Search Results (24,413)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, which presents with painful nodules, abscesses and sinus tracts. Patients suffer from pain, drainage and worsening of mental health and quality of life. Treatment is often difficult. HS is typically associated with obesity and metabolic syndrome; thus, antidiabetics, especially GLP-1 agonists, present a potential therapy option. The aim of this review was to analyze the effects of GLP-1 agonists on patients with HS, including on their cardiovascular risk and quality of life. Methods: A literature search was conducted on Embase and PubMed, yielding 300 papers, of which 10 were used for this review. Results: HS patients using GLP-1 agonists showed improved clinical course with less pain and suppuration. Further, patients’ quality of life and mental health improved and their cardiovascular risk was reduced. Inflammatory parameters showed no significant changes. Patients receiving a higher drug dose of GLP-1 agonists were more likely to show clinical improvement. A reduction in weight or BMI did not correlate with improvements in Hurley stage, pain or depression. Hence, HS patients could be treated with GLP-1 agonists. Conclusions: Therefore, whether patients’ improvement is due to weight loss, or other mechanisms, i.e., GLP-1 agonists’ anti-inflammatory properties, remains to be determined in further studies. Full article

Background/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p < 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p < 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p < 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses. Full article

Currently, GLP-1RAs are peptide drugs, typically administered by injection due to insufficient absorption, and only one GLP-1RA, semaglutide, is available as an orally administered drug. To overcome the absorption challenges of oral peptides, this drug product contains the absorption enhancer SNAC. As the tablet is eroded in the stomach, SNAC neutralizes the acidic gastric environment, thereby protecting the semaglutide from enzymatic degradation. Then, SNAC fluidizes the stomach lipidic membrane to increase semaglutide transcellular permeability across the gastric epithelium. It is necessary to realize that the use of such a unique drug product, that relies solely on the stomach for absorption, is expected to be affected by the extreme gastric anatomy/physiology changes post-MBS. Hence, we analyzed the key mechanisms that may affect the bioavailability of oral semaglutide post-MBS. Several mechanisms appear to potentially reduce oral semaglutide absorption post-MBS, including decreased inner gastric surface area, decreased gastric contractility, and faster gastric emptying. Hence, the effectiveness of the complex formulation, that relies solely on the stomach for the SNAC activity and semaglutide absorption, may be severely hampered post-MBS; clinicians should be aware of the potential malabsorption of oral GLP-1RA post-MBS, and preferably consider subcutaneous therapy until specific pharmacokinetic/clinical data are available. Full article

Antimicrobial peptides (AMPs) have re-emerged as promising anti-infective agents, particularly against multidrug-resistant bacteria; however, their therapeutic development remains constrained by proteolytic degradation, host cell toxicity, and rapid systemic clearance. Rather than focusing solely on sequence discovery, recent efforts have shifted toward structural and supramolecular modification strategies aimed at improving stability, selectivity, and pharmacological performance. This review critically analyzes intramolecular modifications—including phosphorylation, glycosylation, acetylation, methylation, and backbone cyclization—that modulate peptide conformation and resistance to enzymatic degradation. In parallel, extramolecular approaches such as PEGylation, lipidation, and conjugation to antibiotics, siderophores, or antibodies are examined in the context of enhanced targeting and prolonged bioavailability. Particular emphasis is placed on localized delivery systems, including hydrogels, polymeric films, and nanofibrous scaffolds, which enable spatially controlled administration and mitigate systemic exposure. By integrating evidence from ex vivo and in vivo infection models, this work delineates the translational potential and remaining bottlenecks of chemically engineered AMP platforms for skin and soft tissue infections. Full article

The novel strain TD-94 with higher ammonia degradation efficiency was isolated from the activated sludge of SINOPEC and belongs to the family of Alcaligenes faecalis (A. faecalis) based on its 16sRNA sequence and physio-biochemical characteristics. It is a Gram-negative, highly heterotrophic aerobic ammoxidation bacterium that is capable of effectively treating ammonia-nitrogen wastewater. The genome size of strain TD-94 was 4,361,949 bp with a GC content of 56.47% and a total of 4101 genes, which accounted for 89.54% of the total genome length. Analysis of various databases showed that 649 genes were annotated in the GO database; a total of 2712, 4095 and 12 genes were annotated in the KEGG, COG, and ADRB databases, respectively; and there were 24 types of cytochrome P450, 477 signal peptides, and eight secondary metabolites. All these data provide a theoretical basis for the mechanism of action of the strain TD-94. Based on the whole-genome sequencing results, functional genes related to nitrogen metabolism in A. faecalis TD-94, including aerobic ammonia oxidation (AOB), hydroxylamine oxidoreductase (HAO), and pyruvic oxime dioxygenase (POD) were identified. Through growth curve analysis and the identification of functional genes, the nitrogen metabolism pathway of A. faecalis TD-94 was proposed, demonstrating that the strain TD-94 has good denitrification capabilities and a novel degradative pathway. Full article

Elaeagnus mollis oilseed (EMO) meal is a protein-rich by-product that may serve as a novel source of food-derived α-glucosidase inhibitory peptides. This study aimed to obtain EMO peptide fractions with enhanced α-glucosidase inhibition and to clarify the activity, stability and mechanism of the most active fraction. Fourteen proteases were compared, and 3.350 acidic protease was selected to establish an optimized hydrolysis process. The resulting EMO hydrolysate showed an IC₅₀ of 9.11 mg/mL against α-glucosidase and no detectable cytotoxicity towards HEK-293T cells at 0.1–12.0 mg/mL. Ultrafiltration yielded four fractions, among which the 3–10 kDa fraction exhibited the highest inhibition and maintained substantial activity under acidic pH (2–6), −20–50 °C, NaCl ≤ 5% and simulated gastrointestinal digestion. Kinetic analysis indicated mixed-type inhibition, while fluorescence, circular dichroism and molecular docking suggested that peptides in this fraction bind near the catalytic site of α-glucosidase and induce local conformational changes. These findings support EMO-derived 3–10 kDa peptides as stable, non-cytotoxic α-glucosidase inhibitors with potential as functional ingredients for dietary management of type 2 diabetes. Full article

Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg/kg/day) and 17 β-estradiol (EST, 0.5 mg/kg/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) α, ERβ, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ERα and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ERβ antagonist, PHTPP (200 μg/kg/day), was used to clarify the role of ERβ. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg/mL), EMO-treated (2.57 pg/mL) and EST-treated OVX rats (2.64 pg/mL), were higher than that of OVX rats (1.03 pg/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ERβ in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ERβ in colon and cerebral ERα level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ERβ, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Erβ-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals. Full article

Traditional cancer therapies such as surgery, chemotherapy, and antibody-based treatments often face significant barriers, including systemic toxicity, a lack of selectivity, and the emergence of drug resistance. These issues demand innovative and targeted solutions. Peptide-based therapeutics have gained prominence for their ability to disrupt cancer pathways and facilitate targeted drug delivery, offering structural flexibility, precise targeting, and low immunogenicity with minimal effects on healthy tissues. Concurrently, aptamers, which are structured nucleic acid molecules capable of high-affinity molecular recognition, are being developed as both direct therapeutic agents and as targeting ligands for the improved delivery of anticancer drugs. Combining peptide and aptamer technologies with engineered exosomes provides a modular drug delivery system that enhances targeting specificity, stability, and the ability to cross complex biological barriers such as the blood–brain barrier. The emergence of peptide-decorated, aptamer-decorated exosomes represents a new frontier in precision oncology, promising highly selective, biocompatible, and tunable cancer therapies. Further advances are required to overcome challenges in pharmacokinetics, scalable production, and regulatory compliance, but ongoing bioengineering and nanotechnology research continues to accelerate the translation of these innovative strategies toward improved cancer diagnostics and treatment outcomes. This review discusses the synergistic integration of peptides and aptamers with exosome-based delivery systems, highlighting their current applications and future possibilities. Full article

The skin serves as the first line barrier of innate immunity, protecting the body from external influences and maintaining its homeostasis. Exogenous and endogenous stress factors alter the structure and functional properties of the skin. The search for compounds capable of counteracting these processes has allowed the identification of peptides as promising ingredients of products for medicinal and cosmetic applications. This review comprehensively examines the mechanisms of action and dermatological applications of two distinct classes of natural products—endogenous human peptides and those derived from marine organisms. Human peptides exhibit numerous biological functions, including antimicrobial and immunomodulatory ones, as well as promoting antioxidant protection and wound healing. Microbiome-associated peptides are an underestimated but powerful regulator of skin aging through immunomodulation, inflammation control, barrier function maintenance, and selection of the proper microbial community. Peptides from marine organisms exhibit significant structural diversity and a broad spectrum of biological activity, including regenerative effects and effects on antibiotic-resistant microorganisms. This review summarizes current data obtained from in vitro, ex vivo, and clinical studies demonstrating a broad potential of peptides for maintaining skin health. Both peptide classes represent powerful, targeted strategies for innovative dermatological interventions aimed at promoting skin rejuvenation, protection, and overall homeostasis. Full article

This study evaluated the iron-chelating capacity (ICC) of Lupinus mutabilis protein hydrolysate (LMPH) and its peptide fractions obtained through ultrafiltration and purification by immobilized metal ion affinity chromatography (IMAC) and gel filtration chromatography (GFC). Peptides were identified by LC-MS/MS, and their interactions with Fe²⁺ were analysed using molecular docking. LMPH was produced by enzymatic hydrolysis with Alcalase and subsequently subjected to ultrafiltration to concentrate peptides smaller than 2 kDa. This fraction exhibited higher ICC (35.1 mg Fe²⁺·g⁻¹) than the hydrolysate (22.75 mg Fe²⁺·g⁻¹). Sequential purification by IMAC and GFC yielded peptide fractions with enhanced ICC values (45.20 and 13.51 mg Fe²⁺·g⁻¹). A total of 176 peptides were identified by de novo LC-MS/MS sequencing, from which nine were selected based on favourable structure–ICC relationships and absence of predicted toxicity. Molecular docking analysis suggested spatial proximity between Fe²⁺ and the selected peptides. Although stable multi-site binding was not predicted under the applied computational model, the results support the potential of these sequences to interact with Fe²⁺. These findings provide molecular and chemical insights supporting the iron-binding potential of LMPH-derived peptides and highlight their future potential as functional ingredients for preventing and managing iron deficiency. Full article

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists into porous silicon microparticles. While effective in models with lower disease burden, its efficacy against advanced colorectal cancer (CRC) was less promising due to the accumulation of myeloid-derived suppressor cells (MDSCs) in TMEs. In this study, we investigated whether µGCVax-based immunotherapy in advanced CRCs could be potentiated via regulating MDSCs to reprogram the TME. In an advanced CT26 murine CRC model, we assessed µGCVax in combination with oxaliplatin, a standard CRC chemotherapeutic with established immunomodulatory effects. We demonstrated that oxaliplatin was preferentially taken up by monocytic MDSCs (M-MDSCs) and effectively reduced their abundance in the bone marrow, blood, spleen, and tumor. Relief of this immunosuppressive TME increased intratumoral infiltration of antigen-specific CD8⁺ T cells. Ultimately, the combination of oxaliplatin with µGCVax induced robust regression of established CRC tumors. These findings highlight that oxaliplatin synergizes with µGCVax by overcoming MDSC-mediated immunosuppression and enhancing antitumor immunity, representing a promising chemo-immunotherapy strategy for advanced CRC. Full article

Intestinal infections caused by Salmonella enterica serovar Typhi (S. Typhi) remain a global health concern, making preventive strategies and diagnostic tools essential. This study aimed to identify mimotope peptides of the Vi antigen using phage display and assess their recognition by rabbit and 46 human sera, as well as their potential for diagnosis and immunogen design. Rabbits were immunized with the Vi antigen (AgVi) from S. Typhi ATCC 6539, and sera-derived IgG was used for phage biopanning. DNA sequences from selected phagotopes were synthesized as Salmonella mimotope peptides (SMPs), either linear or KLH-conjugated. Their reactivity was tested with ELISAs against AgVi and SMPs, using both rabbit sera and 46 human serum samples. Ten phagotopes were identified, with a consensus motif (D/G–A/V–x–P–x–x–G–x–x–x–x–x), suggesting α-helix structures. Immunization with KLH-conjugated peptides generated specific antibodies, particularly SMPVi/5 and SMPVi/10, which recognized AgVi and their respective peptides. Competitive inhibition assays confirmed that SMPVi/5 reduced the anti-AgVi binding in a dose-dependent manner. In human sera, AgVi recognition occurred in 52% of samples, while SMPVi/5 and SMPVi/10 were recognized in 45%. Overall, SMPVi/5 demonstrated immunogenicity and functional mimicry, supporting its use as a synthetic reagent for serological assays and as a candidate for immunogen design. Full article

Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. Full article

The differential effects of thermolysin and four commercial proteases on soy protein isolate (SPI) were investigated under enzyme-specific hydrolysis conditions to comparatively assess the structural, functional, and instrumental taste differences among the resulting hydrolysates. Under the enzyme-specific hydrolysis conditions, among the enzymes tested, thermolysin induced substantial fragmentation of SPI, with products mainly distributed below 25 kDa and accompanied by marked conformational rearrangement. Thermolysin-treated SPI exhibited the highest total free amino acid content (14.805 mg/g), especially Tyr and Phe, together with the highest solubility (80.52 ± 4.40%), the highest emulsifying activity index (36.11 m²/g), and the strongest antioxidant capacities in 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH), and hydroxyl radical scavenging assays. Electronic tongue analysis further showed that enzymatic hydrolysis generally enhanced umami and richness while reducing astringency relative to native SPI. Notably, SPI-Ther exhibited the most pronounced instrumental taste reconfiguration, characterized by increased umami (9.57) and richness (7.57), but also the highest bitterness (4.75) and aftertaste-B (3.46), indicating a distinct functionality–taste trade-off rather than simple debittering. In contrast, papain generated the highest umami response, whereas trypsin produced the mildest taste profile with the lowest bitterness. Overall, under the enzyme-specific hydrolysis conditions used in this study, thermolysin yielded the most pronounced improvement in the measured functional indices of SPI. However, these findings should be interpreted as a comparative, condition-specific assessment rather than a direct ranking of intrinsic protease specificity, and additional peptide characterization and sensory validation would be needed before taste-oriented applications can be recommended. Full article

This exploratory study evaluated plasma atrial natriuretic peptide (ANP) concentrations in four species of captive cetaceans and their associations with physiological and environmental factors, including husbandry conditions, diet, and management practices. Twenty-six individuals were voluntarily sampled, and blood samples were analyzed using a human-based chemiluminescent immunoassay. Transthoracic echocardiography was also attempted in several individuals but was technically challenging due to interference from the lung tissue and the sternum. The mean plasma ANP concentration in clinically healthy young animals was 44.12 ± 14.62 pg/mL, with no significant differences observed according to age, sex, species, or the presence of mild chronic disease. ANP was detectable across all species using human reagents. In addition, brain natriuretic peptide (BNP), a commonly used cardiac biomarker in humans and other animals, was evaluated for comparison; however, BNP concentrations remained below the detection threshold, possibly reflecting species-specific differences. Importantly, ANP concentrations were not evaluated in animals with clinically significant disease, and therefore the relevance of these findings to diseased populations remains unknown. These results demonstrate that plasma ANP can be measured using existing clinical assays and provide preliminary baseline data for multiple cetacean species. Overall, ANP may offer preliminary insights into physiological variation in managed cetaceans; however, its utility as a biomarker for cardiovascular or systemic health assessment remains to be determined. Full article