The living record of
peptide science.

Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis.

Indian J Crit Care Med

Ashritha A Udupa, Pratibha Todur, Souvik Chaudhuri +8 more

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high mortality rate despite advances in supportive care. Aviptadil, a synthetic analogue of vasoactive intestinal peptide (VIP), exhibits anti-inflammatory potential and cytoprotective effects that may improve pulmonary function. However, its role in improving survival among ARDS patients remains uncertain. This systematic review and meta-analysis aimed to evaluate the effectiveness of aviptadil in improving survival and oxygenation outcomes in ARDS.

CNP inhibits T3 - induced hypertrophic growth in H9c2 cells: Impact of HDAC inhibitor.

Arch Biochem Biophys

Gopinath Nagaraj, Elangovan Vellaichamy

C-type natriuretic peptide (CNP) is a multifaceted paracrine factor that regulates vital physiological functions of the cardiovascular system. The present study was designed to investigate the anti-hypertrophic activity of CNP in the presence and absence of HDAC inhibitor Suberoylanilide hydroxamic acid (SAHA) in T3-induced H9c2 cells. The H9c2 cells were treated with T3 (10 nM) for 48 hours to induce hypertrophic growth. T3 alone-treated cells exhibited an increase in cell size (p < 0.001) as compared with control H9c2 cells. CNP treatment effectively reverted the increased cell size by 61 %, and also altered the expression of hypertrophic marker genes. Interestingly, a significantly enhanced anti-hypertrophic activity was noticed in CNP co-treatment with SAHA, and also a more significant decrease in the expression of hypertrophic marker genes (α-sk, and α-MHC) was also observed. Moreover, CNP treatment with SAHA effectively reversed the T3-induced changes in the expression of Npr1 and Npr2 genes in H9c2 cells. In addition, CNP co-treated with SAHA reversed the T3-induced abnormal calcium influx by normalizing of CaMKII and SERCA2a. The findings of the present study clearly show that CNP co-treatment with SAHA significantly enhances the CNP-mediated anti-hypertrophic activity, probably by restoring Npr1 and Npr2 gene expression and calcium influx. Taken together, we conclude that CNP in combination with SAHA represents a novel therapeutic approach for the treatment and management of cardiac hypertrophy and heart failure.

Natriuretic Peptides as Multisystem Regulators: From Clinical Biomarkers to Therapeutic Targets in Cardio-immunology.

Cardiovasc Drugs Ther

Jathniel Panneflek, Mahmoud Barbarawi, Yasitha Kakarlapudi +3 more

Natriuretic peptides (NPs) ANP, BNP, and CNP extend beyond biomarkers of wall stress to regulators of cardiovascular, renal, metabolic, and immune pathways via cGMP-PKG signaling. We synthesize mechanistic and translational evidence, highlight NP "resistance," and appraise therapeutic strategies that augment NP signaling.

Webb-Dattani syndrome in a 17-year-old girl.

Endocrinol Diabetes Metab Case Rep

Jamilah Saleh Alyami, Wael Mohammad Almistehi, Khalid Ibrahim Alkanhal

Webb-Dattani syndrome (WEDAS) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the ARNT2 gene. It is characterized by a triad of congenital hypopituitarism, structural brain abnormalities, and multisystem developmental defects. We report the case of a 17-year-old girl with WEDAS who presented with global developmental delay, panhypopituitarism, and arginine vasopressin (AVP) deficiency, formerly known as central diabetes insipidus with adipsia, visual impairment, renal anomalies, and spastic quadriplegia. Her endocrine profile revealed deficiencies in ACTH, TSH, and ADH, and gonadotropins, with a possible growth hormone deficiency. Management included hormone replacement with hydrocortisone, levothyroxine, and desmopressin, as well as fluid regulation and supportive care. Despite multiple hospitalizations due to complications including hypernatremia and infections, the patient survived into adolescence - the longest reported survival in this condition to date - before passing away at age 17. This case expands the known clinical phenotype of WEDAS, emphasizing the importance of early recognition, genetic testing, and a multidisciplinary approach to care for affected individuals, particularly in consanguineous populations where the syndrome may be underdiagnosed.

Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide.

Vascul Pharmacol

Yi Ning Choo, Ram Narayanan, Vetriselvan Subramaniyan

Obesity is a chronic, complex condition defined by excessive fat buildup due to an imbalance between caloric consumption and energy expenditure. The significant global rise in prevalence of obesity is associated with numerous comorbidities, such as cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. Conventional management approaches, including diet, exercise, pharmacotherapy, and bariatric surgery, may demonstrate restricted long-term effectiveness owing to inadequate adherence and physiological adjustments. Recent advancements in neuroscience underscore the hypothalamus as a pivotal regulator of energy balance via essential nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), lateral hypothalamic area (LHA), and ventromedial nucleus (VMN). This review examines the therapeutic potential of a new anti-obesity peptide that targets hypothalamic signalling pathways. Preclinical and clinical evidence endorses the utilization of glucagon-like peptide-1 receptor (GLP-1R) agonists and novel multi-receptor drugs such as AMG 133, which integrate GLP-1R activation with glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism. These therapies exhibit improved weight reduction and metabolic enhancement. Moreover, the integration of hypothalamic peptide therapy with lifestyle modifications or post-bariatric care provides synergistic advantages. Notwithstanding favorable results, peptide therapy encounters obstacles such as administration methods, sustained effectiveness, and expense. Overcoming these obstacles is crucial for the effective implementation of peptide-based treatments in sustained clinical obesity control.

A multi-tissue integration of immunocytes and inflammaging biomarkers predicts biological age through LASSO-optimized modeling.

Biogerontology

Jiawei Yang, Haichen Zhang, Qiong Zhang +8 more

Immunosenescence, a recognized hallmark of aging, is characterized by imbalances in immunocyte populations and a state of chronic inflammation. However, the tissue-specific dynamics of these changes and their potential as predictive biomarkers for aging remain poorly characterized. In this study, we established a multi-tissue immunological signature as a robust predictor of biological age by integrating immunocyte and cytokine profiling. Using Sprague-Dawley (SD) rats from five age groups (1-12 months), we systematically quantified 45 immunocyte subsets across peripheral blood, mesenteric lymph nodes, thymus, and spleen using flow cytometry, and profiled 22 serum cytokines/chemokines via Flexible Multi-Analyte Profiling (xMAP). Firstly, classic age-dependent shifts were observed across our rat samples, including progressive thymic involution and depletion of peripheral T-cells. Cytokine levels exhibited age-related chronic inflammation progression, marked by elevated IL-1α, granulocyte colony-stimulating factor (G-CSF), and TNF-α. To integrate these multidimensional datasets into a predictive aging metric, we employed Least Absolute Shrinkage and Selection Operator (LASSO) regression, selecting 22 biomarkers through regularization (λ = 0.111). The integrated model combining cellular and cytokine data demonstrated superior performance (training R2 = 0.957, validation R2 = 0.887), outperforming single-modality models based on immunocytes or cytokines. Notably, splenic parameters dominated the aging signature, contributing seven biomarkers representing 60% of model weight-particularly Th-cell expansion and Tc-cell depletion. Peripheral blood Th-cell proportion emerged as another key predictor. Our findings position the spleen as a critical aging hub and identify peripheral/splenic Th-cell modulation as promising therapeutic targets for age-related immune dysfunction, revealing novel mechanistic insights into aging-associated immune remodeling.

Letter to the Editor - Qualitative evidence submitted by patients to NICE: need for more quality or unrealistic and unfair requirements?

J Comp Eff Res

Rocco Falchetto, Jasmin Barman-Aksözen

Giant Sellar Meningocele: Intact Pituitary Function and New-onset Arginine Vasopressin Deficiency After Surgery.

JCEM Case Rep

Oscar Josué Gómez-Romero, Baldomero González-Virla, Guadalupe Vargas-Ortega +3 more

Sellar and sphenoidal meningoceles are rare entities that can lead to neurological, ophthalmological, and endocrine complications. We report the case of a 28-year-old man with a giant sellar meningocele who presented with chronic headache and bitemporal hemianopsia but with preserved pituitary function at diagnosis. Magnetic resonance imaging revealed a large defect of the sellar floor with herniation of meninges and displacement of the optic chiasm and pituitary gland. The patient underwent endoscopic transsphenoidal repair. Within 24 hours, he developed arginine vasopressin (AVP) deficiency requiring long-term desmopressin therapy, which persisted beyond 6 months, fulfilling the criteria for permanent AVP deficiency. No other pituitary hormone deficits were observed. Visual field impairment did not improve after surgery, although further deterioration was prevented. This case underscores that adult sellar meningoceles can present with intact anterior pituitary function but still carry a risk of isolated permanent AVP deficiency after surgical repair. To our knowledge, this is among the largest adult sellar meningoceles reported with preserved anterior pituitary function at presentation and subsequent permanent isolated AVP deficiency, emphasizing the need for careful perioperative counseling and long-term endocrine follow-up.

Insulinoma Unmasked By Tirzepatide: A Rare Case of Postprandial Hypoglycemia In a Nondiabetic Patient.

JCEM Case Rep

Michael Polisky, Dina Kamel, Jeong-Hee Ku

A 63-year-old woman with obesity presented with severe postprandial hypoglycemia that worsened after starting tirzepatide for weight loss. Further evaluation led to the diagnosis of insulinoma. This case suggests that the use of tirzepatide can provoke severe hypoglycemia episodes in patients with insulinoma and highlights the importance of including insulinoma as a differential diagnosis for hypoglycemia in patients taking incretin-based therapy.

GLP-1 receptor agonists on WHO-EML 2025 list: major breakthrough bounded by persistent challenge.

J Diabetes Metab Disord

Kanimozhi Mani

The World Health Organisation (WHO) periodically updates its Model List of Essential Medicines (EML) and Essential Medicines for Children (EMLc) to address evolving global health priorities. The 24th EML and 10th EMLc, released on 5th September 2025, mark a major milestone by expanding access to twenty new medicines for diabetes, cancer, cystic fibrosis, haemophilia, psoriasis, and blood disorders. Notably, the inclusion of glucagon-like peptide-1 (GLP-1) receptor agonists-semaglutide, liraglutide, dulaglutide-and the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, represents a paradigm shift in the management of type 2 diabetes mellitus (T2DM) and obesity. These agents have demonstrated significant benefits in lowering blood glucose levels, reducing cardiovascular and renal complications, and promoting weight loss in T2DM patients with established cardiovascular disease (CVD), chronic kidney disease (CKD), or obesity. This move aims to bridge the longstanding treatment gap in low- and middle-income countries (LMICs), where high drug costs have limited access to such therapies. Their recognition as essential medicines enables prioritisation of limited resources, facilitates equitable pricing, and supports the development of generics and biosimilars post-patent expiry. This inclusion aligns with Sustainable Development Goal 3.4, which aims to reduce premature mortality from non-communicable diseases (NCDs) by 1/3 by 2030. However, challenges persist, including financial constraints, limited healthcare infrastructure, and risks of irrational use, particularly for obesity alone. Effective implementation through national policies, training, and rational prescribing frameworks is essential to translating this global milestone into tangible public health benefits and to reducing the growing burden of diabetes and obesity worldwide.

High-fat diet-induced obesity accelerates puberty in male rats through SMIM20/phoenixin upregulation.

Front Endocrinol (Lausanne)

Tao Xie, Wei Qin, Dan Zeng +5 more

Controversy exists regarding the relationship between obesity and pubertal onset in boys, and the underlying mechanisms remain unclear.

rbfox1 LoF mutants show disrupted bdnf/trkb2 and crhb/nr3c2 expression and increased cortisol levels during development coupled with signs of allostatic overload in adulthood.

Transl Psychiatry

Adele Leggieri, Judit García-González, Saeedeh Hosseinian +7 more

Mutations in the RBFOX1 gene are associated with psychiatric disorders but how RBFOX1 influences psychiatric disorder vulnerability remains unclear. Recent studies showed that RBFOX proteins mediate the alternative splicing of PAC1, a critical HPA axis activator. Further, RBFOX1 dysfunction is linked to dysregulation of BDNF/TRKB, a pathway promoting neuroplasticity, neuronal survival and stress resilience. Hence, RBFOX1 dysfunction may increase psychiatric disorder vulnerability via HPA axis dysregulation, leading to disrupted development and allostatic overload. To test this hypothesis, we generated a zebrafish rbfox1 loss of function (LoF) line and examined behavioural and molecular effects during development. We found that rbfox1 LoF mutants exhibited hyperactivity, impulsivity and heightened arousal, alongside alterations in proliferation - traits associated with neurodevelopmental and stress-related disorders. In adults, loss of rbfox1 function led to decreased fertility and survival, consistent with allostatic overload. At the molecular level, at larval stages rbfox1 mutants showed increased cortisol levels and disrupted expression of key stress-related genes (bdnf, trkb2, pac1a-hop, crhb, nr3c2). Pharmacological intervention targeting TRKB restored crhb and nr3c2 gene expression and hyperactive and hyperarousal behaviours. In adults, dysregulation of crhb, nr3c2 and bdnf/trkb2 genes was only seen following acute stress exposure. Our findings reveal a fundamental role for RBFOX1 in integrating stress responses through its regulation of BDNF/TRKB and neuroendocrine signalling.

Exploring the carcinoid crisis: insights from a cancer-specific centre.

Endocr Oncol

Maribel Del Olmo-García, Grace Kong, HuiLi Wong +5 more

To assess the prevalence, pre-procedure biomarkers, and management of carcinoid crisis (CC) in a cancer-specific hospital.

The neuro-cutaneous axis: the role of nerve cells in wound healing.

Biochem Biophys Res Commun

Yijing Zhou, Jin Yang, Lin Chen +2 more

This narrative review summarizes the primary regulatory function of the neurocutaneous axis in wound healing. Hemostasis, inflammation, proliferation, and remodeling are the four phases of skin wound healing. Neurons release neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) along with neurotrophic factors. They initiate vasodilation and promote platelet aggregation during the hemostasis phase, regulate immune cell recruitment and activity during the inflammatory phase, promote keratinocyte migration, fibroblast activation, and angiogenesis during the proliferation phase, and participate in the ordered arrangement of collagen and neural reinnervation during the remodeling phase. Furthermore, the clearance of apoptotic cells by macrophage-mediated phagocytosis couples the resolution of inflammation with the onset of regeneration, forming a closed-loop mechanism through signal contact between the neuro-immune-skin cell network. Along with offering theoretical references for wound regeneration, this paper also examines focused therapeutic approaches such as neuropeptide delivery, the synergistic use of conductive materials and electrical stimulation, and stem cell and gene therapy.

Effect of Weight-Neutral Treatment With Semaglutide or Tirzepatide on β-Cell Identity in db/db Mice.

Acta Physiol (Oxf)

Zhaobin Deng, Dongxu Zheng, Jinsook Son +4 more

Insulin resistance and pancreatic β-cell failure are key characteristics of type 2 diabetes (T2D). Impaired β-cell function is associated with loss of β-cell identity, resulting in β-cell dedifferentiation or trans-differentiation to other endocrine cells. We have shown that β-cell dedifferentiation can be reversed, restoring insulin secretion. The aim of this study was to investigate whether semaglutide or tirzepatide treatment can reverse early stages of β-cell dedifferentiation in db/db mice independent of their effect on body weight.

GLP-1-based therapies for obesity: Impact on comorbidities or obesity-related diseases.

Med Clin (Barc)

Nuria Vilarrasa, Silvia Pellitero

Agents targeting the glucagon-like peptide-1 receptor (GLP-1R) are effective in managing metabolic conditions associated with obesity, such as obstructive sleep apnea (OSA), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic kidney disease (CKD). In OSA, studies with first generation GLP-1R agonists (ArGLP-1) and co-agonists (GLP-1/GIP) have demonstrated significant improvements in the apnea-hypopnea index and weight reduction. In MASLD, GLP-1RAs and co-agonists (GLP-1/GIP or GLP-1/glucagon) have shown efficacy in reducing hepatic fat, improving fibrosis, and resolving steatohepatitis, with promising results from trials such as ESSENCE and SYNERGY-NASH. In CKD, semaglutide has been associated with a reduction in renal events and slower disease progression. Beyond their metabolic and cardiovascular benefits, these agents represent a comprehensive approach to treating obesity and its complications, with ongoing research exploring their potential indications in chronic inflammatory diseases such as psoriasis and hidradenitis suppurativa.

Treatment and outcome of a boy with lgG4-related hypophysitis caused by SARS-CoV-2 re-infection.

Front Endocrinol (Lausanne)

Hanming Li, Iatlun Leong, Jianyu He

SARS-CoV-2 infection can directly and indirectly affect the nervous system, including the hypothalamus and pituitary, and potentially cause IgG4-related hypophysitis.

Scalable recombinant production of bioactive human neutrophil peptide-1 in Komagataella phaffii.

AMB Express

Mohd Sadeeq, Chaozhi Wang, Ke Yu +5 more

The escalating crisis of antimicrobial resistance demands novel therapeutics that overcome the limitations of conventional antibiotics. Human α-defensins, such as Human Neutrophil Peptide-1 (HNP-1), represent compelling candidates due to their potent, broad-spectrum antimicrobial activity and membrane-disrupting mechanism. However, clinical translation has been hindered by the absence of scalable production systems capable of delivering high yields of functional peptide. To address this challenge, we developed an efficient expression platform in the yeast Komagataella phaffii. In this system, a codon-optimized HNP-1 sequence was fused to a His6-SUMO tag downstream of the α-factor secretion signal to enhance solubility, folding, and recovery. Initial shake-flask optimization identified pH 6.0 with 96 h of induction as optimal fermentation conditions, yielding 19.75 ± 1.1 mg/L of recombinant protein. Subsequent scale-up to a controlled 5 L bioreactor significantly enhanced production, achieving 122 mg/L of the fusion protein. Following purification and precise cleavage, this process delivered 15.25 mg/L of pure, mature HNP-1 representing, to our knowledge, the highest yield of recombinant HNP-1 reported. The final product demonstrated potent antibacterial activity against Staphylococcus aureus and Escherichia coli while exhibiting excellent hemocompatibility, confirming preservation of native structure and function. This work establishes a scalable production platform for HNP-1 and provides an adaptable framework for expressing other structurally complex antimicrobial peptides with therapeutic potential.

Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon.

J Obes

Riad Mohammed Abdelrahman, Taha Hussein Musa, Ismail Adam Arbab +6 more

Obesity has emerged as a pressing global health challenge, and therapies based on glucagon-like Peptide 1 receptor agonists (GLP-1RAs) have transformed its management. Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label. These drugs not only provide unprecedented efficacy and acceptable safety in weight reduction and glycemic control for patients with obesity and Type 2 diabetes but also hold promise in broader indications, including neurodegenerative disorders, fatty liver disease, dyslipidemia, atherosclerosis, and cardiovascular conditions.

Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?

J Pediatr Endocrinol Metab

Hakan Birinci, Emrullah Arslan, Tansu Değirmenci +1 more

Familial neurohypophyseal diabetes insipidus (DI) is a rare genetic disorder caused by vasopressin deficiency due to AVP gene mutations. This case report describes the genetic findings and clinical profiles of three generations within a family affected by hereditary central DI and managed with desmopressin.