Revitalizing Skin Repair: Unveiling the Healing Power of Livisin, a Natural Peptide Calcium Mimetic.

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida. Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect. Our findings revealed livisin effectively stimulated the migration of keratinocytes, with the underlying mechanisms involved the activation of CaSR as a peptide calcium mimetic. This activation resulted in the stimulation of the CaSR/E-cadherin/EGFR/ERK signaling pathways. Moreover, the therapeutic effects of livisin were partially reduced by blocking the CaSR/E-cadherin/EGFR/ERK signaling pathway. The interaction between livisin and CaSR was further investigated by molecular docking. Additionally, studies using a mouse full-thickness wound model demonstrated livisin could accelerate skin wound healing by promoting re-epithelialization and collagen deposition. In conclusion, our study provides experimental evidence supporting the use of livisin in skin wound healing, highlighting its potential as an effective therapeutic option.

Overexpression of miR-3653 is Associated with HPV Infection and Serves as a Biomarker in Patients with Cervical Cancer.

Background: Human papillomavirus (HPV) is a major cause of cervical cancer (CC) occurrence. This study aimed to explore whether abnormal microRNA (miR)-3653 is associated with HPV infection and to investigate the clinical value of miR-3653 in the diagnosis and prognosis of CC. Methods: Tumor tissues and adjacent non-cancerous tissues were collected from 136 patients with CC. Cervical tissues from 101 patients with uterine fibroids were collected as controls. The expression of miR-3653 was measured by quantitative real-time PCR. The ability of miR-3653 to discriminate between HPV positive (HPV+) and HPV negative (HPV-) CC patients, and to discriminate patients from controls was assessed by receiver operating characteristic analysis. Kaplan-Meier curves and Log rank tests were used to evaluate the relationship of miR-3653 with survival of CC patient. Whether miR-3653 could function as a prognostic indicator was evaluated by univariate and multivariate Cox analyses. Results: miR-3653, highly expressed in CC tissues, was associated with HPV infection, tumor diameter, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis in CC patients. Additionally, miR-3653 was increased in HPV+ controls, CC patients and CC cells. Moreover, miR-3653 could screen HPV+ controls, screen HPV+ patients and screen CC patients. Furthermore, miR-3653 was associated with the survival of CC patients (log-rank P < 0.001) and could serve as an independent prognostic indicator for CC patients. Conclusion: miR-3653, increased in CC, is related to HPV infection and may serve as a diagnostic and prognostic biomarker for CC patients.

Engineering and Structural Insights of a Novel BBI-like Protease Inhibitor Livisin from the Frog Skin Secretion.

The Bowman-Birk protease inhibitor (BBI) family is a prototype group found mainly in plants, particularly grasses and legumes, which have been subjected to decades of study. Recently, the discovery of attenuated peptides containing the canonical Bowman-Birk protease inhibitory motif has been detected in the skin secretions of amphibians, mainly from Ranidae family members. The roles of these peptides in amphibian defense have been proposed to work cooperatively with antimicrobial peptides and reduce peptide degradation. A novel trypsin inhibitory peptide, named livisin, was found in the skin secretion of the green cascade frog, Odorrana livida. The cDNA encoding the precursor of livisin was cloned, and the predicted mature peptide was characterized. The mature peptide was found to act as a potent inhibitor against several serine proteases. A comparative activity study among the native peptide and its engineered analogs was performed, and the influence of the P1 and P2' positions, as well as the C-terminal amidation on the structure-activity relationship for livisin, was illustrated. The findings demonstrated that livisin might serve as a potential drug discovery/development tool.

Exosomal microRNA-588 from M2 polarized macrophages contributes to cisplatin resistance of gastric cancer cells.

BACKGROUND: Gastric cancer is a prevalent malignant cancer with a high incidence and significantly affects the health of modern people globally. Cisplatin (DDP) is one of the most common and effective chemotherapies for patients with gastric cancer, but DDP resistance remains a severe clinical challenge. AIM: To explore the function of M2 polarized macrophages-derived exosomal microRNA (miR)-588 in the modulation of DDP resistance of gastric cancer cells. METHODS: M2 polarized macrophages were isolated and identified by specific markers using flow cytometry analysis. The exosomes from M2 macrophages were identified by transmission electron microscopy and related markers. The uptake of the PKH67-labelled M2 macrophages-derived exosomes was detected in SGC7901 cells. The function and mechanism of exosomal miR-588 from M2 macrophages in the modulation of DDP resistance of gastric cancer cells was analyzed by CCK-8 assay, apoptosis analysis, colony formation assay, Western blot analysis, qPCR analysis, and luciferase reporter assay in SGC7901 and SGC7901/DDP cells, and by tumorigenicity analysis in nude mice. RESULTS: M2 polarized macrophages were isolated from mouse bone marrow stimulated with interleukin (IL)-13 and IL-4. Co-cultivation of gastric cancer cells with M2 polarized macrophages promoted DDP resistance. M2 polarized macrophages-derived exosomes could transfer in gastric cancer cells to enhance DDP resistance. Exosomal miR-588 from M2 macrophages contributed to DDP resistance of gastric cancer cells. miR-588 promoted DDP-resistant gastric cancer cell growth in vivo. miR-588 was able to target cylindromatosis (CYLD) in gastric cancer cells. The depletion of CYLD reversed miR-588 inhibition-regulated cell proliferation and apoptosis of gastric cancer cells exposed to DDP. CONCLUSION: In conclusion, we uncovered that exosomal miR-588 from M2 macrophages contributes to DDP resistance of gastric cancer cells by partly targeting CYLD. miR-588 may be applied as a potential therapeutic target for the treatment of gastric cancer.

LINC01420 Serves as a Novel Prognostic Biomarker and Promotes Cell Proliferation, Migration, and Invasion by Suppressing miR-149-5p in Gastric Cancer.

Gastric cancer (GCa) is the most common human health-threatening malignancy, and its high incidence and poor prognosis. Previous studies have shown that long non-coding RNAs (lncRNAs) are aberrantly expressed in a variety of tumors and are involved in tumor progression. This study aimed to investigate the regulatory role of LINC01420 in GCa cell proliferation migration and invasion, and search for new prognostic biomarkers for GCa. The expression levels of LINC01420 and miR-149-5p in GCa cells were analyzed with reverse transcription-quantitative PCR. Kaplan Meier survival analysis and Cox regression were used to analyze the prognostic value. Luciferase reporter assay was used to detect the interaction between LINC01420 and miR-149-5p. The effects of LINC01420/miR-149-5p axis on GCa cell proliferation, migration and invasion were assessed by CCK-8 and Transwell assays. LINC01420 expression levels were significantly increased in tissues and cell lines of GCa. Kaplan Meier curve results showed that overexpression of LINC01420 predicted poor prognosis. Silencing LINC01420 could inhibit the proliferation migration and invasion of GCa cells. The luciferase reporter assay results indicated that miR-149-5p might be a target of LINC01420 and mediate the effects of LINC01420 on GCa cell proliferation and migration and invasion. In conclusion, this study demonstrates an important regulatory role of the LINC01420/miR-149-5p axis in GCa progression and it provides a novel and significant biomarker for GCa treatment and prognosis.

Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation.

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair.

Alpha- and gamma-mangostins exhibit anti-acne activities via multiple mechanisms.

Objective: Acne is a chronic skin disease that involves four key pathogenic factors: excess sebum production, ductal epidermal hyperproliferation, Propionibacterium acnes (P. acnes) colonization, and skin inflammation. Mangostins are well-known for their anti-bacterial and anti-inflammatory effects, suggesting that mangostins may have therapeutic potential for acne. The present study aimed to explore the anti-acne effects of mangostins from the perspective of multiple pathogenic mechanisms of acne. Methods: The effects of α- and γ-mangostins on the growth of P. acnes and lipase activity were analyzed. Their effects on P. acnes-induced keratinocyte proliferation were examined by CCK-8. The expression of inflammatory genes and activation of NF-κB and MAPK signaling pathways were detected by quantitative real-time PCR and western blotting, respectively. Results: Alpha- and γ-mangostins not only inhibited the growth of P. acnes, but also reduced the proliferation of keratinocytes induced by heat-killed P. acnes. Furthermore, α- and γ-mangostins were able to suppress P. acnes-induced expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in keratinocytes by inhibiting the activation of NF-κB and MAPK signaling pathways. Discussion and conclusions: Mangostins appeared to possess multiple anti-acne activities, including the inhibition of P. acnes growth, regulation of keratinocytes proliferation, and attenuation of skin inflammatory reaction. Hence, mangostins might be developed into a potential therapeutic agent for the treatment of acne.