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Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management.
Liver Int
Anna-Elisabeth Minder, Louisa G Kluijver, Jasmin Barman-Aksözen +2 more
The erythropoietic protoporphyrias consist of three ultra-rare genetic disorders of the erythroid heme biosynthesis, including erythropoietic protoporphyria (EPP1), X-linked protoporphyria (XLEPP) and CLPX-protoporphyria (EPP2), which all lead to the accumulation of protoporphyrin IX (PPIX) in erythrocytes. Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light. The quantification of PPIX in erythrocytes with a metal-free PPIX ≥3 times the upper limit of normal confirms the diagnosis. Protoporphyria-related complications include liver failure, gallstones, mild anaemia and vitamin D deficiency with reduced bone mineral density. The management is focused on preventing phototoxic reactions and treating the complications. Vitamin D should be supplemented, and DEXA scans in adults should be considered. In EPP1, even in cases of biochemically determined iron deficiency, supplementation of iron may stimulate PPIX production, resulting in an increase in photosensitivity and the risk of cholestatic liver disease. However, for patients with XLEPP, iron supplementation can reduce PPIX levels, phototoxicity and liver damage. Because of its rarity, there is little data on the management of EPP-related liver disease. As a first measure, any hepatotoxins should be eliminated. Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life.
Collagen Peptide Supplementation during Training Does Not Further Increase Connective Tissue Protein Synthesis Rates.
Med Sci Sports Exerc
Marius Kirmse, Theo M Lottmann, Nicola R Volk +4 more
Protein supplementation increases postexercise muscle protein synthesis rates and, as such, supports exercise-induced muscle conditioning. Collagen protein has been suggested as the preferred protein source to stimulate muscle connective protein synthesis rates during recovery from exercise. Here we assessed the effects of hydrolyzed collagen peptide supplementation on both myofibrillar as well as muscle connective protein synthesis rates during 1 wk of strenuous resistance exercise training.
Novel Applications of CE-ICP-MS/MS: Monitoring of Antiaging GHK-Cu Cosmetic Component Encapsulation in Liposomes.
Electrophoresis
Joanna Zajda, Emilia Wadych, Karolina Ogórek +2 more
The hyphenation of the separation technique with the high-sensitive mass spectrometry detection is one of the driving forces of modern analysis enabling measurements in complex matrices. In particular, capillary electrophoresis coupled to inductively coupled plasma tandem mass spectrometry allows for speciation analysis of selected analytes with a superior resolution. The mild, physiological-friendly conditions of this separation technique offer the unique advantage of analyzing chemical entities in their intact form, which has been successfully exploited in various areas. Herein, we report the pioneering application of such a hyphenated technique in the cosmetic field to investigate the encapsulation of copper tripeptide complex (GHK-Cu) in liposomes. By monitoring copper and phosphorus signals, the formation of liposomes via a simple ethanol injection method was confirmed, and the concentration of GHK-Cu in the liposomes was assessed. The application of coupling of capillary electrophoresis with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) in cosmetic studies could lead to the development of diverse liposomal formulations with preferential properties and expand their accessibility.
Impact of chronic intranasal oxytocin administration on face expression processing in autistic children: a randomized controlled trial using fMRI.
Mol Autism
Matthijs Moerkerke, Nicky Daniels, Stephanie Van der Donck +6 more
Difficulties with (non-verbal) social communication, including facial expression processing, constitute a hallmark of autism. Intranasal administration of oxytocin has been considered a potential therapeutic option for improving social difficulties in autism, either by enhancing the salience of social cues or by reducing the social stress and anxiety experienced in social encounters.
Palmitoyl copper peptide and acetyl tyrosine complex enhances melanin production in both A375 and B16 cell lines.
Biochem Biophys Res Commun
Minhua Hong, Yingyue Gui, Jiayao Xu +8 more
Copper peptide, a low molecular weight peptide composed of glycyl-L-histidyl-l-lysine-copper, possesses anti-aging, anti-inflammatory, and wound healing properties. In this study, we investigated the effects of a combination agent CP-AcT, composed of palmitoyl copper peptide (pal-GHK-Cu) and acetyl tyrosine (N-Acetyl-l-tyrosine), on melanin production in the human malignant melanoma cell line A375 and the mouse melanoma cell line B16. Firstly, the cytotoxicity of CP-AcT at various concentrations (0-8 μg/mL) on HaCat, HFF, A375, and B16 cells was evaluated. Subsequently, the effects of the CP-AcT on tyrosinase activity both extracellular and intracellularly, as well as on melanin production in two melanoma cell lines, were evaluated under conditions that did not compromise cell viability. Additionally, quantitative gene plex (QGP) combined with branched DNA (bDNA) technology was used to analyze the effects of CP-AcT on the expression of melanin-related genes in A375 cells, with a focus on five specific genes. Finally, the effects of the CP-AcT on the expression of three proteins involved in the biosynthesis pathway of melanin: tyrosinase (TYR), dopachrome tautomerase (DCT), and endothelin 3 (EDN3) were analyzed. The results indicate that the complex CP-AcT effectively promotes melanin production in both types of melanoma cells.
Exploring the Anxiolytic Potential of NPY by a Dipeptidyl Peptidase-IV Inhibitor in an Animal Model of PTSD.
Int J Neuropsychopharmacol
Matan Dahan, Joseph Zohar, Doron Todder +2 more
The regulatory neuropeptide Y (NPY) is implicated in anxiety and post-traumatic stress disorder (PTSD)-related behaviors. NPY exerts its effects through 5 receptor subtypes, with Y1 and Y2 receptors being predominantly expressed in the rat brain. Activation of Y1 by full-length NPY1-36 induces anxiolytic effects, whereas Y2 binds truncated peptides, eliciting region-specific anxiogenic responses. Dipeptidyl peptidase-IV (DPP-IV) cleaves NPY, thereby modulating its functionality. Sitagliptin, a DPP-IV inhibitor (DPP-IV-I), inhibits the degradation of various vasoactive peptides, including cerebral NPY. As such, the therapeutic potential of DPP-IV-I following a traumatic event remains inconclusive. We assessed the effects of a highly selective DPP-IV-I, administered either shortly after the stressor or intermittently over 3 days, on behavioral outcomes using the predator scent stress (PSS) model of PTSD.
Mineralocorticoid receptor activates postnatal adiposity in zebrafish lacking proopiomelanocortin.
J Cell Physiol
Jithine J Rajeswari, Erin Faught, Helio Santos +1 more
The proopiomelanocortin (Pomc)-derived peptides, including adrenocorticotropic hormone and α-melanocyte stimulating hormone (α-Msh), play both a central and a peripheral role in modulating the stress response. The central role is predominantly associated with nutrient homeostasis, while peripherally they play an important role in the synthesis of glucocorticoids (GCs) in response to stress. Pomc mutations are a major risk factor in the development of early-onset childhood obesity in humans. This is attributed primarily to their central effects on melanocortin receptor dysfunction leading to hyperphagia and reduced energy expenditure, while the peripheral mechanism contributing to obesity has largely been unexplored. Here, we tested the hypothesis that Pomc mutation-mediated adrenal insufficiency and the associated changes in GC signaling contribute to postnatal adiposity using zebrafish as a model. We generated a ubiquitous Pomc knockout zebrafish that mimicked the mammalian mutant phenotype of adrenal insufficiency and enhanced adiposity. The loss of Pomc inhibited stress-induced cortisol production and reprogrammed GC signaling by reducing glucocorticoid receptor responsiveness, whereas the mineralocorticoid receptor (Mr) signaling was enhanced. Larval feeding led to enhanced growth and adipogenesis in the Pomc mutants, and this was inhibited by eplerenone, an Mr antagonist. Altogether, our results underscore a key role for Mr signaling in early developmental adipogenesis and a possible target for therapeutic intervention for early-onset childhood obesity due to Pomc dysfunction.
Self-assembled Arginine-Glycine-Aspartic Acid Mimic Peptide Hydrogels as Multifunctional Biomaterials for Wound Healing.
ACS Appl Mater Interfaces
Zeba Ahmadi, Diksha Jha, Santosh Yadav +5 more
Clinical management of nonhealing ulcers requires advanced materials that can enhance wound closure rates without relying on the release of drugs or other growth factors to obviate systemic deleterious side effects. In our previous work, we synthesized an integrin-binding cell adhesive MNH2 {Fmoc-FFβAR(K)βA-NH2 consisting of an RGD mimic, [R(K)], with an amide terminus}, MOH {Fmoc-FFβAR(K)βA-OH consisting of an RGD mimic, [R(K)], with acid terminus}, and MR (Fmoc-FFβARGDβA-NH2 consisting of an RGD peptide, reference) with multifunctional activity. Here, we reported the synthesis, characterization, and performance of a reversed derivative, R-MNH2 (Fmoc-FFβA(K)RβA-NH2 consisting of an RGD mimic, [K(R)], with an amide terminus) of an antimicrobial cell adhesive peptide, MNH2. Both peptides (MNH2 and R-MNH2) were found to interact with αvβ3 integrin, as shown by docking studies; however, they differed in cell adhesive properties, hydrogel formation, and antimicrobial efficacy. Later, the wound healing ability of a series of RGD/RGD peptide mimics (MR, R-MNH2, MNH2, and MOH) was studied in a methicillin-resistant Staphylococcus aureus (MRSA)-infected Balb/c mouse model. All studied peptides showed cell adhesion and wound healing properties; however, only the amide-terminal RGD peptide mimic, MNH2, and its reversed derivative, R-MNH2, showed antimicrobial activity in both in vitro and in vivo studies. Of these, MNH2 showed the highest integrin-mediated spreading, migration, and proliferation of dermal cells in vitro as well as in vivo. Therefore, the MNH2 peptide mimic represents a paradigm shift in the development of dermoconductive strategies to treat chronic wounds.
Premature cognitive decline in a mouse model of tuberous sclerosis.
Aging Cell
J Krummeich, L Nardi, C Caliendo +13 more
Little is known about the influence of (impaired) neurodevelopment on cognitive aging. We here used a mouse model for tuberous sclerosis (TS) carrying a heterozygous deletion of the Tsc2 gene. Loss of Tsc2 function leads to mTOR hyperactivity in mice and patients. In a longitudinal behavioral analysis, we found premature decline of hippocampus-based cognitive functions together with a significant reduction of immediate early gene (IEG) expression. While we did not detect any morphological changes of hippocampal projections and synaptic contacts, molecular markers of neurodegeneration were increased and the mTOR signaling cascade was downregulated in hippocampal synaptosomes. Injection of IGF2, a molecule that induces mTOR signaling, could fully rescue cognitive impairment and IEG expression in aging Tsc2+/- animals. This data suggests that TS is an exhausting disease that causes erosion of the mTOR pathway over time and IGF2 is a promising avenue for treating age-related degeneration in mTORopathies.
MOTS-c relieves hepatocellular carcinoma resistance to TRAIL-induced apoptosis under hypoxic conditions by activating MEF2A.
Exp Cell Res
Haiying Shen, Junjie Nie, Xiaojun Wang +4 more
Mitochondrial ORF of the 12S rRNA type-c (MOTS-c) as an AMPK agonist can regulate the expression of adaptive nuclear genes to promote cell homeostasis. However, the investigation of MOTS-c in hepatocellular carcinoma (HCC) is insufficient. This study aims to reveal the role of MOTS-c on HCC cell apoptosis.
Neuroprotective and neuroregenerative drugs after severe traumatic brain injury : A narrative review from a clinical perspective.
Wien Klin Wochenschr
Ivan Grgac, Guenther Herzer, Wolfgang G Voelckel +2 more
Traumatic brain injuries cause enormous individual and socioeconomic burdens. Survivors frequently struggle with motor handicaps as well as impaired cognition and emotion. In addition to the primary mechanical brain damage, complex secondary mechanisms are the main drivers of functional impairment. Many of these pathophysiological mechanisms are now well known: excitotoxic amino acids, breakdown of the blood-brain barrier, neuroinflammation with subsequent damage to cell organelles and membranes, cerebral edema, and apoptotic processes triggering neuronal death; however, paracrine resilience factors may counteract these processes. Specific neuroprotective and neuroregenerative intensive care therapies are few. This review highlights medical approaches aimed at mitigating secondary damage and promoting neurotrophic processes in severe traumatic brain injury. Some pharmacologic attempts that appeared very promising in experimental settings have had disappointing clinical results (progesterone, cyclosporine A, ronopterin, erythropoietin, dexanabinol). Thus, the search for drugs that can effectively limit ongoing posttraumatic neurological damage is ongoing. Some medications appear to be beneficial: N‑methyl-D-aspartate receptor (NMDA) antagonists (esketamine, amantadine, Mg++) reduce excitotoxicity and statins and cerebrolysin are known to counteract neuroinflammation. By supporting the impaired mitochondrial energy supply, oxidative processes are inhibited and neuroregenerative processes, such as neurogenesis, angiogenesis and synaptogenesis are promoted by citicoline and cerebrolysin. First clinical evidence shows an improvement in cognitive and thymopsychic outcomes, underlined by own clinical experience combining different therapeutic approaches. Accordingly, adjuvant treatment with neuroprotective substances appears to be a promising option, although more randomized prospective studies are still needed.
Pro-adrenomedullin associates with congestion in acute heart failure patients.
ESC Heart Fail
Benedikt N Beer, Saman Keshtkaran, Caroline Kellner +7 more
Congestion is a major determinant of outcomes in acute heart failure. Its assessment is complex, making sufficient decongestive therapy a challenge. Residual congestion is frequent at discharge, increasing the risk of re-hospitalization and death. Mid-regional pro-adrenomedullin mirrors vascular integrity and may therefore be an objective marker to quantify congestion and to guide decongestive therapies in patients with acute heart failure.
Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.
J Coll Physicians Surg Pak
Ailing Cao, Fanchao Feng, Xianmei Zhou
This systematic review was conducted to assess the curative effect of Thymosin alpha 1 in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Six electronic databases including EMBASE, PubMed, Cochrane Library, China National Knowledge Infrastructure Database, Chinese Biomedical Database, and Wanfang Database were searched for eligible papers focusing on the thymosin alpha 1 treatment in AECOPD patients. The effectiveness outcomes included T cell subset, pulmonary function, arterial blood gases, and the length of hospital stay. Stata and Review Manager Software were used for data analysis. Thirty-nine randomised controlled trials with a total of 3,329 patients were included. Compared with the control treatment, Thymosin alpha 1 therapy significantly improved forced expiratory volume in 1 second [MD = 0.29, 95% (0.26, 0.32), p <0.001] and the ratio of forced expiratory volume in the first second to forced vital capacity [MD = 6.24, 95% (3.83, 8.65), p <0.001], increased the arterial partial pressure of oxygen [MD = 7.24, 95% (3.42, 11.07), p = 0.0002], lowered the arterial partial pressure of carbon dioxide [MD = -5.85, 95% (-9.38, -2.33), p = 0.001], shortened the length of hospital stay [MD = -5.39, 95% (-7.82, -2.97), p <0.001], raised the level of CD4+ T lymphocytes count [MD = 7.54, 95%(6.66, 8.41), p <0.001] and the ratio of CD4+/CD8+ [MD = 0.40, 95% (0.34, 0.46), p <0.001], and decreased level of CD8+ T lymphocytes count [MD = -2.74, 95% (-3.86, -1.63), p <0.001]. Thymosin alpha 1 could significantly boost the immune function, and improve pulmonary function and arterial blood gas of AECOPD patients than routine treatment only. More high-quality randomised controlled trials are needed to further confirm Thymosin alpha 1 efficacy. Key Words: Thymosin alpha 1, Efficacy, Acute exacerbation of chronic obstructive pulmonary disease, Meta-analysis.
Microtubule stabilising peptides: new paradigm towards management of neuronal disorders.
RSC Med Chem
Shubhangi Bhargava, Riya Kulkarni, Bhaskar Dewangan +7 more
Neuronal cells made of soma, axon, and dendrites are highly compartmentalized and possess a specialized transport system that can convey long-distance electrical signals for the cross-talk. The transport system is made up of microtubule (MT) polymers and MT-binding proteins. MTs play vital and diverse roles in various cellular processes. Therefore, defects and dysregulation of MTs and their binding proteins lead to many neurological disorders as exemplified by Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and many others. MT-stabilising agents (MSAs) altering the MT-associated protein connections have shown great potential for several neurodegenerative disorders. Peptides are an important class of molecules with high specificity, biocompatibility and are devoid of side effects. In the past, peptides have been explored in various neuronal disorders as therapeutics. Davunetide, a MT-stabilising octapeptide, has entered into phase II clinical trials for schizophrenia. Numerous examples of peptides emerging as MSAs reflect the emergence of a new paradigm for peptides which can be explored further as drug candidates for neuronal disorders. Although small molecule-based MSAs have been reviewed in the past, there is no systematic review in recent years focusing on peptides as MSAs apart from davunetide in 2013. Therefore, a systematic updated review on MT stabilising peptides may shed light on many hidden aspects and enable researchers to develop new therapies for diseases related to the CNS. In this review we have summarised the recent examples of peptides as MSAs.
Novel enzyme-resistant pancreatic polypeptide analogs evoke pancreatic beta-cell rest, enhance islet cell turnover, and inhibit food intake in mice.
Biofactors
Wuyun Zhu, Neil Tanday, Ryan A Lafferty +2 more
Pancreatic polypeptide (PP) is a postprandial hormone secreted from pancreatic islets that activates neuropeptide Y4 receptors (NPY4Rs). PP is known to induce satiety but effects at the level of the endocrine pancreas are less well characterized. In addition, rapid metabolism of PP by dipeptidyl peptidase-4 (DPP-4) limits the investigation of the effects of the native peptide. Therefore, in the present study, five novel amino acid substituted and/or fatty acid derivatized PP analogs were synthesized, namely [P3]PP, [K13Pal]PP, [P3,K13Pal]PP, [N-Pal]PP, and [N-Pal,P3]PP, and their impact on pancreatic beta-cell function, as well as appetite regulation and glucose homeostasis investigated. All PP analogs displayed increased resistance to DPP-4 degradation. In addition, all peptides inhibited alanine-induced insulin secretion from BRIN-BD11 beta cells. Native PP and related analogs (10-8 and 10-6 M), and especially [P3]PP and [K13Pal]PP, significantly protected against cytokine-induced beta-cell apoptosis and promoted cellular proliferation, with effects dependent on the NPY4R for all peptides barring [N-Pal,P3]PP. In mice, all peptides, except [N-Pal]PP and [N-Pal,P3]PP, evoked a dose-dependent (25, 75, and 200 nmol/kg) suppression of appetite, with native PP and [P3]PP further augmenting glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) induced reductions of food intake. The PP peptides had no obvious detrimental effect on glucose tolerance and they did not noticeably impair the glucose-regulatory actions of GLP-1 or CCK. In conclusion, Pro3 amino acid substitution of PP, either alone or together with mid-chain acylation, creates PP analogs with benefits on beta-cell rest, islet cell turnover, and energy regulation that may be applicable to the treatment of diabetes and obesity.
Cholecystokinin and gastrin as immune modulating hormones: Implications and applications.
Cytokine Growth Factor Rev
Gustav van Niekerk, Lara Kelchtermans, Elias Broeckhoven +3 more
Cholecystokinin (CCK) and gastrin are gastrointestinal hormones traditionally recognised for their roles in digestion. However, it has been recognised that these hormones may also modulate immune function. Here, we examine the immune-modulating effects of CCK and gastrin, and explore the functional significance of this dual role. In addition to the direct effect of these hormones on immune cell function, we discuss why hormones that regulate complex physiological and behavioural aspects of digestion might also influence immune responses. Notably, recent findings highlight the importance of these hormones in promoting a tolerogenic hepatic environment, particularly as the liver encounters gut-derived inflammogens following a meal. Additionally, the neuro-immune crosstalk mediated by CCK suggests that this hormone may influence immune responses indirectly via the gut-brain axis, especially in the context of infection or inflammation. Furthermore, the role of CCK in inducing feeding cessation and satiety appears to be repurposed during sickness behaviour, such as the loss of appetite during infection. Collectively, these observations suggest that nutritional strategies, including permissive underfeeding or fasting, could have important clinical implications. A deeper understanding of the dual roles of CCK and gastrin in digestion and immunity may pave the way for novel therapeutic approaches that leverage these pathways for improved disease management and treatment outcomes.
The biased apelin receptor agonist, MM07, reverses Sugen/hypoxia-induced pulmonary arterial hypertension as effectively as the endothelin antagonist macitentan.
Front Pharmacol
Thomas L Williams, Duuamene Nyimanu, Rhoda E Kuc +4 more
Introduction: Pulmonary arterial hypertension (PAH) is characterised by endothelial dysfunction and pathological vascular remodelling, resulting in the occlusion of pulmonary arteries and arterioles, right ventricular hypertrophy, and eventually fatal heart failure. Targeting the apelin receptor with the novel, G protein-biased peptide agonist, MM07, is hypothesised to reverse the developed symptoms of elevated right ventricular systolic pressure and right ventricular hypertrophy. Here, the effects of MM07 were compared with the clinical standard-of-care endothelin receptor antagonist macitentan. Methods: Male Sprague-Dawley rats were randomised and treated with either normoxia/saline, or Sugen/hypoxia (SuHx) to induce an established model of PAH, before subsequent treatment with either saline, macitentan (30 mg/kg), or MM07 (10 mg/kg). Rats were then anaesthetised and catheterised for haemodynamic measurements, and tissues collected for histopathological assessment. Results: The SuHx/saline group presented with significant increases in right ventricular hypertrophy, right ventricular systolic pressure, and muscularization of pulmonary arteries compared to normoxic/saline controls. Critically, MM07 was as at least as effective as macitentan in significantly reversing detrimental structural and haemodynamic changes after 4 weeks of treatment. Discussion: These results support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.
RANKL treatment restores thymic function and improves T cell-mediated immune responses in aged mice.
Sci Transl Med
Jérémy C Santamaria, Jessica Chevallier, Léa Dutour +11 more
Age-related thymic involution, leading to reduced T cell production, is one of the major causes of immunosenescence. This results in an increased susceptibility to cancers, infections, and autoimmunity and in reduced vaccine efficacy. Here, we identified that the receptor activator of nuclear factor κB (RANK)-RANK ligand (RANKL) axis in the thymus is altered during aging. Using a conditional transgenic mouse model, we demonstrated that endothelial cells depend on RANK signaling for their cellularity and functional maturation. Decreased RANKL availability during aging resulted in a decline in cellularity and function of both endothelial cells and thymic epithelial cells, contributing to thymic involution. We then found that, whereas RANKL neutralization in young mice mimicked thymic involution, exogenous RANKL treatment in aged mice restored thymic architecture as well as endothelial cell and epithelial cell abundance and functional properties. Consequently, RANKL improved T cell progenitor homing to the thymus and boosted T cell production. This cascade of events resulted in peripheral T cell renewal and effective antitumor and vaccine responses in aged mice. Furthermore, we conducted a proof-of-concept study that showed that RANKL stimulates endothelial cells and epithelial cells in human thymic organocultures. Overall, our findings suggest that targeting the RANK-RANKL axis through exogenous RANKL administration could represent a therapeutic strategy to rejuvenate thymic function and improve T cell immunity during aging.
Topical Transdermal Administration of Supramolecular Self-Assembled Carnosine for Anti-Melanin and Anti-Aging.
Adv Healthc Mater
De Bai, Zhenyuan Wang, Lin Xie +3 more
The structure of natural proteins has inspired the hypothesis that L-carnosine (LC), acetyl carnosine (AC), and decarboxy carnosine (DC) self-assemble into highly bioactive carnosine with supramolecular structures. These structures are proposed to combat skin pigmentation and aging through the coordination of weak interactions between molecules. Simulations are conducted to ascertain the precise free energies of the potential supramolecular structures and to identify the equilibrium structure. The mechanism of transdermal action of supramolecular carnosine is investigated through experiments and molecular dynamics simulations. The results demonstrate that supramolecular carnosine exhibits a more pronounced reactivity with the skin than LC, primarily due to the interaction of AC and DC with the lipid matrix, which reduces interfacial resistance. The anti-photoaging and anti-glycation cell models demonstrate that supramolecular carnosine upregulates the expression of the Nrf2 protein, activates the antioxidant defense system of melanocytes, inhibits the expression of the receptor for advanced glycosylation end products (AGEs), and reduces the level of AGEs in vivo. Moreover, supramolecular carnosine has demonstrated satisfactory whitening efficacy in cells and clinical efficacy tests, thereby underscoring its considerable potential for biomedical and aesthetic applications.
Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease.
Front Immunol
Xiaoke Li, Kaiqi Chen, Ruonan Liu +2 more
The defense mechanisms of the vertebrate brain against infections are at the forefront of immunological studies. Unlike other body parts, the brain not only fends off pathogenic infections but also minimizes the risk of self-damage from immune cell induced inflammation. Some neuropeptides produced by either nerve or immune cells share remarkable similarities with antimicrobial peptides (AMPs) in terms of size, structure, amino acid composition, amphiphilicity, and net cationic charge. These similarities extend to a wide range of antibacterial activities demonstrated in vitro, effectively protecting nerve tissue from microbial threats. This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms. Importantly, the majority of these antimicrobial neuropeptides (9 out of 12) also possess significant anti-inflammatory properties, potentially playing a key role in preserving immune tolerance in various disorders. However, the connection between this anti-inflammatory property and the brain's infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain's defense strategy against pathogens, marking an exciting direction for future research.