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Clinical Characteristics of Iron Deficiency in Patients with Chronic Heart Failure at a Major Referral Centre in Southern Nigeria.
Niger Med J
Aisha O Ajala, Boma Oyan, Sotonye Dodiyi-Manuel +4 more
Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF) and is associated with reduced functional capacity, diminished quality of life, and increased mortality. This study aimed to determine the prevalence of ID and its clinical characteristics.
Case Report: ACTH-independent Cushing's syndrome caused by isolated micronodular adrenal disease in a 23-month-old girl.
Front Endocrinol (Lausanne)
Marta Valério, Gonçalo P Croca, Joana Simões +4 more
Cushing's syndrome in early childhood is rare and may be particularly challenging to diagnose when adrenal imaging is unrevealing. We report the case of a 23-month-old girl who presented with rapid weight gain, cushingoid appearance, hypertrichosis, severe hypertension, irritability, and developmental regression. Biochemical assessment confirmed adrenocorticotropic hormone (ACTH)-independent hypercortisolism, with suppressed ACTH, loss of circadian cortisol rhythm, lack of cortisol suppression following dexamethasone administration, and increased 24-hour urinary free cortisol excretion. Adrenal magnetic resonance imaging showed morphologically normal adrenal glands. Adrenal computed tomography was not performed, to avoid additional ionising radiation after a non-diagnostic adrenal MRI in a 23-month-old child. Adrenal scintigraphy with ¹³¹I-NP-59 after metyrapone-induced suppression demonstrated bilateral adrenal uptake, slightly more prominent on the right. The patient underwent right adrenalectomy. Histopathological examination showed micronodular adrenocortical hyperplasia without pigmentation, atypia, or malignant features, consistent with isolated micronodular adrenal disease. Following surgery, blood pressure, metabolic abnormalities, cutaneous manifestations, and motor function improved markedly. Steroid supplementation was required for only 3 days post-operatively, with no evidence of persistent adrenal insufficiency. At 3 years of follow-up, there were no clinical features of recurrent hypercortisolism, blood pressure remained normal without antihypertensive therapy, body mass index had markedly improved, and available biochemical parameters were reassuring. This case highlights that isolated micronodular adrenal disease should be considered in very young children with ACTH-independent Cushing's syndrome even when adrenal magnetic resonance imaging is normal. Functional adrenal imaging may be useful in selected cases, and unilateral adrenalectomy may achieve durable remission while delaying permanent adrenal insufficiency.
Clinical utility of adrenal venous sampling for functional lateralization in ACTH-independent autonomous cortisol secretion: relevance in non-decisive imaging.
Eur J Endocrinol
Tetsuya Kawahara, Mikio Toda, Maiko Kanagawa +3 more
Determining functional laterality in adrenocorticotropic hormone (ACTH)-independent autonomous cortisol secretion remains challenging when imaging demonstrates bilateral or non-decisive adrenal findings. We evaluated whether adrenal venous sampling (AVS) improves lateralization in this clinically challenging subgroup.
GLP-1 Receptor Agonist Therapy for Obesity Under Japan's Optimal Use Guideline: A Prospective Real-World Study of Lifestyle Pre-Treatment, Time-Limited Treatment Cap, and Post-Cessation Regain.
Diabetes Obes Metab
Susumu Inamine, Yasunori Uesato
Japan's optimal use guideline restricts insurance-reimbursed GLP-1 receptor agonist (GLP-1 RA) therapy for obesity to patients completing a mandatory 6-month lifestyle intervention, caps treatment at 68 weeks (semaglutide 2.4 mg) or 72 weeks (tirzepatide), and mandates subsequent washout. We evaluated the clinical implications of this regulated program in a real-world cohort of patients with obesity treated with semaglutide or tirzepatide, with particular attention to pre-treatment weight change during the mandated lifestyle phase, on-treatment response, and post-cessation weight regain.
Safety and efficacy of glucagon like peptide-1 receptor agonism-based therapies in end-stage renal disease: A systematic review and meta-analysis.
Endocr Pract
Deep Dutta, Sweekruti Jena, Kunal Mahajan +3 more
No systematic review and meta-analysis (SRM) has analyzed the safety and efficacy of glucagon like peptide-1 receptor agonism-based therapies (GLP1RA-BT) in people with end stage renal disease (ESRD) [GFR<15ml/min/1.73m2 or on renal replacement therapy (RRT)]. Hence this SRM analyzed the safety and efficacy of GLP1RA-BT in ESRD.
Curculigoside A alleviates metabolic dysfunction-associated steatohepatitis by targeting Rab30 to improve lipid homeostasis.
Phytomedicine
Yue Shi, Yiwen Han, Hairong Zhang +5 more
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatocellular lipid overload, hepatic inflammation, and fibrotic remodeling. Impaired lipid droplet clearance and fatty acid oxidation (FAO) contribute to MASH progression, yet the molecular regulators coordinating these processes remain insufficiently defined.
CD163+ red pulp macrophages interact with marginal metallophilic macrophages during blood-stage malaria to maintain splenic architecture.
Immunity
Katharina Mauel, Daria Hirschmann, Nelli Blank-Stein +10 more
The spleen harbors distinct macrophage subsets that support circulatory homeostasis and initiate immune responses, but the ontogeny and long-term dynamics of these populations remain incompletely understood. Here, we identified a transcriptionally and developmentally distinct CD163-expressing red pulp macrophage (CD163high RPM) population that arose from yolk sac progenitors and occupied a vascular-associated niche. Using fate-mapping models, we showed that CD163- RPMs were progressively replenished by monocytes during aging, whereas CD163high RPMs were mainly self-maintaining. During blood-stage malaria, CD163high RPMs were rapidly depleted, failed to recover despite parasite clearance, and were replaced by CD163- monocyte-derived RPMs. Single-cell RNA sequencing and genetic mouse models revealed that CD163 deficiency exacerbated structural disintegration of the marginal zone and selectively impaired marginal metallophilic macrophage (MMM) recovery, underscoring a CD163-dependent RPM-MMM crosstalk. This study reveals that the sustained loss of a specialized, yolk sac-derived CD163high RPM subset rewires splenic architecture and inter-macrophage crosstalk long after malaria resolution.
Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.
Aging Dis
Khoshnur Jannat, Sang-Bong Lee, Hong-Ryeol Jung +4 more
Parkinson's disease is a neurodegenerative condition characterized by the accumulation of misfolded and aggregated α-synuclein in Lewy bodies and neurites. These protein aggregates contribute to neurodegeneration and motor symptoms such as bradykinesia, rigidity, and tremor. While the ubiquitin-proteasome system degrades soluble α-synuclein, aggregated and oligomeric forms are primarily cleared via the autophagy-lysosomal pathway. Mutations of the SNCA gene exacerbate α-synuclein aggregation and significantly impair its clearance, highlighting the importance of targeting toxic α-synuclein species. Strategies such as promoting autophagosome formation via 5'-AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) or facilitating autophagosome maturation via RAB7-a member of the RAS oncogene family-and related effectors, have shown promise in enhancing autophagy and reducing α-synuclein pathology. Pharmacological agents such as rapamycin, trehalose, and nilotinib have demonstrated preclinical efficacy in enhancing α-synuclein clearance and alleviating disease features. Concurrently, immunotherapy approaches, including passive and active immunization, aim to enhance the immune system's ability to recognize and eliminate toxic α-synuclein species. Emerging strategies such as peptide-based therapies aim to inhibit aggregation or promote degradation of α-synuclein. At the same time, nanotechnology enables the targeted delivery of therapeutic agents across the blood-brain barrier with improved efficiency. Additionally, novel AUTOTAC (autophagy-targeting chimera) platforms offer a precision strategy to tag α-synuclein for autophagic degradation. This review explores many advances in autophagy-mediated aggregated α-synuclein clearance, emphasizing its potential as a therapeutic strategy to address the limitations of current symptomatic treatments and slow the progression of Parkinson's disease.
Stress in rearing: Biochemical and growth impacts of acoustic exposure in juvenile Dicentrarchus labrax.
Mar Pollut Bull
M Mauro, P Giner-Tarazona, V Espinosa +9 more
Acoustic pollution is an emerging concern in aquaculture, where continuous exposure to noise can affect the welfare of farmed fish. Juvenile fish may be more susceptible to acoustic disturbances during their growth phases, which could potentially affect their physiological responses. The European seabass (Dicentrarchus labrax) is an important species in aquaculture due to its economic value and widespread farming, making it a relevant model for studying the effects of acoustic pollution on farmed species. This study aimed to evaluate the short-term effects (30 min, 3 h, 24 h, and 7 days) of traffic noise exposure on the cellular responses of juvenile Dicentrarchus labrax, using whole-body analyses. Acoustic emissions were recorded from four different fishing vessels at distances between 10-15 m, with recordings played back randomly separated by 10 to 30-second intervals of silence between consecutive emissions. The biomarkers tested included heat shock protein 70 (HSP70), superoxide dismutase (SOD), glutathione peroxidase (GPx), adrenocorticotropic hormone (ACTH), cortisol, glucose, esterase, and alkaline phosphatase. The results revealed significant alterations in these parameters after just 30 min of exposure, with a tendency toward recovery after 7 days. Furthermore, a statistically significant reduction in growth rates was observed in exposed individuals. Although these findings may not apply to all species of farmed fish, they provide valuable insights into minimizing acoustic impacts and improving animal welfare in aquaculture environments.
Cutaneous Manifestations of Carcinoid Tumor and Syndrome.
Clin Dermatol
James Mackenzie, George G Kels, Mary Kate Staunton +1 more
Carcinoid syndrome refers to the signs and symptoms a patient experiences secondary to a carcinoid tumor or another well-differentiated neuroendocrine tumor, which secretes serotonin and other peptides that enter the bloodstream; only 10% of patients with carcinoid tumors experience carcinoid syndrome. Common findings include facial flushing, tachycardia, and shortness of breath. Carcinoid tumors usually originate in the gastrointestinal (G.I.) tract. They are slow growing but can metastasize to the liver, lymph nodes, and elsewhere. Primary or metastatic cutaneous carcinoid tumors present as pink, fast-growing dermal or subcutaneous nodules. The diagnostic workup includes a thorough history and physical examination of the entire body, including a urinary 24-hour 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A. Management of carcinoid syndrome initially includes the use of somatostatin analogs, diet, medication regulation, and clinical monitoring. More aggressive treatment, such as peptide receptor radionuclide therapy or everolimus, an mTOR inhibitor, may be required.
Pulmonary Arterial Hypertension-Targeted Therapy for Pulmonary Hypertension Associated with Left Heart Disease: Bayesian and Frequentist Meta-Analysis of Randomized Controlled Trials.
Am J Cardiol
Yuko Kiyohara, Taku Sakai, Lina M Freeman +9 more
Pulmonary hypertension associated with left heart disease (PH-LHD) is the most prevalent form of pulmonary hypertension. Despite the recent advances in medications for pulmonary artery hypertension (PAH), it remains unclear whether PAH-targeted therapy is effective in patients with PH-LHD.
Acute Nutritional Axonal Neuropathy in the Setting of Semaglutide-Associated Gastrointestinal Intolerance: A Case Report.
Case Rep Neurol
Chloe J Cohan, Liam Townley, Erik Ortega
The aim of the study was to report a unique case of severe sensorimotor polyneuropathy due to acute nutritional axonal neuropathy (ANAN) associated with thiamine and other vitamin deficiencies in the setting of semaglutide-related malnutrition, emphasizing early recognition and intervention to prevent permanent neurologic injury.
The role of walking speed and leg proprioception in foot clearance for older transtibial prosthesis users.
Prosthet Orthot Int
Anna C Pogharian, Kiley L Armstrong, Jenny A Kent +2 more
Falling is a concern for both older persons and transtibial prosthesis users (TTPUs), with older TTPUs potentially facing compounded risk. Older adults and TTPUs display foot clearance (FC) behavior that may contribute to increased tripping risk. Further, a person's knowledge of their leg orientation in space (ie proprioception) plays a role in managing FC and is affected by age and prosthesis use.
Biomarkers of systemic disease burden and outcomes after transcatheter tricuspid edge-to-edge repair.
BMC Cardiovasc Disord
Johannes Schlegl, Marwin Bannehr, Michael Lichtenauer +7 more
Risk stratification after transcatheter tricuspid edge-to-edge repair (T-TEER) remains challenging, particularly in patients with advanced right-sided heart failure and systemic disease burden. Biomarkers reflecting inflammation, stress response and multiorgan dysfunction may provide additional prognostic information in this setting.
Open-Label, Balanced, Randomized, Single-Dose, Three-Treatment, Three-Sequence, Three-Period, Three-Way Crossover Oral Bioequivalence Study of Desmopressin Acetate Oral Solution.
Clin Pharmacol Drug Dev
Adam Christensen, Axay Parth, Mansi Kotak +3 more
Desmopressin is first-line therapy for central diabetes insipidus, also known as arginine vasopressin deficiency, but presents dosing challenges due to its narrow therapeutic index. This open-label, randomized, three-way crossover study evaluated the bioequivalence of a new desmopressin acetate oral solution (50 mcg/mL) compared to desmopressin acetate tablets (200 mcg) in 75 healthy adults. In a balanced, three-sequence, three-period design with 14-day washout periods, participants received a single 600-mcg dose of test product and reference product under fasted conditions. Plasma desmopressin concentrations were measured using a validated liquid chromatography-electrospray ionization tandem mass spectrometry method, and primary pharmacokinetic parameters (maximum plasma concentration [Cmax], area under the plasma concentration-time curve from time 0 to the last measurable concentration [AUC0-t], AUC from time 0 extrapolated to infinity [AUC0-∞]) were derived from resulting concentration-time profiles. Bioequivalence was assessed using analysis of variance on log-transformed parameters, with 90% confidence intervals (CIs) for geometric mean ratios 80%-125%. Results demonstrated bioequivalence between formulations, with geometric mean ratios of 101.9% (93.9%-110.5%) for Cmax, 103.7% (94.8%-113.5%) for AUC0-t, and 103.7% (94.9%-113.3%) for AUC0-∞. Both formulations exhibited similar pharmacokinetic profiles with 1.0 h median time to maximum concentration, ∼3.6 h mean elimination half-life, and 30%-33% intrasubject variability. Five adverse events were reported by five participants (6.7%), including two cases of hyponatremia (reference group) and one case of vomiting (test group); all were mild to moderate and resolved completely. This study establishes bioequivalence between desmopressin acetate oral solution and tablets, supporting regulatory approval of the oral solution formulation.
Crinecerfont: emerging role in the management of congenital adrenal hyperplasia.
Expert Rev Endocrinol Metab
Olga Fedorova, Henrik Falhammar
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare genetic endocrine disorder characterized by impaired cortisol synthesis, excessive adrenal androgen production, and elevated adrenocorticotropic hormone (ACTH) concentrations. The current standard of care involves supraphysiologic doses of glucocorticoids to suppress ACTH and manage androgen excess, often leading to long-term complications.
Expert Consensus to Explore the Definition and Characterization of Methamphetamine-Associated Pulmonary Arterial Hypertension and Key Treatment Considerations.
CHEST Pulm
Roham Zamanian, Peter J Leary, Therese Sargent +12 more
Methamphetamine use can result in methamphetamine-associated pulmonary arterial hypertension (Meth-APAH). Compared with idiopathic pulmonary arterial hypertension (PAH), Meth-APAH may have a worse clinical course.
Semaglutide-associated NAION: a proposed 'two-hit' model involving buried optic disc drusen and sustained hypohydration.
Br J Ophthalmol
Guohong Zhao, Nan Ma, Yan Yang +2 more
Semaglutide-associated non-arteritic anterior ischaemic optic neuropathy (NAION) mechanisms are unclear. We report a 28-year-old man with type 2 diabetes who developed right NAION 4-5 months after starting semaglutide. Multimodal imaging confirmed NAION and bilateral buried optic disc drusen. The affected eye was short, whereas the fellow eye was highly myopic and longer. Serial bioimpedance showed a 1.9 L decline in total body water over 7 weeks, with preserved fat mass and stable extracellular-to-total-body-water (ECW/TBW) ratio. We propose a hypothesis-generating 'two-hit' model in which anatomical susceptibility and sustained hypohydration together precipitate NAION. Heightened clinical awareness may be warranted and prospective studies are required.
[The Effect of MiR-100-5p on the Biological Behaviors of Pediatric Acute Myeloid Leukemia Cells by Targeting IGF1R].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
Ying Yang, Cong-Mei DU, Yin Sun +1 more
To investigate the effect of miR-100-5p on the biological behaviors of pediatric acute myeloid leukemia (AML) cells by targeting insulin-like growth factor 1 receptor (IGF1R ).
Semaglutide in Practice: Insights from a Retrospective Case Series at a Jharkhand Tertiary Care Hospital.
J Assoc Physicians India
Ajay Kumar Jha, Ashok Sunder
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, real-world evidence from Indian populations remains limited. This study aimed to assess the effectiveness and safety of semaglutide on glycemic control, body weight, and metabolic parameters in patients with T2DM in a real-world clinical setting.