Search Results (2,036)

Kiwifruit (Actinidia spp.) is a globally important economic fruit with high nutritional value. Fruit peelability, defined as the mechanical ease of separating the peel from the fruit flesh, is a critical quality trait influencing consumer experience and market competitiveness and has emerged as a critical breeding target in fruit crop improvement programs. The present review systematically synthesized existing studies on kiwifruit peelability, and focused on its evolutionary trajectory, genotypic divergence, quantitative evaluation, possible underlying mechanisms, and artificial manipulation strategies. Kiwifruit peelability research has advanced from early exploratory studies in New Zealand (2010s) to systematic investigations in China (2020s), with milestones including the development of evaluation metrics and the identification of genetic resources. Genotypic variation exists among kiwifruit genera. Several Actinidia eriantha accessions and the novel Actinidia longicarpa cultivar ‘Guifei’ exhibit superior peelability, whereas most commercial Actinidia chinensis and Actinidia deliciosa cultivars exhibit poor peelability. Quantitative evaluation highlights the need for standardized metrics, with “skin-flesh adhesion force” and “peel toughness” proposed as robust, instrument-quantifiable indicators to minimize operational variability. Mechanistically, peelability is speculated to be governed by cell wall polysaccharide metabolism and phytohormone signaling networks. Pectin degradation and differential distribution during fruit development form critical “peeling zones”, whereas ethylene, abscisic acid, and indoleacetic acid may regulate cell wall remodeling and softening, collectively influencing skin-flesh adhesion. Owing to the scarcity of easy-to-peel kiwifruit cultivars, artificial manipulation methods, including manual peeling benchmarking, lye treatment, and thermal peeling, can be employed to further optimize kiwifruit peelability. Currently, shortcomings include incomplete genotype-phenotype characterization, limited availability of easy-peeling germplasms, and a fragmented understanding of the underlying mechanisms. Future research should focus on methodological innovation, germplasm development, and the elucidation of relevant mechanisms. Full article

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction. Full article

Skin autofluorescence (SAF) detection technology represents a noninvasive, convenient, and cost-effective optical detection approach. It can be employed for the differentiation of various diseases, including metabolic diseases and dermatitis, as well as for monitoring the treatment efficacy. Distinct from diffuse reflection signals, the autofluorescence signals of biological tissues are relatively weak, making them challenging to be captured by photoelectric sensors. Moreover, the absorption and scattering properties of biological tissues lead to a substantial attenuation of the autofluorescence of biological tissues, thereby worsening the signal-to-noise ratio. This has also imposed limitations on the development and application of compact-sized autofluorescence detection systems. In this study, a compact LED light source and a CMOS sensor were utilized as the excitation and detection devices for skin tissue autofluorescence, respectively, to construct a mobile and wireless skin tissue autofluorescence detection system. This system can achieve the detection of skin tissue autofluorescence with a high signal-to-noise ratio under the drive of a simple power supply and a single-chip microcontroller. The detection time is less than 0.1 s. To enhance the stability of the system, a pressure sensor was incorporated. This pressure sensor can monitor the pressure exerted by the skin on the detection system during the testing process, thereby improving the accuracy of the detection signal. The developed system features a compact structure, user-friendliness, and a favorable signal-to-noise ratio of the detection signal, holding significant application potential in future assessments of skin aging and the risk of diabetic complications. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Background and clinical significance: Trichoblastomas are rare, mixed epithelial tumors with a mesenchymal component and hair follicle differentiation. Case presentation: Herein, we present a case report of a 51-year-old female patient presenting to the obstetrics and gynecology department with complaints of edema and erythema of the right Bartholin gland, and a lesion measuring 2 cm on the right lateral edge of the mons pubis, towards the inguinal fold. Marsupialization of the Bartholin gland was performed, as well as an incision into the pubo-inguinal lesion, which the patient depicted as grossly resembling an ingrown hair. Upon incision into the pubic–inguinal lesion, it was dark brown in color and spontaneously popped out of the subcutis, without an attempt at enucleation. Histology and subsequent immunohistochemistry of the lesion showed a blue basaloid tumor with an extensive pigment component located deep in the dermis that was sharply demarcated from the surrounding tissues. Conclusion: Immunohistochemistry was diffusely and strongly positive for epithelial markers; melanocytic markers were positive only in dendritic melanocytes dispersed within the tumors, and the proliferative index was low. As such, the tumor was identified as melanotrichoblastoma. Full article

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of keratinocytes and infiltration of inflammatory cells. Significant challenges remain in developing effective and safe targeted therapies for psoriasis. Here, we reported the discovery of novel cystamine derivatives for the treatment of psoriasis. These compounds effectively attenuated LPS-induced inflammation in vitro, and the optimal candidate CS1 ameliorated imiquimod-induced psoriasis-like inflammation in mice. Mechanistically, CS1 bound and inhibited the deacetylase HDAC6, subsequently inhibited the AKT, MAPK, and STAT3 pathways, attenuated the hyperproliferation and altered differentiation of keratinocytes and reduced the infiltration of immune cells. These findings suggest that HDAC6 may serve as a potential target for drug development in the treatment of psoriasis. Full article

Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated conditions with significant impact on quality of life. Emerging evidence reveals a notable epidemiological and pathogenic overlap between HS and IBD, particularly CD. Although a bidirectional association between HS and IBD has been well documented, current evidence supports a causal effect of IBD on the development of HS, while a causal relationship in the opposite direction has yet to be established. The present review explores the important association between these immune-mediated conditions and further highlights shared risk factors, genetic predispositions and immunopathogenic mechanisms, such as dysbiosis and cytokine dysregulation, involved in both HS and IBD. Diagnostic challenges, especially in differentiating perianal HS from perianal CD, are also discussed. The coexistence of HS and IBD impacts disease severity, treatment response, and overall management strategies. Shared therapeutic approaches, such as TNF-α inhibitors and JAK inhibitors, are considered promising options for effectively managing patients affected by both conditions. Nevertheless, deeper understanding of the gut–skin axis that will offer potential for more precise interventions in patients with simultaneous HS and IBD is considered imperative. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article

Anthocyanins are important phenolic compounds in grape skins, affecting the color, oxidation resistance, and aging ability of red wine. In recent years, global warming has had a negative effect on anthocyanin biosynthesis in grape berries. Ethylene serves as a crucial phytohormone regulating the development and ripening processes of fruit; however, the specific molecular mechanism and the regulatory network between ethylene signaling and the anthocyanin biosynthesis pathway remain incompletely understood. In this study, 400 mg/L ethephon (ETH) solution was sprayed onto the surface of grape berries at the lag phase (EL-34), and the changes in anthocyanin-related genes and metabolites were explored through transcriptomic and metabolomic analysis. The results showed that ETH treatment increased Brix and pH in mature berries. In total, 35 individual anthocyanins were detected, in which 21 individual anthocyanins were enhanced by ETH treatment. However, the anthocyanin profile was not affected by exogenous ethylene. Transcriptomics analysis showed that there were a total of 825 and 1399 differentially expressed genes (DEGs) 12 h and 24 h after treatment. Moreover, key structural genes in the anthocyanin synthesis pathway were strongly induced, including VvPAL, VvCHS, VvF3H, VvF3′5′H, VvDFR and VvUFGT. At the maturity stage (EL-38), the expression levels of these genes were still higher in EHT-treated berries than in the control. ETH treatment also influenced the expression of genes related to hormone biosynthesis and signal transduction. The ethylene biosynthesis gene (VvACO), ethylene receptor genes (VvETR2, VvERS1 and VvEIN4), ABA biosynthesis gene (VvNCED2), and ABA receptor gene (VvPYL4) were up-regulated by ETH treatment, while the auxin biosynthesis gene (VvTAA3) and seven genes of the auxin-responsive protein were inhibited by exogenous ethylene. Meanwhile, ETH treatment promoted the expression of the sugar transporter gene (VvEDL16) and two sucrose synthase genes (VvSUS2 and VvSUS6). In EHT-treated berries, 19 MYB and 23 ERF genes were expressed differently compared with the control (p < 0.05). This study provides the theoretical foundation and technical support for the regulation of anthocyanin synthesis in non-climacteric fruit. Full article

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article