Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Environmentally relevant aged nanoplastics amplify oxidative stress-associated inhalation toxicity and delay lung clearance.
Redox Biol
Soyeon Jeon, Jun Hui Jeon, Gyuri Kim +2 more
Airborne micro- and nanoplastics are emerging environmental contaminants of increasing concern, yet their inhalation toxicity and pulmonary fate remain insufficiently understood. In this study, we investigated how particle morphology and surface oxidation influence pulmonary inflammation and clearance using environmentally relevant, size-controlled polystyrene (PS) nanoplastics. Spherical and fragmented PS were generated via bottom-up and top-down approaches, respectively, and subjected to ultraviolet irradiation to simulate environmental aging. Fragmented and ultraviolet (UV)-aged nanoplastics exhibited enhanced surface oxidation and a higher intrinsic oxidative potential than pristine spherical particles. Following a single pulmonary exposure in mice via pharyngeal aspiration at doses of 25-100 μg per mouse, these environmentally transformed nanoplastics induced more severe acute pulmonary inflammation. In particular, UV-aged fragmented PS (100 μg per mouse) increased neutrophil counts by 3.9-fold compared with pristine spherical PS, along with increased pro-inflammatory cytokine production, which was closely associated with particle-derived oxidative reactivity. Although acute inflammatory responses were largely reversible, time-course analysis of lung burden after a single non-overload exposure (25 μg per mouse) revealed delayed pulmonary clearance of fragmented nanoplastics relative to spherical particles, with estimated clearance half-lives of 13.5 days for pristine spherical PS and 27.4 days for UV-aged fragmented PS. Overall, this study demonstrates that nanoplastics most relevant to real-world environmental exposure may pose a greater risk of respiratory health effects, along with prolonged lung residence.
Salivary glucocorticoid receptor gene DNA methylation and cortisol output in relation to lifestyle, psychological distress, and cognition in university students.
Psychoneuroendocrinology
Samira Rostami, Adrià Bermudo-Gallaguet, Neus Camins-Vila +4 more
University students often experience high psychosocial stress and lifestyle irregularities that may affect hypothalamic-pituitary-adrenal axis regulation and epigenetic regulation of the glucocorticoid receptor gene (NR3C1). This study examined associations of lifestyle factors with peripheral NR3C1 DNA methylation and cortisol output, and their relationships with psychological distress and cognitive function.
Icariin Regulates Acne Pathophysiology and Extracellular Matrix Protein Synthesis: Implications for Acne Vulgaris and Atrophic Acne Scar Management.
Exp Dermatol
Dong Hyo Kim, Ji Young Yoon, Jun Hyo Lee +2 more
Icariin, the principal active compound of Epimedium species used in traditional East Asian medicine, exhibits anti-inflammatory and lipid-regulating effects. However, its effects on human sebocytes and dermal fibroblasts, which could be implicated in the management of acne and atrophic scarring, remain unexplored. This study aimed to evaluate the effects of icariin on human sebocytes, keratinocytes and dermal fibroblasts. Icariin's effects on cell viability, lipid synthesis, inflammation, abnormal keratinization and extracellular matrix (ECM) synthesis were assessed using human SEB-1 sebocytes, HaCaT keratinocytes and Detroit 551 fibroblasts. Icariin modestly promoted the proliferation of SEB-1 sebocytes, HaCaT keratinocytes and Detroit 551 fibroblasts. It reduced mRNA levels of lipogenic and proinflammatory markers in SEB-1 sebocytes and HaCaT keratinocytes. Icariin counteracted arachidonic acid-induced lipogenesis in SEB-1 sebocytes in parallel with modulation of the insulin-like growth factor 1 receptor/Akt signalling pathway. In Detroit 551 fibroblasts, it enhanced ECM protein expression and reduced the expression of ECM-degrading enzymes, accompanied by upregulation of platelet-derived growth factor receptor and latent transforming growth factor β binding protein 4. In conclusion, this study demonstrates that icariin modulates key pathophysiological processes of acne and promotes ECM synthesis, suggesting its potential as a novel therapeutic agent for managing both acne and atrophic acne scars.
Dibutyl phthalate induces sarcopenia via TNFα/TNFR1-mediated proteolytic and pyroptotic axes: evidence from NHANES and experimental models.
Front Immunol
Xiangjiao Yi, Junyan Li, Xintong Long +9 more
Environmental exposure to plasticizer dibutyl phthalate (DBP) is increasingly implicated in skeletal muscle decline, yet the effects and underlying mechanisms remain elusive. This study investigates the impact of DBP on skeletal muscle using a cross-scale integration of epidemiological modeling, computational toxicology, and experimental validations. Mixture modeling of 3,514 NHANES adults (2011-2018) demonstrated that combined phthalate exposure negatively correlated with skeletal muscle mass not only in aged but also in young populations. DBP metabolite monobutyl phthalate (MBP) emerged as the predominant toxic driver, mediated by inflammation and oxidative stress (Uric acid to High-density lipoprotein cholesterol Ratio, 20.8%). Phenotypically, in vitro/in vivo models showed that DBP exposure impairs myogenic differentiation, drives transition from oxidative-glycolytic type IIA fibers toward glycolytic type IIB fibers, and depletes regenerative Pax7+ satellite cells, accompanied by myofiber atrophy and lipid infiltration, mirroring environmentally-induced myosteatosis. Mechanistically, systems-level analyses and molecular docking suggest a predictive model wherein DBP/MBP could act as pseudo-ligands that dock into the active pocket of the primary trigger TNFα, which specifically upregulates TNFR1 (but not TNFR2), driving dual pathological axes: a proteostatic collapse (ubiquitin-proteasome overactivation and autophagy) and GSDMD-dependent pyroptosis. Pharmacological intervention with Morroniside successfully inhibited TNFα-driven dual axes, restoring homeostasis and alleviating DBP-induced atrophy. Ultimately, our findings expand the traditional paradigm of sarcopenia beyond age-related decline and nutritional deficits, establishing it additionally as an environmentally-driven metabolic pathology and a pressing public health risk. Furthermore, we redefine phthalate toxicity from generalized endocrine disruption to a targeted, receptor-mediated event driven by the TNFα/TNFR1 axis, culminating in environmental sarcopenia.
Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.
bioRxiv
Adriana Reyes-Ordoñez, Tianhui Hina Zhou, Tarun C Rao +3 more
The adult skeletal muscle regenerates robustly upon injury, but this regenerative capacity rapidly declines with age. In this study, we identify the lanthionine synthetase C-Like (LanCL) proteins, mammalian homologs of the bacterial peptide cyclase LanC, as positive regulators of muscle regeneration in middle-aged mice. In a barium chloride-induced injury model, we found the protein levels of LanCL1 and LanCL2 to increase during an early phase of regeneration in middle-aged (12-month-old) but not young adult (4-month-old) mice. Utilizing a mouse line lacking all three LanCL proteins (LanCL triple KO or LTKO), we examined a potential role of LanCL in injury-induced muscle regeneration. Consistent with an age-dependent function of LanCL, we observed a delayed regeneration of the tibialis anterior (TA) muscle after injury, as reflected by reduced sizes of regenerating myofibers at day 7 after injury in middle-aged (but not young) LTKO compared to age-matched WT mice. Although the pool size of quiescent satellite cells (Pax7+) was comparable between 12-month-old LTKO and WT muscles without injury, the number of Pax7+ cells was significantly higher in regenerating LTKO muscles at day 5 after injury, accompanied by drastically decreased numbers of MyoD+ and MyoG+ cells, as well as increased numbers of proliferating cells. In addition, we detected elevated expression of pro-inflammatory cytokines in regenerating LTKO muscles, while the number of macrophages was similar comparing LTKO and WT muscles. Taken together, our observations suggest that in aging muscles LanCLs are important for proper timing of inflammation resolution and regeneration upon injury.
Ease of Use, Ease of Learning, and Convenience of the CagriSema Dual-Chamber Pen: Results From a Usability Study in Adults With Overweight, Obesity, or Type 2 Diabetes.
J Diabetes Sci Technol
Walter Gulisano, Gitte Ter-Borch, Paul Brown +6 more
This study evaluated the usability of the CagriSema dual-chamber pen, a single-dose, single-use, pre-filled autoinjector for once-weekly subcutaneous administration of a fixed-dose combination of cagrilintide and semaglutide. Adults with overweight/obesity (n = 85) or type 2 diabetes (n = 65) performed simulated injections after standardized training. Endpoints included injection completeness, task durations, and user feedback via the Injection Device Experience and Acceptability-Ease of Use and Convenience Questionnaire (IDEA-ECQ; content validity supported by cognitive interviews, n = 50). All but one participant completed the injection successfully. Median training time was 3 minutes, and time to prepare and inject was 15 seconds. Participants rated the device easy/very easy to use (100%), easy/very easy to learn (98.7%), and an injection with the pen convenient (99.3%). Results were consistent across populations and unaffected by prior device experience.
Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes : A Phase 2b Randomized Clinical Trial.
Ann Intern Med
Ming Liu, Zhifeng Cheng, Li Lu +12 more
Bofanglutide is a novel glucagon-like peptide-1 receptor agonist under development for type 2 diabetes mellitus (T2DM) and overweight and obesity.
A trispecific GLP-1/anti-GIPR/FGF21 peptibody exhibits favorable metabolic effects in a diet-induced obesity model.
Biomed Pharmacother
Yuxuan Liu, Xiaojun Liu
Metabolic diseases such as obesity and type 2 diabetes are complex disorders involving multiple dysregulated pathways, which may limit the efficacy of single-target therapies. To address this challenge, we developed a trispecific peptibody integrating glucagon-like peptide-1 receptor (GLP-1R) agonism, glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism, and fibroblast growth factor 21 (FGF21) pathway activation. This study evaluated the pharmacological activity and metabolic effects of the trispecific construct in preclinical models.
Effect of Retatrutide, a Novel Triple Receptor Agonist, on Blood Pressure and Lipid Levels: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
High Blood Press Cardiovasc Prev
Luis E Simental-Mendía, Laura Jazel Barragán-Zúñiga, Valeria Reyes-Avitia
It has been reported that glucagon-like peptide-1 (GLP-1) agonists or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists exert beneficial effects on blood pressure and lipid profile. However, the impact of triple agonist retatrutide on these metabolic markers remains to be elucidated.
Quantification of "Mercy Sex" in Heterosexual Women.
J Sex Marital Ther
Nikita Guptan, James A Simon
Women with hypoactive sexual desire disorder (HSDD) lack the thoughts, desire, or receptivity to sexual desire, causing personal difficulty and distress (DSM IV-TR). However, HSDD clinical trials evaluating testosterone therapy, flibanserin, and bremelanotide spanning nearly a decade show women with HSDD, encompassing low to no sexual desire, are still engaging in sexual activity. We aimed to define this sexual activity as "mercy sex", quantify its frequency, and provide hypothetical explanations for this behavior. We reviewed baseline data on sexually satisfying events (SSEs) from a representative convenience sample of published, peer-reviewed, prospective, randomized, placebo-controlled trials of women with HSDD. Baseline data were assessed across time, age, reproductive status, and geography. Women in these studies engaged in "mercy sex" about 2.5 times/month despite their documented HSDD. These results have important implications for further HSDD clinical research, as mercy sex frequency may skew therapeutic efficacy while having significant implications in calculating trial sample size, and assessing a clinically meaningful response to therapy, when SSEs are used as a primary endpoint. Although this paper explores only a biopsychosocial explanation for the phenomenon of mercy sex in clinical trials of HSDD therapies, it provides a valuable understanding that will benefit patients, clinicians, and researchers.
Neuroprotective Effect of Intraperitoneal Humanin-G in Retinal Degeneration of Royal College of Surgeons Rats.
Res Sq
Bin Lin, Kevin Schneider, Mustafa Ozgul +2 more
This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression in Royal College of Surgeons (RCS) rats with retinal pigment epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21, RCS rats received twice a week intraperitoneal injection of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with electroretinography (ERG) and optokinetic testing (OKT). Then the rats were euthanized for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results showed that high dose HNG at 4 weeks after first injection (WAFI) was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. At 4 WAFI, ERG showed no difference between either low or high dose of HNG and sham injection, while the visual acuity in rats treated with high dose HNG showed significant improvement. Our findings suggested that HNG can modulate gene expression and improve vision, thus may be a potential treatment for retinal degeneration diseases.
Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.
Theranostics
Fulin Zhou, Xianglong Zhou, Jiheng Xiao +7 more
Mechano-immunology is an interdisciplinary field that examines how mechanical forces-including endogenous tissue stresses and exogenous stimuli-modulate immune cell function in the maintenance of homeostasis and the progression of disease. As the primary load-bearing framework of the body, the musculoskeletal system depends on coordinated mechanical loading to sustain immune balance and tissue repair. With aging, reduced physical activity, progressive matrix stiffening, and impaired mechanosensing in immune-cells converge to disrupt this mechano-immune axis, undermining immune clearance, inflammatory regulation, and regenerative capacity within musculoskeletal tissues. These alterations collectively contribute to the onset and progression of osteoarthritis, osteoporosis, and other degenerative musculoskeletal disorders. This review summarizes current advances in understanding the mechanisms of mechano-immunology within the musculoskeletal system under physiological conditions and delineates its involvement in the initiation and progression of degenerative diseases. Emerging strategies, including exercise-based interventions, controlled mechanical stimulation, and biomaterial engineering approaches targeting mechano-immune pathways, are also discussed as potential means to restore musculoskeletal homeostasis during aging.
Associations Between Hair Heavy Metal Concentrations and Frailty in Mexican Adults: a Cross-Sectional Study.
Res Sq
Mario Ulises Pérez-Zepeda, Karla Julieta Esquivel-García, María José Pérez-Guzmán +2 more
Background : Exposure to heavy metals is increasingly recognized as a potential risk factors for health conditions and its accumulation across life has become of interes in older adults. Older adults may be susceptible because of accumulated exposure, reduced clearance, and greater vulnerability. Whether heavy metals contribute to frailty in community-dwelling adults, and whether their effect is modified by social vulnerability or sex, remains unclear. Methods . Cross-sectional analysis of 2018 wave of the Mexican Health and Aging Study (MHAS). Hair samples from 2,671 participants aged 18 to 99 years were analyzed (EPA method 6020B). Frailty was operationalized with a 60-item frailty index (FI). Associations between each log-metal and FI were estimated with crude and covariate-adjusted linear (OLS) regression with heteroscedasticity-consistent (HC3) standard errors, and with fractional-logit regression. False-discovery-rate correction was applied. Effect modification by SVI and by sex was assessed. Results . 2,590 participants had a valid FI. In crude analyses, most metals were inversely associated with the FI. After adjustment, only cobalt retained inversely associated, which did not survive FDR correction. No metals were significant in multivariable models. Inverse association of vanadium and copper with the FI was confined to participants with higher social vulnerability; at low SVI these slopes were null or positive. Conclusions . In this sample, individual hair concentrations of heavy metals were not robustly associated with frailty after adjustment. The results suggest that the relationship between trace metals and frailty may be small and highly context-dependent.
ACE/ACE2 axis in cardiovascular disease and COVID-19: Molecular insights and therapeutic perspectives.
J Cardiovasc Thorac Res
Sony Peter, Thiruchenduran Mohana, Dhanavel Anandhi +8 more
The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and cardiovascular health. Angiotensin-converting enzyme (ACE) facilitates the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that contributes to hypertension and heart failure. Conversely, ACE2 converts angiotensin II into angiotensin-(1-7), a vasodilator with protective cardiovascular effects. An imbalance between ACE and ACE2 activities has been increasingly associated with the progression of cardiovascular diseases and complications related to COVID-19. This review analyzed 100 relevant studies published up to May 2024, identified through a comprehensive literature search on PubMed and Scopus. The findings highlighted that dysregulation of the ACE/ACE2 axis exacerbates cardiovascular dysfunction. The interaction of SARS-CoV-2 with ACE2 reduces its protective function, intensifying inflammatory responses and leading to complications such as lung injury and heart failure. Additionally, genetic polymorphisms in ACE and ACE2 influence individual susceptibility and severity of COVID-19. Promising therapeutic strategies, including ACE2-based peptides and angiotensin II receptor modulators, are under investigation but require further clinical validation. Targeting the ACE/ACE2 axis could provide effective treatment options for cardiovascular disease and COVID-19-related complications, warranting further in-depth research.
Relationship between serum potassium concentration, NT-pro-BNP, and risk of MACE in elderly patients with chronic heart failure.
Turk Gogus Kalp Damar Cerrahisi Derg
Fang Lin, ZhangXin Fan
This study aimed to investigate the association between serum potassium concentration, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels, and short-term major adverse cardiovascular events (MACE) in elderly patients with chronic heart failure (CHF) after percutaneous coronary intervention (PCI), and to evaluate their predictive value.
Association between NT-pro-BNP levels and endothelial dysfunction assessed by digital thermal monitoring in patients with coronary artery disease.
Front Cardiovasc Med
Ji-Hung Wang, I-Min Su, Bang-Gee Hsu
Endothelial dysfunction is a key mechanism in the progression of coronary artery disease (CAD). N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a biomarker of myocardial wall stress, has been associated with vascular abnormalities beyond overt heart failure. However, its relationship with endothelial function, as assessed via digital thermal monitoring (DTM), in patients with CAD remains unclear.
Cost-Effectiveness Analysis of Age-Specific N-Terminal Pro-B-Type Natriuretic Peptide Thresholds for Heart Failure Diagnosis in China: Protocol for a Markov Model-Based Study.
JMIR Res Protoc
Changyuan Liu, Jing Wang, Shuangning Ding +1 more
Heart failure (HF) imposes a substantial clinical and economic burden in China. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) is widely used in the diagnostic pathway for HF, conventional thresholds are largely derived from Western populations and may not be fully applicable to Chinese adults.
Early life Oxytocin treatment Attenuates Seizure Susceptibility in Male, but not Female, Fmr1 -KO Mice.
bioRxiv
Jasmine Chavez, Julie C Lauterborn, Gary Lynch +1 more
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, and is frequently accompanied by seizures. Early-life treatment with the hormone oxytocin (OXT) improves social behavior and cognitive function in rodent models of autism with intellectual disability, including FXS, but potential OXT treatment effects on seizure susceptibility have not been evaluated. Here we tested, in both sexes, if intranasal OXT (iOXT) or saline (iSAL) during the second postnatal week reduces audiogenic seizures (AGS) in the Fmr1 -Knockout (KO) mouse model of FXS. OXT given daily from postnatal day (P) 7 to P13 significantly reduced the incidence and severity of AGS and the latency to seize in adult male Fmr1 -KOs. Female KOs exhibited less severe seizures that were unaffected by treatment. Wild type mice did not exhibit AGS independent of treatment. To test if antiepileptic effects of iOXT are age-dependent, a separate cohort received iOXT daily from P30 to P36. Male KOs receiving later treatments exhibited robust seizures that were comparable between OXT- and SAL-treatment groups, suggesting that OXT's enduring antiepileptic effects are confined to early postnatal treatments. Tests of acute OXT effects in adulthood demonstrated an attenuation of male Fmr1 -KO AGS at testing 30-60 min and 1 day post-treatment but these effects were not evident 15 days later. These findings reveal marked sex differences in the propensity for audiogenic seizures in Fmr1 -KO mice and demonstrate that early-life OXT treatment mitigates seizure susceptibility in males FXS model mice.
Dampened HPG axis activity and altered ovarian gene transcription in Dummerstorf high-fertility mouse line FL2.
Endocr Connect
Carolin L M Ludwig, Simon Bohleber, Anja Baufeld +5 more
Animal models of enhanced fertility are rare, as most genetically modified mouse models with reproductive phenotype display subfertility or infertility. Here we describe the ovarian phenotype of the Dummerstorf line 2 (FL2) mouse strain, which exhibits high fertility and has been selectively bred for increased fertility over more than 190 generations. This long-term selection, outbred mouse line almost doubled the litter size to 21.5 (FL2) compared to 11.3 (unselected control line, ctrl) without showing any signs of growth retardation in the offspring. Here we show that FL2 females ovulate 25.0 oocytes per cycle compared to 13.2 in ctrl. FL2 mice remain in the estrus phase for a shorter period during a 12-day observation period. Follicle-stimulating hormone (FSH) levels are decreased, both in estrus and diestrus, compared to ctrl, whereas Luteinizing hormone (LH) levels are unaffected. The mRNA expression levels in the pituitary gland correspond to the gonadotropin levels in the blood. Progesterone levels are decreased in estrus in FL2. Hypothalamic expression levels of Gonadotropin-releasing hormone (GnRH) are decreased in diestrus. Holistic gene expression analysis indicates complex and differential regulation in estrus and diestrus in ovaries of FL2 compared to ctrl. Especially genes of the TGF-β pathway (such as Bmp3, Bmp7, Inhba) and the Wnt pathway (such as Sfrp4, Mkrn1) are differentially expressed in ovaries of FL2 females. These data indicate that reduced activity of the hypothalamic-pituitary-gonadal axis (in particular, lower levels of GnRH, FSH and progesterone), combined with altered gene transcription in the ovaries, leads to higher ovulation rates in order to achieve the breeding objective of improved fertility.
Adrenal insufficiency after long-term high-dose ethinylestradiol use in a transgender woman.
JCEM Case Rep
Nagisa Aoki, Tomomi Taguchi, Satoshi Oda +3 more
A 42-year-old transgender woman, assigned male at birth, was referred for the evaluation of hypertension, and was found to have hypercortisolemia with suppressed adrenocorticotropic hormone (ACTH). The patient also presented with obesity and gynecomastia, along with reduced levels of gonadotropins, testosterone, and insulin-like growth factor 1 (IGF-1), with no adrenal lesions on imaging. These findings were attributed to more than 20 years of unsupervised high-dose oral ethinylestradiol use for breast feminization, with doses approximately 4 times higher than those typically prescribed for women. After discontinuation of ethinylestradiol, her hypertension improved, but a rapid ACTH stimulation test demonstrated an inadequate cortisol response, consistent with secondary adrenal insufficiency. Hydrocortisone replacement therapy with gradual tapering led to normalization of her ACTH, cortisol, gonadotropin, and IGF-1 levels. Subsequent ACTH stimulation and corticotropin-releasing hormone tests confirmed the recovery of adrenal function, enabling the cessation of hydrocortisone therapy. Thus, long-term high-dose oral ethinylestradiol may be associated not only with apparent hypercortisolemia attributable to increased corticosteroid-binding globulin, but also, possibly through increased free cortisol, with suppression of the hypothalamic-pituitary-adrenal axis. When a transgender woman taking supraphysiological doses of oral estrogen discontinues estrogen therapy, adrenal insufficiency potentially requiring transient steroid replacement should be considered.