Background: Caesarean section is associated with postoperative pain and wound-related morbidity. Topical agents that promote early wound healing may enhance postoperative recovery. This randomized, placebo-controlled clinical trial evaluated the effect of HealFast Silver Ointment on pain and early wound-healing parameters after Caesarean section. Methods: Two hundred women who underwent Caesarean section were randomly allocated into two groups: a placebo group and a HealFast Silver Ointment group, each consisting of 100 women. The intervention was applied topically three times daily for three weeks. Outcomes were assessed at baseline, week 1, and week 3, and included pain intensity using the Visual Analogue Scale, transepidermal water loss, tissue oxygenation assessment, and wound surface morphology using Visioscan. Results: Baseline characteristics were comparable between groups. At week 3, the Visual Analogue Scale score decreased from 8.13 ± 0.93 to 1.33 ± 0.71 in the treated group, compared with 8.15 ± 1.47 to 7.03 ± 1.95 in the placebo group. Transepidermal water loss decreased from 34.13 ± 6.89 to 6.84 ± 3.99 in the treated group, compared with 32.70 ± 6.67 to 30.77 ± 6.69 in the placebo group. O2C increased from 40.08 ± 6.36 to 57.48 ± 7.19 in the treated group, compared with 40.80 ± 6.70 to 45.00 ± 6.84 in the placebo group. Significant time × group interactions were observed for the main clinical and physiological outcomes. Conclusions: HealFast Silver Ointment was associated with reduced postoperative pain, improved epidermal barrier recovery, increased tissue oxygenation, and improved wound surface morphology during the first three weeks after Caesarean section. Larger registered multicenter trials with longer follow-ups are needed to confirm these findings.
Skin pigmentation is regulated by intrinsic and extrinsic factors and is closely associated with melanogenesis and cellular homeostasis. Autophagy is a cellular self-digestion process that contributes to homeostatic regulation, but its role in melanogenesis remains to be further clarified. This study investigated whether berberine chloride (BBC), an isoquinoline alkaloid, modulates melanin production through autophagy-related signaling in B16-F1 melanoma cells. Tyrosinase activity was examined by tyrosinase zymography, extracellular melanin levels in the culture supernatant were measured after BBC treatment, and the expression of melanogenesis-, mitogen-activated protein kinase (MAPK)-, and autophagy-related proteins was analyzed by Western blotting. BBC inhibited tyrosinase activity and reduced extracellular melanin levels in a dose-dependent manner. BBC also increased phosphorylated extracellular signal-regulated kinase (p-ERK) levels while decreasing melanogenesis-related protein expression. In addition, BBC modulated MAPK signaling and the expression of autophagy-associated proteins. Small interfering RNA-mediated knockdown of Atg5, Beclin1, or ERK partially restored extracellular melanin levels in BBC-treated cells. These findings suggest that BBC suppresses melanogenesis in B16-F1 melanoma cells in association with ERK and autophagy-related signaling.
Titanium dioxide, a traditional physical sunscreen agent, has long faced persistent challenges related to light transmission (manifesting as whitening and an unnatural white cast on the skin), high photocatalytic activity, and cytocompatibility concerns. In this work, a composite sunscreen material, mesoporous silica (MSN)@TiO2, was designed and synthesized by loading titanium dioxide (TiO2) onto dendritic mesoporous silica. Leveraging the high transparency of dendritic mesoporous silica, MSN@TiO2 exhibits 30% higher visible light transmittance than commercially available titanium dioxide. In addition, encapsulation within the silica carrier reduces the photocatalytic activity of MSN@TiO2 to one-seventh of that of commercially available titanium dioxide. Furthermore, we evaluated the cytocompatibility of MSN@TiO2. Cell Counting Kit-8 (CCK-8) assay results demonstrate that MSN@TiO2 has a less pronounced effect on L929 cells proliferation compared with commercial TiO2, indicating favorable L929 cell-based cytocompatibility. This strategy demonstrates that MSN@TiO2 combines a natural appearance with low photocatalytic activity, offering distinct advantages over conventional titanium dioxide in composite sunscreen materials.
Proteoglycans (PGs) are intricate macromolecules decorated with linear polysulfated glycosaminoglycans (GAGs) that play critical roles in orchestrating a wide range of physiological and pathological events. Advances in the utilization of recombinant enzymes and biosynthetic pathways have expedited the production of defined and homogeneous GAGs, helping overcome traditional barriers of chemical synthesis. Furthermore, the synthesis of GAG chains has been increasingly integrated with other critical structural elements, most notably the core proteins. Robust synthetic methodologies toward well-defined GAGs and entire PG structures are critical because there is a lack of comprehensive structure-function data that addresses the PG architecture as a unified glycoconjugate. The construction of homogeneous PG is a formidable and rapidly evolving frontier in chemical biology, and the latest developments in this arena are summarized in this review.
Transition metals are essential nutrients that serve as metabolic cofactors and signaling agents in every cell type across all kingdoms of life. Owing to their relatively low abundance and high chemical reactivity, living organisms have evolved dedicated biochemical pathways to ensure active acquisition and targeted delivery of transition metals to their proper locations across biological length scales spanning tissues to cells to proteins, thus promoting beneficial physiology and avoiding detrimental pathology. Here we summarize recent advances in the discovery of copper metalloadaptor and zinc metallochaperone proteins that reveal new foundational chemical principles of biological metal homeostasis.
De novo protein design is reshaping how synthetic biology specifies and controls molecular function. Recent advances in generative modeling, sequence design and structure prediction enable molecular interactions to be created from scratch, reducing reliance on natural solutions and extensive experimental screening. These approaches support the design of compact, stable binding proteins, programmable interaction modules, and higher-order assemblies with defined geometry and regulatory behavior. As a result, de novo proteins are increasingly used to modulate signaling pathways, direct molecular targeting, and organize functional architectures across diverse biological contexts. Although challenges remain in predicting behavior in complex environments and balancing multiple design objectives, continued methodological progress is establishing de novo scaffolds as versatile, composable elements for the next-generation of synthetic biology.
Plants are a vast reservoir of natural products with diverse structural scaffolds, making them an invaluable source for discovering novel enzymes that catalyze unique and evolutionarily specialized metabolic transformations in biosynthetic pathways. Rapid advances in genomics, metabolomics, protein structure prediction, and heterologous pathway reconstruction have enabled the identification of numerous cryptic biosynthetic enzymes responsible for key scaffold-forming and tailoring reactions in metabolism. Particularly notable are the discoveries of plant-derived enzymes that catalyze challenging chemical transformations, including oxidative carbon-carbon bond rearrangements, atypical cycloadditions, radical-mediated coupling reactions, and iterative scaffold remodeling. This review summarizes major advances in enzyme discovery in plant natural product biosynthesis in recent years, focusing on emerging catalytic mechanisms, strategies for elucidating pathways, and evolutionary relationships, and highlights their implications for synthetic biology, metabolic engineering, and the sustainable production of valuable natural products.
Many cellular processes are regulated through the conditional association of existing proteins, motivating methods that provide precise spatial control over protein proximity. Controlling and imaging protein proximity in living cells has traditionally relied on separate tools: chemical actuators to induce protein interactions and fluorescent reporters to monitor protein proximity. Chemically induced proximity (CIP) achieves this by using small molecules to conditionally recruit one protein to another. Here, we review the evolution of CIP strategies from non-covalent to covalent and hybrid systems, and discuss recent scaffold designs that combine proximity induction and optical reporting within a single molecular scaffold. These advances establish modern CIP scaffolds as unified platforms for simultaneously controlling and imaging protein interactions.
Glycosyltransferases (GTs) install and remodel glycans that regulate protein function and shape extracellular matrices and microbial envelopes. Recent high-resolution structures, enabled by cryo-EM and X-ray crystallography, and increasingly complemented by AI-assisted modeling, now capture GTs in mechanistically informative states, including donor-acceptor complexes, gated conformations, and membrane polymerases engaged with nascent chains. In parallel, molecular simulations, including MD and QM/MM methodologies, are being used in selected GTs to map free-energy landscapes and resolve how active-site electrostatics and conformational changes tune reaction pathways across the SN1-SN2 continuum. We highlight recent advances in protein-directed GTs that initiate glycosylation on Ser/Thr, hydroxylysine, Asn, or Arg, and in glycan remodeling GTs that modify mature N-glycans or lipid-linked oligomannose precursors. We also discuss polymerizing and lipid-acceptor GTs that couple catalysis to translocation, scaffolding, or product release. Together, these studies show how transient catalytic states, loop closure, acceptor distortion, and atypical catalytic strategies control reaction trajectory, substrate selectivity, and processivity, while exposing opportunities for inhibition.
How can a single monosaccharide control nearly every human cellular feature? This question has hounded the O-GlcNAc field since 1984. Despite identifying thousands of O-GlcNAc proteins, high-throughput datasets have only deepened the mystery. This Current Opinion highlights chemical biology tools (current as of 2023-2026) that reveal coordinated O-GlcNAc networks in physiology and disease. We review five areas: (1) systems-level maps of tissue-specific OGT interactomes and substrates; (2) spatiotemporal tools for precise glycosylation manipulation; (3) multiplexed detection assays for O-GlcNAc activities alongside other PTMs; (4) targeted modulation via nontraditional inhibitors, noncatalytic OGT scaffolding, and ligand-directed assembly; and (5) disease models uncovering tissue-specific effects. Recent OGA inhibitor clinical challenges in Phase 1 and 2 studies pose existential questions about drugging O-GlcNAc, but recent advances covered in this Opinion propose insights for safe therapeutic targeting. Through the lens of new chemical biology tools, we see detailed patterns in how nutrient-responsive O-GlcNAcylation subtly regulates cellular decision-making.
Recognition of large f-block ions underlies advances in targeted radionuclide therapy and rare-earth element separations. Like the lanthanide-binding protein lanmodulin, the 18-membered macrocycle macropa displays reverse-size selectivity characterized by its preference for binding large metal ions. Its diaza-18-crown-6 scaffold enables efficient complexation of therapeutically relevant radiometals, such as 225Ac, 223Ra, and 213Bi, while accommodating diagnostic partners, including 203Pb and radiolanthanides. In parallel, systematic differences in stability constants across the lanthanide series enable size-based discrimination in separation chemistry. Macropa and its derivatives have been deployed in different strategies to recover and purify rare-earth elements and minor actinides. This manuscript describes recent studies on modifications of macropa, including cavity expansion, alteration of donor atoms, backbone rigidification, chelator-embedded 18F incorporation, and acyclic variants to demonstrate that effective selectivity arises from balancing preorganization, donor strength, and conformational adaptability. These studies establish macropa-based scaffolds as synthetic systems that bridge radiopharmaceutical coordination chemistry and rare-earth element separations.
In recent years, the rapid clinical advancement and expansion of nuclear imaging and therapy agents have (re)invigorated the field of radioisotope research due to progress and wider accessibility of radioisotope production. Many isotopes with decay properties suitable for imaging and therapy can be produced using low-energy cyclotrons; however, chemical labeling strategies enabling the incorporation of these isotopes into disease-/tissue-targeted radiopharmaceuticals are an active and rapidly expanding area of research. In this review, we survey key contemporary radiometal chelation strategies. One strategy encompasses the use of multifunctional, promiscuous azamacrocyclic chelators capable of binding divalent and trivalent radioactive isotopes for positron emission tomography, single-photon emission computed tomography, and radiotherapy with β- or α emitters of disparate sizes, charges, and chemical properties. The second strategy focuses on natural-product inspired and oxygen-rich approaches, capitalizing on their high affinity for biologically inert, high valent trivalent/tetravalent and pentavalent, oxophilic metal ions.
Centella asiatica (L.) Urb. (Apiaceae) is widely incorporated into dermatological and wound-healing formulations, where dechlorophylization is commonly used to improve extract stability, although its biological consequences are not fully understood. In this study, an ethanolic extract of C. asiatica leaves (CAE) was compared with a dechlorophylized C. asiatica extract (DCAE) in terms of cytotoxicity, wound-healing, anti-inflammatory, and antimicrobial activities, complemented by network pharmacology analysis. DCAE exhibited improved cytocompatibility, remaining non-cytotoxic up to 100 µg/mL, whereas CAE showed cytotoxic effects above 25 µg/mL. In contrast, CAE demonstrated superior wound-healing performance, reducing the residual wound area to 21.77% compared with 36.81% for DCAE and inducing higher Ki67 expression (1.94-fold versus 1.58-fold). These findings suggest that chlorophyll-associated constituents may contribute to keratinocyte proliferation and re-epithelialization. Although DCAE was enriched in pentacyclic triterpenes, including asiatic acid, asiaticoside, madecassic acid, and madecassoside, it showed stronger anti-inflammatory effects by more effectively suppressing CXCL10, IL-6, TNF-α, and IL-8 expression. Both extracts displayed weak antibacterial activity but moderate antifungal effects against Candida albicans, likely mediated through membrane disruption. Network pharmacology further indicated that wound-healing activity is associated with the regulation of COL1A1 and VEGFA through quercetin, kaempferol, and asiatic acid by way of the PI3K-Akt and MAPK signaling pathways, whereas anti-inflammatory effects involve modulation of PTGS2 and TNF through the NF-κB and IL-17 pathways. Overall, DCAE enhances cytocompatibility and anti-inflammatory activity, while CAE retains stronger regenerative capacity. These findings support the rational design of tailored formulations for specific dermatological applications, such as promoting wound repair or alleviating chronic skin inflammation.
The application repertoire of industrial biotechnology is constrained by the reaction scope of natural biocatalysis, which covers only a fraction of the accessible chemical space. To expand the versatility of biomanufacturing, abiological organometallic catalysts can be integrated into synthetic biology in the form of artificial metalloenzymes (ArMs). ArMs have been developed for a broad range of new-to-nature reactions, and in recent years multiple examples of their successful implementation in vivo have been demonstrated. Nevertheless, whole-cell ArM catalysis remains at the stage of fundamental research, and hybrid metabolic systems incorporating ArMs have yet to be realized at scale. In this review, we summarize the recent advances in whole-cell ArM catalysis and outline the challenges associated with in vivo ArM incorporation. We highlight the additional complexity that arises when transitioning from simple whole-cell biotransformations to metabolic engineering with ArMs and discuss potential strategies to achieve efficient integration of ArMs into biosynthetic pathways.
Glycosaminoglycans (GAGs) are complex carbohydrates ubiquitously expressed on cell surfaces and within the extracellular matrix, where they regulate essential biological processes through sequence- and sulfation-dependent interactions. Major GAG classes, including heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA), exhibit diverse sulfation patterns that encode specific molecular recognition events. Deciphering their structure-activity relationships has been hindered by intrinsic heterogeneity and limited access to well-defined materials. This review focuses on the recent advances in the chemical synthesis of GAGs, highlighting strategies that enable precise control over GAG structure and sulfation patterns. Recent innovations in protecting group design, stereoselective glycosylation, and automated assembly have significantly improved synthetic efficiency, facilitating the construction of increasingly complex and biologically relevant structures and advancing the rational design of GAG-based tools and therapeutics.
Non-surgical aesthetic procedures, including energy-based devices and injectable therapies, have become increasingly popular worldwide, creating distinct skincare needs for peri-procedural recovery and long-term post-procedure maintenance. This narrative review summarizes current evidence on cosmetic peptides as adjunctive skincare across both phases. A structured literature search was conducted in PubMed, Embase, and Google Scholar, only including peptides with an International Nomenclature of Cosmetic Ingredients (INCI) designation and defined amino acid sequences. Available clinical evidence suggests potential roles for cosmetic peptides in two interconnected scenarios. In peri-procedural care—spanning pre-procedure conditioning through post-procedure recovery—signal peptides, carrier peptides, and antimicrobial peptides have demonstrated benefits in accelerating healing and reducing erythema, edema, and bruising. As a long-term adjuvant strategy, signal peptides, neurotransmitter-inhibiting peptides, and whitening peptides may contribute to collagen remodeling, wrinkle reduction, and pigment control. Although enzyme-inhibiting peptides currently lack direct clinical evidence, their proposed mechanisms suggest potential for future investigation. However, the evidence remains limited by small sample sizes, short follow-up periods, heterogeneous peptide formulations and treatment protocols, and frequent use of proprietary multi-ingredient products. Overall, cosmetic peptides represent a potential adjunctive approach in aesthetic medicine. Larger, well-designed randomized controlled trials are needed to establish their clinical value and long-term safety.
The application of natural bioactive compounds in cosmeceutical products, particularly as skin-lightening agents, has received increasing interest. Caulerpa racemosa, a green macroalga of the Chlorophyta division, contains beneficial nutrients that are applicable as food and cosmeceutical ingredients. This study investigated the in vitro effect of the ethanolic extract of C. racemosa (CR) on regulation of melanogenic-related signaling and gene expression in SK-MEL-5 human melanoma-derived cells. Identification of bioactive components revealed that catechin, rutin, and quercetin as flavonoid contents were found in CR extract, analyzed using HPLC. The expressions of microphthalmia-associated transcription factor (MITF), extracellular signal-regulated kinase (ERK) signaling molecules, and melanogenic-related molecules were analyzed via Western blotting and qPCR. The CR extract treatment applied to SK-MEL-5 cells decreased the MITF protein expression level, which correlated with increased pERK expression, and no cytotoxic effect was observed. The subsequent treatment reduced the expression of melanogenesis-related genes (TYR, TYRP1, MC1R, and DCT) that were downstream targets of MITF. This study provides preliminary evidence that CR extract may modulate melanogenesis-related signaling. However, the specific bioactive compounds responsible for the observed effects remain to be identified, as the extract contains a complex mixture of phytochemicals. Further fractionation studies are needed to pinpoint the active constituents. The variability of extract composition due to seasonal and geographical factors should be considered for future standardization.
Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and assess the preliminary clinical performance of a topical herbal cream containing C. sativa and C. longa extracts. Ethanolic extracts were analyzed using UHPLC and GC-MS. Antioxidant, antibacterial, cytotoxicity, and nitric oxide inhibition assays were performed. Molecular docking studies were conducted against inflammation-related protein targets. A pilot clinical study evaluated the effects of the herbal cream in patients with eczema and psoriasis over four weeks using EASI, PASI, and DLQI scores. The herbal formulation contained cannabinoids, terpenoids, and curcuminoids with measurable antioxidant activity. The extract exhibited low cytotoxicity and moderate inhibition of nitric oxide production in LPS-stimulated macrophages (0.0001–0.1 mg/mL). Docking analyses suggested favorable interactions between selected phytochemicals and inflammation-associated targets. Preliminary clinical observations indicated improvements in EASI (from 4.11 ± 3.14 to 1.28 ± 1.46), PASI (from 39 to 16.2), and DLQI (from 6.25 ± 5.25 to 1.00 ± 0.82) scores among study completers. The herbal cream demonstrated antioxidant and anti-inflammatory properties and showed preliminary clinical potential in inflammatory skin disorders. Larger controlled clinical studies are required to confirm efficacy and establish therapeutic value.
