UNASSIGNED: The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivation for reward. Although relaxin-3 is the endogenous agonist for RXFP3, it can also bind to and activate RXFP1 and RXFP4. Consequently, research has been focused on the development of RXFP3-specific peptides and small-molecule ligands to validate the relaxin-3/RXFP3 system as a novel drug target.
UNASSIGNED: This review provides an overview of patents on the relaxin-3/RXFP3 system covering ligand development and pharmacological studies since 2003. Related patents and literature reports were obtained from established sources including SciFinder, Google Patents, and Espacenet for patents and SciFinder, PubMed, and Google Scholar for literature reports.
UNASSIGNED: There has been an increasing amount of patent activities around relaxin-3/RXFP3, highlighting the importance of this novel neuropeptide system for drug discovery. The development of relaxin-3 derived peptides and small-molecule modulators, as well as behavioral studies in rodents, have shown that the relaxin-3/RXFP3 system is a promising drug target for treating various metabolic and neuropsychiatric diseases including obesity, anxiety, and alcohol addiction.

Recent preclinical research exploring how neuropeptide transmitter systems regulate motivated behavior reveal the increasing importance of sex as a critical biological variable. Neuropeptide systems and their central circuits both contribute to sex differences in a range of motivated behaviors and regulate sex-specific behaviors. In this short review, we explore the current research of how sex as a biological variable influences several distinct motivated behaviors that are modulated by the melanin-concentrating hormone (MCH) neuropeptide system. First, we review how MCH regulates feeding behavior within the context of energy homeostasis differently between male and female rodents. Then, we focus on MCH\'s role in lactation as a sex-specific process within the context of energy homeostasis. Next, we discuss the sex-specific effects of MCH on maternal behavior. Finally, we summarize the role of MCH in drug-motivated behaviors. While these topics are traditionally investigated from different scientific perspectives, in this short review we discuss how these behaviors share commonalities within the larger context of motivated behaviors, and that sex differences discovered in one area of research may impact our understanding in another. Overall, our review highlights the need for further research into how sex differences in energy regulation associated with reproduction and parental care contribute to regulating motivated behaviors.

Neuropeptides represent the most diverse family of neurotransmitters counting numerous members and even more G protein-coupled receptors, all of which are potential targets for drug development. Here, we focus on galanin and its three receptors by describing their possible involvement in pain and regeneration. Although animal experiments indicate that galanin, together with other molecules, may act as an endogenous system protecting against pain and improving nerve growth, these results have so far not been translated into patient treatments.

Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing.
Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides\' pain modulation in the orofacial region, especially in the trigeminal system.
OBJECTIVE: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain.
METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides\' functions and mechanisms as well as promising targets for orofacial pain control.
RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated.
CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.

Epilepsy is one of the most prevalent chronic neurological disorders characterized by frequent unprovoked epileptic seizures. Epileptic seizures can develop from a broad range of underlying abnormalities such as tumours, strokes, infections, traumatic brain injury, developmental abnormalities, autoimmune diseases, and genetic predispositions. Sometimes epilepsy is not easily diagnosed and treated due to the large diversity of symptoms. Undiagnosed and untreated seizures deteriorate over time, impair cognition, lead to injuries, and can sometimes result in death. This review gives details about epilepsy, its classification on the basis of International League Against Epilepsy, current therapeutics which are presently offered for the treatment of epilepsy. Despite of the fact that more than 30 different anti-epileptic medication and antiseizure drugs are available, large number of epileptic patients fail to attain prolonged seizure independence. Poor onsite bioavailability of drugs due to blood brain barrier poses a major challenge in drug delivery to brain. The present review covers the limitations with the state-of-the-art strategies for managing seizures and emphasizes the role of nanotechnology in overcoming these issues. Various nano-carriers like polymeric nanoparticles, dendrimers, lipidic nanoparticles such as solid lipid nanoparticles, nano-lipid carriers, have been explored for the delivery of anti-epileptic drugs to brain using oral and intranasal routes. Nano-carries protect the encapsulated drugs from degradation and provide a platform to deliver controlled release over prolonged periods, improved permeability and bioavailability at the site of action. The review also emphasises in details about the role of neuropeptides for the treatment of epilepsy.

Acne vulgaris is one of the most prevalent skin conditions, affecting almost all teenagers worldwide. Multiple factors, including the excessive production of sebum, dysbiosis of the skin microbiome, disruption of keratinization within hair follicles, and local inflammation, are believed to trigger or aggravate acne. Immune activity plays a crucial role in the pathogenesis of acne. Recent research has improved our understanding of the immunostimulatory functions of microorganisms, lipid mediators, and neuropeptides. Additionally, significant advances have been made in elucidating the intricate mechanisms through which cutaneous innate and adaptive immune cells perceive and transmit stimulatory signals and initiate immune responses. However, our understanding of precise temporal and spatial patterns of immune activity throughout various stages of acne development remains limited. This review provides a comprehensive overview of the current knowledge concerning the immune processes involved in the initiation and progression of acne. Furthermore, we highlight the significance of detailed spatiotemporal analyses, including analyses of temporal dynamics of immune cell populations as well as single-cell and spatial RNA sequencing, for the development of targeted therapeutic and prevention strategies.

Neuropeptides are involved in almost all physiological activities of insects. Their classification is based on physiological function and the primary amino acid sequence. The pyrokinin (PK)/pheromone biosynthesis activating neuropeptides (PBAN) are one of the largest neuropeptide families in insects, with a conserved C-terminal domain of FXPRLamide. The peptide family is divided into two groups, PK1/diapause hormone (DH) with a WFGPRLa C-terminal ending and PK2/PBAN with FXPRLamide C-terminal ending. Since the development of cutting-edge technology, an increasing number of peptides have been sequenced primarily through genomic, transcriptomics, and proteomics, and their functions discovered using gene editing tools. In this review, we discussed newly discovered functions, and analyzed the distribution of genes encoding these peptides throughout different insect orders. In addition, the location of the peptides that were confirmed by PCR or immunocytochemistry is also described. A phylogenetic tree was constructed according to the sequences of the receptors of most insect orders. This review offers an understanding of the significance of this conserved peptide family in insects.

OBJECTIVE: To systematically investigate previously examined biomarkers in blood, urine, cerebrospinal fluid, tear fluid, and saliva of patients with cluster headache.
BACKGROUND: Cluster headache is a condition with extensive clinical challenges in terms of diagnosis and treatment. Identification of a biomarker with diagnostic implications or as a potential treatment target is highly warranted.
METHODS: We conducted a systematic review including peer reviewed full text of studies that measured biochemical compounds in either blood, urine, cerebrospinal fluid, tear fluid, or saliva of patients with cluster headache diagnosed after the implementation of the International Classification of Headache Disorders (1988) written in English, Danish, Swedish, or Norwegian. Inclusion required a minimum of five participants. The search was conducted in PubMed and EMBASE, in September 2022, and extracted data were screened by two authors. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting systematic reviews were followed. The Newcastle-Ottawa Scale was used to assess the risk of bias in case-controlled studies.
RESULTS: We included 40 studies involving 832 patients with cluster headache and 872 controls, evaluating 80 potential biomarkers. The risk of bias for case-controlled studies was a median of 6 (range: 3-8) and 20 studies out of 40 (50%) were of fair or good quality. Most studies were identified within three groups: hypothalamic-regulated hormones, inflammatory markers, and neuropeptides. Among the hypothalamic hormones, cortisol was the most frequently investigated (N = 7) and was elevated in cluster headache in most of the studies. The most frequently examined inflammatory marker was interleukin 1 (N = 3), but findings were divergent. Calcitonin gene-related peptide was the most investigated neuropeptide (N = 9) and all studies found increased levels during attacks.
CONCLUSIONS: Biomarker findings have been inconsistent and widely non-specific for cluster headache, which explains why none of the previous studies succeeded in identifying a unique biomarker for cluster headache, but instead contributed to substantiating the underlying pathophysiologic mechanisms. Several of the examined biomarkers could hold promise as markers for disease activity but are unfit for a clear distinction from both controls and other headaches.

The neurobiology of autism is complex, but emerging research points to potential abnormalities and alterations in neurogenesis. The aim of the present review is to describe the advances in the understanding of the role of selected neurotrophins, neuropeptides, and other compounds secreted by neuronal cells in the processes of postnatal neurogenesis in conjunction with autism. We characterize the fundamental mechanisms of neuronal cell proliferation, generation of major neuronal cell types with special emphasis on neurogenic niches - the subventricular zone and hippocampal areas. We also discuss changes in intracellular calcium levels and calcium-dependent transcription factors in the context of the regulation of neurogenesis and cell fate determination. To sum up, this review provides specific insight into the known association between alterations in the function of the entire spectrum of molecules involved in neurogenesis and the etiology of autism pathogenesis.