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HOTAIR promotes the progression of B-cell acute lymphoblastic leukemia by regulating the miR-326/IGF-1R axis and activating the PI3K/AKT signaling pathway.
Hematology
Xue-Mei Zhao, Ya-Qin Jiang, Xin Wen +8 more
B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy. Long non-coding RNAs (lncRNAs) play important roles in hematological diseases; nevertheless, their mechanistic contributions to B-ALL are still poorly defined.
Comparative efficacy of GLP-1 RA, tirzepatide and SGLT-2 inhibitors in metabolic liver disease: A network meta-analysis.
Br J Clin Pharmacol
Andrej Belančić, Christina Antza, Anastasios Poutachidis +6 more
Metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, is a major cause of chronic liver dysfunction worldwide, creating an urgent need for effective treatments. This systematic literature review (SLR) and network meta-analysis (NMA) systematically reviews and compares the efficacy and safety of glucagon-like peptide-1 receptor agonists, tirzepatide and sodium-glucose co-transporter-2 inhibitors for this condition. The results of the SLR and NMA were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Selection of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension: A Comprehensive Narrative Review.
Adv Ther
Naomi G Habib, Ankita Adhia, David Lopez +2 more
One of the major mechanisms in the pathogenesis of pulmonary arterial hypertension (PAH) is mediated by elevated levels of endothelin (ET)-1, which activates both ETA and ETB receptors in the pulmonary vasculature. Endothelin receptor antagonists (ERAs) are established treatments for PAH, and three agents-bosentan, ambrisentan, and macitentan-are approved for use in adults in the USA. All are orthosteric antagonists of ET-1 and bind with high affinity to the ETA receptor, which is found largely on vascular smooth muscle cells (SMCs) and involved in vasoconstriction. Bosentan and macitentan also bind to the ETB receptor, which is upregulated on SMCs and downregulated on endothelial cells in PAH, resulting in vasoconstriction, cell proliferation, and vascular remodeling. Studies show all three ERAs are efficacious in treating PAH as monotherapy or in combination with other PAH drugs and are generally well tolerated, but all can cause fetal harm and are contraindicated in pregnancy. However, there are no head-to-head clinical trials providing a comprehensive comparison of the overall efficacy and safety of ERAs in PAH. Consequently, we examined the literature on ERAs in PAH through a targeted search of the PubMed/MEDLINE database. This narrative review explores the role of ET-1 in PAH underlying the rationale for ET receptor antagonism. It also discusses the differing physicochemical and pharmacokinetic properties of each ERA and how these unique characteristics influence their receptor binding and kinetics, mechanisms of action, therapeutic effects, dosing frequency, and safety in PAH. In the absence of head-to-head clinical trials assessing their comparative efficacy and safety, it is important to understand both the similarities and the distinguishing characteristics of the three ERAs approved in PAH, to inform individualized treatment selection.
Orexin signaling across the female lifespan: developmental, reproductive, and aging perspectives from humans and animal models.
Front Neuroendocrinol
Katarzyna Kirsz, Dorota A Zięba
Orexin-A and orexin-B are hypothalamic neuropeptides that coordinate arousal, metabolic, and reproductive functions through orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). This review synthesizes evidence from humans, experimental models, and domestic species to examine how orexin signaling modulates female physiology across the lifespan. Perinatally, orexin activation supports neonatal survival by stabilizing respiration, feeding, and sleep-wake organization. During puberty, orexins integrate metabolic and circadian cues to regulate gonadotropin-releasing hormone output and reproductive onset. In pregnancy and lactation, central and peripheral adaptations coordinate maternal metabolism, uteroplacental communication, and prolactin-dependent lactation. In aging, reduced orexin tone contributes to sleep fragmentation, metabolic dysregulation, and cognitive decline. Therapeutically, dual orexin receptor antagonists and intranasal orexin delivery illustrate stage-specific intervention strategies. Evidence across life stages derives from human, rodent, and large-animal models and must be interpreted within species-, sex-, and stage-specific biological constraints. Collectively, orexin signaling represents a conserved integrative network with health relevance.
Growth differentiation factor 11 attenuates doxorubicin-induced cardiotoxicity by inhibiting myocardial pyroptosis and oxidative stress.
Mol Cell Biochem
Jiangping Ye, Yehong Liu, Feng Xu +8 more
Doxorubicin (DOX) is limited in clinical application because of its cardiotoxicity. One of the key elements of DOX-induced cardiotoxicity is pyroptosis, a kind of programmed cell death brought on by immunity and followed by inflammatory response. Growth differentiation factor (GDF) 11 plays an significant role in oxidative stress and inflammation. The purpose of this work was to determine if GDF11 inhibits oxidative stress and pyroptosis in order to lessen the cardiotoxicity caused by DOX. SD rats were used to establish an in vivo model by intraperitoneal injection of DOX and induction of GDF11 overexpression in the heart using adeno-associated virus type 9 (AAV9). Human cardiomyocytes (AC16) were used to create the in-vitro model. By measuring the degree of cardiac function, cardiac fibrosis, inflammation, and oxidative stress; using transmission electron microscopy to examine the rat heart's microstructure; analyzing the expression of proteins of pyroptosis and oxidative stress-associated nuclear factor E2-related factor (Nrf-2)/heme oxygenase-1 (HO-1) pathway, the protective mechanism of GDF11 against DOX-induced cardiotoxicity was explored. GDF11 decreased the expression level of cardiac function, oxidative stress and inflammation-related indexes, attenuated the degree of DOX-induced cardiac fibrosis, and had some protective effects against damage to the rat heart's microstructures. Besides, GDF11 decreased the level of oxidative stress and restored the levels of anti-oxidative stress and other proteins, including Nrf-2, while also reduced the expression of DOX-induced pyroptosis-related proteins. GDF11 attenuates DOX-induced cardiotoxicity by inhibiting pyroptosis and oxidative stress, which provides new ideas for clinical improvement of DOX-induced myocardial injury.
GDF11 protects against sepsis-induced myocardial injury and cardiac dysfunction by targeting the Nrf2 signaling pathway-dependent ferroptosis.
Int Immunopharmacol
Haibo Zhang, Yutian Mi, Chunling Kong +4 more
Sepsis, a systemic inflammatory response syndrome caused by infection, can lead to life-threatening multi-organ dysfunction. Among its complications, sepsis-induced cardiomyopathy (SIC) represents one of the most severe conditions with poor prognosis. Currently, pharmacological options for clinical management of SIC are limited and often yield suboptimal outcomes, necessitating the urgent exploration of novel therapeutic strategies. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, possesses a variety of biological properties. Importantly, recent studies have highlighted the crucial protective role of GDF11 in various cardiovascular diseases. However, to date, there have been no reports on the alterations and effects of GDF11 in SIC. In this study, we initially observed a significant downregulation of GDF11 expression in both myocardium and serum of C57BL/6 J mice treated with lipopolysaccharide (LPS). Subsequently, through endogenous overexpression of GDF11 or exogenous supplementation with recombinant GDF11, we found that GDF11 mitigated lipid peroxidation-dependent ferroptosis by inhibiting iron accumulation and ameliorating mitochondrial dysfunction, thereby alleviating cardiac dysfunction and myocardial injury in septic mice. Additionally, our cellular experiments demonstrated that GDF11 could also inhibit LPS-induced ferroptosis in neonatal mouse cardiomyocytes. Nevertheless, blocking the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway using ML385 in vivo or Nrf2 siRNA in vitro abrogated the above protective effects of GDF11 against SIC. Taken together, our findings show that GDF11 may alleviate SIC by inhibiting cardiomyocyte ferroptosis through activation of the Nrf2 signaling pathway, suggesting GDF11 as a potential therapeutic target for treating patients with sepsis.
Systemic Effects of Teprotumumab Treatment on Thyroid Function in Patients With Thyroid Eye Disease: A Retrospective Study.
Ophthalmic Plast Reconstr Surg
Rafaella C Penteado, Suzan Sargsyan, Leo L T Meller +5 more
Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, has demonstrated significant efficacy in treating thyroid eye disease. While its ophthalmic benefits are well established, limited data exist regarding its effects on thyroid hormone regulation.
Immunomodulatory Effects of the Antimicrobial Peptide KR-20: Implications for Trichomoniasis.
Molecules
María G Ramírez-Ledesma, Eva E Ávila, Nayeli Alva-Murillo
Trichomoniasis is the most prevalent non-viral sexually transmitted infection worldwide and is caused by Trichomonas vaginalis. The development of resistance against the standard treatment, metronidazole, highlights the need for alternative therapeutic approaches. The role of innate immune cells is crucial for understanding trichomoniasis; however, the contribution of monocytes remains poorly characterized. We previously reported that the antimicrobial peptides LL-37 and its derivative KR-20 are trichomonacidal. In other systems, LL-37 displays immunomodulatory effects. Nevertheless, whether these peptides modulate monocyte responses in the presence of T. vaginalis remains unknown, which was the aim of this study. U937 monocytes were co-incubated with LL-37 or KR-20 (3 h), with or without parasite. Monocyte metabolic activity, nitric oxide production, and relative expression of innate immune genes were assessed. LL-37 decreased monocyte metabolic activity and upregulated TNF-α expression (10 and 5 μM, respectively) in parasite-challenged monocytes. Meanwhile, KR-20 (2.5-10 μM) preserved metabolic activity, bound microbial components (LPS), reduced parasite-induced nitric oxide production, and downregulated the expression of IL-8, TNF-α, IL-1β, and COX-2 in infected monocytes. This work provides initial evidence that KR-20 modulates innate immune response in monocytes during T. vaginalis infection, suggesting its potential-yet to be fully validated-as an immunomodulatory candidate for trichomoniasis.
Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents.
EBioMedicine
Christian E Edvardsson, Louise Adermark, Sam Gottlieb +11 more
Alcohol use disorder (AUD) remains a major public health problem, with few effective medications currently available. However, peptides of the gut-brain axis appear to offer promising therapeutic targets for AUD as they influence the mesolimbic reward circuitry.
Role of endogenous incretin hormones, GLP-1 and GIP, in cardiovascular physiology.
Can J Physiol Pharmacol
Khushali Trivedi, Vernon W Dolinsky
Obesity, type 2 diabetes (T2D), and cardiovascular disease are closely related conditions contributing to the global rise in cardiometabolic disease. Incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have emerged as critical regulators of glucose metabolism, pancreatic function, and cardiovascular physiology. However, despite increasing clinical use of GLP-1 receptor agonists and dual GLP-1/GIP agonists, the precise mechanisms by which endogenous incretins influence cardiovascular tissues remain incompletely understood, particularly in the context of obesity and T2D. This review explores the signalling mechanisms and physiological actions of natural endogenous GLP-1 and GIP, with a focus on cardiovascular physiology. Endogenous GLP-1 promotes insulin secretion, β-cell survival, and appetite suppression, and exerts protective effects on the endothelium. GLP-1 also reduces inflammation, enhances nitric oxide production, and improves myocardial glucose utilization during ischemia. Endogenous GIP is involved in insulin secretion, β-cell survival, and adipogenesis. In obesity and T2D, incretin secretion and insulinotropic effects are altered. The therapeutic potential of GLP-1 receptor agonists and emerging dual GLP-1/GIP agonists has been shown to aid in managing metabolic dysfunction and, more recently, in preventing cardiovascular complications.
Cardio-Obesity and Therapeutic Advances: Intersections Between Excess Adiposity, Cardiovascular Risk, and Pharmacologic Interventions.
Curr Atheroscler Rep
Diana De Oliveira-Gomes, Alfonso Martinez de Majo, Angie Ardila-Delgado +4 more
This review examines the mechanistic pathways linking obesity and cardiovascular disease, with particular emphasis on recent advancements in pharmacologic therapies. It evaluates the cardiovascular effects of novel anti-obesity medications and their integration into current treatment paradigms. Additionally, these pharmacologic strategies are contextualized alongside lifestyle interventions and metabolic bariatric surgery.
Melatonin mitigates hormonal toxicity in cannabis-treated female Wistar rats: involvement of cannabinoid receptor.
J Cannabis Res
A Oluwasola
Consumption of Cannabis sativa (CS), a well known psychoactive substance may impose threat on the hormonal activities of the body, hence, a protective measure is needed to prevent this threat. This study investigates the effects of melatonin and CS together with its receptors (cannabinoid receptors 1 and 2) on hormonal toxicity in female rats.
Early treatment with nootkatone prevents pressure overload-induced ventricular remodeling and heart failure.
Front Pharmacol
Zhongyuan Liu, Zixin Zhou, Wenjing Yuan +4 more
Heart failure (HF) represents the clinical end stage of most cardiovascular diseases and remains a major cause of mortality, morbidity, and poor quality of life worldwide. In the present study, we use a mouse model induced by abdominal aortic constriction (AAC) that mimics HF and evaluate the potential therapeutic effects of nootkatone (NKT) on this model. Ejection fraction (EF) and fractional shortening (FS) progressively deteriorated in the AAC mice. The AAC mice were treated with NKT for 8 weeks starting on the eighth day post-AAC. Early NKT treatment prevented cardiac dysfunction in the AAC mice at 8 and 12 weeks after administration, along with thinner left ventricular posterior wall, lower left ventricular mass and ratio of heart weight/tibial length, and fewer cardiomyocyte areas. Furthermore, we found that NKT significantly reduced the expression levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), collagen types Ⅰ and Ⅲ, TGF-β1, Smad3, and the phosphorylation of Smad3. Furthermore, NKT decreased the activation of cardiac fibroblasts and myocardial fibrosis in the AAC mice. Our data suggest that NKT can delay or reverse the progression of HF after AAC and reduce myocardial hypertrophy and fibrosis possibly via inhibition of the TGF-β1/Smad3 signaling pathway.
Genetic Syndromes and Multimorbidity in Adults with Congenital Heart Disease and Heart Failure: Insights from the PATHFINDER-CHD Registry.
J Clin Med
Ann-Sophie Kaemmerer-Suleiman, Fritz Mellert, Stephan Achenbach +25 more
Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18-68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio-extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD.
Functional Divergence of adcyap1b Splice Variants in Regulating Pituitary Hormone Expression in the Chinese Tongue Sole (Cynoglossus semilaevis).
Int J Mol Sci
Qian Zhang, Xihong Li, Yue Zhang +5 more
Sexual size dimorphism (SSD) refers to the phenomenon where males and females of the same species exhibit differences in overall or partial body size, and it is widespread among mammals, birds, reptiles, and fish. Notably, this dimorphism is significantly influenced by the sexually dimorphic secretion of growth hormone (gh), a key pituitary-derived growth regulator. Commonly, the secretion of gh is positively regulated by glucagon family members such as growth hormone-releasing hormone (ghrh) and adenylate cyclase-activating polypeptide 1 (adcyap1). To explore the stimulators for pituitary hormones (especially gh) in the teleost, we performed genome-wide identification and functional characterization of the glucagon family on Chinese tongue sole (Cynoglossus semilaevis) that exhibits typical female-biased sexual size dimorphism. Four members of adcyap1/vasoactive intestinal polypeptide(vip)/ghrh family and ten members of their receptor family were identified. Expression pattern analysis revealed high expression of adenylate cyclase-activating polypeptide 1b (adcyap1b) and its receptors in the brain. Moreover, two alternative splice variants for the adcyap1b gene were discovered, resulting from the skipping of exon 4. Following the acquisition of the two eukaryotic recombinant protein splice variants (ADCYAP1b_tv1 and ADCYAP_tv2) from HEK 293T cells, incubation experiments were conducted using C. semilaevis pituitary cell line. The results demonstrated that both variants promoted the expression of gh, pro-opiomelanocortin (pomc), and corticoliberin (crh), but ADCYAP1b_tv1 had a significantly stronger effect and uniquely stimulated prolactin (prl) and somatolactin (sl). This study demonstrates a functional divergence between the two ADCYAP1b splice variants in teleosts, with ADCYAP1b_tv1 acting as a more potent and versatile pituitary hormone stimulator. Further research on their receptor-binding affinity and downstream signaling pathways would be valuable for exploring the mechanism underlying sexual size dimorphism.
Spatiotemporal characterization of ghrelin and cholecystokinin levels in the gastrointestinal tract of juvenile Sparus aurata: effects of feeding status and diet composition.
Front Endocrinol (Lausanne)
Anyell Caderno, Patrik Tang, Verónica de Las Heras +5 more
Appetite regulation in fish relies on complex neuroendocrine pathways within the brain-gut axis, with ghrelin (Ghrl) and cholecystokinin (Cck) as central players. However, their spatial distribution along the gastrointestinal tract (GIT) and responses to feeding status remain poorly understood in teleosts. This study investigated: i) the baseline distribution of Ghrl and Cck levels along the GIT of juvenile Sparus aurata fed a commercial diet; ii) their temporal dynamics during short-term fasting and refeeding; and iii) the influence of diet composition on their spatiotemporal profiles. Juveniles were fed for 92 days with: i) a control diet containing 20% fishmeal (CT); ii) a plant protein diet replacing 60% of fishmeal with hydrolyzed plant protein (PP); and iii) the PP diet supplemented with 2% LB-GreenGrape functional additive (GG). Fish were sampled at 2, 6, and 24 h post-feeding (Cf), after 7 days of fasting (Ft), and at 2, 6, and 24 h post-refeeding (Rf). Hormone levels were quantified across five GIT segments, including the stomach (S1) and four equal intestinal segments (S2-S5). Baseline characterization revealed elevated Ghrl content in S3 and S5, whereas Cck levels were highest in S5. During fasting, Ghrl levels declined, while Cck increased in S1, S2, and S5 with distinct temporal patterns. After refeeding, gastric Ghrl levels (S1) decreased within 24 h, potentially reflecting secretion into plasma and involvement in hunger signaling, although plasma levels were not measured. In contrast, Cck levels in the anterior intestine (S2) rose sharply 24 h after refeeding, suggesting an anticipatory response to refeeding, possibly related to a dual role involving both rapid satiety signaling and preparatory modulation of digestive activity. The PP and GG diets maintained high gastric Ghrl (S1) and lowered intestinal Cck (S2) levels after feeding, especially in the PP diet. This pattern may either prolong satiety and reduce feed intake or reflect changes in hormone release due to lower caloric intake, with the PP diet lowering growth and feed efficiency, partially offset by the functional additive. The study maps Ghrl and Cck in the S. aurata GIT, showing spatial, temporal, and dietary regulation, with implications for aquaculture nutrition.
Sex-related differences in aggressive and emotional behavior in mice with the conditional inactivation of limbic Npy1r.
Horm Behav
Silvia Paterlini, Laura Gioiosa, Riccardo Panelli +5 more
Anxiety- and depression-related disorders are frequently associated with deficits in social behavior, including excessive aggression and violence, which may arise from disruptions in the neural circuits regulating emotions and social interactions. Sex differences play a crucial role in modulating emotional and social behaviors, particularly aggression and anxiety. Neuropeptide Y (NPY) and its Y1 receptor (Y1R) are involved in regulating various physiological functions, including emotional behavior and stress response. We previously demonstrated that conditional knockout of Npy1r gene in the forebrain excitatory neurons (Npy1rrfb mutant mice) increased anxiety-like behavior and hypothalamus-pituitary-adrenocortical axis reactivity and decreased body weight growth in a sex-dependent manner. In the present study we investigated how the depletion of the Npy1r gene in limbic areas might affect male and female mice by using a test battery aimed at assessing anxiety-like, social and aggressive behavior as well as response to novelty. Our results showed reduced exploratory behavior and increased anxiety in response to a novel environment in Npy1rrfb mice, with females exhibiting more pronounced effects. In contrast, only Npy1rrfb males showed reduced neophobia and increased impulsivity in response to a novel palatable food. Moreover, reduced limbic Npy1r expression decreased territorial aggression and increased defensive behaviors only in males. These findings reveal that limbic Y1R modulates anxiety, social interaction, and aggression in a sex-dependent manner. Moreover, they uncover a novel role for Y1R in regulating intermale aggression and suggest sex-specific links between NPY-Y1R signaling and the modulation of motivational and emotional responses.
Migrant blackbirds (Turdus merula) on stopover have higher plasma PYY compared to residents: A validation and proof-of-concept.
Horm Behav
Alexander T Baugh, Jesko Partecke, Natalie Wellbrock +5 more
Migratory birds expend substantial energy during flight and often rely on stopovers to refuel. Foraging behavior during stopover might vary with fuel loss and food availability though likely involves higher food intake rates than in non-migratory (resident) individuals. In mammals, hormones such as leptin signal information about energy balance and satiety. In contrast the gut hormone peptide YY (PYY), which rises rapidly after feeding and suppresses appetite in mammals, might serve a similar functional role in songbirds, which lack functional leptin. We validated and measured plasma PYY in migrant and resident Common Blackbirds (Turdus merula) on Helgoland, a key North Sea stopover site, during peak autumn migration. Migrants exhibited significantly higher circulating PYY levels than residents, possibly reflecting increased or differential foraging. PYY was unrelated to body condition or fat stores. This proof of concept study justifies future work on plasma PYY and other metabolic signals and their potential influence on avian migratory decision making.
Development of a Robust, Rapid and Reliable Tandem Mass Spectrometry Method for the Measurement of Sildenafil, Bosentan and their Major Metabolites.
Indian J Clin Biochem
Mohammad Ahmad Bik, Duygu Eryavuz Onmaz, Karam Mazin Kamil Gharab +4 more
Pulmonary arterial hypertension (PAH) is a lethal, progressive disease with a complex pathogenesis. Bosentan, a dual endothelin receptor antagonist, and sildenafil, a phosphodiesterase type 5 inhibitor, are used to treat PAH. In this study, we aimed to develop a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) to measure the levels of bosentan, sildenafil, and their active metabolites in patients with PAH. We have developed an LC-MS/MS measurement procedure using a liquid-liquid extraction to measure serum drug concentrations and validated the procedure according to Clinical and Laboratory Standards Institute (CLSI) protocols. Finally, the validated method was used to measure the levels of sildenafil, bosentan, and their metabolite in pediatric PAH patients. The method was linear in the range of 0.975-1000 ng/ml and 0.76-3125 ng/ml for sildenafil and bosentan, respectively. LOQ values of sildenafil and bosentan were determined as 1.95 and 1.50 ng/ml, respectively. A method for measuring the levels of sildenafil and bosentan was developed that is rapid, robust, inexpensive, and requires a small serum volume. In addition, the validated method measured these drugs' levels and metabolites in pediatric patients with PAH. The results show that the established method can routinely monitor drug levels.
Secondary narcolepsy and cognitive dysfunction related to craniopharyngioma: a case study.
BMC Neurol
Amelia Nur Vidyanti, Atika Rahmadini, Rifki Habibi Rahman +3 more
Craniopharyngiomas, benign tumors of the sellar region, frequently disrupt hypothalamic function, leading to endocrine and neurological sequelae, including sleep disorders.