers offer a rational strategy to convert this redox liability into tumour-selective benefit through exposure shaping, stimulus-responsive release, and conservative, clinically familiar excipient choices. Emerging designs—including long-circulating systems, ROS/GSH-activated approaches, and antioxidant interface engineering—aim to flatten peak-related toxicity while sustaining intratumoural pharmacodynamic thresholds. Co-delivery platforms may further synchronize pharmacology to overcome resistance, pairing plumbagin with cytotoxins or pathway modulators through programmable release sequencing. Looking ahead, AI/ML-guided formulation and imaging-integrated theranostics can support biomarker-driven dose selection and a pragmatic Phase I roadmap that adheres to transparent CMC principles. Collectively, these advances position plumbagin-based nanomedicine as a credible, mechanism-informed phytotherapeutic strategy for breast cancers with high unmet need, warranting carefully designed translational studies.
Diverse technologies are used to design nucleic acid aptamers to achieve targeted therapeutics, engineer diagnostic tools to detect specific biomolecules associated with disease-oriented signaling pathways, and develop drug delivery systems. Despite the availability of many methods, including systematic evolution of ligands by exponential enrichment, there is no reliable method that can address aptamer-target binding energetics during aptamer design. We have developed a technique to do so, combining theoretical and computational methods. In this energy-based method, we calculate drug-target binding energies (DTBEs) and monitor phenomenological drug-target binding energetics related to drug-target association/dissociation processes, considering screened Coulomb interactions (SCIs) among a distribution of functional charges in a complex of an aptamer or aptamer building block (ABB) and target biomolecule in the biological environment where interactions take place. An ABB is any nucleotide: adenine, guanine, cytosine, uracil (for RNA), or thymine (for DNA). We have designed a set of novel aptamers for phosphatidylcholine, an important biomolecule relevant to various therapeutics, that are outlined here. In summary, our drug designing method involves constructing an aptamer using a seed-and-grow approach, optimizing SCIs, and selecting aptamer length based on the trend of DTBE in an aqueous environment, where aptamers interact with target(s). This novel technique, the screened Coulomb interaction approach (SCIA), ensures the discovery of target-specific aptamers as the target specificity is inherently incorporated during the aptamer design phases. SCIA is expected to significantly enhance aptamer discovery research and help develop aptamer-based therapeutics for diseases where specific drug targets are known.
Reactive Oxygen Species (ROS)-induced cell and organ toxicity is a common element in human disease patho-mechanisms. PrC-210 is a new free-radical scavenger that substantially suppresses ROS damage in pre-clinical animal disease models. Here we determined PrC-210 pharmacokinetic and toxicokinetic performance in a large animal pig model as a forestep to Phase 1 safety studies in humans. Using a newly created LC-MS assay to measure plasma PrC-210 levels, we determined that: i) an IV or oral PrC-210 bolus dose yielded easily measurable plasma concentrations, which returned to baseline within an hour (IV) or 8–10 h (oral), ii) at the same IV mg/kg dose, female pig plasma PrC-210 AUC levels were 13–15 % higher than males; this presumably reflects less vasculature per unit tissue mass, iii) a primary toxicity, vomiting, followed simple PrC-210 plasma toxicokinetics for both IV and oral doses, and was absent at IV PrC-210 NOAEL (5.0 mg/kg bw) and oral PrC-210 NOAEL (70.0 mg/kg bw) doses that are at least two-fold higher than the highest PrC-210 dose that would be administered therapeutically, iv) no significant changes in blood cell populations were seen through 7 days following an IV PrC-210 bolus NOAEL dose, v) no significant changes in any of 15 blood chemistry parameters were seen through 7 days following an IV PrC-210 NOAEL dose, and vi) no discernible visible nor histologic organ or tissue pathology was seen in necropsies performed at 7 days post-IV dose. This study supports continued development of PrC-210 for Phase 1 human studies.
The skin acts as a vital barrier against the environment, and injuries can lead to acute or chronic wounds. Chronic wounds often heal slowly and are more susceptible to infection. Postbiotics, defined as preparations of inactivated microorganisms or their bioactive components, have demonstrated potential to promote wound repair. Compared with live probiotics, postbiotics are safer, more stable, and easier to standardise, while still supporting tissue repair via antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects. Compounds such as exopolysaccharides, short-chain fatty acids, antimicrobial peptides, enzymes, vitamins, and cell-free supernatants can enhance fibroblast growth, collagen production, keratinocyte migration, angiogenesis, and immune balance. Postbiotics derived from Lactobacillus, Bifidobacterium, Bacillus, and commensal Staphylococcus species act through multiple signalling pathways. They reduce pro-inflammatory cytokines, promote alternatively activated M2 macrophage polarisation, and facilitate restoration of the skin barrier. Recent developments in hydrogels, nanofibers, and encapsulated delivery systems have improved the stability and availability of postbiotic compounds at wound sites, making them more effective. Despite promising results from preclinical studies and early clinical trials, challenges remain in standardizing production, defining regulatory frameworks, and generating strong clinical evidence. Future studies should focus on identifying key bioactive molecules using advanced omics approaches, developing targeted delivery systems, and evaluating postbiotic therapies in well-designed clinical trials. Overall, postbiotics provide a safe and versatile approach to accelerate wound healing and may serve as an alternative or complement to conventional treatments.
Fragile X syndrome (FXS), a leading inherited cause of intellectual disability and autism, arises from loss of the RNA-binding protein FMRP and consequent dysregulation of synaptic mRNA translation. No clinically approved therapies exist to restore FMRP function. A recent study showed that a Tat-conjugated FMRP fragment spanning residues 1–297 (FMRP N-tat) can transiently reduce hyperexcitability in an FXS mouse model, supporting peptide replacement as a feasible therapeutic strategy. Extending this concept, Leguay et al. demonstrated in FXS patient iPSC-derived neurons that N-tat reconstitutes interactions with endogenous protein partners correcting dysregulated translation and mitochondrial defects. However, despite recapitulating several functions of full-length FMRP, the in vivo effects of N-tat remain short-lived, highlighting challenges in stability and the potential need for additional functional domains. Herein, this commentary outlines both the promise of N-tat–based protein replacement and the remaining gaps that must be addressed to achieve clinically durable restoration of FMRP function.
Type 2 diabetes mellitus (T2DM) represents a major global health challenge, emphasizing the need for effective strategies to manage postprandial hyperglycemia. Inhibition of α-glucosidase, a key enzyme involved in carbohydrate digestion, is a well-established therapeutic approach. In this study, melatonin, an indoleamine with diverse biological activities, was investigated as a scaffold for the development of novel α-glucosidase inhibitors. Among the derivatives evaluated, 4EBM emerged as the most potent inhibitor, exhibiting an IC50 value of 37.20 ± 0.64 μM and demonstrating greater potency than the standard drug, acarbose. Kinetic studies, molecular docking, and molecular dynamics (MD) simulations indicated that 4EBM acts as a competitive inhibitor by directly interacting with key residues (Y158, F178, Q279, R315, and R442) within the α-glucosidase active site. Furthermore, in silico predictions suggested that several derivatives containing naphthalene, biphenyl, or trifluoromethylphenyl moieties exhibited stronger binding affinities than 4EBM. These findings underscore the potential of melatonin derivatives as promising lead compounds for the development of more effective α-glucosidase inhibitors for T2DM management, while also enhancing the current understanding of indoleamine scaffolds in enzyme inhibition.
Bioactive metabolites derived from algae are gaining popularity as safe and effective compounds for the development of new skincare products around the world. In this study, the cosmeceutical effects of Malaysian brown algae Sargassum aquifolium (S. aquifolium) extracts were investigated. The investigation began with phytochemical analysis and antioxidant activities. The anti-photoaging and anti-inflammation properties of S. aquifolium water and ethanol extracts were then tested against UVB-induced HaCaT keratinocytes and LPS-induced RAW264.7 macrophages, respectively. S. aquifolium ethanol and water extracts are high in phenolic and flavonoid compounds and have high DPPH radical scavenging and reducing power activity. The ethanol extract was found to have remarkable anti-photoaging properties by downregulating COX-2 (1.2-fold) and MMP-1 (3.1-fold) expressions, as well as anti-inflammatory properties by suppressing iNOS via NO suppressions and inhibiting TNF-α (45%) and IL-6 secretion (98%). According to liquid chromatography-mass spectrometry (LC-MS) analysis S. aquifolium ethanol extract also contains carbohydrates, lipids, carotenoids, terpenes, pigments, benzofuran, and phloroglucinol. In conclusion, bioactive metabolites isolated from S. aquifolium ethanol extract have been shown to exhibit improved antioxidant, antiphotoaging, and anti-inflammatory capabilities, suggesting that they could be used as a cosmeceutical agent.
The gut microbiota has emerged as a determinant of onset, progression, and response to treatment of many cancers. The current research in oncology indicates that microbial metabolites like short-chain fatty acids (SCFAs), secondary bile acids, indole derivatives, and polyamines are not passive metabolic end products but potent bioactive mediators. These molecules directly modulate cellular signaling pathways, immune modulation, and the tumor microenvironment. Depending on their concentration and the overall physiological environment, these metabolites may be tumorigenic or protective, anticancer in effect. Significantly, by controlling immune reactions and drug metabolism, microbiota-derived metabolites have been reported to modulate and enhance the activity of chemotherapeutic agents, radiotherapy, and immunotherapeutic protocols.In spite of these advances, it is still difficult to apply microbiome research to clinical oncology. Some of the key hurdles are high interindividual heterogeneity in gut microbial structure, lack of standardized analysis pipelines, and incomplete understanding of mechanistic crosstalk between the host and microbiome. This heterogeneity makes reproducibility tricky and reduces the predictive value of microbiota-directed interventions in oncology. However, emerging advances in metabolomics, synthetic biology, and systems-level medicine are enabling personalized therapy discovery. Such technological advances facilitate massive profiling and individually customized modulation of microbial metabolites, thus promoting the development of metabolite-directed or microbiota-targeted adjuvant strategies that promise augmented specificity and therapeutic efficacy.This review integrates existing knowledge, translational hurdles, and new trends in the translation of microbiome-derived metabolites towards precision cancer treatment. As the evidence increasingly places the gut microbiota at the interface of controlling and predicting tumor behavior and outcomes of therapy, it is a promising system for therapeutic and biomarker development. Translating these microbial metabolites by combining biotechnological and computational approaches can usher in a new era for precision oncology that is reconcilable with host–microbiome physiologies.
Three-dimensional (3D) printing has rapidly evolved into a transformative platform for drug delivery, offering capabilities that extend far beyond the customization possible with traditional manufacturing. This review critically evaluates the major 3D-printing technologies FDM, SLS, SLA/CLIP, SSE, and multi-material inkjet and compares their suitability across oral, transdermal, implantable, and bioprinted systems. Emphasis is placed on material limitations, polymer–drug compatibility challenges, quality-control constraints, and regulatory barriers that currently restrict translation. Recent advancements in nano-enabled formulations, stimuli-responsive architectures, and high-resolution multi-material systems are examined to illustrate how structural design directly influences pharmacokinetics and therapeutic performance. The review concludes with a forward-looking synthesis that highlights emerging opportunities in AI-assisted dosage design, 4D shape-morphing platforms, and point-of-care manufacturing workflows. Together, these insights provide a comprehensive and critical understanding of the technological, material, and regulatory factors shaping the future of 3D-printed drug delivery. By advancing innovation in pharmaceutical manufacturing and enabling more equitable access to personalized therapies, 3D printing represents a pivotal evolution toward patient-centric drug delivery solutions
