The living record of
peptide science.

Pharmacological and metabolic effects of Bifidobacterium triple viable capsules and Five-animal Play in patients with impaired glucose tolerance.

Pak J Pharm Sci

Yu Yang, Xiangyong Gan, Qilin Xiao +9 more

Impaired glucose tolerance (IGT) is a reversible pre-diabetic condition characterized by early disruptions in insulin resistance and glucose control. Wingless-type MMTV integration site family member 5a/ secreted frizzled-related protein 5 (Wnt5a/Sfrp5) signaling and GLP-1 modulation have been identified as possible treatment approaches.

Type 2 Diabetes in Pregnancy: Management and Novel Therapies.

Clin Obstet Gynecol

Gianna Wilkie

Type 2 diabetes mellitus (T2DM) is estimated to affect 2% of all pregnancies, and it is associated with numerous adverse perinatal outcomes. Glycemic monitoring and strict glycemic control are required to improve overall outcomes. Insulin is the mainstay of treatment, with limited data regarding newer medications like glucagon-like peptide 1 receptors agonists (GLP-1 RAs), dual incretin agonists like tirzepatide, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i). This chapter will provide a review of the current available literature regarding T2DM management in pregnancy.

Psychosocial and Biological Factors Associated with Non-Suicidal Self-Injury in Chinese Child and Adolescent Inpatients with Major Depressive Disorder.

Neuropsychiatr Dis Treat

Chao Liu, Xue-Yan Zhu, Yan-Ni Shi +8 more

This study assessed the prevalence and associated psychosocial and biological factors of non-suicidal self-injury (NSSI) in Chinese child and adolescent inpatients diagnosed with major depressive disorder (MDD) by DSM-5 criteria.

Novel Hybrid Peptide ML-2 with Antibacterial and Antibiofilm Activity Against Pseudomonas aeruginosa.

Curr Microbiol

Shenghua Wu, Yanping Shi, Yang He +4 more

Antimicrobial resistance significantly contributes to treatment failures in bacterial infections and poses a major global public health challenge, urgently necessitating the development of new antimicrobial agents, such as antimicrobial peptides (AMPs), which represent a promising drug class. This study aimed to develop a novel, highly effective, low-toxicity antimicrobial agent employing a hybridization strategy to fuse the broad-spectrum AMP LL-37 with the low-toxicity Musca domestica antifungal peptide-1 A. The resulting hybrid peptides (ML-1, ML-2, and ML-3) exhibited markedly reduced cytotoxicity and hemolytic activity relative to LL-37. Notably, ML-2 demonstrated broad-spectrum antimicrobial activity, with particularly exerted effective antibacterial and antibiofilm effects against Pseudomonas aeruginosa in vitro. Moreover, with excellent stability, ML-2 retained activity against P. aeruginosa following pepsin treatment and thermal stress. Importantly, P. aeruginosa developed resistance to ML-2 more slowly than to the potent antibiotic ciprofloxacin. Mechanistically, ML-2 killed bacteria by increasing cell membrane permeability and disrupting cell integrity. Altogether, these findings suggest that the hybrid peptide ML-2 has potential as a novel antimicrobial agent against P. aeruginosa.

Decoding the Heart Failure Peptidome.

Circ Heart Fail

Christian T Madsen, Jan C Refsgaard, Geert H D Voordes +8 more

Peptides such as angiotensin II and brain natriuretic peptide are pivotal in diagnosing and treating heart failure (HF). However, unbiased systematic studies of the peptidome in patients with HF are lacking. Deciphering the plasma peptidome might significantly improve the diagnosis, prognostication, and treatment of patients with HF.

Retraction Note: Neurotrophic effects of Cerebrolysin in the Mecp2308/Y transgenic model of Rett syndrome.

Acta Neuropathol

Edith Doppler, Edward Rockenstein, Kiren Ubhi +7 more

Clinical and Metabolic Outcomes of Adrenalectomy Versus Conservative Management in Mild Autonomous Cortisol Secretion.

Horm Metab Res

Seda Karslı, Selin Çelik, Özge Şahin Kimyon +3 more

Adrenalectomy and conservative management are therapeutic approaches for mild autonomous cortisol secretion; however, their comparative clinical impact in routine practice remains uncertain. We aimed to evaluate real-world hormonal, clinical, and metabolic outcomes according to the treatment strategy in patients with mild autonomous cortisol secretion. This single-center retrospective observational study included consecutive patients with adrenal incidentaloma fulfilling guideline-based diagnostic criteria for mild autonomous cortisol secretion between January 2015 and December 2024. Sixty-five patients with complete hormonal evaluation and follow-up data were analyzed and classified into surgery (n=23) and conservative (n=42) groups. Demographic characteristics, adenoma features, comorbidities, hormonal parameters, and metabolic outcomes were assessed at baseline and at the final follow-up. The median follow-up duration was approximately 3 years and similar between groups (p>0.05). At baseline, the body mass index, adenoma size, and cortisol levels after the 1-mg dexamethasone suppression test were significantly higher, while adrenocorticotropic hormone levels were lower in the surgery group (p=0.02, p=0.02, p=0.036, and p<0.01, respectively). During the follow-up, adrenocorticotropic hormone levels increased and post-dexamethasone suppression test cortisol levels significantly decreased after adrenalectomy (p=0.001 and p=0.036, respectively), whereas metabolic parameters and comorbidity profiles remained largely unchanged. In the conservative group, total cholesterol increased modestly over time (p=0.048), with no significant changes in other clinical outcomes. No significant difference in comorbidity progression was observed between treatment strategies. In this real-world cohort, adrenalectomy resulted in clear hormonal improvement without parallel short-term metabolic or clinical benefits compared with conservative management. These findings highlight the heterogeneous clinical expression of mild autonomous cortisol secretion and underscore the importance of individualized patient selection for surgery.

Sacubitril/Valsartan as a Cardiac Radioprotector.

Int J Radiat Oncol Biol Phys

Mihaela Ghita-Pettigrew, Brianna N Kerr, Kathryn H Brown +12 more

The role of the natriuretic peptides in radiation heart injury (RHI) has not been thoroughly examined. Pharmacologic modulation of the natriuretic peptide system with sacubitril/valsartan (sac/val) has led to improvements in heart failure therapy, and preliminary data suggest that RHI is associated with decreased atrial natriuretic peptide (ANP). In this study, we assessed sac/val as a radioprotector in a partial-heart irradiation mouse model and explored preliminary trends in patients receiving thoracic irradiation.

Loss of endothelin-2 in pulmonary neuroendocrine cells promotes the development of hypoxia-induced pulmonary hypertension.

Clin Sci (Lond)

Yoko Suzuki, Risa Ramadhiani, Gusty Rizky Teguh Ryanto +8 more

Pulmonary hypertension (PH) encompasses a clinical spectrum of diseases with high morbidity and poor survival rates. Over the decades, many studies have reported that endothelin-1 (Edn1) plays a role in several subtypes of PH. However, the beneficial effects of its targeted drugs are only found in patients with group 1 pulmonary arterial hypertension but not in group 3 PH, which is related to lung diseases and hypoxia. In the present study, we revealed contrasting findings for Edn1 and its highly similar peptide endothelin-2 (Edn2) in hypoxia-induced PH. Edn2 expression exhibited a distinct and transient pattern under hypoxic conditions. Moreover, epithelial cell-specific Edn2-knockout mice showed exacerbated PH phenotypes compared with wild-type mice. We further demonstrated that acute changes in oxygen levels, but not the low-oxygen condition, were pivotal for Edn2 expression regulation, suggesting that Edn2 is involved in oxygen sensing. Supporting these findings, the specific deletion of Edn2 in sensory-specialised lung cells called pulmonary neuroendocrine cells led to an exacerbated PH phenotype. In conclusion, our study revealed a previously unknown protective role of Edn2 in the development of hypoxia-induced PH. Owing to the contradictory findings between Edn1 and Edn2 in the pathogenesis of lung diseases, careful consideration is required when using endothelin receptor antagonists for PH associated with lung disease and hypoxia.

Thymosin α1-induced secretion of the IL-15/RA complex by THP-1-derived dendritic cells restrains HIV latency in vitro.

Virulence

Chaoyu Chen, Jingna Xun, Jiangrong Wang +8 more

Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully elucidated. Peripheral blood mononuclear cells (PBMCs) were obtained from people living with HIV-1 (PLWH). In vitro, THP-1 cells were differentiated into mature monocyte-derived dendritic cells (MoDCs) and co-cultured with PBMCs under various conditions. Intracellular HIV-1 p24 levels, CD8+ T and NK cell functionality, and reservoir size were evaluated. In vitro, Tα1 stimulation of MoDCs resulted in significant immune response and secretion of IL-15/RA complex (p < 0.001). This interaction with IL-2 Rβ/γ receptors on T cells enhanced the intracellular secretion of CCL3/5, IFN-γ, and TNF-α in CD8+ T cells (p < 0.05), which inhibited p24 levels in CD4+ T cells (p = 0.002), and reduced HIV-1 integrated DNA levels (p = 0.012). Furthermore, the secretion levels of IFN-γ, TNF-α, and GZMB in NK cells and proportion of CD8+ TVM cells significantly increased following co-culture. These alterations were found to be markedly inversely associated with reservoir size and reactivation. However, these effects were observed in PBMCs from immunological responders (CD4+ T cell count > 350 cells/µL) rather than nonresponders. Tα1 enhances CD8+ T cell function, promotes TVM proliferation, and suppresses reservoir size and reactivation via IL-15 pathway activation in dendritic cells, which warrants testing in functional cure trials in the future.

Endogenous cathelicidin protects against Toxoplasma gondii-associated liver damage.

Infect Immun

Yi Lin Tan, Paloma Cavalcante, Karina M Cirone +6 more

Toxoplasmosis, a disease caused by apicomplexan Toxoplasma gondii (Tg), is associated with various neuropsychiatric and behavioral conditions. Toxoplasmosis can cause serious complications for those with weakened immune systems and during pregnancy. Cathelicidins, peptides with antimicrobial and immunomodulatory functions, are critical factors in host defense against microbes, but their role in parasitic infections is less well understood. This study demonstrates the protective function of endogenous cathelicidin against hepatic damage caused by Tg infection in an oral infection model. We challenged wild-type (Camp+/+) and cathelicidin-deficient (Camp-/-) mice with low-virulent Type II strain of Tg (ME-49) cysts. Our findings demonstrate that Camp-/- mice exhibited more severe clinical manifestations, higher mortality rates, and more pronounced hepatic damage compared to their Camp+/+ counterparts. Histological liver examinations indicated significant necrotic hepatitis in Camp-/- mice, correlating with increased local concentrations of pro-inflammatory cytokines and proteomic upregulation of poly(ADP-ribose) polymerase 3 and guanylate-binding proteins. Increased cerebral inflammation and Tg cystogenesis were also observed in Camp-/- mice. Systemically, Camp-/- mice presented elevated levels of pro-inflammatory mediators, specifically interferon-gamma (Ifn-γ) and tumor necrosis factor-alpha (Tnf-α). In cultured macrophages, endogenous cathelicidin increased after Tg challenge, while Camp-/- bone marrow-derived macrophages released higher amounts of Tnf-α than their counterparts. We conclude that cathelicidin protects against liver injury and systemic deterioration induced by Tg infection by downregulating the synthesis of pro-inflammatory cytokines.

GLP-1 receptor agonists and sexual function in women and men: a narrative review of emerging evidence and the need for further research.

Sex Med Rev

Zaher Merhi

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may influence reward-related and sexual behaviors.

Efficacy of rhBNP in heart failure with atrial fibrillation combined with poor conventional therapy response and recurrence risk factors.

Am J Transl Res

Huijuan Shang, Xiaojun Wang, Xiaoyin Shi +1 more

To evaluate the efficacy of recombinant human brain natriuretic peptide (rhBNP) in patients with acute decompensated heart failure (ADHF) complicated with atrial fibrillation (AF) and poor response to conventional treatment.

Integrin α5β1 in head and neck squamous cell carcinoma: expression, mechanisms, and clinical implications.

Am J Cancer Res

Bo Wu, Hong-Zhi Ma, Jun-Jun Shang +3 more

Head and neck squamous cell carcinoma (HNSCC) represents a significant global health challenge associated with high mortality. A major obstacle in its management is therapeutic resistance, which limits the efficacy of existing treatment modalities. Altered expression of integrins, a family of cell adhesion receptors, has been shown to influence tumor proliferation, migration, and invasion. Among them, integrin α5β1, a member of the RGD (Arg-Gly-Asp)-recognizing integrin subfamily, has emerged as a potentially critical mediator of HNSCC progression and therapeutic resistance, according to a growing body of research. In this review, we assess the evidence regarding the aberrant expression of integrin α5β1 in HNSCC, with a particular focus on common subtypes such as oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC). We then summarize its potential value as a diagnostic and prognostic marker. Furthermore, we discuss the molecular mechanisms that regulate integrin α5β1 and its downstream signaling, especially in the context of therapy resistance. Finally, we outline the potential clinical applications and future research directions related to targeting integrin α5β1. Collectively, this paper aims to synthesize the current knowledge of integrin α5β1 in HNSCC, providing a foundation for the development of personalized, tumor-specific diagnostic tools and targeted therapies.

Updates in the Treatment of Pediatric Pulmonary Arterial Hypertension.

Cardiol Rev

Danya Z Jafri, James M Beck, Samantha A Kaplan +8 more

Pediatric pulmonary arterial hypertension (PAH) is a relentless and potentially fatal disease marked by elevated pulmonary vascular resistance and pulmonary pressure as a result of unchecked vascular remodeling, proliferation, and dysfunction. While pharmacological treatment algorithms for adult PAH are well-established and frequently updated, pediatric PAH treatment guidelines in the United States are generally based on limited clinical trials and expert opinion, leaving clinicians to extrapolate from adult data and expert consensus rather than pediatric-specific, evidence-based protocols. Endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin-pathway agents remain the therapeutic cornerstone, yet clinical practice is being reshaped by pivotal therapeutic developments. Recent advances highlight differences in monotherapy versus combination pharmacological regimens, alongside active trials investigating interventional/surgical procedures in the amelioration of long-term outcomes. This review seeks to consolidate contemporary data and clinical trial highlights to reflect a necessary shift toward precise, developmentally informed pharmacotherapy in children, underscoring the pressing need for an updated pharmacological guideline that incorporates pediatric-specific trials and harmonizes labeling and long-term safety surveillance in the treatment of pediatric PAH.

Metabolic and cellular physiological differences between embryonic breast and leg muscle satellite cells in chickens.

Poult Sci

Jongryun Kim, Jeongeun Lee, Dongjin Yu +6 more

This study aimed to compare the anatomical characteristics of embryonic chicken muscle satellite cells (CMSCs) derived from breast and leg muscles of 18-day-old embryos. We analyzed the cellular behaviors related to proliferation, metabolism, and differentiation capacity. Breast-derived CMSCs exhibited significantly higher proliferation rates and accelerated cell cycle progression, as evidenced by a higher S phase distribution and lower G2/M phase distribution compared to leg-derived CMSCs. In addition, immunofluorescence staining for myogenic regulatory factors revealed that breast-derived CMSCs exhibited higher expression levels of paired box protein 7 (PAX7), consistent with elevated PAX7 and myogenic differentiation 1 (MYOD) mRNA expression compared with leg-derived CMSCs. In contrast, leg-derived CMSCs showed significantly higher expression of myogenin (MYOG). Moreover, leg-derived CMSCs exhibited significantly higher mitochondrial respiratory activity indices, including oxygen consumption rate and basal respiration. In differentiation capacity analysis, the leg-derived CMSCs formed structurally more developed myotubes, and the expression of muscle-specific genes (MYOD, MYOG, MYH1E, MYH7, TNNI1, TNNI2) was also significantly higher. These findings suggest that breast-derived CMSCs exhibit superior proliferative capacity, while leg-derived CMSCs possess enhanced myogenic differentiation potential, as supported by their increased oxidative phosphorylation activity and elevated expression of differentiation-related markers. In conclusion, the anatomical origin of CMSCs significantly influences their proliferative and differentiation capacities as well as their metabolic properties, providing a valuable basis for selecting optimal cell sources for cultured meat production and meat quality improvement.

Liraglutide reduces the apoptosis of feeding and appetite-suppressing neurons in the hypothalamus of obese rats association with the PI3K/AKT/Foxo1 pathway.

Exp Brain Res

Wei Yang, Zelin Yang, Shuyu Lu +4 more

Obesity-induced inflammation in the hypothalamus disrupts the function of neurons that regulate appetite, particularly proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons in the arcuate nucleus (ARC). Although Liraglutide, a GLP-1 analogue, exhibits neuroprotective properties, the underlying molecular mechanisms are unclear. In this study, we investigated whether Liraglutide protects hypothalamic neurons via the PI3K/AKT/Foxo1 pathway.

Transcriptional competence defines the heterochromatin nucleating potential of isolated MSR units.

Nat Commun

Yi-Hsuan Lo, Nicholas Shukeir, Galina Erikson +6 more

In mouse cells, constitutive heterochromatin is associated with underlying arrays of A/T-rich DNA repeat elements, called the major satellite repeats (MaSat or MSR). We examine >18,000 MSR copies in mouse ES cells and identify that heterochromatin forms only at transcriptionally competent MSR units. To directly dissect the function of MSR DNA, we insert isolated MSR units into an inert genomic region that is repeat- and gene-free. Insertion of three or more intact MSR units induces heterochromatic histone marks, recruitment of HP1 and incorporation of histone H1. Only transcriptionally competent MSR units, but not permutated MSR variants or LINE1 5'UTR elements, nucleate de novo heterochromatin. MSR-derived transcription is bi-directional and MSR-originating transcripts are attenuated by the RNAPII-associated Integrator complex. Instructively, multi-copy intact MSR units impart an unwound DNA template that facilitates RNAPII engagement. Together, this study uncovers a DNA/RNA-based logic and transcription-coupled mechanism for the nucleation of heterochromatin.

Exenatide attenuates neuroinflammation and rescues sepsis-induced depressive behavior and cognitive dysfunction in a mouse model.

Neuroscience

Shenhai Liu, Qiao Chen, Hui Liu +4 more

Sepsis elevates the risk of depression and cognitive impairment. Glucagon-like peptide-1 (GLP-1) analogues exhibit neuroprotective potential, yet their effects on sepsis-induced depression (SID) remain unelucidated. This study explored whether exenatide (Exe) alleviates depressive-like behaviors and cognitive deficits in a murine SID model.

Muscle atrophy associated with glucagon-like Peptide-1 receptor agonists: A population-based observational study.

Clin Nutr

Angela T H Kwan, Moiz Lakhani, Roger S McIntyre

Background and AimEmerging evidence suggests that weight loss associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be in part attributable to changes in lean mass, which has potential clinical implications. This study evaluates the disproportionate reporting of muscle atrophy in association with GLP-1 RA therapy using real-world global data.. MethodsWe analyzed reports of muscle atrophy submitted to the FDA Adverse Event Reporting System (FAERS) database from October 2003 to March 2024 using the validated pharmacovigilance tool OpenVigil 2.1. Disproportionality was assessed using reporting odds ratios (RORs) with 95 % confidence intervals (CIs), the standard metric for pharmacovigilance signal detection worldwide. To contextualize associations, disproportionality estimates were calculated using niacin, simvastatin, and the complete FAERS database (all other drugs) as comparators. ResultsA total of 142 cases of muscle atrophy were identified with GLP-1 RA therapy, the majority occurring in adults aged 18-64 years (43 % female, 57 % male). Disproportionality analysis showed pharmacovigilance signals for semaglutide (ROR = 2.39, 95 % CI = 1.63-3.52) and tirzepatide (ROR = 1.69, 95 % CI = 1.14-2.50), indicating increased reporting of muscle atrophy relative to all other drugs in FAERS. In contrast, exenatide (ROR = 0.26, 95 % CI = 0.12-0.55) and liraglutide (ROR = 0.27, 95 % CI = 0.09-0.83) were associated with significantly lower reporting odds. All significant signals satisfied thresholds of p < 0.05 and IC025 > 0.. ConclusionsCertain GLP-1 receptor agonists demonstrate a pharmacovigilance signal of disproportionate reporting of muscle atrophy. These findings should be interpreted as signal detection rather than evidence of causality and highlight the need for future studies incorporating objective measures of muscle mass and function..