Synthetic Analogues Research Articles

Flavin‐Catalyzed, Photochemical Conversion of Dehydroalanine into 4,5‐Dihydroxynorvaline

The chemical synthesis of unnatural amino acids (UAA) is a key strategy for preparing designed peptides, including pharmaceutically active compounds. Alterations of existing amino acid residues such as dehydroalanine (Dha) are particularly important since selected positions can be addressed without the necessity of a complete de novo synthesis. The intriguing UAA 4,5‐dihydroxynorvaline (Dnv) is found in a variety of naturally occurring peptides and biologically active compounds. However, no method is currently available to modify an existing peptide with this residue. We report the use of flavin catalysts and visible light irradiation for this challenge, which serves as a versatile strategy for converting Dha into Dnv. Our study shows that excited flavins are competent hydrogen atom abstraction catalysts for ethers and acetals, which allows masked 1,2‐dihydroxyethylene functionalization from 2,2‐dimethyl‐1,3‐dioxolane. The masked diol was successfully coupled to Dha residues, and a series of Dnv‐containing products is reported. A mild and orthogonal protocol for deprotection of the acetal group was also identified, allowing free Dnv‐modified peptides to be obtained. This method provides a straightforward strategy for Dnv functionalization, which is envisioned to be crucial for accessing natural products and synthetic analogues with pharmaceutical activity.

Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications.

Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.

Natural and Bioinspired Lipidic Alkynylcarbinols as Leishmanicidal, Antiplasmodial, Trypanocidal, Fungicidal, Antibacterial, and Antimycobacterial Agents.

The present review article recapitulates for the first time the antipathogenic biological data of a series of lipidic natural products and synthetic analogues thereof characterized by the presence in their structure of an alkynylcarbinol unit. The cytotoxic properties of such natural and bioinspired compounds have been covered by several literature overviews, but to date, no review article detailing their activity against pathogens has been proposed. This article thus aims at providing a comprehensive overview of the field including early studies from the 1970s and 1980s with a specific focus on results published from the late 1990s until nowadays. Publications presenting the data of almost 50 different natural products are reported. Detailed activities encompass the fields of leishmanicidal, antiplasmodial, trypanocidal, fungicidal, and mainly antibacterial and antimycobacterial compounds. The few published studies aimed at exploring the structure-activity relationship in these series are also described. Around 15 different synthetic analogues of natural products, selected among the most active reported, are also presented. The rare data available regarding the antipathogenic mode of action of these products are recalled, and finally, a comparative analysis of the available biological data is proposed with the aim of identifying the key structural determinants for the bioactivity against pathogens of these unusual compounds.

Introduction of Nicotine Analogue-Containing Oral Pouch Products in the United States.

In 2023, 6-methyl nicotine (6MN), a synthetic nicotine analogue, was introduced in US-marketed electronic cigarette products advertised as exempt from regulation. It is unknown whether the use of 6MN has spread to the oral nicotine pouch product category that has become increasingly popular. Industry reports and the USPTO database were searched for informationon 6-methyl nicotine products. The search terms "Metatine", "Nixotine", "Imotine" and "pouches" were shortlisted and used to identify US-marketed pouch products. Ingredient contents were compared to popular products, and safety warnings and regulatory statements assessed in context with US state and federal regulations. Two US-based brands, "MG" and "Hippotine" pouches, were identified in August 2024, advertised to contain "Imotine"-trademarked 6MN. MG Pouches are marketed in four youth-appealing flavors. "Hippotine"-branded pouches are marketed in two flavors. 6MN contents ranged between 8mg - 25mg with almost identical ingredient lists otherwise. Products list extensive addiction and health warnings, including warnings not to operate vehicles. Vendors state that these are not a tobacco product, implicating that federal and state tobacco regulations do not apply. The spread of nicotine analogues to additional product categories such as oral pouches is concerning, especially given the high 6MN contents that exceed nicotine contents in popular US-marketed oral nicotine pouch products. Legislators and regulators need to provide certainty about the regulatory status of nicotine analogues to prevent further erosion of tobacco flavor bans and other regulations.

Formulation and Evaluation of Acyclovir Loaded Transferosomal Gel for Transdermal Drug Delivery

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. Keywords: Transferosome, Transdermal drug delivery system, Acyclovir, 32 Fractional factorial design, Carbopol 934

Citral-thymol based synergistic shellac coatings enhanced shelf life of Kinnow fruit stored under low temperature conditions

Microbial spoilage incurs the main cause of reduced shelf life of Kinnow during storage and transportation. This study aimed to evaluate the postharvest application of plant-derived citral and thymol-based shellac wax coatings on ‘Kinnow’ mandarin under controlled conditions (5–7 °C, 90–95 % relative humidity (RH)) over a 75-day storage period. The fruit were coated with shellac wax (SH) supplemented with citral (1.0 %, CSH), thymol (1.0 %, TSH) and citral-thymol combined formulation (1.0 %, CTSH (1:1)). Rheology studies revealed that the Herschel–Bulkley model was the best fit for all coating solutions, ensuring desirable spreadability and adhesion. The CTSH-coating outperformed all other treatments by reducing mean spoilage to 0.46% as compared to commercial shellac (6.71%) over a period of 75 days under cold store conditions. The treated fruit could control the physiological weight loss to 5.73 % as compared to commercial SH coatings (7.62 %) for 60 days. The study concluded that CTSH-coated Kinnow fruit can be stored up to 60 days under cold store conditions at 5–7 °C and 90–95 % RH with acceptable fruit quality (sensory score 7.83). The activities of cell wall degrading enzymes such as Pectin methylesterase (PME) and cellulase were also found to be retarded, contributing to prolonged shelf life. Therefore, these coatings may offer a green substitute to the synthetic analogues, with no health side effects for extending the postharvest shelf life of Kinnow up to 60 days under cold store conditions.

The Mechanism of Mycobacterial (p)ppGpp Synthetase Inhibition by Synthetic Erogorgiaene Analog

The Mechanism of Mycobacterial (p)ppGpp Synthetase Inhibition by Synthetic Erogorgiaene Analog

A Chemical Toolbox to Unveil Synthetic Nature-Inspired Antifouling (NIAF) Compounds.

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with copper as an alternative to the traditionally used tributyltin (TBT); however, some of them were recently found to accumulate in coastal waters at levels that are deleterious for marine organisms. More ecological alternatives were pursued, some of them based on the marine organism mechanisms' production of specialized metabolites with AF activity. However, despite the investment in research on AF natural products and their synthetic analogues, many studies showed that natural AF alternatives do not perform as well as the traditional metal-based ones. In the search for AF agents with better performance and to understand which molecular motifs were responsible for the AF activity of natural compounds, synthetic analogues were produced and investigated for structure-AF activity relationship studies. This review is a comprehensive compilation of AF compounds synthesized in the last two decades with highlights on the data concerning their structure-activity relationship, providing a chemical toolbox for researchers to develop efficient nature-inspired AF agents.

Natural Plant Materials as a Source of Neuroprotective Peptides.

In many circumstances, some crucial elements of the neuronal defense system fail, slowly leading to neurodegenerative diseases. Activating this natural process by administering exogenous agents to counteract unfavourable changes seems promising. Therefore, looking for neuroprotective therapeutics, we have to focus on compounds that inhibit the primary mechanisms leading to neuronal injuries, e.g., apoptosis, excitotoxicity, oxidative stress, and inflammation. Among many compounds considered neuroprotective agents, protein hydrolysates and peptides derived from natural materials or their synthetic analogues are good candidates. They have several advantages, such as high selectivity and biological activity, a broad range of targets, and high safety profile. This review aims to provide biological activities, the mechanism of action and the functional properties of plant-derived protein hydrolysates and peptides. We focused on their significant role in human health by affecting the nervous system and having neuroprotective and brain-boosting properties, leading to memory and cognitive improving activities. We hope our observation may guide the evaluation of novel peptides with potential neuroprotective effects. Research into neuroprotective peptides may find application in different sectors as ingredients in functional foods or pharmaceuticals to improve human health and prevent diseases.

Exogenous strigolactone alleviates post-waterlogging stress in grapevine

With global climate change, the frequent occurrence of intense rainfall and aggravation of waterlogging disasters have severely threatened the plant growth and fruit quality of grapevines, which are commercially important fruit crops worldwide. There is accordingly an imperative to clarify the responses of grapevine to waterlogging and to propose appropriate remedial measures. Strigolactone (SL) is a phytohormone associated with plant abiotic stress tolerance, while, its function in plant responses to waterlogging stress remain undetermined. In this study, systematic analyses of the morphology, physiology, and transcriptome changes in grapevine leaves and roots under post-waterlogging and GR24 (a synthetic analog of SL) treatments were performed. Morphological and physiological changes in grapevines in response to post-waterlogging stress, including leaf wilting and yellowing, leaf senescence, photosynthesis inhibition, and increased anti-oxidative systems, could be alleviated by the application of GR24. Moreover, transcriptome analysis revealed that the primary gene functions induced by post-waterlogging stress changed over time; however, they were consistently associated with carbohydrate metabolism. The GR24-induced leaf genes were closely associated with carbohydrate metabolism, photosynthesis, antioxidant systems, and hormone signal transduction, which were considered vital aspects that were influenced by GR24 in grapevine to induce post-waterlogging tolerance. Concerning the roots, an enhancement of microtubules and cytoskeleton for cell construction in GR24 application was proposed to facilitate root system recovery after waterlogging. With this study, we comprehend the knowledge regarding the responses of grapevines to post-waterlogging and the ameliorative effect of GR24 with the insight to the transcriptome changes during these processes.

In vitro Antileishmanial Activity and In Silico Molecular Modeling Studies of Novel Analogs of Dermaseptins S4 and B2.

Leishmaniasis is responsible for approximately 65,000 annual deaths. Various Leishmania species are the predominant cause of visceral, cutaneous, or mucocutaneous leishmaniasis, affecting millions worldwide. The lack of a vaccine, emergence of resistance, and undesirable side effects caused by antileishmanial medications have prompted researchers to look for novel therapeutic approaches to treat this disease. Antimicrobial peptides (AMPs) offer an alternative for promoting the discovery of new drugs. In this study, we detail the synthesis process and investigate the antileishmanial activity against Leishmania (Viannia) braziliensis for peptides belonging to the dermaseptin (DS) family and their synthetic analogs. The MTT assay was performed to investigate the cytotoxicity of these peptides on the murine macrophage cell line RAW 264.7. Subsequently, we performed molecular modeling analysis to explore the structure-function correlation of the derivatives interacting with the parasitic membrane. All examined derivatives displayed concentration-dependent antileishmanial effect at low concentrations. Their effectiveness varied according to the peptide's proprieties. Notably, peptides with higher levels of charge demonstrated the most pronounced activities. Cytotoxicity assays showed that all the tested peptides were not cytotoxic compared to the tested conventional drug. The structure-function relationships demonstrated that the charged N-terminus could be responsible for the antileishmanial effect observed on promastigotes. Collectively, these results propose that dermaseptins (DS) might offer potential as promising candidates for the development of effective antileishmanial therapies.

Multi-modal and bi-directional effects of a synthetic Δ9-Tetrahydrocannabinol (THC) analogue, Nabilone, on spatio-temporal binding windows: Evidence from the projected hand illusion.

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of Δ9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1-2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment.

Trinucleotide cap analogs with triphosphate chain modifications: synthesis, properties, and evaluation as mRNA capping reagents.

The recent COVID-19 pandemics have demonstrated the great therapeutic potential of in vitro transcribed (IVT) mRNAs, but improvements in their biochemical properties, such as cellular stability, reactogenicity and translational activity, are critical for further practical applications in gene replacement therapy and anticancer immunotherapy. One of the strategies to overcome these limitations is the chemical modification of a unique mRNA 5'-end structure, the 5'-cap, which is responsible for regulating translation at multiple levels. This could be achieved by priming the in vitro transcription reaction with synthetic cap analogs. In this study, we combined a highly efficient trinucleotide IVT capping technology with several modifications of the 5' cap triphosphate bridge to synthesize a series of 16 new cap analogs. We also combined these modifications with epigenetic marks (2'-O-methylation and m6Am) characteristic of mRNA 5'-ends in higher eukaryotes, which was not possible with dinucleotide caps. All analogs were compared for their effect on the interactions with eIF4E protein, IVT priming, susceptibility to decapping, and mRNA translation efficiency in model cell lines. The most promising α-phosphorothiolate modification was also evaluated in an in vivo mouse model. Unexpected differences between some of the analogs were analyzed using a protein cell extract pull-down assay.

Somatostatin peptides prevent increased human colonic epithelial permeability induced by hypoxia.

Mesenteric ischemia increases gut permeability and bacterial translocation. In human colon, chemical hypoxia induced by 2,4-dinitrophenol (DNP) activates basolateral intermediate conductance K+ (IK) channels (designated KCa3.1 or KCNN4) and increases paracellular shunt conductance/permeability (GS), but whether this leads to increased macromolecule permeability is unclear. Somatostatin (SOM) inhibits IK channels and prevents hypoxia-induced increases in GS. Thus, we examined whether octreotide (OCT), a synthetic SOM analog, prevents hypoxia-induced increases GS in human colon and hypoxia-induced increases in total epithelial conductance (GT) and permeability to FITC-dextran 4000 (FITC) in rat colon. The effects of serosal SOM and OCT on increases in GS induced by 100 µM DNP were compared in isolated human colon. The effects of OCT on DNP-induced increases in GT and transepithelial FITC movement were evaluated in isolated rat distal colon. GS in DNP-treated human colon was 52% greater than in controls (P = 0.003). GS was similar when 2 µM SOM was added after or before DNP treatment, in both cases being less (P < 0.05) than with DNP alone. OCT (0.2 µM) was equally effective preventing hypoxia-induced increases in GS, whether added after or before DNP treatment. In rat distal colon, DNP significantly increased GT by 18% (P = 0.016) and mucosa-to-serosa FITC movement by 43% (P = 0.01), and 0.2 µM OCT pretreatment completely prevented these changes. We conclude that OCT prevents hypoxia-induced increases in paracellular/macromolecule permeability and speculate that it may limit ischemia-induced gut hyperpermeability during abdominal surgery, thereby reducing bacterial/bacterial toxin translocation and sepsis.NEW & NOTEWORTHY Somatostatin (SOM, 2 µM) and octreotide (OCT, 0.2 µM, a long-acting synthetic analog of SOM) were equally effective in preventing chemical hypoxia-induced increases in paracellular shunt permeability/conductance in isolated human colon. In rat distal colon, chemical hypoxia significantly increased total epithelial conductance and transepithelial movement of FITC-dextran 4000, changes completely prevented by 0.2 µM OCT. OCT may prevent or limit gut ischemia during abdominal surgery, thereby decreasing the risk of bacterial/bacterial toxin translocation and sepsis.

Effectiveness of tranexamic acid on intra- and postoperative bleeding in Bimaxillary osteotomies: a retrospective study.

Perioperative bleeding is a serious concern during orthognathic surgery. Tranexamic acid (TXA), a synthetic lysine analog with antifibrinolytic properties, reduces blood loss across various surgical fields. This study aimed to investigate the effectiveness of preoperative TXA administration in reducing intraoperative and postoperative blood loss following combined Le Fort I and sagittal split ramus osteotomies at our hospital. This single-center, retrospective cohort study included patients who underwent combined Le Fort I and sagittal split ramus osteotomies between November 2017 and October 2022. The primary outcome was the volume of intraoperative blood loss. Among 1,329 eligible patients, 87 were included in the analysis (32 in the TXA group and 55 in the control group, where no TXA was administered). The median (interquartile range) intraoperative blood loss was 200.0 (157.5-237.5) mL in the TXA group and 260.0 (180.0-350.0) mL in the control group, showing a significant difference between the groups (p = 0.0365). However, postoperative blood drainage within 24h and 24-48h did not differ significantly between the two groups. A single intravenous administration of TXA was associated with a decrease in intraoperative bleeding without severe adverse events during combined Le Fort I and sagittal split ramus osteotomies. However, postoperative blood loss, nausea, vomiting, and autologous blood transfusion were not significantly associated with this administration.

Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways.

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.

Calorimetry and structural analysis of uranyl sulfates with rare topologies

Abstract Uranyl sulfate minerals are the most rapidly expanding group of uranium minerals, with dozens of species described in the past decade from the localities of White Canyon, U.S.A. and Jáchymov, Czech Republic. Synthetic analogs of a suite of uranyl sulfate minerals were crystallized, characterized, and the standard-state enthalpies of formation (ΔHfo) were determined. Synthetic lussierite is monoclinic, space group Cc, a = 9.2896, b = 28.685, c = 9.6155 Å, β = 93.504°. Synthetic geschieberite is ortho-rhombic, space group Pna21, a = 13.7408, b = 7.2713, c = 11.5844 Å. The standard-state enthalpies of formation from the binary oxides for lussierite, péligotite, shumwayite, geschieberite, and bluelizardite are –3214 ± 78, –2026 ± 33, –587 ± 22, –966.1 ± 10.9, and –2084 ± 21 kJ/mol, respectively, while the standard-state enthalpies of formation of each phase from its elements are –9743 ± 78, –7220 ± 33, –5255 ± 22, –3916 ± 20, and –7117 ± 21 kJ/mol, respectively. The ΔHfo of péligotite was accurately estimated using the ΔHfo of lussierite, bluelizardite, and literature values of the oxide components of each phase. This implies that estimates can be made accurately of the ΔHfo of uranyl sulfates of minerals without synthetic analogs.

An insight into the role of ESIPT/TICT-based antioxidant flavone analogues in fluoro-probing diabetes-induced viscosity changes: a unified experimental and theoretical endeavour.

Potent antioxidants, like 3-hydroxy flavones, attracted considerable attention due to their excited state intramolecular proton transfer (ESIPT)-based fluorescence behaviour. This article is an interesting demonstration of a series of synthetic 3-hydroxy flavone analogues having high antioxidant activity as molecular rotor-like viscosity probes. Among these flavone analogues, 4'-N,N-dimethylamino-3-hydroxy flavone (3) is the most potent one, showing the twisted intramolecular charge transfer (TICT)-dependent fluoroprobing activity toward the blood viscosity changes associated with diabetes and free fatty acids (FFA)-induced nuclear viscosity changes of MIN6 cells. The TICT dynamics of (3), which instigates its viscosity probing activity, was comprehended with the help of DFT-based computational studies. Abnormal cellular viscosity changes are the pathological traits for various diseases, and non-toxic flavone-based viscosity probes can be useful for diagnosing such pathological conditions.

Unlocking the Potential: Amylin-Based Therapies as Novel Interventions for Addressing the Nexus of Obesity and Cardiovascular Health

The rising prevalence of obesity and cardiovascular diseases demands innovative therapeutic strategies. This paper explores the potential of amylin-based therapies in addressing the intricate interplay between obesity and cardiovascular health. Amylin, a hormone co-secreted with insulin, regulates glucose metabolism, appetite, and gastric emptying. Despite its established role in diabetes management, recent research highlights its promise in addressing obesity. Pramlintide, a synthetic amylin analog, emerges as a promising intervention for obesity, overcoming limitations of current treatments. Cardiovascular diseases, closely linked to obesity, prompt exploration of amylin's potential cardiovascular benefits. The study examines vasodilatory effects, anti-inflammatory properties, and anti-atherosclerotic effects associated with amylin. Amylin-based therapies, including pramlintide and the investigational drug AM833 (cagrilintide), are scrutinized for their impact on blood pressure, lipid profiles, and cardiovascular markers. Beyond weight loss, the study explores changes in body composition, insulin sensitivity, and lipid metabolism. The safety profile of amylin analogs, particularly pramlintide, is discussed, emphasizing their generally well-tolerated nature with manageable gastrointestinal side effects. In conclusion, amylin-based therapies present a novel approach to address the complex connections between obesity and cardiovascular diseases. The study highlights their potential in modifying body composition, improving metabolic parameters, and influencing cardiovascular outcomes. As research progresses, amylin-based strategies may offer innovative approaches to enhance metabolic and cardiovascular health, potentially reducing the global burden of cardiovascular diseases.

Maternal immune activation exerts long-term effects on activity and sleep in male offspring mice.

Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral powerunder heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.