Search Results (1,224)

Hair serves essential functions, including mechanical sensing, head protection, and body temperature regulation, while also playing a significant role in human aesthetics. However, factors such as hormonal imbalances, autoimmune disorders, infections, and psychological stress contribute to the widespread issue of hair loss, particularly among the elderly, adversely affecting self-confidence and self-esteem. Although treatments such as minoxidil, finasteride, and dutasteride have received regulatory approval, their associated side effects, such as sexual dysfunction, neuropsychiatric issues, and cardiovascular symptoms, can impede patient recovery. While follicular unit transplantation and stem cell therapy show promising outcomes, they are not suitable for all types of hair disorders. Short peptides that mimic intracellular signals and exhibit diverse biological effects have emerged as a promising approach for stimulating hair regrowth. By combining different formulations and nanosystems, the limitations of short peptides can be effectively addressed. This review systematically summarizes recent advances in peptide-based treatments for hair loss, highlighting their advantages and limitations. Full article

In an era marked by rising stress-related disorders and cardiovascular morbidity, understanding how the brain and heart adapt to environmental, physiological, and social stressors has become an urgent biomedical priority. This review advances an integrative framework centered on sociostasis, defined as the dynamic regulation of physiological state through social interaction, and its intersection with hormesis, a biphasic adaptive response to controlled stress that enhances resilience. We focus on four evolutionarily conserved neuropeptides, vasopressin, oxytocin, corticotropin-releasing hormone, and the urocortins, which serve as molecular bridges linking social behavior, neuroendocrine signaling, autonomic regulation, and cardiovascular function. Operating within an organized autonomic architecture, these systems calibrate responses to acute and chronic stress. Their context-dependent synergy enables adaptive flexibility under manageable challenge but may promote maladaptive cardiovascular remodeling when chronically dysregulated. Genetic vulnerability, developmental adversity, and persistent psychosocial stress can shift neuroendocrine–autonomic set points, increasing susceptibility to hypertension, endothelial dysfunction, and stress-induced cardiomyopathy. Conditioning and preconditioning paradigms illustrate how repeated exposure to subthreshold stressors primes cardiovascular tissues for future insults, enhancing ischemic tolerance and adaptive gene expression. We propose that cardiovascular hormesis depends not only on stimulus intensity but also on the integrity of neuroautonomic regulatory mechanisms that support recovery and flexibility. Vagal efficiency, a dynamic index of cardioinhibitory regulation, is discussed as a potential translational metric of adaptive capacity. By integrating molecular, physiological, and psychosocial perspectives, this framework conceptualizes cardiovascular resilience as an emergent property of coordinated hormetic signaling, neuropeptidergic modulation, autonomic regulation, and social buffering. Translational implications include peptide-based therapies, autonomic biofeedback, and behavioral interventions designed to enhance stress adaptability. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal endocrine L cells that activates the GLP-1 receptor (GLP-1R), leading to glucose-dependent insulin secretion and suppression of glucagon release. In recent years, GLP-1R agonists (GLP-1RAs) have become one of the leading therapeutic options for the treatment of type 2 diabetes mellitus; however, for a long time clinically approved GLP-1RAs were limited to peptide drugs unsuitable for oral administration. The discovery of the “first-in-class” small molecule agonist danuglipron in 2018 demonstrated the feasibility of orally available GLP-1RAs and stimulated the development of numerous danuglipron-like compounds, some of which showed increased efficacy over the prototype. In this study, we report the design and synthesis of novel GLP-1RAs based on a regioisomeric danuglipron scaffold, 1H-benzo[d]imidazole-5-carboxylic acid. A series of 35 compounds was synthesized and evaluated in vitro for cytotoxicity and GLP-1R agonistic activity using a cAMP accumulation assay. A potent lead compound 12r (pEC₅₀ = 7.72, pCC₅₀ < 3.60) was found which is a close structural analog of danuglipron with reduced cytotoxicity and excellent selectivity over two other class B GPCRs, including GCGR and GIPR. Despite decreased potency compared to danuglipron, the obtained results hold promise for further optimization and provide valuable structure–activity relationship insights. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective treatments for obesity, but substantial weight regain is common after therapy is discontinued. This study investigated whether probiotic strains with anti-obesity effects could enhance GLP-1RA-induced weight loss and attenuate post-treatment weight rebound. Methods: Candidate lactic acid bacteria were screened for anti-obesity efficacy in a high-fat-diet (HFD)-induced obese mouse model, and the selected strain was further characterized using metabolomic profiling of culture supernatants. To examine its interaction with GLP-1RA therapy, obese mice received dulaglutide for 4 weeks and were monitored for 2 weeks after treatment withdrawal, while the probiotic was orally administered for a total of 6 weeks. Body weight, glycemic parameters, and muscle strength were assessed throughout the study. Results: Limosilactobacillus fermentum GB102 reduced body weight and improved glycemic control in HFD-fed mice. These metabolic benefits were associated with alterations in circulating metabolic hormones, including adipokines, along with attenuated inflammatory responses in adipose tissue. Metabolomic profiling revealed that GB102 produced high levels of succinic acid, a metabolite previously linked to thermogenic activation. This strain increased whole-body energy expenditure in HFD-fed mice, produced glutamine, and showed enhanced conversion of arginine into ornithine and citrulline. When combined with dulaglutide, GB102 enhanced weight loss, preserved muscle strength, and attenuated both weight regain and glycemic rebound following dulaglutide withdrawal. Conclusions: These findings suggest that energy-metabolism-enhancing probiotics such as GB102 may enhance the metabolic effects of GLP-1RA therapy and help attenuate weight regain after treatment discontinuation. Full article

Background: Altered gut microbiota and gut-derived inflammation impair glucose regulation and promote metabolic endotoxemia, yet evidence on probiotic effects across combined glycaemic, inflammatory and short-chain fatty acid (SCFA) outcomes remains limited. This study investigated the effects of a 12-week multi-species probiotic on glucose homeostasis, incretin hormones, inflammatory biomarkers and circulating SCFAs in adults with subthreshold depression. Methods: In a 12-week double-blind, randomised, placebo-controlled trial, 39 adults with subthreshold depression were allocated to either a probiotic supplement containing Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 and Bifidobacterium longum 04 (n = 19) or placebo (n = 20). Fasting glucose, insulin, HOMA-IR, glucose-dependent insulinotropic peptide (GIP), high-sensitivity C-reactive protein (hs-CRP), lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14) and SCFAs were evaluated at three time points: baseline, week 6 and week 12. Between-group and treatment × time effects were analysed using general linear models. Results: Probiotic supplementation significantly reduced fasting glucose at 12 weeks compared with placebo (−1.8 vs. 0.1 mmol/L; p = 0.036). In the probiotic group, greater reductions in GIP (p = 0.012; p = 0.037), LBP (p < 0.001), sCD14 (p = 0.002; p = 0.001) and hs-CRP (p = 0.047) were also observed compared with placebo. Plasma SCFA concentrations remained largely unchanged, with no significant treatment × time interactions, except for higher valerate levels at 12 weeks in the probiotic group (p = 0.019). Conclusions: Twelve weeks of multi-species probiotic supplementation improved fasting glucose, reduced incretin and inflammatory biomarkers and attenuated metabolic endotoxemia, without alterations in circulating SCFAs. These findings support beneficial modulation of metabolic–immune pathways and highlight the promising role of probiotics to enhance glucose regulation and systemic inflammatory tone in adults with subthreshold depression. Full article

Abiotic stresses severely constrain crop productivity by disrupting cellular redox homeostasis and hormone signaling. Although individual stresses differ in origin, plant responses converge on a conserved regulatory system centered on reactive oxygen species (ROS) and phytohormone crosstalk. Controlled ROS production in chloroplasts, mitochondria and the apoplast functions as a signaling mechanism that interacts dynamically with abscisic acid, auxin, ethylene, jasmonate and cytokinin pathways through shared regulatory nodes, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and redox-sensitive transcriptional cascades. Endogenous metabolites, including phenolics, terpenoids, carotenoids, alkaloids, polyamines, glutathione and signaling peptides, are embedded within this network and modulate its amplitude and sensitivity. In parallel, non-microbial biostimulants derived from seaweeds, higher plants, protein hydrolysates and humic substances have been widely reported to enhance crop performance under abiotic stress. However, mechanistic integration between biostimulant research and plant stress signaling remains limited. In this review, we propose that terrestrial plant- and algal-derived biostimulants act not as external substitutes for hormones or antioxidants but as modulators of endogenous ROS–hormone signaling hubs. We first synthesize the current understanding of redox–hormone integration under abiotic stress, then examine endogenous metabolites as intrinsic regulators of this network, followed by an analysis of biostimulants in relation to shared regulatory nodes. By positioning biostimulant action within the established redox–hormone network, we provide a mechanistic framework that links stress biology with agronomic application and supports rational strategies to enhance crop resilience. Full article

In penaeids, the major yolk protein precursor vitellogenin is synthesized in both the hepatopancreas and the ovary. While ovarian vitellogenin expression is clearly regulated by hormones from the X-organ/sinus gland in the eyestalk, regulation in the hepatopancreas remains poorly understood. Here, we performed transcriptome profiling stratified by endogenous hepatopancreatic vitellogenin gene (Maj-Vg1) expression levels in immature kuruma prawn Marsupenaeus japonicus. Pathway enrichment analysis identified the insulin, mechanistic target of rapamycin (mTOR), glucagon, and AMP-activated protein kinase (AMPK) pathways as candidate modules associated with the control of hepatopancreatic Maj-Vg1 expression. Analysis of differentially expressed genes identified slit-like (Slit) and calreticulin (Calr) as genes potentially involved in the regulation of Maj-Vg1 expression. In ex vivo hepatopancreas explants, insulin-like peptide 1 from this species induced Maj-Vg1 and was accompanied by the upregulation of lipogenic markers (Max-like protein X (Mlx) and acetyl-CoA carboxylase (Acc)), consistent with vitellogenin’s lipid-transport role. Expression patterns of Calr, tuberous sclerosis complex 1 and 2 (Tsc1 and Tsc2) suggest regulatory inputs beyond insulin signaling, indicating context-dependent regulation. Taken together, these data identify metabolic status as an important contributor to hepatopancreatic Maj-Vg1 expression and define further research targets, including mTOR, AMPK, glucagon, and the Slit/Roundabout axis, for understanding vitellogenesis in penaeids. Full article

Background/Objectives: Adults with congenital heart disease (CHD) have a substantially higher risk of ischemic stroke than the general population. Circulating biomarkers such as N-terminal pro B-type natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and microalbuminuria have been associated with adverse cardiovascular outcomes in CHD, but their role in predicting cerebrovascular events remains uncertain. Methods: Prospective cohort study including 372 adults with CHD [median age 34 years (IQR 23–42); 57.8% male] followed at a tertiary center between 2017 and 2022. Baseline assessments included demographic characteristics, CHD anatomical complexity, cardiovascular risk factors, NT-pro-BNP, hs-CRP, lipid profile, and 24-h urinary albumin excretion. The primary endpoint was incident ischemic stroke during a median follow-up of 6.3 years (IQR 3.9–8.3). Univariable Cox proportional hazards models were used to identify predictors of stroke. Results: During follow-up, 13 patients (3.5%) experienced ischemic stroke. Patients with stroke were significantly older [51 (46–64) vs. 30 (23–40) years; p < 0.001] and had a higher prevalence of dyslipidemia (61.5% vs. 15.0%; p < 0.001). NT-pro-BNP levels were markedly higher in patients with stroke [369 (218–604) vs. 64 (21–172) pg/mL; p < 0.001]. No significant differences were observed between groups in renal function parameters, hs-CRP, thyroid-stimulating hormone, or urinary albumin excretion rate. In Cox analyses, older age and dyslipidemia were the strongest predictors of stroke (p < 0.001). Arterial hypertension, diabetes mellitus, and higher NT-pro-BNP levels were also associated with increased stroke risk (p < 0.05), whereas CHD anatomical complexity, NYHA functional class, and cyanosis were not. Conclusions: In adults with CHD, ischemic stroke was mainly associated with traditional cardiovascular risk factors and elevated NT-pro-BNP levels rather than anatomical disease complexity or functional status. Full article

Objective: To evaluate the efficacy of Roux-en-Y gastric bypass (RYGB) in improving glucose regulation and metabolic parameters in feline diabetes mellitus (FDM). Methods: FDM was experimentally induced via partial pancreatectomy, splenectomy, and dexamethasone administration. Following insulin stabilization, the RYGB cohort underwent gastric bypass, while the medical management group received glargine insulin. Untreated diabetic controls were monitored for 12 weeks. Blood glucose (GLU), fructosamine (FRU), biochemical profiles, and metabolic hormones were evaluated pre- and post-intervention. Hepatic and pancreatic tissues were collected for histopathological examination. Results: GLU and FRU concentrations in the RYGB group were significantly lower than in diabetic controls (p < 0.05), remaining comparable to the insulin-treated group (p > 0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly reduced post-RYGB (p < 0.05), closely matching insulin therapy outcomes (p > 0.05). Hormonal assays demonstrated decreased gastric inhibitory polypeptide (GIP) and elevated glucagon-like peptide-1 (GLP-1) in RYGB cats. Histopathologically, the RYGB group exhibited attenuated hepatic steatosis and a higher density of pancreatic islet cells with abundant cytoplasm compared to the control groups. Conclusions: RYGB effectively restores glycemic control and metabolic hormone balance in FDM, promoting morphological improvements in pancreatic islets and offering a highly promising alternative therapy for diabetic felines. Full article

Background/Objective: GHRP-6 is a GH secretagogue hexapeptide with expanding and promising cardioprotective effects. Having determined 0.4 mg/kg as the minimum effective dose for enhancing inotropy based on echocardiographic parameters in healthy rats, we implemented a non-reperfusion myocardial infarct model, with its consequent left ventricle wall thinning and ballooning, via permanent left descending coronary artery ligation. Methods: Rats were assigned to three groups: sham-operated/normal rats, infarcted + saline-treated control rats, and infarcted + GHRP-6-administration rats. Treatments were initiated post-surgery and continued for 7 days. On day 7, the animals were echocardiographically and histologically evaluated. For mitochondrial proteomic analysis, an additional 12 healthy rats were used. Six animals received GHRP-6 or normal saline and were observed for 6 h after the inoculation. Results: Here, we show that GHRP-6 attenuated myocardial tissue demise, reduced myocardial interstitial fibrosis/scarring, and integrally improved left ventricle physiology. The proteomic analysis indicated that the GHRP-6 cardioprotective effects may be theoretically mediated by the concerted upregulation of proteins/pathways involved in fatty acid beta-oxidation, apoptosis prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Conclusions: GHRP-6 is a potent cardioprotective candidate attenuating morphological and functional outcomes caused by late ischemia. Full article

Background/Objectives: Humans have at least 26 bitter taste receptors (T2Rs), and among these, bitter taste receptor 14 (T2R14) is highly expressed in both oral and extraoral tissues. Over 100 bitter ligands can activate T2R14, including hormones, vitamins, plant compounds, and peptides. Previous studies suggest that bitter tastants such as quinine and caffeine can inhibit G protein-coupled receptor kinases (GRKs) and delay T2R signal termination. Our earlier research showed that peptides from alcalase and chymotrypsin hydrolysates of beef proteins inhibited quinine-dependent calcium release through T2R4, with AGDDAPRAVF and ETSARHL showing the greatest effectiveness. However, the effect of these antagonistic peptides on other T2Rs, such as T2R14 signaling, remains unknown. This study aimed to evaluate the ability of these beef protein-derived peptides to activate or inhibit T2R14 signaling and the involvement of GRK2 in signal termination. Methods and Results: Our results indicate that the above two antagonist peptides significantly inhibit T2R14 activity. Furthermore, GRK2 knockout in HEK cells stably expressing T2R14 decreases intracellular calcium release, as measured by the area under the curve (AUC), and also delays the fall time (indication of desensitization) of the calcium response when exposed to the T2R14 agonist diphenhydramine (DPH) or beef protein-derived agonist peptide TMTL. Next, we measured the effects of these ligands on cAMP accumulation, and our results suggest no significant change in cAMP levels upon treatment with beef protein-derived peptides. Conclusions: Thus, this study showed that beef protein-derived peptides can function as both T2R inhibitors and mediate T2R14 desensitization through GRK2 signaling. These antagonistic food protein-derived peptides inform strategies to enhance nutrition, such as promoting healthier food choices by reducing bitterness and thereby improving the palatability of health-promoting bitter foods, such as fruit and vegetable extracts, as well as bitter medications. Full article

The islet amyloid polypeptide (IAPP) is a peptide hormone playing key biological roles, including glucose homeostasis and regulation of food intake, conferring high therapeutic potential to treat metabolic disorders. Nonetheless, IAPP is mainly known as the major component of the amyloid fibrils observed in the pancreatic islets of patients afflicted with type 2 diabetes, and the accumulation of these insoluble protein deposits correlates closely with the loss of pancreatic β-cells. The inherent aggregation propensity of this peptide hormone is not only associated with the pathogenesis of type 2 diabetes but also complicates the design of IAPP derivatives for the treatment of metabolic disorders. Accordingly, elucidating the molecular mechanisms by which IAPP self-assembles into amyloid fibrils is critical to identify chemical strategies to arrest aggregation, as well as to design safe and stable IAPP-derived therapeutics. This review aims at presenting the different mechanistic models of IAPP aggregation and how to exploit this information to identify inhibitors of amyloid formation and non-aggregating peptide agonists. After discussing the conformational conversions allowing IAPP to undergo a mainly disordered monomeric conformation into ordered cross-β-sheet quaternary supramolecular structures, we present chemical strategies to prevent amyloid deposition and to develop non-aggregating peptide-based therapeutics. Full article

Energy homeostasis arises from a complex interplay between gut-derived hormones, the central nervous system, and pancreatic function. Beyond the classical incretin axis, a broad spectrum of gut peptides acts in concert to coordinate appetite regulation, nutrient sensing, gastric motility, and systemic bioenergetic balance. Perturbation of this network contributes to metabolic disorders such as obesity, type 2 diabetes, and cachexia, underscoring its pivotal role in physiological and pathological energy regulation. This review provides an integrated analysis of the mechanisms through which gut–brain–pancreas communication maintains metabolic homeostasis, with particular attention to the dynamic cross-talk between peripheral endocrine signals and central regulatory circuits. Alterations in these pathways are examined in relation to their impact on energy expenditure and substrate utilisation, alongside recent translational efforts exploiting multi-receptor peptide agonism and combinatorial hormonal modulation to restore metabolic equilibrium. Emerging therapeutic approaches increasingly aim to engage multiple bioenergetic pathways simultaneously, supported by advances in peptide engineering and molecular design. By conceptualising metabolic regulation as a coordinated network rather than a linear hormonal cascade, this article delineates a physiological and translational framework for next-generation interventions targeting bioenergetic dysfunction in human disease. Full article

Background/Objectives: Insulin and glucagon are key hormones in metabolic regulation. There are limited comparative data on how common rodent anesthetic regimens influence hormone secretion, leading to misinterpretation of results. We aimed to compare the effects of several anesthetic regimens on insulin and glucagon secretion using the physiologically relevant isolated perfused rat pancreas model. Methods: Six commonly used rodent anesthetic regimens were assessed for their ability to induce surgical depth of anesthesia. Once achieved, the pancreas was vascularly isolated and perfused. After euthanasia, the pancreas was stimulated with glucose and glucagon-like peptide-1 (GLP-1). Insulin and glucagon were measured in the effluent using radioimmunoassay. Results: Anesthesia with Hypnorm^® (fentanyl/fluanisone)/midazolam produced the most physiological responses, meaning that insulin was secreted in response to hyperglycemia and GLP-1, and glucagon was secreted under hypoglycemia. Ketamine/dexmedetomidine anesthesia abolished insulin dynamic secretion and blunted glucagon secretion. Isoflurane/buprenorphine anesthesia partially suppressed insulin secretion, but it still followed a physiological pattern in response to glucose fluctuations. However, it abolished the dynamic glucagon responses to glucose. Three additional anesthetic regimens failed to produce surgical depth anesthesia and were therefore not further analyzed. Conclusions: Different anesthetic regimens altered pancreatic hormone secretion. Fentanyl/fluanisone/midazolam was associated with dynamic insulin and glucagon secretion, whereas ketamine/dexmedetomidine and isoflurane/buprenorphine altered the pattern and/or magnitude of hormone secretion. Overall, the choice of anesthesia is a critical variable in animal experimentation for metabolic studies and may confound the interpretation of results. Full article