The living record of
peptide science.

LL-37 selectively targets Plasmodium-infected erythrocytes and exhibits antimalarial activity.

PLoS Pathog

Xiaoqin He, Yutong Zhang, Junchao Lou +6 more

Malaria control is challenged by the emergence of resistance to virtually all antimalarial drugs, from the frontline artemisinin to other classes, highlighting the critical need for new therapies. This study demonstrates that the human antimicrobial peptide LL-37 exhibits antiplasmodial activity against both drug-sensitive and drug-resistant parasites in vitro. LL-37 selectively targets infected red blood cells through membrane disruption mediated by phosphatidylserine externalization and cholesterol depletion. Elevated plasma LL-37/CRAMP levels were observed in malaria patients and infected mice, and exogenous LL-37/CRAMP administration reduced parasitemia, improved survival, and modulated pro-inflammatory cytokine levels in a mouse model. CRAMP-deficient mice showed higher susceptibility to infection, underscoring its role in host defense. Our findings reveal a naturally occurring host defense mechanism centered on LL-37/CRAMP, which acts through direct targeting of the infected erythrocyte membrane. However, therapeutic administration after infection establishment showed limited efficacy, likely due to rapid peptide degradation in vivo, and the effective concentrations required for direct killing in vitro are substantially higher than endogenous systemic levels. The reduction in systemic cytokines observed in treated mice is likely primarily attributable to decreased parasite burden rather than direct immunomodulation. Further studies are needed to evaluate stabilized analogs, optimized delivery strategies, and combination approaches before therapeutic applications can be considered.

LL-37 and bacterial DNA complexes in dental plaque: Implications for biofilm structure, innate immunity, and periodontal pathogenesis.

J Oral Biosci

Gen Tanabe, Taiki Mori, Mariko Hanaoka +2 more

Dental plaque is a highly organized polymicrobial biofilm, in which extracellular DNA serves as a vital structural and functional component of the extracellular matrix. The human antimicrobial peptide LL-37 plays an important role in oral innate defense, exhibiting both antimicrobial and immunomodulatory activities. Our recent study indicated that LL-37 forms stable complexes with bacterial DNA in dental plaque. This review summarizes current knowledge of the molecular mechanisms and immunological consequences of LL-37-bacterial DNA interactions in dental plaque, highlighting their potential implications in biofilm structure, innate immunity, and periodontal pathogenesis.

Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study.

Lancet Psychiatry

Heidi Taipale, Mark Taylor, Markku Lähteenvuo +3 more

People with diabetes have an elevated risk of developing depression, anxiety, and suicide. GLP-1 receptor agonists are licensed to treat diabetes and obesity, but data on whether these medications alleviate or exacerbate anxiety, depression, and self-harm are mixed. We studied the risk of worsening mental illness in people already diagnosed with depression, anxiety, or both who were prescribed antidiabetic medications including GLP-1 receptor agonists.

Multimodal evidence chain of iron overload, inflammation, and dysfunction: an integrated predictive model of early cardiac injury in pediatric transfusion-dependent β-thalassemia.

Front Cardiovasc Med

Panyan Zhou, Caili Li, Xiaomei Gao +3 more

Despite standardized transfusion and chelation therapy, children with transfusion-dependent β-thalassemia (TDT) remain at high risk for cardiac dysfunction due to iron overload. Conventional ejection fraction assessment lacks sensitivity for early injury. This study evaluated multimodal indicators to develop a robust early-warning model.

Total body water to lean body mass ratio predicts mortality in patients with chronic heart failure: a prospective, observational study.

Front Nutr

Linfeng Xie, Bryan Richard Sasmita, Yuhe Zhao +4 more

Malnutrition and sodium water retention are some of the most common complications of chronic heart failure (CHF). To date, several parameters or risk stratification tools have been established to predict one's volume or nutritional status. Unfortunately, there is no biomarker that may reflect both conditions, thus, in this study, we established a novel biomarker known as total body water (TBW) to lean body mass ratio (LBM) ratio (TLR). Accordingly, we also assessed the prognostic value of TLR in CHF patients.

Effect of Fluid Restriction in Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Cardiol Rev

Maryam Sajid, Shahzaib Ahmed, Taimor Mohammed Khan +6 more

Fluid restriction is frequently recommended for patients with heart failure (HF) to prevent volume overload, yet its clinical benefit remains uncertain. This meta-analysis compared the efficacy and safety of fluid restriction versus liberal fluid intake in HF by systematically searching PubMed, Scopus, and Cochrane CENTRAL through May 2025 for randomized controlled trials evaluating fluid restriction (≤1.5 L/d) compared with liberal intake in adults with HF. Outcomes included re-hospitalization, mortality, weight, thirst, quality of life (QoL), intravenous diuretic use, and serum biomarkers such as sodium, creatinine, and brain natriuretic peptide. Ten randomized controlled trials involving 1465 participants (731 fluid restriction; 734 liberal intake) were included. Fluid restriction was associated with a 29% relative reduction in re-hospitalization (relative risks [RR] 0.71; 95% confidence interval [CI], 0.50-1.02; P = 0.06; I2 = 52%) and mortality (RR 0.71; 95% CI, 0.43-1.18; P = 0.19; I2 = 0%), although neither reached statistical significance. Weight reduction favored fluid restriction (weighted mean difference [WMD] -1.58 kg; 95% CI, -3.92 to 0.76), but findings varied across studies. No significant differences were observed for thirst (WMD 4.96), QoL (standardized mean difference [SMD] 0.15), intravenous diuretic use, sodium levels (WMD 0.90 mmol/L), creatinine (WMD -0.10 mg/dL), or brain natriuretic peptide (WMD -51.41 pg/mL). Subgroup analysis showed that liberal fluid intake significantly reduced creatinine in chronic compensated HF, whereas no benefit was found in acute decompensated HF. Sensitivity analyses identified one outlier trial as the primary source of heterogeneity. Overall, fluid restriction does not significantly improve outcomes in HF, and liberal fluid intake appears safe, supporting more individualized fluid strategies.

Invasive Confirmation of Microvascular Recovery Parallel to Left Ventricular Functional Restoration.

JACC Case Rep

Takumi Toya, Takumi Kondo, Otoya Sekine +7 more

Coronary microvascular dysfunction (CMD) is increasingly implicated in heart failure, but reversal with guideline-directed medical therapy (GDMT) is rarely documented using invasive physiology.

Management of infertility in women with hypothalamic hypogonadotropic hypogonadism: an expert opinion.

Reprod Biol Endocrinol

Geoffroy Robin, Lorraine Maitrot-Mantelet, Sophie Dubourdieu +4 more

Hypothalamic gonadotropin-releasing hormone (GnRH) plays a central role in regulating the pituitary-gonadal axis. The pulsatility of GnRH release is critical for maintaining the function of GnRH receptors and the secretion pattern of gonadotropins, namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which regulate endocrine function and follicular growth and maturation. During the luteal phase, LH is crucial for supporting a functional corpus luteum and stimulating it to produce progesterone, estradiol and relaxin.Hypothalamic hypogonadotropic hypogonadism originates from a deficiency in GnRH secretion. Low circulating gonadotropin levels subsequently lead to reduced ovarian function and anovulation. This condition may be congenital or acquired, for example through functional hypothalamic amenorrhoea (FHA) or FHA combined with polycystic ovarian morphology (PCOM). Pulsatile GnRH therapy plays a pivotal role in restoring the physiological menstrual cycle and selecting a dominant follicle in these women, thereby inducing ovulation and achieving fertility. There is extensive literature accounting for a high ovulation rate and consequently high pregnancy and birth rates per cycle, with a lower risk of adverse outcomes.

Exploring the behavioural and biochemical effects of cordycepin in PTSD-like behaviour using an early life stress mouse model.

Biochem Biophys Res Commun

Subhranil Mukherjee, Anusha Govindula, Madhavan Nampoothiri +2 more

Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition triggered and precipitated by exposure to severe, life-threatening trauma. Emerging evidence implicates the involvement of neuroinflammatory processes in the exacerbation and progression of PTSD. Cordycepin (COR), a natural compound, is reported to alleviate neuroinflammation via downregulating NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes. The present study aimed to extrapolate the neuroprotective mechanism of COR against PTSD in mice. Swiss albino mice experienced PTSD-like symptoms due to sequential stressors in first 30 days at critical intervals. Mice exhibiting PTSD-like behaviour were treated with fluoxetine (FLU, 10 mg/kg), an antidepressant drug, and COR (10 and 50 mg/kg). Four behavioural tests were performed in mice to assess the four symptom clusters similar to human PTSD. At the end of the study, immunoassays were performed for serum corticotropin releasing hormone (CRH) and corticosterone (CORT) levels as well as brain neuroinflammation markers including interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interleukin-1β (IL-1β) and NLRP3. Behavioural assays demonstrated PTSD-like clusters in mice as observed in clinics. These cluster were associated with elevated levels of brain cytokines IL-6, TNF-α, IL-1β and NLRP3. Dysregulation of hypothalamus-pituitary-adrenal (HPA) axis was evident from significant decline in CORT levels. FLU significantly attenuated the four clusters of PTSD with negative effect on brain cytokines. COR demonstrated a dose-dependent response with 50 mg/kg showing consistent improvement in both behavioural and biochemical parameters. Overall, COR exhibited promising activity in this model and may serve as a potential natural therapeutic strategy to investigate for the management of PTSD in clinics.

Early hypocortisolism with persistent remission following osilodrostat in a patient with long-standing Cushing disease.

JCEM Case Rep

Liat Sasson, Ilan Shimon

Cushing syndrome is a disorder of endogenous hypercortisolism characterized by increased morbidity and mortality; when surgery is not curative or feasible, medical therapies targeting pituitary adrenocorticotropic hormone or adrenal cortisol production are essential. We report a case of early-onset hypocortisolism and sustained remission following a brief osilodrostat therapy in a 70-year-old woman with Cushing disease who had been treated for many years with pasireotide and metyrapone. Ten days after initiating osilodrostat, she developed clinical signs of adrenal insufficiency and a low morning serum cortisol of 2.8 µg/dL (SI: 76 nmol/L) (reference range 7-25 µg/dL [SI: 193-690 nmol/L]); osilodrostat was discontinued, and glucocorticoid replacement was initiated, remaining glucocorticoid-replacement dependent at low doses for 2 months. Over subsequent follow-up of over 20 months, her 24-hour urinary free cortisol normalized, and she maintained persistent biochemical and clinical eucortisolism off all Cushing therapy, with no relapse of hypercortisolism. She also experienced weight loss of 16.5 kg and marked improvement in diabetes control, enabling discontinuation of insulin and glucagon-like peptide-1 (GLP-1) receptor agonist therapy. This is among the earliest documented cases of osilodrostat-induced hypocortisolism with long sustained hormonal remission after treatment discontinuation, emphasizing the need for early monitoring and prolonged follow-up.

Synthetic somatostatin analogs ameliorate endothelial injury due to hydrochloric acid treatment.

Environ Toxicol Pharmacol

Saikat Fakir, Khadeja-Tul Kubra, Madan Sigdel +2 more

Endothelial barrier dysfunction is a key feature of lung injury induced by hydrogen chloride gas, which is converted to HCl in tissues. Synthetic somatostatin analogs (SSA), such as Lanreotide and Octreotide, are prescribed in clinics for acromegaly and neuroendocrine tumor treatment. Recent findings suggest that those FDA-approved drugs can ameliorate inflammatory lung disease. This study aims to assess the potential protective effects of SSA against HCl-induced endothelial injury in vitro, utilizing bovine pulmonary artery endothelial cells. Our observations suggest that HCl exposure impairs endothelial cell viability and proliferation, increases paracellular and transendothelial permeability, and induces reactive oxygen species generation, as expected. Octreotide and Lanreotide treatment alleviate the aforementioned toxic effects and exert anti-inflammatory effects in the impaired endothelial cells. Those data inform us on the potential protective effects of SSA in HCl-induced endothelial injury and inflammation, suggesting that they could be repurposed to ameliorate respiratory complications due to toxicant exposure.

Change in dapagliflozin trial eligibility status and prognosis among patients with acute heart failure with preserved ejection fraction.

J Chin Med Assoc

Lo-Chieh Ling, Wei-Ming Huang, Hao-Chih Chang +6 more

Disease-modifying therapy for heart failure with preserved ejection fraction (HFpEF) remains limited. The Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial demonstrated the benefits of disease‑modifying therapy and outlined the eligibility criteria for this treatment. The present study investigated how often treatment eligibility changes after hospitalization for acute decompensation and whether eligibility at discharge influences 1-year outcomes.

Analgesic use and changes in renal function in patients with heart failure in a real-world setting: a descriptive study using an electronic medical record database.

Am Heart J Plus

Ryo Ishida, Toshio Takano, Hironobu Tokumasu +1 more

To evaluate the incidence of analgesic use and changes in the estimated glomerular filtration rate (eGFR) of patients with heart failure (HF), with and without analgesic use in a real-world Japanese setting.

The potential role of aging on acute phase proteins and hypotalamus-pituitary-adrenal axis: A representative cohort study in pregnant mares.

Vet Anim Sci

Deborah La Fauci, Pietro Medica, Esterina Fazio +3 more

Pregnancy in mares triggers physiological adaptations involving changes in inflammatory biomarkers, particularly acute-phase proteins (APPs), and the activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, the extent to which these responses are influenced by maternal age remains unclear. The hypothesis of this study was that both APP profile and HPA axis activity during gestation are modulated by the age of the mare. Accordingly, the objective was to evaluate these variables throughout pregnancy and assess the impact of age on their physiological regulation. A total of 41 Spanish Purebred mares were evaluated: n. 31 were pregnant (n. 15 of ≤10 years; n. 16 of >10 years old) and n. 10 were non-pregnant mares. Pregnant mares were monitored monthly throughout gestation, to assess temporal changes in APPs and HPA axis activity. Blood samples were collected to measure serum amyloid A (SAA), haptoglobin (Hp), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and cortisol (CORT) concentrations. Statistical analysis included repeated measures ANOVA, and t-tests to assess biomarker differences by age and pregnancy status. Pregnant mares, particularly older individuals, showed elevated concentrations of inflammatory and endocrine markers compared to non-pregnant ones (p < 0.05). These findings demonstrate that pregnancy significantly alters inflammatory and endocrine biomarkers in mares; therefore, older pregnant individuals showed more pronounced and sustained increases compared to both younger pregnant and non-pregnant mares. This suggests that maternal age influences the physiological adaptation to pregnancy, particularly in the regulation of the HPA axis and acute-phase response.

Postinjury Carnosine Treatment Prevents Neurotrophic Factor Decline in Denervated Muscle and Spinal Cord After Traumatic Injury.

Eur J Neurosci

Karolina Kucharova, Tomas Kuruc, Martina Magurova +5 more

Local intraspinal or intramuscular administration of brain-derived or glial cell line-derived neurotrophic factors (BDNF, GDNF) is known to protect neural tissue after traumatic spinal cord injury (SCI). In this study, we investigated whether oral supplementation with antioxidant carnosine, a natural dipeptide, could stimulate endogenous production of these neuroprotective molecules within the neural and muscle microenvironment 6 weeks after SCI. We assessed the effects of 6-week carnosine treatment in female Zucker rats, administered either before (CB-I) or after injury (CA-I). The impact of thoracic SCI and carnosine treatment was evaluated in in/active microenvironments of fore limb and hind limb muscles, along with their corresponding innervation regions. To better understand how carnosine treatment affects the neural microenvironment, we analysed mRNA expression levels of neurotrophic factors and their receptors. We also examined molecules that may indicate which cell types are involved in producing or responding to BDNF or GDNF in the spinal cord. Six weeks after thoracic SCI, we observed better locomotor recovery in CA-I compared to CB-I treated rats. In the hind limb, posttraumatic carnosine treatment prevented SCI-induced reductions in BDNF and GDNF protein levels. Additionally, this treatment blocked the SCI-induced reduction of GDNF protein levels and the oligodendrocyte-specific gene Olig2 in the lumbar and cervical spinal cord segments. Interestingly, the postinjury treatment elevated the gene expression in BDNF receptor- and astrocyte-specific genes in the cervical segments. The finding that carnosine may prevent BDNF and GDNF declines in denervated hind limb muscles positions this dipeptide as a promising candidate for inclusion in future combination therapies.

D[His26]NPY, an agonist of NPY receptor 1, averts traumatic stress-induced behavioral deficits in male and female rats.

Psychopharmacology (Berl)

Arax Tanelian, Bistra Nankova, Moshe Weiss +1 more

Enhancing cultured meat production with ginseng leaf-stem extract: a novel supplementation approach to promote porcine muscle stem cell growth.

Food Sci Anim Resour

Su Min Park, Do Hyun Kim, Hyuk Cheol Kwon +4 more

Ginsenosides, including ginsenoside Re (G-Re), exert muscle-protective effects, and ginseng leaves and stems are rich in G-Re. Cultured meat has garnered attention as a sustainable alternative to conventional meat production methods. The proliferation and differentiation of muscle satellite cells (MuSCs) are essential for meat production. Herein, we examined the effects of ginseng leaf-stem extract (G-LSE) on the growth, differentiation, and myotube formation of MuSCs. The G-Re content of G-LSE was quantified using LC-MS/MS. MuSCs were treated with G-LSE (0, 0.25, 0.5, 1, 2, and 4 mg/mL for 48 h). Cell proliferation and cell cycle analyses were performed. Myogenic factors, the AKT/mammalian target of rapamycin (mTOR) signaling pathway, and FoxO3a were detected using real-time PCR, Western blotting, and immunofluorescence analyses. At concentrations of 0.25, 0.5, and 1 mg/mL, G-LSE enhanced cell proliferation over 7 days in a concentration-dependent manner. G-LSE also promoted cell cycle progression. Treatment with G-LSE increased mRNA levels of myogenic differentiation 1 (MyoD), myogenin (MyoG), and myosin heavy chain after 7 days in a concentration-dependent manner. G-LSE also elevated cellular protein levels of MyoD and MyoG. A 7-day treatment with 1 mg/mL G-LSE maintained high MyoG levels and morphological transition to myotubes. Myogenic proliferation and differentiation were mediated via AKT/mTOR activation and inhibition of FoxO3a nuclear translocation. G-LSE promotes porcine MuSC proliferation and differentiation by activating AKT/mTOR signaling and inhibiting FoxO3a nuclear translocation. G-LSE could be a novel plant-derived supplement for promoting MuSC growth and differentiation, particularly in cultured meat production.

Interaction of Sepsis, Disuse, and Aging on Skeletal Muscle Function and Remodeling in Male and Female Mice.

Acta Physiol (Oxf)

Diana C Muller, Franccesco P Boeno, Gisienne Reis +7 more

Sepsis is associated with skeletal muscle weakness and atrophy, particularly in older and immobilized patients; however, how sepsis interacts with disuse, reloading, aging, and biological sex remains poorly defined.

Renal Outcomes of GLP-1 Receptor Agonists and Tirzepatide Across CKD Stages and Metabolic Phenotypes (Type 2 Diabetes and/or Overweight/Obesity): A Scoping Review.

Diabetes Ther

Jorge Rico-Fontalvo, Rodrigo Daza-Arnedo, Alicia Elbert +6 more

Diabetes mellitus is the leading global cause of chronic kidney disease (CKD) and end-stage renal disease. Although cardiovascular outcomes have improved substantially, renal risk remains high. Glucagon-like peptide 1 (GLP-1) receptor agonists and the dual GLP-1/GIP agonist tirzepatide have demonstrated potential cardiorenal benefits, but renal evidence has not been systematically mapped across CKD stages and metabolic phenotypes. This scoping review aimed to identify and describe clinical evidence on renal outcomes associated with GLP-1-based therapies in adults with type 2 diabetes and/or overweight/obesity, with or without CKD.

Intestinal neuroendocrine cells (STC-1 cells) exposed to skim milk powder with a high content of Maillard reactants show an attenuated secretion of incretins.

J Dairy Sci

Mona Landin-Olsson, Birgitte Ekholm, Charlotte Erlanson-Albertsson +1 more

Incretins such as glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play crucial roles in postprandial glucose management. GLP-1 and GIP stimulate insulin release in conjunction with meals and are responsible for up to 75% of the insulin secretion. Incretins are therefore very important for maintenance of normal blood glucose levels. Dairy foods are crucial for adequate nutrition at a young age, and skim milk powder in infant formula is frequently used. However, stored skim milk powder has been found to reduce the islet cell mass of the pancreas in experimental studies. The aim of this study was to investigate the potential effect of stored skim milk powder on incretin release from intestinal cells. Intestinal endocrine cells (STC-1 cells) were incubated with fresh and stored skim milk powder, the latter containing 70-fold higher amounts of Maillard reactants. The cells' viability, proliferation, and release of incretins were measured after 24 h. Both the viability and proliferation of the STC-1 cells decreased significantly during incubation with stored skim milk powder. The release of GLP-1 and GIP was suppressed in a dose-dependent manner by stored skim milk powder compared with fresh milk powder. The clinical significance for the development of diabetes and obesity, due to this observed weak release of incretins induced by stored skim milk powder containing high amount of Maillard reactants, requires further studies.