Komipharm International (South Korea)

IntroductionXenotransplantation offers a potential solution to the critical shortage of donor organs; however, graft survival is limited by xeno-immune activation and coagulation dysregulation. Regulatory macrophages (Mregs) are known for their immunomodulatory capacity, yet their cross-species function in the context of xenotransplantation remains unclear. This study investigates the immunoregulatory properties of pig-derived Mregs (pMregs) as a potential donor-derived cellular therapy.MethodspMregs were generated from pig CD14⁺ monocytes using M-CSF and IFN-γ. Phenotypic characterization was performed by flow cytometry, and functional assays evaluated cytokine secretion, T-cell suppression, and induction of FOXP3⁺ regulatory T cells across pig, monkey, and human lymphocytes. An in vitro xenogeneic inflammation model was established by exposing human M1 macrophages to pig endothelial cells to assess inflammatory cytokine responses and expression of coagulation-related genes.ResultspMregs exhibited a canonical Mreg phenotype (CD14⁺CD16⁺CD163⁺PD-L1⁺DHRS9⁺CD32⁻CD169⁻) and secreted IL-10 and TGF-β. Functionally, pMregs suppressed T-cell proliferation across pig, monkey, and human species and induced FOXP3⁺ regulatory T cells. In the xenogeneic inflammation model, pMregs attenuated inflammatory cytokine production in human M1 macrophages and downregulated mRNA expression of coagulation-associated genes, including TF and PAR-1.DiscussionThese findings highlight the cross-species immunosuppressive activity and coagulation-regulatory capacity, suggesting the potential relevance to xenograft injury. pMregs may therefore serve as a promising candidate for further investigations as a donor-derived immunoregulatory cell type to complement genetically engineered pig grafts.

Peptides are recognized as multifunctional bioactive ingredients in cosmetic science, as they offer diverse beneficial effects such as skin rejuvenation, anti-aging, and skin barrier enhancement. In this study, we applied a cheminformatics-assisted peptidomimetic design platform to design novel peptides targeting heat shock protein 47 (Hsp47), a collagen-specific molecular chaperone that is downregulated during skin aging. Using molecular fingerprint similarity-based peptide design and protein–peptide docking simulations, five candidate peptides were screened, among which ICP-1225 (TY) emerged as a potent stimulator of Hsp47 and collagen (COL1A1 and COL3A1) expression in dermal fibroblasts. To improve stability and skin penetration, fatty acid-conjugated derivatives of ICP-1225 were synthesized, and acetyl-TY (ICP-1236) demonstrated the most consistent upregulation of Hsp47 and collagen in vitro. Restoration of Hsp47 protein expression and dermal collagen levels in UVB-damaged ex vivo human skin explants was also observed. These findings highlight the potential of cheminformatics-assisted peptide design in the development of next-generation cosmetic actives. ICP-1236 represents a promising anti-wrinkle candidate through the modulation of Hsp47 and collagen pathways, warranting further clinical evaluation.

Atopic dermatitis (AD) is a chronic inflammatory dermatological disorder characterized by skin barrier dysfunction, dry skin, pruritus, and aberrant immune responses to external stimuli. Although polynucleotides (PNs) have anti-inflammatory properties, their effect on AD remains unexplored. This study investigated the effects of PNs on a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. The effects were evaluated by the dermatitis severity score (DSS), the spleen index, the serum immunoglobulin E (IgE) concentration, trans-epidermal water loss (TEWL), histological findings, and the expression levels of cytokine mRNA and filaggrin protein in skin tissue. Topical application of PNs significantly reduced the DSS, the spleen index, the serum IgE concentration, and TEWL compared with the control. Additionally, histopathological analysis showed that PNs reduced epidermal and dermal thickness, the mast cell count, collagen deposition, and eosinophil infiltration in the dermis. Moreover, PNs significantly downregulated the expression of key inflammatory cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), in affected skin tissue. Immunohistochemical (IHC) staining and Western blot revealed that PNs inhibited DNCB-induced suppression of filaggrin. A combination of hyaluronic acid (HA) and PNs showed enhanced efficacy compared with PNs alone, particularly for reducing the serum IgE concentration and TEWL and increasing filaggrin expression. These results suggest that PNs are potential candidates to treat AD because they possess anti-inflammatory properties and improve skin barrier function.

Bovine mastitis, primarily caused by Staphylococcus aureus, significantly affects the dairy industry by reducing milk production and quality. The rise of antibiotic-resistant bacteria has prompted the need for alternative treatments. The three newly isolated bacteriophages, OPT-SA02, OPT-SC01, and OPT-SX11, were isolated from chicken fecal and sewage samples in South Korea. These bacteriophages were characterized via physiological and genomic analyses, identifying their therapeutic potential against S. aureus-induced mastitis. The bacteriophages were identified as members of the Herelleviridae family, exhibiting stability across broad pH (2-12) and temperature (37-70°C) ranges, as well as strong antibacterial activity at low multiplicity of infection (MOI) levels. Genomic analysis revealed that the conservation of lysis-related genes (holin and endolysin) is responsible for their lytic capabilities. Additionally, protein structural predictions revealed multi-domain structures in their endolysins, enhancing their lytic potential. These findings suggest that OPT-SA02, OPT-SC01, and OPT-SX11 show significant promise as alternative treatments for bovine mastitis.IMPORTANCEBovine mastitis, caused by pathogens such as Staphylococcus aureus and Staphylococcus xylosus, remains a major challenge in dairy farming, leading to significant economic losses and reduced milk quality. The increasing prevalence of antibiotic-resistant strains further complicates treatment, emphasizing the need for alternative strategies. This study identifies three newly isolated bacteriophages with effective antibacterial activity against these pathogens and provides comprehensive genomic and structural insights into their mechanisms. Genomic characterization revealed conserved lytic cassettes and genetic diversity within related bacteriophages, offering a deeper understanding of their evolutionary relationships and potential applications. Furthermore, protein structure analysis of the endolysin derived from these bacteriophages identified multi-domain architectures with preserved catalytic cores, underscoring their lytic efficacy against bacterial cell walls. These findings advance the understanding of the genetic and structural mechanisms of bacteriophage-mediated lysis and highlight their potential as sustainable tools for managing bovine mastitis and improving milk quality in dairy farming.

Several studies have suggested that adiponectin is an anti-aging molecule based on its potential involvement of adipose tissue in skin aging. In this study, we investigated the anti-photoaging efficacy of an adiponectin expression-stimulating peptide derivative, pentasodium tetracarboxymethyl hexanoyl dipeptide-12 (PTHD-12), in in vitro and ex vivo human skin explant models. A double-blind, randomized, comparator placebo-controlled study was performed to confirm clinical efficacy. After irradiation with 50 mJ/cm2 of UVB, a UV-induced decrease in adiponectin expression and an increase in inflammatory cytokines in cultured human dermal fibroblasts were prevented by the PTHD-12 treatment test peptide. Mitigation of cellular senescence and senescence-associated secretory phenotype (SASP) expressions induced by UVB (50 mJ/cm2) exposure were also mitigated by the post-treatment of PTHD-12, which was also observed in an ex vivo human skin explant model. The restoration of filaggrin, loricrin, and claudin-1 protein expression in a cultured human skin explant was observed. A clinical study further confirmed that the restoration of UVB-induced skin damage, represented by increased skin redness and trans-epidermal water loss, was accelerated by the use of test peptide PTHD-12-containing products. These results suggest that targeting adiponectin may be a plausible strategy for the development of anti-aging ingredients.

This study introduces a comprehensive approach to enhancing SiNx nanofilters for exosome isolation from bovine milk using the electrophoretic oscillation-assisted tangent-flow ultrafiltration (EPOTF) process. Reinforcing the nanofilter with electro-spun poly(vinylidene fluoride) (PVDF) fibers significantly improved durability under high-pressure conditions, withstanding nearly 2.8 times greater pressures than nonreinforced nanofilters. The PVDF-fiber-coated nanofilters achieved a flow rate of over 70 mL min-1, compared to just 25 mL min-1 for nonreinforced nanofilters. A filter housing system with copper electrodes isolated from the solution flow path further enhanced the electrical stability of the entire system, widening the EPO voltage range while reducing the risk of corrosion and contamination. The PVDF-fiber-coated nanofilter with the electrode in a separated housing efficiently prevented clogging and bioparticle agglomeration, maintaining constant filtration performance across various voltages and duty cycles. Biochemical analyses confirmed the high concentration and structural integrity of exosomes isolated at high flow rates. Long-term tests verified the superior performance of PVDF-coated filters, successfully filtering 3400 mL of milk over 24 h. These results demonstrate the potential of these advances for highly efficient exosome isolation while maintaining the integrity and shape of exosomes, offering promise for the future of exosome isolation research.

African swine fever virus (ASFV) has substantially spread worldwide, resulting in significant economic losses in the swine industry. Despite extensive research, no ASF vaccine has surpassed the effectiveness of live attenuated vaccines. For instance, the live attenuated vaccine ASFV-G-ΔI177L/ΔLVR has demonstrated good efficacy and safety, along with prolonged persistence of ASF antibodies after vaccination. Therefore, we aimed to evaluate its potential for protection against highly virulent homologous ASF viruses based on changes in the farm environment. To this end, we challenged domestic pigs with a virulent field strain of ASFV following intramuscular immunization with ASFV-G-ΔI177L/ΔLVR. We further assessed its genomic stability and long-term antibody persistence in immunized domestic pigs. All vaccinated pigs exhibited high antibody positivity, with higher levels of antibodies observed at the time of challenge. These high ASF vaccine antibodies were maintained for approximately 2 months after vaccination. In addition, no organ or tissue damage was observed in the vaccinated animals. Our findings demonstrate the applicability of this vaccine candidate in the prevention of ASFV infection in the swine industry.

Despite the potential benefits of cannabidiol as a skin-soothing ingredient, its regulatory status hampers its general use in cosmetic products in many countries. To develop an alternative to cannabidiol, fatty acid amide molecules mimicking the chemical structure of endocannabinoids were manufactured using a lipase-catalyzed process. A mixture of fatty acid amides from sunflower oil and 1-amino propan-3-ol was synthesized using an immobilized lipase reaction, and the activation of cannabinoid receptor 1 (CB1R) was measured using a cAMP assay. The anti-inflammatory activity of the endocannabimimetic ingredients was evaluated in cultured human monocytes and ex vivo human skin explant models. A clinical study was conducted to address the skin hydration, skin barrier function, and skin redness, and the ratio of the interleukin-1-receptor antagonist (IL1-RA) to IL-1α in corneocytes, as a marker for skin sensitivity, were also measured. As a result, the activation of CB1R by endocannabimimetic ingredients was observed in cAMP assays, and a reduction in inflammatory responses by human monocytes induced by lipopolysaccharide treatment were also observed. External stress-induced inflammatory responses were reduced in ex vivo human skin explants. Improvements in skin hydration and barrier function were observed in a clinical study. A significant decrease in skin redness and the IL-1RA to IL-1α ratio was also observed. Endocannabimimetic ingredients, as alternatives to cannabidiol, can be used in skin-soothing cosmetics to increase skin hydration, improve skin barrier function, and reduce skin sensitivity.

IntroductionPatients with atopic dermatitis (AD) have impaired barrier function, which decreases skin hydration, weakens their defense against microorganisms, and culminates in increased inflammatory responses. Here, we conducted a clinical trial to evaluate the efficacy of a multi-lamellar emulsion (MLE) containing the pseudoceramide PC-9S and a synthetic sphingosine kinase 1 (SPHK1) activator, Defensamide™, in improving mild-to-moderate atopic dermatitis.MethodsForty patients aged ≥ 2 years were randomized into a combined-therapy group treated with the MLE containing PC-9S and Defensamide™ plus a topical corticosteroid and a topical-corticosteroid-only group. Assessments based on therapeutic methods included the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin dryness, a visual analogue scale (VAS) of itchiness, a VAS of sleep disturbance, patient satisfaction, and the Dermatology Life Quality Index (DLQI).ResultsThirty-eight patients completed this study. In the combined-therapy group, significant improvements in clinical and instrumental measures such as EASI scores, skin hydration, and skin dryness were noted at 4 weeks compared to baseline, but such improvements were not noted in the topical corticosteroid-only group. Subjective assessments of itching and sleep disturbance and DLQI scores also showed significant improvements in the combined-therapy group.ConclusionCombined therapy with the MLE containing Defensamide™ and PC-9S and with topical corticosteroid demonstrated superior clinical outcomes compared with topical corticosteroid monotherapy. Our findings underscore the potential of MLE-containing formulations as effective adjunctive therapies for AD, offering both objective and subjective symptomatic relief and enhancing patients' quality of life.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-024-01254-5.