Post-inflammatory hyperpigmentation (PIH) results from inflammatory responses that leave persistent dark spots around pores after acne lesions are resolved. This pigmentation is caused by increased melanogenesis in melanocytes stimulated by acne-causing bacteria, followed by phagocytosis of excess melanin by macrophages that remain in the dermis. Therefore, to eliminate PIH caused by acne, it is essential not only to suppress excessive melanin synthesis by melanocytes but also to promote the degradation of melanin retained within macrophages. In this study, we investigated whether a culture extract of Bacillus velezensis AmoreLumina (AL), containing more than 80% moranoline (1-Deoxynojirimycin), could inhibit acne-induced pigmentation. Moranoline reduces melanin synthesis by inhibiting the glycosylation of tyrosinase, a key melanogenic enzyme, thereby suppressing its activity. The extract suppressed the upregulation of melanogenic enzymes (tyrosinase, TRP1, and TRP2) and melanin production in melanocytes exposed to acne bacteria, while promoting melanin degradation via macrophage lysosomal activity, as assessed by the relative protein expression level of p62 using Western blotting. Furthermore, in an ex vivo human skin model subjected to acne and ultraviolet radiation-induced pigmentation, treatment with the extract (0.2%) significantly reduced pigmentation (relative delta L 2.98, p value < 0.01). These findings suggest that cosmetic or pharmaceutical formulations incorporating AL extract or moranoline may potentially improve PIH caused by acne-related inflammation.

Valorizing agricultural byproducts into functional ingredients is highly desirable. Herein, plant-derived nanovesicles (PDNVs) from Paris polyphylla stems/leaves (SL-EXO) exhibited potent anti-melanogenic properties, whereas root-derived PDNVs were ineffective. In vitro, SL-EXO achieved 92.66% cell-free tyrosinase inhibition, while α-arbutin was 49.78%. In vivo, SL-EXO ameliorated the pigmentation-driving oxidative/senescent microenvironment in zebrafish and reduced macroscopic melanin by ~66%. Crucially, SL-EXO reversed α-MSH-induced hyperpigmentation in B16F10 cells while maintaining excellent biocompatibility up to 0.15 mg/mL, displaying a vastly superior safety margin compared to α-arbutin (which induced cytotoxicity at 0.075 mg/mL). To decode this, multi-omics profiling revealed that SL-EXO utilizes a chloroplast-derived biomimetic lipid architecture (enriched in MGDG/DGDG) to efficiently deliver potent flavonoid payloads. Molecular docking demonstrated exceptional predictive structural affinities (binding energies up to -10.9 kcal/mol) between these phytochemicals and AKT1. Finally, pharmacological rescue assays validated that SL-EXO arrests melanogenesis by targeting the AKT1 pathway, thereby downregulating the p-AKT/p-GSK3/MITF signaling cascade and silencing melanogenic genes. This study establishes a rigorous multi-omics paradigm for upcycling botanical wastes into exceptionally safe and efficacious natural anti-melanogenic nanotherapeutics.

Cronkhite-Canada syndrome is a rare, non-hereditary polyposis syndrome characterized by non-specific gastrointestinal symptoms accompanied by alopecia, cutaneous hyperpigmentation, and nail dystrophy. Characteristic endoscopic findings are diffuse sessile polypoid lesions with edematous mucosa. We report a case of a 44-year-old woman in whom intestinal ultrasound and CT revealed diffuse mucosal thickening and an ileocecal intussusception-findings that may not be pathognomonic but are highly unusual in adults. These imaging features served as critical red flags that directed the clinical suspicion toward Cronkhite-Canada syndrome and prompted timely endoscopic confirmation.

Lower leg lipodystrophy can be distressing to patients. Liposuction can contour the ankle, calf, and medial knee areas but requires the understanding of anatomy, thorough preoperative evaluation, and diligent postoperative care. Previous studies focused on a single liposuction technique. In this preliminary report, the authors presented a multimodal technique for lower leg liposculpture for aesthetic lower leg contouring and discussed lessons learned. The authors performed a retrospective review of patients undergoing bilateral liposculpture contouring using a combination of laser, power-assisted, and fine-cannula liposuction of the ankles and calves with or without medial knee contouring between 2021 and 2025. Patients undergoing unilateral procedures, revision surgery, or surgery for lipedema were excluded, as were cases involving liposuction limited to the ankles or knees. Of 40 cases undergoing lower leg liposuction procedures, 30 involved liposculpture of the ankles, calves, and medial knees. The average lipoaspirate was 793 ± 418 cc (range, 300-2700 cc) from each leg. The mean operative duration was 115 ± 33 min (range, 72-200 min), including concurrent procedures. The mean follow-up was 4.2 ± 4.3 months (range, 1 week to 20.5 months). Three patients experienced complications: one developing skin hyperpigmentation, one with scar thickening, and one with pressure injury with cellulitis and prolonged edema. The application of lower leg liposuction has been limited by concerns about complications. The authors present a multimodal approach to lower leg liposculpture. With appropriate preoperative assessment, patient counseling, and postoperative care, this approach can improve lower leg aesthetics with limited adverse events. Level of Evidence: 4 (Therapeutic) For image description, please refer to the figure legend and surrounding text.

Pigmentation abnormalities, ranging from hypo- to hyperpigmentation, can serve as biomarkers of developmental disruption in fish exposed to environmental contaminants. However, the mechanistic pathways underlying these alterations remain poorly understood. Studies have shown that pattern formation in fish development requires specific pigment cell interactions. Motivated by experimental observations of pigmentation alterations following contaminant exposure, we investigate how pollutants influence pigment cell self-organization using a continuum reaction-diffusion-advection framework. The model incorporates non-local Morse-type kernels to describe short- and long-range interactions among melanophores and xanthophores. Our results show that perturbations to the strengths of adhesion or repulsion can drive transitions between stripes, spots and mixed patterns, reproducing phenotypes characteristic of fish pigmentation mutants. In particular, homotypic interactions are sensitive to contamination, leading to pronounced changes in melanophore density and resulting pigmentation patterns. Time-dependent simulations indicate that pigment changes from early short-term contaminant exposure may be recoverable, whereas prolonged exposure can lead to sustained pigment loss. In a growing fish, contaminant-induced changes in cell-cell interactions directly influence stripe formation rate, stripe number and pigmentation levels. Overall, our study provides insight into the mechanistic link between experimentally observed pigmentation alterations and the changes in spatial patterns of adult fish.

Microphthalmia-associated transcription factor (MITF) is a master regulator of melanogenesis but remains undruggable. We designed anthraquinone-2-carboxylic acid-based PROTACs; EF4 exhibited the most potent degradation in A375B16-F10 cells with minimal cytotoxicity. CETSA and proteasome inhibition assays confirmed target engagement, and molecular docking revealed a stable MITF-EF4-CRBN ternary complex. ADMET profiling showed favorable properties (MW 564.6, logP 2.62, bioavailability 0.55). Compared to E6, EF4 had fewer drug-likeness violations, better skin permeability (log Kp = -7.76 cm/s), and superior synthetic accessibility. These findings highlight EF4 as a promising lead for skin-targeted MITF degraders.

Clinically refractory melasma remains difficult to treat because it is driven by a multidimensional pathological microenvironment that includes melanocyte hyperactivity, aberrant vascular growth, oxidative stress and chronic inflammation. Single-pathway therapies therefore often produce incomplete or transient responses. To remodel this microenvironment more broadly, we developed a bioinspired, stimulus-responsive co-delivery microneedle platform (TXA/Exo@HAMA-PBA MNs). Inspired by the backward-curved barbs on the tick hypostome, the microneedles were engineered with outward-facing barbs to improve anchoring within skin tissue. Chemically, adipose-derived stem cell exosomes (ADSC-Exos) acted as bioactive crosslinking nodes. They were coupled to the HAMA-PBA matrix through ROS-sensitive dynamic boronate ester bonds, while tranexamic acid (TXA) was physically co-encapsulated. After insertion into ROS-rich melasma-like lesions, oxidative cleavage of carbon-boron bonds accelerated matrix degradation and promoted on-demand release of both payloads. Mechanistically, this platform produced an asymmetric but coordinated blockade of the pathological microenvironment: ADSC-Exos mainly scavenged local ROS, including ·OH, whereas TXA preferentially disrupted abnormal capillary networks. Together, they suppressed melanogenesis through the MITF/TYRP1 cascade and shifted macrophages from a pro-inflammatory M1 phenotype towards a tissue-reparative M2 phenotype. In a UV/progesterone-induced mouse model of melasma validated by bulk RNA sequencing, the system produced multidimensional microenvironmental regulation and visible depigmentation. This bioinspired, spatiotemporally responsive co-delivery microneedle platform integrates complementary and synergistic therapeutic actions and offers a translational strategy for complex, multifactorial hyperpigmentary disorders.

The Dibenzofuran (DBF) scaffold represents a fundamental pharmacophore present in a wide spectrum of biologically active compounds. Its incorporation into molecular frameworks has been consistently associated with enhanced pharmacological potency, often surpassing that of structurally related analogs at equivalent concentrations. Numerous DBF-containing molecules have exhibited diverse therapeutic activities, including anti-microbial, anti-cancer, anti-amyloidogenic (particularly against transthyretin amyloidogenesis), anti-fungal, anti-inflammatory, anti-hyperglycemic, anti-hyperpigmentation, immunosuppressive, anti-HIV-1, anti-malarial, antipyretic, and analgesic effects. Understanding the chemical architecture of these compounds, particularly the influence of distinct functional groups on biological activity, offers valuable insights into their mechanisms of action. Moreover, Structure-Activity Relationship (SAR) analyses provide a rational basis for optimizing DBF derivatives and identifying molecular features responsible for their pharmacological diversity. This review categorizes and evaluates existing DBF derivatives, emphasizing their bioactivities, mechanisms of action, and therapeutic potential. The findings highlight the versatility of the DBF core as a multifunctional structural framework in modern drug design and discovery. Given its broad biological relevance, further exploration of DBF-based scaffolds through computational modeling, molecular docking, and synthetic modifications is recommended to identify novel analogs with improved selectivity, efficacy, and safety profiles. Such efforts could accelerate the development of next-generation therapeutics, establishing DBF as a cornerstone for innovative pharmaceutical research.

Facial wrinkles are a major concern in aesthetic dermatology, particularly in patients with darker phototypes, in whom laser treatments require careful parameter selection to minimize pigmentary adverse events. This retrospective study evaluated the effectiveness and tolerability of a nanosecond Q-switched 1064 nm Nd laser for the management of facial photoaging in Asian patients. Fifty Asian patients with Fitzpatrick skin types III-IV and facial wrinkles underwent three monthly treatment sessions with a Q-switched 1064 nm Nd: YAG laser. Clinical outcomes were assessed using the Fitzpatrick Wrinkle and Elastosis Scale, standardized pre- and post-treatment photographs, pain Visual Analogue Scale, and adverse event monitoring. Mean Fitzpatrick Wrinkle and Elastosis Scale score significantly decreased from 4.54 ± 1.55 at baseline to 3.42 ± 0.97 at three-month follow-up after the last treatment, corresponding to a mean absolute reduction of 1.12 ± 0.75 points. Forty-one patients showed an improvement of at least one FWS point, while thirteen patients improved by two or more points. Nine patients remained stable, and no clinical worsening was observed. Treatment was well tolerated, with a mean pain score of 2.0 ± 0.78. Mild transient erythema occurred in four patients, while no cases of blistering, scarring, burns, hypopigmentation, or post-inflammatory hyperpigmentation were recorded. Nanosecond Q-switched 1064 nm Nd laser treatment may represent a well-tolerated option for mild-to-moderate facial photoaging in Asian skin. However, the retrospective design, lack of a control group, and absence of instrumental objective measurements should be considered when interpreting these findings.