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Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats.
Bull Exp Biol Med
M A Konstantinopolsky, I V Chernyakova, L G Kolik
Activity of a peptide tuftsin analogue Selank was studied in outbred rats using the naloxone-precipitated morphine withdrawal model. Single intraperitoneal injection of Selank in an anxiolytic dose of 0.3 mg/kg reduced the total index of morphine withdrawal syndrome by 39.6%, significantly (р<0.0001) attenuated convulsive reactions, ptosis, and posture disorders, and 9-fold increased the tactile sensitivity threshold in morphine-dependent rats in comparison with the group of active control; at the same time, Selank was slightly inferior to diazepam in a dose of 2 mg/kg by pharmacological activity (the decrease in total index of morphine withdrawal syndrome by 49.3% and 13-fold increase in sensitivity threshold). Thus, Selank, like diazepam, weakens the aversive signs of morphine withdrawal in rats with opiate dependence.
Provocative tests with Kisspeptin-10 and GnRH set the scene for determining social status and environmental impacts on reproductive capacity in male African lions (Panthera leo).
Gen Comp Endocrinol
Mike Ludwig, Claire Newton, Ané Pieters +4 more
Understanding the hypothalamic factors regulating reproduction facilitates maximising the reproductive success of breeding programmes and in the management and conservation of threatened species, including African lions. To provide insight into the physiology and pathophysiology of the hypothalamic-pituitary-gonadal reproductive axis in lions, we studied the luteinising hormone (LH) and steroid hormone responses to gonadotropin-releasing hormone (GnRH) and its upstream regulator, kisspeptin. Six young (13.3 ± 1.7 months, 56.2 ± 4.3 kg) and four adult (40.2 ± 1.4 months, 174 ± 6 kg) male lions (Ukutula Conservation Centre, South Africa) were used in this study. Lions were immobilised with a combination of medetomidine and ketamine and an intravenous catheter was placed in a jugular, cephalic or medial saphenous vein for blood sampling at 10-min intervals for 220 min. The ten-amino acid kisspeptin which has full intrinsic activity (KP-10, 1 µg/kg) and GnRH (1 µg/kg) were administered intravenously to study their effects on LH and steroid hormone plasma concentrations, measured subsequently by ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Basal LH levels were similarly low between the age groups, but testosterone and its precursor levels were higher in the adult animals. Adult lions showed a significant LH response to KP-10 (10-fold) and GnRH (11-fold) administration (p < 0.05 and P < 0.001, respectively) whereas in young lions LH increased significantly only in response to GnRH. In adults alone, testosterone and its precursors steadily increased in response to KP-10, with no significant further increase in response to GnRH. Plasma levels of glucocorticoids in response to KP-10 remained unchanged. We suggest that provocative testing of LH and steroid stimulation with kisspeptin provides a new and sensitive tool for determining reproductive status and possibly an index of exposure to stress, environmental insults such as disease, endocrine disruptors and nutritional status. 272 words.
Mitochondrial derived peptide MOTS-c prevents the development of heart failure under pressure overload conditions in mice.
J Cell Mol Med
Peng Zhong, Jianye Peng, Yewen Hu +2 more
MOTS-c, a mitochondrial-derived peptide (MDP), has been shown to have multiple biological activities such as antioxidation, anti-inflammation, and anti-apoptosis properties. In the present study, we aimed at evaluating the therapeutic effect of MOTS-c peptide in an animal model of heart failure. The heart failure mouse model was made by transverse aortic constriction (TAC) operations. The MOTS-c peptide was administrated subcutaneously by using an osmotic pump. At the end of the animal experiment, cardiac function was evaluated by echocardiography, and heart tissues were subjected to histological and molecular analysis. In vitro cultured H9C2 cells were used to test the effects of MOTS-c overexpression on cell death in response to H2 O2 stimulation. Our study showed that MOTS-c peptide attenuated TAC-induced cardiac dysfunction and remodelling. In addition, the MOTS-c peptide reduced the inflammatory response and upregulated the antioxidant capacity, coupled with the activation of the AMPK pathway in the heart of the TAC mouse model. In in vitro cultured cardiac cells, overexpression of MOTS-c was shown to activate the AMPK pathway and protect cell apoptosis in response to H2 O2 stimulation. Taken together, our study suggested that MOTS-c peptides may have therapeutic potential in treating HF.
Pharmacologic therapeutic options for sexual dysfunction.
Curr Opin Obstet Gynecol
Claire S Burton, Kavita Mishra
Sexual problems are reported by up to 45% of individuals assigned female at birth. Although sexual function is a complex biopsychosocial construct, there are a number of pharmacologic treatment options aimed at addressing the changing vaginal hormonal milieu in postmenopausal individuals and moderating the excitatory and inhibitory aspects of the central nervous system in those with hypoactive sexual desire disorder.
The antimicrobial peptide Magainin-2 interacts with BamA impairing folding of E. coli membrane proteins.
Front Chem
Angela Di Somma, Carolina Cané, Antonio Moretta +6 more
Antimicrobial peptides (AMPs) are a unique and diverse group of molecules endowed with a broad spectrum of antibiotics properties that are being considered as new alternative therapeutic agents. Most of these peptides are membrane-active molecules, killing bacteria by membrane disruption. However, recently an increasing number of AMPs was shown to enter bacterial cells and target intracellular processes fundamental for bacterial life. In this paper we investigated the mechanism of action of Maganin-2 (Mag-2), a well-known antimicrobial peptide isolated from the African clawed frog Xenopus laevis, by functional proteomic approaches. Several proteins belonging to E. coli macromolecular membrane complexes were identified as Mag-2 putative interactors. Among these, we focused our attention on BamA a membrane protein belonging to the BAM complex responsible for the folding and insertion of nascent β-barrel Outer Membrane Proteins (OMPs) in the outer membrane. In silico predictions by molecular modelling, in vitro fluorescence binding and Light Scattering experiments carried out using a recombinant form of BamA confirmed the formation of a stable Mag-2/BamA complex and indicated a high affinity of the peptide for BamA. Functional implications of this interactions were investigated by two alternative and complementary approaches. The amount of outer membrane proteins OmpA and OmpF produced in E. coli following Mag-2 incubation were evaluated by both western blot analysis and quantitative tandem mass spectrometry in Multiple Reaction Monitoring scan mode. In both experiments a gradual decrease in outer membrane proteins production with time was observed as a consequence of Mag-2 treatment. These results suggested BamA as a possible good target for the rational design of new antibiotics since this protein is responsible for a crucial biological event of bacterial life and is absent in humans.
Exercise and Metabolic Health: The Emerging Roles of Novel Exerkines.
Curr Protein Pept Sci
İbrahim Türkel, Berkay Özerkliğ, Muhammed M Atakan +3 more
Physical inactivity is a major cause of chronic diseases. It shortens the health span by lowering the age of the first chronic disease onset, which leads to decreased quality of life and increased mortality risk. On the other hand, physical exercise is considered a miracle cure in the primary prevention of at least 35 chronic diseases, including obesity, insulin resistance, and type 2 diabetes. However, despite many scientific attempts to unveil the health benefits conferred by regular exercise, the underlying molecular mechanisms driving such benefits are not fully explored. Recent research shows that exercise-induced bioactive molecules, named exerkines, might play a critical role in the regulation of metabolic homeostasis and thus prevent metabolic diseases. Here we summarize the current understanding of the health-promoting effects of exerkines secreted from skeletal muscle, adipose tissue, bone, and liver, including MOTS-c, BDNF, miR-1, 12,13-diHOME, irisin, SPX, OC, GDF15, and FGF21 on obesity, insulin resistance, and type 2 diabetes. Identifying the systemic health benefits of exerkines may open a new area for the discovery of new pharmacological strategies for the prevention and management of metabolic diseases.
Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves α7AChRs on interneurons in hippocampal slices from rat.
Neurosci Lett
Rodion V Kondratenko, Igor S Povarov, Sergey N Kolbaev +5 more
Noopept (NP) is a proline-containing dipeptide with nootropic and neuroprotective properties. We have previously shown that NP significantly increased the frequency of spontaneous IPSCs in hippocampal CA1 pyramidal cells mediated by the activation of inhibitory interneurons in stratum radiatum. The cholinergic system plays an important role in the performance of cognitive functions, furthermore multiple behavioral and clinical facts link NP with the cholinergic system. The present study was undertaken to reveal the possible interaction of NP with neuronal nicotinic acetylcholine receptors (nAChRs). Currents were recorded from rat hippocampal neurons using the whole-cell, patch-clamp technique. NP (5 µM) increased the action potential firing frequency recorded from GABAergic interneurons in the stratum radiatum (SR) of CA1 region. This effect was almost completely abolished by the application of the α7 nAChR-selective antagonists α-bungarotoxin (α-BGT; 6 nM) and methyllycaconitine (MLA; 20 nM). The increase in the frequency of spontaneous IPSCs in CA1 pyramidal cells induced by NP was also eliminated by α7 nAChRs antagonists. These results imply the involvement of α7 nAChRs in the modulation of hippocampal neuronal activity caused by NP and indicate that a7 nAChRs are an important site of action of NP.
CAN'T INTUBATE, CAN'T OXYGENATE: 
A RARE CASE OF A DIFFICULT AIRWAY DUE TO NONHEREDITARY ANGIOEDEMA.
Acta Clin Croat
Điđi Delalić, Vinko Borčić, Ingrid Prkačin
Angioedema is a form of allergic mediated by histamine and non-allergic mediated by bradykinin and can be lethal if not recognized and treated promptly. This case demonstrates the proper diagnosis of and intervention in rapid onset severe angioedema. A 68-year-old male came to the emergency department with a complaint of dyspnea that started two hours before. He had type II diabetes, chronic kidney disease and several different antihypertensive medications, including an ACE inhibitor for hypertension. During physical examination, the patient was hypertensive, tachycardic, tachypnoic, and edematous. During his stay in the ED he was treated with a combination of corticosteroids, antihistamines and epinephrine, but the patient's edema and dyspnea worsened and his oxygen saturation started to deteriorate with a progression of skin edema. Intubation was not possible due to the large edema of the tongue, so a tracheotomy was done. An ampule of icatibant was administered and rapid regression of the edema, along with the stabilization of the patient's vital signs, followed after five minutes. The patient was discharged home after five days with a recommendation of discontinuing the ACE inhibitor. While non-hereditary angioedema is not a rare condition, emergency physicians should be adequately educated about it.
GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway.
Int J Mol Sci
Zongkui Wang, Peng Jiang, Fengjuan Liu +9 more
Growth differentiation factor 11 (GDF11), belonging to the transforming factor-β superfamily, regulates anterior-posterior patterning and inhibits neurogenesis during embryonic development. However, recent studies recognized GDF11 as a rejuvenating (or anti-ageing) factor to reverse age-related cardiac hypertrophy, repair injured skeletal muscle, promote cognitive function, etc. The effects of GDF11 are contradictory and the mechanism of action is still not well clarified. The objective of the present study was to investigate effects of GDF11 on PC12 neural stem cells in vitro and to reveal the underlying mechanism. We systematically assessed the effects of GDF11 on the life activities of PC12 cells. GDF11 significantly suppressed cell proliferation and migration, promoted differentiation and apoptosis, and arrested cell cycle at G2/M phase. Both TMT-based proteomic analysis and phospho-antibody microarray revealed PI3K-Akt pathway was enriched when treated with GDF11. Inhibition of ALK5 or PI3K obviously attenuated the effects of GDF11 on PC12 neural stem cells, which exerted that GDF11 regulated neural stem cells through ALK5-dependent PI3K-Akt signaling pathway. In summary, these results demonstrated GDF11 could be a negative regulator for neurogenesis via ALK5 activating PI3K-Akt pathway when it directly acted on neural stem cells.
Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities.
Biomed Pharmacother
Jiayu Lv, Yumeng Li, Shuqing Shi +4 more
Patients with heart failure (HF) usually present with skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors of HF prognosis. Abnormal mitochondrial metabolism has been identified as one of the earliest signs of skeletal muscle injury in HF and is associated with pathological alterations in muscle, manifested as muscle wasting, myocyte atrophy and apoptosis, fiber type shift, impaired contractile coupling, and muscle fat infiltration. In this review, we update the evidence for skeletal muscle mitochondrial remodeling in HF patients or animal models, including the impairments in mitochondrial ultrastructure, oxidative metabolism, electron transport chain (ETC), phosphorylation apparatus, phosphotransfer system, and quality control. We also focus on molecular regulatory mechanisms upstream of mitochondria, including circulating factors (e.g., RAAS, TNF-α IL-6, IGF-1, GH, ghrelin, adiponectin, NO) and molecular signals within myocytes (e.g., PGC-1α, PPARs, AMPK, SIRT1/3, ROS, and MuRF1). Besides the therapies targeting the signaling pathways mentioned above, such as AdipoRon and elamipretide, we further summarize other potential pharmacological approaches like inhibitors of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4), as well as some natural products, which may have the beneficial effects on improving the skeletal muscle mitochondrial function of HF. Targeting myocyte mitochondrial biogenesis, oxidative metabolism, oxidative phosphorylation, and reduction of oxidative stress injury are promising future opportunities for the prevention and management of skeletal muscle myopathy in HF.
Supraspinal melatonin MT2 receptor agonism alleviates pain via a neural circuit that recruits mu opioid receptors.
J Pineal Res
Luca Posa, Danilo De Gregorio, Martha Lopez-Canul +9 more
Melatonin, through its G protein-coupled receptor (GPCR) (MTNR1B gene) MT2 , is implicated in analgesia, but the relationship between MT2 receptors and the opioid system remains elusive. In a model of rodent neuropathic pain (spared nerve injured [SNI]), the selective melatonin MT2 agonist UCM924 reversed the allodynia (a pain response to a non-noxious stimulus), and this effect was nullified by the pharmacological blockade or genetic inactivation of the mu opioid receptor (MOR), but not the delta opioid receptor (DOR). Indeed, SNI MOR, but not DOR knockout mice, did not respond to the antiallodynic effects of the UCM924. Similarly, the nonselective opioid antagonist naloxone and the selective MOR antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) blocked the effects of UCM924 in SNI rats, but not the DOR antagonist naltrindole (NTI). Electrophysiological recordings in the rostral-ventromedial medulla (RVM) revealed that the typical reduction of the firing activity of pronociceptive ON-cells, and the enhancement of the firing of the antinociceptive OFF-cells, induced by the microinjection of the MT2 agonist UCM924 into the ventrolateral periaqueductal gray (vlPAG) were blocked by MOR, but not DOR, antagonism. Immunohistochemistry studies showed that MT2 receptors are expressed in both excitatory (CaMKIIα+ ) and inhibitory (GAD65+ ) neuronal cell bodies in the vlPAG (~2.16% total), but not RVM. Only 0.20% of vlPAG neurons coexpressed MOR and MT2 receptors. Finally, UCM924 treatment induced an increase in the enkephalin precursor gene (PENK) in the PAG of SNI mice. Collectively, the melatonin MT2 receptor agonism requires MORs to exert its antiallodynic effects, mostly through an interneuronal circuit involving MOR and MT2 receptors.
Distinct Impairments Characterizing Different ADNP Mutants Reveal Aberrant Cytoplasmic-Nuclear Crosstalk.
Cells
Maram Ganaiem, Gidon Karmon, Yanina Ivashko-Pachima +1 more
(1) Background: Activity-dependent neuroprotective protein (ADNP) is essential for neuronal structure and function. Multiple de novo pathological mutations in ADNP cause the autistic ADNP syndrome, and they have been further suggested to affect Alzheimer's disease progression in a somatic form. Here, we asked if different ADNP mutations produce specific neuronal-like phenotypes toward better understanding and personalized medicine. (2) Methods: We employed CRISPR/Cas9 genome editing in N1E-115 neuroblastoma cells to form neuron-like cell lines expressing ADNP mutant proteins conjugated to GFP. These new cell lines were characterized by quantitative morphology, immunocytochemistry and live cell imaging. (3) Results: Our novel cell lines, constitutively expressing GFP-ADNP p.Pro403 (p.Ser404* human orthologue) and GFP-ADNP p.Tyr718* (p.Tyr719* human orthologue), revealed new and distinct phenotypes. Increased neurite numbers (day 1, in culture) and increased neurite lengths upon differentiation (day 7, in culture) were linked with p.Pro403*. In contrast, p.Tyr718* decreased cell numbers (day 1). These discrete phenotypes were associated with an increased expression of both mutant proteins in the cytoplasm. Reduced nuclear/cytoplasmic boundaries were observed in the p.Tyr718* ADNP-mutant line, with this malformation being corrected by the ADNP-derived fragment drug candidate NAP. (4) Conclusions: Distinct impairments characterize different ADNP mutants and reveal aberrant cytoplasmic-nuclear crosstalk.
Molecular Mechanisms and Health Benefits of Ghrelin: A Narrative Review.
Nutrients
Zheng-Tong Jiao, Qi Luo
Ghrelin, an endogenous brain-gut peptide, is secreted in large quantities, mainly from the stomach, in humans and rodents. It can perform the biological function of activating the growth hormone secretagogue receptor (GHSR). Since its discovery in 1999, ample research has focused on promoting its effects on the human appetite and pleasure-reward eating. Extensive, in-depth studies have shown that ghrelin is widely secreted and distributed in tissues. Its role in neurohumoral regulation, such as metabolic homeostasis, inflammation, cardiovascular regulation, anxiety and depression, and advanced cancer cachexia, has attracted increasing attention. However, the effects and regulatory mechanisms of ghrelin on obesity, gastrointestinal (GI) inflammation, cardiovascular disease, stress regulation, cachexia treatment, and the prognosis of advanced cancer have not been fully summarized. This review summarizes ghrelin's numerous effects in participating in a variety of biochemical pathways and the clinical significance of ghrelin in the regulation of the homeostasis of organisms. In addition, potential mechanisms are also introduced.
Crotalphine Modulates Microglia M1/M2 Phenotypes and Induces Spinal Analgesia Mediated by Opioid-Cannabinoid Systems.
Int J Mol Sci
Flavia S R Lopes, Aline C Giardini, Morena B Sant'Anna +5 more
Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated. Thus, the central effect of crotalphine was evaluated on the partial sciatic nerve ligation (PSNL)-induced chronic neuropathic pain model. Crotalphine (100 µg/kg, p.o.)-induced analgesia on the 14th day after surgery lasting up to 24 h after administration. This effect was prevented by intrathecal administration of CB1 (AM251) or CB2 (AM630) cannabinoid receptor antagonists. Besides that, crotalphine-induced analgesia was reversed by CTOP, nor-BNI, and naltrindole, antagonists of mu, kappa, and delta-opioid receptors, respectively, and also by the specific antibodies for β-endorphin, dynorphin-A, and met-enkephalin. Likewise, the analgesic effect of crotalphine was blocked by the intrathecal administration of minocycline, an inhibitor of microglial activation and proliferation. Additionally, crotalphine decreased the PSNL-induced IL-6 release in the spinal cord. Importantly, in vitro, crotalphine inhibited LPS-induced CD86 expression and upregulated CD206 expression in BV-2 cells, demonstrating a polarization of microglial cells towards the M2 phenotype. These results demonstrated that crotalphine, besides activating opioid and cannabinoid analgesic systems, impairs central neuroinflammation, confirming the neuromodulatory mechanism involved in the crotalphine analgesic effect.
Collagen peptide supplementation for pain and function: is it effective?
Curr Opin Clin Nutr Metab Care
Shiloah A Kviatkovsky, Robert C Hickner, Michael J Ormsbee
Connective tissue injuries are prevalent in active and aging populations, leading to chronic pain and decreased function. Turnover of this tissue is not well understood, especially as it relates to aging and injury. Supplementation of collagen peptides has been shown to improve connective tissue recovery and pain through increased collagen production.
Efficacy of 12 weeks oral beta-alanine supplementation in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled trial.
J Cachexia Sarcopenia Muscle
Jana De Brandt, Wim Derave, Frank Vandenabeele +8 more
Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD.
Causes and outcomes of hepatic fibrosis in persons living with HIV.
Curr Opin HIV AIDS
Debra W Yen, Kenneth E Sherman
The epidemiology of liver disease in people living with HIV has evolved since the arrival of effective hepatitis C virus (HCV) treatment. Nonalcoholic fatty liver disease (NAFLD) in HIV patients is highly prevalent while hepatitis D, hepatitis E, and occult hepatitis B remain underappreciated. We discuss mechanisms of fibrosis in HIV and review clinical outcomes of HIV-associated liver diseases.
Improved Muscle Regeneration into a Joint Prosthesis with Mechano-Growth Factor Loaded within Mesoporous Silica Combined with Carbon Nanotubes on a Porous Titanium Alloy.
ACS Nano
Xiang Wei, Qin Chen, Lingtong Bu +6 more
Total joint replacement (TJR) is widely applied as a promising treatment for the reconstruction of serious joint diseases but is usually characterized by critical loss of skeletal muscle attachment to metal joint prostheses, resulting in fibrous scar tissue formation and subsequent motor dysfunction. Tissue engineering technology may provide a potential strategy for skeletal muscle regeneration into metal joint prostheses. Here, a porous titanium (Ti) alloy scaffold coated with carbon nanotubes (CNTs) and mesoporous silica nanoparticles (MSNs) through electrophoretic deposition (EPD) was designed as a mechano-growth factor (MGF) carrier. This two-layered coating exhibits a nanostructured topology, excellent MGF loading, and prolonged release performance via covalent bonding to improve myoblast adhesion, proliferation and myogenic differentiation in porous Ti alloy scaffolds without cytotoxicity. The Akt/mTOR signaling pathway plays a key role in this process. Furthermore, in vivo studies show that the scaffold promotes the growth of muscle, rather than fibrotic tissue, into the porous Ti alloy structure and improves muscle-derived mechanical properties, the migration of satellite cells, and possibly immunomodulation. In summary, this nanomaterial-coated scaffold provides a practical biomaterial platform to regenerate periprosthetic muscle tissue and restore comparable motor function to that of the natural joint.
A resveratrol derivative modulates TRH and TRH-like peptide expression throughout the brain and peripheral tissues of male rats.
Endocrinol Diabetes Metab
Albert Eugene Pekary, Albert Sattin
Resveratrol and related polyphenols have therapeutic effects ranging from treatment of depression, Alzheimer's and Parkinson's disease, obesity, diabetes, neurodegeneration and ageing. TRH and TRH-like peptides, with the structure pGlu-X-Pro-NH2 , where 'X can be any amino acid reside, have reproductive, caloric-restriction-like, anti-ageing, pancreatic-β cell-enhancing, cardiovascular and neuroprotective effects. We hypothesize that TRH and TRH-like peptides are mediators of the therapeutic actions of the resveratrol derivative pterostilbene (PT).
Boosting Cosmeceutical Peptides: Coupling Imidazolium-Based Ionic Liquids to Pentapeptide-4 Originates New Leads with Antimicrobial and Collagenesis-Inducing Activities.
Microbiol Spectr
Ana Gomes, Lucinda J Bessa, Iva Fernandes +8 more
Following our previous reports on dual-action antibacterial and collagenesis-inducing hybrid peptide constructs based on "pentapeptide-4" (PP4, with amino acid sequence KTTKS), whose N-palmitoyl derivative is the well-known cosmeceutical ingredient Matrixyl, herein we disclose novel ionic liquid/PP4 conjugates (IL-KTTKS). These conjugates present potent activity against either antibiotic-susceptible strains or multidrug resistant clinical isolates of both Gram-positive and Gram-negative bacterial species belonging to the so-called "ESKAPE" group of pathogens. Noteworthy, their antibacterial activity is preserved in simulated wound fluid, which anticipates an effective action in the setting of a real wound bed. Moreover, their collagenesis-inducing effects in vitro are comparable to or stronger than those of Matrixyl. Altogether, IL-KTTKS exert a triple antibacterial, antifungal, and collagenesis-inducing action in vitro. These findings provide solid grounds for us to advance IL-KTTKS conjugates as promising leads for future development of topical treatments for complicated skin and soft tissue infections (cSSTI). Further studies are envisaged to incorporate IL-conjugates into suitable nanoformulations, to reduce toxicity and/or improve resistance to proteolytic degradation. IMPORTANCE As life expectancy increases, diseases causing chronic wound infections become more prevalent. Diabetes, peripheral vascular diseases, and bedridden patients are often associated with non-healing wounds that become infected, resulting in high morbidity and mortality. This is exacerbated by the fact that microbes are becoming increasingly resistant to antibiotics, so efforts must converge toward finding efficient therapeutic alternatives. Recently, our team identified a new type of constructs that combine (i) peptides used in cosmetics to promote collagen formation with (ii) imidazolium-based ionic liquids, which have antimicrobial and skin penetration properties. These constructs have potent wide-spectrum antimicrobial action, including against multidrug-resistant Gram-positive and Gram-negative bacteria, and fungi. Moreover, they can boost collagen formation. Hence, this is an unprecedented class of lead molecules toward development of a new topical medicine for chronically infected wounds.