Jinbong Park

Microneedle technology offers a minimally invasive, pain‐free platform for drug delivery with high patient compliance and dosing precision. However, these systems struggle to adhere to curved, moist biological surfaces with dynamic movements, which require flexible substrates for conformity and rigid needles for penetration, resulting in a fundamental mechanical mismatch. Here, we present a root‐inspired microneedle array patch (R‐MAP) that integrates rigid microneedles and flexible substrates via lattice‐based mechanical interlocking. Peel‐off tests revealed a three‐fold increase in interfacial bonding force compared to non‐interlocked controls. Ex vivo evaluations confirmed stable penetration and reliable adhesion under dynamic conditions. To further enhance wet‐surface retention, we introduced a hydrogel adhesion layer, enabling in vivo attachment to porcine oral mucosa for over 5 h without detachment despite extreme rubbing conditions. This work provides a structurally robust, adaptable solution for challenging drug delivery environments, expanding the applicability of microneedles to curved, moist surfaces with dynamic movements including oral and dermal tissues.

Psoriasis therapy is constrained by the poor bioavailability and cutaneous delivery of natural compounds. To address this, we develop an innovative carrier‐free hydrogel (BBR‐MF gel) via molecular co‐assembly of berberine (BBR) and mangiferin (MF). This self‐assembled system forms a stable, shear‐thinning, and self‐healing network driven by π–π stacking and hydrogen bonding, enabling injectable administration and enhances skin retention for synergistic drug delivery. In an imiquimod‐induced murine psoriasis model, topical application of the BBR‐MF gel significantly alleviate clinical and histopathological symptoms, outperforming individual BBR or MF treatments. Transcriptomic analysis revealed potent downregulation of the IL‐17 and NF‐κB signaling pathways. Mechanistically, the gel directly inhibits neutrophil extracellular trap formation (NETosis) and, by altering the neutrophil secretome, subsequently attenuates the activation of NF‐κB and STAT3 pathways in keratinocytes, thereby disrupting a critical pathogenic immune‐epidermal crosstalk. The hydrogel exhibit excellent biocompatibility both in vitro and in vivo. This work presents a safe and effective self‐assembled nanoplatform that not only augments the synergistic efficacy of natural products but also unveiled a multimodal mechanism targeting NETosis and inflammatory signaling, offering a promising translational strategy for psoriasis and related inflammatory diseases.

Inflammatory lung diseases are characterized by complex immune dysregulation and structural tissue damage, demanding the development of novel therapeutic and diagnostic strategies. Exosomes (Exos) have emerged as promising alternatives to address these challenges by serving as key mediators and effective therapeutic nanocarriers. This review systematically analyzes the multifunctional roles of Exos derived from various sources, including immune cells, mesenchymal stem cells (MSCs), lung structural cells, and non-mammalian sources such as plants and milk, in the context of inflammatory lung diseases. These vesicles modulate critical pathological processes, such as macrophage polarization, oxidative stress, and programmed cell death, by delivering functional cargos, including miRNAs and proteins. Studies demonstrating the antioxidant properties of Exos are classified, and their roles in attenuating oxidative stress-mediated lung injury are discussed. Furthermore, engineering and priming strategies, as well as airway-directed delivery methods such as nebulization, are reported to enhance therapeutic efficacy and targeting. Evidence also indicates that plant-derived Exos could be scalable and safer alternatives to mammalian cell-derived Exos. Collectively, Exos represent a next-generation platform for precision medicine, functioning as potent therapeutic agents and efficient drug-delivery systems for the treatment of complex inflammatory lung diseases.

Alzheimer's disease (AD) is characterized by multifactorial pathological processes, including cholinergic dysfunction and oxidative stress, highlighting the need for safer, multi‐target interventions beyond current synthetic acetylcholinesterase (AChE) inhibitors. In the present study, we screened ethanolic extracts from various edible and medicinal plants to identify natural sources with cholinesterase‐modulating activity and found that Sparassis crispa ( S. crispa ) extract exhibited robust AChE inhibitory activity. The extract also demonstrated significant antioxidant capacity and protected rat pheochromocytoma cells against oxidative stress–induced cytotoxicity. Chemical characterization using gas chromatography–mass spectrometry identified ergosterol as a major bioactive constituent of S. crispa extract. Ergosterol directly inhibited AChE activity in vitro and was subsequently evaluated in vivo using a trimethyltin chloride (TMT)–induced mouse model of cognitive impairment. Dietary supplementation with S. crispa extract significantly improved spatial working memory and attenuated TMT‐induced elevation of brain AChE activity. Notably, ergosterol supplementation produced dose‐dependent improvements in both spatial working memory and aversive learning, accompanied by restoration of cholinergic function and reduction of lipid peroxidation in brain tissues. No signs of hepatic toxicity were observed following ergosterol administration. Collectively, these findings demonstrate that S. crispa extract exerts cognitive benefits through combined modulation of cholinergic dysfunction and oxidative stress, and identify ergosterol as a key bioactive contributor to these effects. This study provides mechanistic insight into the neuroprotective potential of S. crispa and supports its development, together with ergosterol, as functional food–derived candidates for the prevention or mitigation of cognitive decline.

Obesity is a complex metabolic disorder characterized by excessive fat accumulation and is closely associated with non‐alcoholic fatty liver disease (NAFLD), a condition that increases the risk of metabolic complications such as insulin resistance, type 2 diabetes, and cardiovascular diseases. JI017 is a recently optimized multi‐herbal formula composed of Angelica gigas , Zingiber officinale , and processed Aconitum carmichaeli . Clinical records of these three herbs indicate their potentially synergistic anti‐obesity effects. This study was conducted to verify the effects of JI017 in an animal model of obesity‐associated NAFLD. The effect of JI017 on glucose metabolism, white adipose tissue (WAT) adipogenesis, brown adipose tissue (BAT) thermogenesis, liver oxidative stress, and gut microbiota composition was assessed. The results showed that JI017 improved glucose sensitivity, reduced WAT mass by suppressing PPARγ and C/EBPα expression, and increased BAT thermogenesis through upregulation of UCP1 and PGC‐1α. Additionally, JI017 reduced liver oxidative stress by increasing HO‐1 and NRF2 expression and modulated the gut microbiota by restoring the Firmicutes / Bacteroidetes ratio. These findings on the multi‐targeted effects of JI017 suggest its potential as a promising therapeutic approach for metabolic diseases including NAFLD.

AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that serves as a central metabolic sensor and regulator of energy balance at both the cellular and organismal levels

Background/Aim: Cordyceps militaris, a medicinal fungus, is renowned for its anticancer properties. To maximize its therapeutic efficacy, this study aimed to optimize the extraction and preparation methods of Cordyceps militaris and evaluate its effects on non-small cell lung cancer (NSCLC). Additionally, the study explored the potential of natural products as novel therapeutic agents. Materials and Methods: Network pharmacology was employed to identify key compounds in Cordyceps militaris, including cordycepin and adenosine. Various extraction conditions, including temperature (50°C to 121°C) and duration (up to 72 h), were systematically tested. Freeze-drying and spray-drying methods were compared for their ability to preserve the bioactivity of the extracts. Lung cancer cell lines (LLC1, H460, H1299) were treated with the optimized extracts, and their effects on cell viability, migration, and colony formation were evaluated. Apoptotic markers were analyzed using western blotting. Results: Cordyceps militaris extracts optimized at 80°C for 24 h demonstrated the highest levels of cordycepin (505.59 ppm) and adenosine (81.80 ppm). Freeze-dried extracts obtained using this method exhibited significantly greater anticancer activity compared to spray-dried extracts. The optimized extract suppressed proliferation, migration, and clonogenic potential of lung cancer cells in a dose-dependent manner. Apoptosis-related pathways were activated, as evidenced by enhanced caspase-3 and PARP cleavage. Network pharmacology and molecular docking confirmed that cordycepin and adenosine target key proteins, including P53 and EGFR, to induce apoptosis. Conclusion: This study underscores the importance of optimizing extraction and drying methods to enhance the therapeutic potential of Cordyceps militaris. Furthermore, the findings highlight its promise as a natural anticancer agent, particularly for lung cancer.

Mallotus furetianus is traditionally used as folk medicine on Hainan Island, China. Given the significance of the pharmacokinetic interaction between herbs and drugs, we investigated the effects of Mallotus furetianus ethanol extract (MFE) on CYP3A activity in rats. The major bioactive constituents of MFE, gallic acid (GA) and epigallocatechin gallate (EGCG), were analyzed by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) for MFE standardization. Rats were orally administered 320 mg/10mL/kg MFE or water (control) once a day for 7 days. Two hours after the last MFE treatment, the rats were euthanized, and the livers and small intestines were excised. The activity of CYP3A was measured in hepatic and intestinal microsomes, and the expression in hepatic and intestinal tissues was assessed by qRT-PCR and western blot. In the pharmacokinetics experiment, rats were administered MFE as described above. Two hours after the final dose of MFE, a 15 mg/kg midazolam solution was orally administered. Blood samples were collected before and after midazolam administration. Midazolam plasma concentration and 1-hydroxymidazolam formation in microsomes were measured by LC-MS/MS methods.CYP3A activity in hepatic microsomes exhibited a significant decrease in MFE treatment group, while no change was observed in intestinal microsomes. MFE treatment significantly increased CYP3A1 activity, as well as mRNA and protein expression in the small intestine but reduced these parameters in the liver. However, CYP3A2 remained unaffected by MFE treatment. Pharmacokinetics study showed that administration of MFE for 7 days significantly reduced the Cmax of midazolam from 919 ± 70 ng / mL to 708 ± 91 ng /mL. Conversely, t1/2 was increased from 0.45 ± 0.08 h in the control group to 0.69 ± 0.15 h in the MFE group.Collectively, our study indicated that MFE could modulate CYP3A1 activity and expression of CYP3A1, subsequently changing the metabolism of midazolam in rats.