KPV

Abstract

Oral delivery of peptide therapeutics remains challenging due to gastrointestinal (GI) degradation and poor intestinal absorption. Here, we propose a self-immolative peptide prodrug conjugate (SIPPC) platform for inflammation-targeted oral delivery, integrating a hydrophilic polyethylene glycol segment, a reactive oxygen species (ROS)-responsive hydrophobic self-immolative module, and a hydrolyzable scaffold, which collectively enable spontaneous assembly into micelle-like nanoparticles. Using three anti-inflammatory peptides (KPV, Ac-QAW, and IRW), we demonstrated that the engineered conjugates exhibit remarkable GI stability, efficient mucus penetration, and ROS-responsive release at inflamed sites. In colitis mice, the KPV-based conjugate (proKPV) achieved a 3.8-fold greater colonic accumulation than free KPV, with enhanced efficacy even at a 20-fold lower dose. Beyond therapeutic effects in the colitis model, oral proKPV substantially accumulated in inflamed lungs and exhibited potent anti-inflammatory efficacy in mice with acute lung injury. Ac-QAW and IRW-based conjugates exhibited comparable benefits, underscoring SIPPC as a transformative paradigm for oral peptide therapeutics, offering substantial promise for clinical translation in inflammatory disorders.

Abstract

Inflammatory bowel diseases (IBDs) are chronic disorders affecting the gastrointestinal tract, causing severe inflammation and tissue damage. Current treatments often have adverse effects, underscoring the need for alternatives. This article is a short review of host defense peptides (HDPs), which have emerged as promising candidates for IBDs because of their antimicrobial and immunomodulatory properties. The HDPs cited include cathelicidins [e.g. LL-37-Tα1, lipid transfer protein (LTP), C-L, KR-12], defensins [e.g. human alpha defensin 5 (HD-5), human beta-defensin 2 (hBD2)], cecropins (e.g. CC34), microcins [e.g. microcin J25 (MccJ25)], brevinins (e.g. chensinin-1), proline-rich antimicrobial peptides (PrAMPs) (e.g. abaecin), type V peptides [e.g. vasopressin-neurophysin (VP-NP)], and alpha-melanocyte-stimulating hormone (α-MSH) (e.g. KPV). HDPs have immunoregulatory mechanisms, downregulating the nuclear factor kappa B (NF-κB) pathway, modulating cytokine release, and restoring homeostasis. The data suggest that HDPs have therapeutic potential for IBDs, offering a way to reduce side effects, and we focus on this issue here.

Abstract

Wound healing is a complex and dynamic process that requires the coordination of cellular, molecular, and physiological events to restore tissue integrity. Despite notable advances in treatment strategies, optimizing healing outcomes, particularly in chronic wounds, remains a major challenge. Emerging evidence highlights the therapeutic promise of peptides, especially tripeptides, in accelerating tissue repair through diverse mechanisms. These short peptides regulate key processes such as cell migration, proliferation, and differentiation, while also modulating inflammation, promoting angiogenesis, and facilitating extracellular matrix (ECM) remodeling. This review, covering studies published between 2016 and 2025, explores the role of tripeptides in enhancing wound repair, emphasizing their biological functions, mechanisms of action, and therapeutic applications. Recent findings demonstrate that tripeptides can stimulate fibroblast migration, enhance collagen deposition, and support angiogenesis. In addition, they exhibit antimicrobial and anti-inflammatory properties, making them valuable candidates for both acute and chronic wound management. GHK-based formulations, including nanoparticle conjugates, hydrogels, and clinical derivatives such as TriHex and TriHex 2.0, enhance fibroblast migration, ECM remodeling, collagen and elastin synthesis, and wound closure while providing antimicrobial activity. KdPT mitigates hyperglycemia-induced oxidative stress and restores keratinocyte function, whereas KPV-loaded hydrogels reduce inflammation, promote tissue regeneration, and combat MRSA infections. Additionally, lipotripeptides (DICAMs) inhibit and disrupt bacterial biofilms, and GPE supports neuroprotection and regeneration through ERK and PI3K/Akt signaling activation. Beyond wound repair, this review also discusses comparative physicochemical properties and wound healing applications of tripeptides versus larger peptides, factors influencing their performance, strategies for combination with biomaterial scaffolds, and emerging applications in fields such as cancer and cosmetics. Collectively, tripeptides represent a promising class of multifunctional bioactive molecules in wound care, offering novel avenues for targeted tissue regeneration. Future research should focus on improving their stability, bioavailability, and delivery systems to fully harness their clinical potential in regenerative medicine.

Abstract

NLRP3 functions as a critical intracellular danger sensor for inflammasome activation, playing a crucial role in autoimmune diseases. Vitiligo progression has been linked to NLRP3, yet its specific involvement in melanocytes of vitiligo remains poorly understood. In this study, we demonstrate that NLRP3 expression is significantly upregulated in the melanocytes of vitiligo patients and melanoma-Treg-induced vitiligo mouse model. Genetic knockout of NLRP3 effectively alleviates vitiligo progression in these mice. Our mechanistic investigations reveal that the downregulation of the E3 ligase β-TrCP1 in vitiligo melanocytes decreases K27-linked ubiquitination levels of NLRP3, which in turn weakens its interaction with the autophagy receptor NDP52. This disruption impairs the selective autophagic degradation of NLRP3, leading to hyperactivation of inflammation and pyroptosis in melanocytes, thereby accelerating vitiligo pathogenesis. Notably, melanocyte-specific knockdown of NLRP3 using lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos) carrying Nlrp3 shRNA significantly alleviates vitiligo development. This study elucidates the mechanism by which autophagy dysfunction mediated excessive NLRP3 inflammasome activation in melanocytes contributes to vitiligo pathogenesis, highlighting potential therapeutic strategies targeting these pathways for the treatment of vitiligo and other pigment-related skin diseases. Overview of disrupted NLRP3 autophagic degradation in vitiligo melanocytes. In healthy melanocytes, NLRP3 expression is upregulated when subjected to oxidative stress, along with an increase in the E3 ligase β-TrCP1, which enhances the K27-linked ubiquitination of NLRP3 and further strengthens its binding to the autophagy receptor protein NDP52, thus effectively suppressing the excessive inflammatory response. Whereas in the melanocytes of vitiligo patients, decreased expression of β-TrCP1 leads to downregulation of K27-linked ubiquitination in NLRP3, thus inhibiting its autophagic degradation. The persistent activation of NLRP3 in vitiligo melanocytes promotes the cleavage of pro-IL-1β and GSDMD. GSDMD-N subsequently forms pores on the cell membrane, which causes the release of IL-1β and results in melanocyte pyroptosis. In our study, we utilize KPV-Lipos with Nlrp3 shRNA to precisely knockdown NLRP3 expression in melanocytes and effectively alleviate vitiligo development, which provide a potentially promising strategy for the treatment of vitiligo. MC, melanocytes.

Abstract

This study compared the efficacy and safety of two highly purified (HP) human menopausal gonadotropin (hMG) preparations, Gynogen HP and Menopur, in women undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF). A multicenter, randomized, active-controlled noninferiority comparative study was conducted between 2019 and 2021. Women aged 21-40 undergoing COS for their first or second IVF cycle, with or without intracytoplasmic sperm injection, were randomized to receive either Gynogen HP or Menopur. The primary endpoint was to determine the total number of oocytes retrieved. Key secondary endpoints included total hMG dose, days of hMG stimulation, fertilization rate, implantation rate, clinical pregnancy rate and safety. A total of 150 patients were randomized into two groups: 77 received Gynogen HP and 73 received Menopur COS. The primary endpoint, the number of oocytes retrieved (mean ± standard deviation (SD)), was similar between the Gynogen HP (6.3 ± 3.39) and Menopur (6.7 ± 4.52) groups. The least square (LS) mean values were 5.9 for the Gynogen HP and 6.3 for Menopur, with an LS mean difference of - 0.4 (95% CI: -1.83, 1.07; P = 0.6067), indicating that noninferiority as the lower limit of the 95% CI was above the non-inferiority threshold of -2.0. Secondary efficacy endpoints and safety analysis showed no significant differences between groups. Gynogen HP is noninferior and therapeutically equivalent to Menopur in terms of the number of oocytes retrieval, with a comparable safety profile. These results support the use of Gynogen HP for COS in women undergoing IVF as a part of assisted reproduction techniques.

Abstract

Airborne particulate matter (PM) poses a major environmental risk that impairs skin health by triggering oxidative stress, inflammation, and cell death. In this study, we investigated the protective effects of Lysine-Proline-Valine (KPV)-an endogenous peptide derived from α-melanocyte-stimulating hormone-against oxidative damage and inflammation induced by fine PM (PM10) in human HaCaT keratinocytes. Our results show that PM10 markedly suppresses HaCaT cell proliferation via cytotoxic effects and induces a pro-inflammatory response by increasing IL-1β secretion. Notably, treatment with 50 μg/mL of KPV restored cell viability and reduced IL-1β secretion disrupted by PM10 exposure. To counteract PM10-induced cell death, KPV inhibited reactive oxygen species (ROS) production, which is responsible for activating extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Additionally, KPV decreased the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and IL-1β through suppression of the redox-sensitive transcription factor nuclear, factor-kappa B in PM10-treated HaCaT cells. Against PM10-induced inflammation, KPV effectively blocked ROS-mediated caspase-1 activation, reducing IL-1β secretion. In a three-dimensional (3D) skin model, KPV treatment effectively attenuated the inflammatory cell death induced by PM10. Collectively, these findings suggest that KPV protects keratinocytes by mitigating PM10-induced pyroptosis and holds potential as a therapeutic agent for preventing environmental pollutant-related skin damage, with promising applications in functional cosmetics and skin-protective treatments.