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Zein Scaffold Preparation for Cultivated Meat.
J Biomed Mater Res A
Edward B Gordon, Amin Nikkhah, Sabrina Madiedo-Podvrsan +2 more
Cellular agriculture represents the intersection of biomaterials and cell science aimed at achieving high-quality, protein-rich, sustainable products. Developing cultivated meat products that address environmental and societal challenges requires the use of natural materials that support the replication of the characteristics of traditional meats while supporting cell growth in a scalable, low environmental impact process. Here, we utilize porogen leaching to form porous zein scaffolds that provide mechanical properties (Young's Modulus of 294 ± 102 kPa) and composition (75%-80% water and 20%-25% protein and cells) mimicking commercially available meat (e.g., rump roast), while supporting the growth of immortalized bovine satellite muscle cells. Over 2 weeks, cells showed significant growth and surface coverage even after initial low attachment. Enzyme-based food softening methods were used to reduce the mechanical properties of the scaffolds to replicate the consumer post purchasing process of tenderizing meat. The process developed was analyzed by life cycle assessment (LCA). The LCA results indicated that deionized water used for leaching the porogen was the primary contributor to environmental impact (e.g., global warming and water consumption), highlighting that scaffold environmental sustainability is influenced not only by feedstock selection but also by processing decisions. The zein scaffolds demonstrated promising mechanical, chemical, and cell supportive characteristics for cellular agriculture goals. Future research should focus on zein processing and sensory analyses to ensure meat-like outcomes in the final products, as well as sustainable design of scale up processes.
Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK Signaling Pathway.
Drug Des Devel Ther
Zhen Zhang, Delong Niu, Wenjie Qiu +3 more
Type 2 diabetes mellitus (T2DM) is a major risk factor for periodontitis, often leading to exacerbated alveolar bone loss. Ferroptosis, an iron-dependent regulated cell death pathway, contributes to osteoblast dysfunction under diabetic conditions. The non-canonical Wnt5a/Ror2 pathway is pivotal in inflammation and bone metabolism. Semaglutide, a long-acting GLP-1 receptor agonist, may modulate this pathway and protect osteoblasts from ferroptosis, however, its role in diabetic periodontitis remains unclear.
Lifestyle First and Lifestyle Always, Does Not Mean Lifestyle Only: Reimagining Cardiometabolic Care in the Era of GLP-1 Receptor Agonists.
Am J Lifestyle Med
Elizabeth Joy, Jonathan Bonnet
The rapid uptake of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and tirzepatide, has transformed the management of obesity, diabetes, and cardiometabolic disease, producing substantial weight loss, improved glycemic control, and reduced cardiovascular and renal risk. This article advances a guiding principle for contemporary care: "lifestyle first and lifestyle always, but not lifestyle only." While GLP-1 RAs have reshaped clinical practice and reinforced recognition of obesity as a biologically mediated disease, pharmacotherapy alone cannot resolve the complex behavioral, physiologic, and social drivers of cardiometabolic risk. Discontinuation of GLP-1 RAs without structured lifestyle support commonly results in weight regain, and medication does not address sarcopenia, physical deconditioning, sleep, stress, psychosocial determinants, or social connection. Lifestyle behaviors, high-quality nutrition, regular physical activity including resistance training, restorative sleep, stress management, social connectedness, and a sense of purpose, constitute the physiological and behavioral foundation for durable health gains. GLP-1 RAs are therefore positioned not as substitutes for lifestyle change, but as catalysts that create metabolic and psychological conditions that are favorable to adopting and sustaining healthy behaviors. Integrated, interprofessional models that combine pharmacologic and lifestyle strategies, supported by policy and systems change, are proposed as the emerging standard for long-term cardiometabolic health.
After the Prescription: The Clinical Support Gap in Telehealth-Based GLP-1 Care.
J Med Internet Res
Anna Zucker
GLP-1 medications offer promise for obesity management and are increasingly accessible via digital platforms. In this News and Perspectives article, JMIR Correspondent Anna Zucker reports on the gap in clinical support that could undermine their potential benefits.
Differential Biliary Adverse Event Signals Among Glp-1 Receptor Agonists: A FAERS Disproportionality Analysis.
Dig Dis Sci
Huda Alvina, Chidera N Jaffar, Abdelkader Onwuzo +2 more
Biliary adverse events (AEs) have been reported with glucagon-like peptide-1 receptor agonists (GLP-1RAs), but within-class differences remain unclear.
Evaluation of the safety profile of glucagon-like peptide-1 receptor agonists: a focus on thyroid cancer-related adverse events by using the European pharmacovigilance database.
Pharmacol Rep
Antonietta Anatriello, Valerio Liguori, Ciro Pentella +6 more
The therapeutic landscape for the treatment of type 2 diabetes mellitus (T2DM) has greatly evolved with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, concerns regarding their potential association with thyroid cancer have emerged. The aim of this study is to analyze individual case safety reports (ICSRs) involving GLP-1 RAs, focusing on thyroid cancer-related adverse events (AEs) using the European pharmacovigilance database.
Mitophagy in kidney and lung epithelial cells: molecular mechanisms, crosstalk, and therapeutic interventions.
Front Physiol
Xiaoxi Zhou, Jing Sun, Lining Miao +1 more
Mitophagy is a central component of mitochondrial quality control in both renal tubular and alveolar epithelial cells, where mitochondrial homeostasis is essential for barrier integrity, energy supply, and stress adaptation. Increasing evidence indicates that mitophagy is highly context-dependent across kidney and lung diseases: insufficient mitochondrial clearance is commonly linked to persistent mitochondrial dysfunction, epithelial senescence, and fibrotic remodeling, whereas dysregulated or excessive mitophagy may aggravate epithelial vulnerability under severe inflammatory or infectious stress. In this review, we summarize the molecular regulation of epithelial mitophagy, including PINK1/Parkin-dependent and receptor-mediated pathways, and examine its divergent roles in acute and chronic injury states in the kidney and lung. We further discuss a proposed mitophagy-centered framework for kidney-lung crosstalk. Current evidence is strongest for kidney-to-lung communication, particularly through circulating mitochondrial damage-associated molecular patterns and inflammatory mediators after acute kidney injury, whereas lung-to-kidney links remain supported mainly by organ-level inflammatory, hypoxemic, and hemodynamic mechanisms rather than direct evidence of pulmonary epithelial mitophagy-driven renal injury. Overall, the available literature supports mitophagy as an important mechanistic interface in epithelial injury, but not yet as a fully validated bidirectional epithelial axis. Future therapeutic strategies should therefore aim to restore mitophagy homeostasis in a disease- and stage-specific manner rather than uniformly enhancing or suppressing mitochondrial clearance.
EXPRESS: Oscillating Hypercapnia Induces Neural Abundant Protein Efflux and Potential Depletion in Health and Chronic Traumatic Brain Injury.
J Cereb Blood Flow Metab
Andrew Mayer, Tracey V Wick, Upasana Nathaniel +11 more
Emerging preclinical and clinical evidence suggests that low frequency hemodynamic oscillations drive CSF flow, which in turn mediates glymphatic clearance. The current study investigated whether CO2-induced low frequency hemodynamic oscillations during magnetic resonance imaging would increase clearance of proteins (glial fibrillary acidic protein, neurofilament light chain, ptau217 and brain-derived tau) from brain to blood, and temporarily improve cognitive performance in individuals with chronic traumatic brain injury (TBI) and age/sex-matched healthy controls. Results indicated that cerebrovascular reactivity, normalized CSF volume, and predicted brain age significantly differed between chronic TBI and controls, while bulk CSF flow differed only at trend levels. Multiple protein concentrations were significantly increased at ~45 minutes post-hypercapnia, decreased at ~90 minutes, and returned to pre-hypercapnia levels by ~150 minutes. Protein efflux was more strongly associated with total CSF volume and total white matter volume rather than cerebrovascular reactivity or bulk CSF flow. Both groups exhibited reduced cognitive interference post-hypercapnia, and hypercapnia associated symptoms quickly returned to baseline levels. In conclusion, hypercapnia temporarily increases clearance of multiple neural abundant proteins into blood, and this effect is moderated by atrophy. Current results suggest that hypercapnia may therapeutically combat pathological protein aggregation post-trauma, and prophylactically during normal aging.
Reduced plasma APJ levels and APLNR G212A polymorphism in Syrian patients with coronary artery disease.
Curr Med Res Opin
Maisaa Hassan Abd-Alkareem, Hussam Eddin Mohammed Shibli, Faizeh Ali Alquobaili
Coronary artery disease (CAD) remains a leading global cause of mortality. The apelin/apelin receptor (APJ) system has emerged as a novel pathway implicated in cardiovascular regulation and disease progression. This pioneering case-control study, the first conducted in a Syrian population, investigated the association of the apelin receptor G212A polymorphism and plasma APJ levels with CAD susceptibility.
Targeting Gut Microbiota by DPP-4 Inhibitors in Obesity: Mechanistic Insights and Therapeutic Implications.
Curr Nutr Rep
Mansour Alanazi, Hayder M Al-Kuraishy, Ahmed A Mohamed +4 more
Obesity is a complex metabolic disorder driven by factors such as chronic inflammation, insulin resistance, and significant alterations in the gut microbiota. Dipeptidyl peptidase-4 (DPP-4), an enzyme primarily known for inactivating incretin hormones like glucagon-like peptide-1 (GLP-1), is now recognized as a critical link between metabolic dysfunction and gut microbiome dysbiosis. This review aims to examine the mechanistic role of DPP-4 and its inhibitors in obesity, specifically focusing on how they modulate the gut microbiome to influence host energy balance and metabolic health.
[Advances in the role of adrenal microenvironment in maintaining homeostasis under inflammatory stress].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
Juan He, Lin Huang
Sepsis is one of the major diseases threatening human health. Under inflammatory stress, the rapid activation of glucocorticoids (GCs) and catecholamines (CAs) in the adrenal gland is crucial for maintaining the body's homeostasis. During severe inflammation, impairment of the hypothalamic-pituitary-adrenal (HPA) axis leads to suppressed secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACHT). However, studies reveal that the systemic glucocorticoid levels can remain normal or even elevated, suggesting a transition in the stress response mechanism from the central, pituitary-dependent regulatory system to local, pituitary-independent regulatory mechanisms. Among the various potential mechanisms, activation of the local adrenal microenvironment plays a significant role. In this microenvironment, interactions between adrenal cortical cells, medullary cells, vascular endothelial cells, and various immune cells contribute to the sustained production of GCs, which is pivotal in maintaining the internal homeostasis. This review focuses on the role of the local adrenal microenvironment in regulating the secretion of GCs and CAs, key hormones for maintaining homeostasis under inflammatory stress, with the aim of providing new insights into the etiology and pathogenesis of adrenal diseases.
Prognostic Value of Preoperative Left Ventricular End-Diastolic Dimension in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation With the Venus-A Valve.
Echocardiography
Baiqiang Mei, Zhaoyan Xu, Jian Li +9 more
Severe aortic stenosis (AS) leads to chronic pressure overload of the left ventricle (LV). We explored the prognostic value of preoperative left ventricular end-diastolic dimension (LVEDD) dilation in patients with severe AS.
Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury.
Sci Rep
Alperen Kutay Yıldırım, Hüseyin Demirtaş, Abdullah Özer +1 more
Ischemia-reperfusion (I/R) injury remains a major complication in peripheral arterial disease, characterized by oxidative stress, inflammation, and apoptosis. Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, has demonstrated cytoprotective properties in multiple tissues. This study aimed to evaluate the protective effects of BPC 157 in a rat model of lower limb I/R injury. Twenty-four male Wistar albino rats were randomized into four groups (n = 6): SHAM, B (BPC 157 only), IR (I/R), and IRB (I/R + BPC 157). I/R was induced by abdominal aortic clamping for 45 min followed by 2 h of reperfusion. BPC 157 (20 µg/kg, intraperitoneal) was administered at the 45th minute of ischemia in B and IRB groups. Biochemical markers (MDA, SOD, TAS, TOS) were measured in serum. Gene expression of Il-6, Hif-1α, p53, Bcl-2, Bax, and Casp3 was assessed by qRT-PCR, while immunohistochemistry evaluated VEGF, eNOS, IL-6, and Caspase-3 expression. Histopathological changes were scored with hematoxylin-eosin and Masson's trichrome staining. I/R significantly increased MDA, TOS, p53, Bax, Casp3, Hif-1α, Il-6, and histopathological injury scores, while reducing SOD, TAS, and VEGF expression. Bcl-2 mRNA was not significantly reduced by I/R compared with SHAM; however, BPC 157 significantly increased Bcl-2 expression compared with IR. In the IRB group, BPC 157 reduced MDA and TOS, restored SOD and TAS, downregulated p53, Bax, and Casp3, reduced IL-6 and Caspase-3 immunoreactivity, and partially restored VEGF expression. Histological analysis confirmed improved muscle architecture and reduced collagen deposition in IRB compared with IR. BPC 157 appears to exert protective effects against skeletal muscle I/R injury by attenuating oxidative stress, modulating apoptosis, reducing inflammation, and supporting angiogenic activity. These findings suggest that BPC 157 may represent a potential therapeutic candidate for mitigating reperfusion injury; however, further studies with larger cohorts and dose-response evaluations are required to confirm these effects and establish clinical relevance.
Efficacy and acceptability of liraglutide for obesity in people with HIV: results of an open-label clinical trial in South Africa.
Clin Infect Dis
Ngundu Behuhuma, Gugulethu Gasa, Anne Derache +15 more
In the Liraglutide for Obesity in HIV (LIROH) trial, we evaluated the efficacy and acceptability of liraglutide plus lifestyle counselling on weight and cardiometabolic health markers, along with the effect of discontinuation of therapy, among people with HIV (PWH) and a body mass index (BMI) ≥ 30 kg/m2 in rural South Africa.
Multi-omic profiling reveals Retatrutide alleviates adipose tissue fibrosis via metabolic reprogramming and tissue repair.
Diabetol Metab Syndr
Qingyang Li, Weilun Cheng, Jingyan Zhang +9 more
Retatrutide, a novel GIP, GLP-1, and glucagon receptor triple agonist, exhibits unprecedented weight-reducing efficacy in clinical trials, yet the molecular basis of its systemic metabolic benefits remains unclear.
FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.
Redox Biol
Zhengxiang Lv, Xiaodong Liu, Zhiwei Zhou +4 more
Neurodegenerative diseases (NDDs) lack effective disease-modifying therapies. The FOXO transcription factors serve as integrative hubs of cellular stress responses, operating through cell-autonomous homeostasis, intercellular coordination, intracellular quality control, and cell fate decisions four hierarchical tiers. This review systematically examines isoform-specific functions: FOXO1 governs metabolic reprogramming and mitochondrial biogenesis; FOXO3 acts as the principal oxidative stress sensor with context-dependent neuroprotective or pro-apoptotic outputs; FOXO4 regulates cellular senescence; and FOXO6 maintains synaptic metabolic support. These functions vary across cell types and disease stages, with post-translational modifications determining functional transitions. FOXO proteins participate in complex interactions with disease-specific pathological proteins, either promoting clearance and repair or exacerbating neurodegeneration depending on stress intensity and chronicity. Therapeutic strategies targeting FOXO remain in preclinical and early clinical stages. Key challenges include disease stage-dependent dosing, cell-type-specific delivery, blood-brain barrier penetration, and metabolic side effects. Future directions emphasize biomarker-guided patient stratification and precision interventions aligned with the spatiotemporal dynamics of FOXO signaling. Unlike prior reviews focusing on single pathways or diseases, this work integrates isoform-specific, stage-dependent, and cell-type-resolved FOXO functions into a unifying hierarchical framework.
Thyronines and Thyronamines Dual Modulators of Synaptic Plasticity, Cognitive Decline, and Geriatric Depression in the Aging Brain.
Behav Brain Res
Nahi Sabih Alruwaili, Hayder M Al-Kuraishy, Mohamed N Fawzy +3 more
The aging brain induces cognitive deterioration and geriatric depression via synaptic dysfunction, neuroinflammation, and bioenergetic failure. Recent evidence identifies thyroid hormones (thyronines: T3, T4) and their decarboxylated derivatives (thyronamines, especially 3-iodothyronamine, T1AM) as essential endogenous regulators of these processes. Thyronines influence both genomic and non-genomic pathways in glutamatergic, GABAergic, cholinergic, and monoaminergic signaling, thereby modulating learning and memory. With aging, diminished expression of thyroid hormone transporters (MCT8, OATP1C1) and compromised astrocytic conversion of T4 to T3 result in brain-specific hypothyroidism, facilitating amyloid-β accumulation, tau hyperphosphorylation, and hippocampal dysfunction. In contrast, T1AM stimulates trace amine-associated receptor 1 (TAAR1), promoting ERK1/2 phosphorylation, triggering autophagy through mTOR inhibition, and diminishing Aβ neurotoxicity in preclinical models. In geriatric depression, thyronines regulate monoaminergic transmission, whereas T1AM metabolites affect histaminergic pathways. Both hypothyroidism and hyperthyroidism significantly elevate the risk of Alzheimer's disease via distinct mechanisms: deficiency hinders glucose transport and amyloid-beta clearance, whereas excess disrupts mitochondrial respiration and activates stress kinases. The U-shaped dose-response relationship highlights the necessity for precise therapeutics. Selective modulators of thyronine and thyronamine receptors with improved brain penetration are promising approaches for addressing age-related cognitive decline and late-life depression.
Adult cardiovascular dysfunction induced by peri-pubertal high-fat diet exposure is mediated by the renin-angiotensin axis in male rats.
Nutr Res
Maiara Vanusa Guedes Ribeiro, Anna Rebeka Oliveira Ferreira, Letícia Ferreira Barbosa +10 more
This study investigated whether the renin-angiotensin system (RAS) is associated with the hypertension and metabolic syndrome induced by high-fat diet exposure during the peri-pubertal phase in rats. At postnatal day (PN) 30, male Wistar rats were randomly selected to be fed a normal diet (NF, 4.5% of fat) until PN 120 or a high-fat diet (HF, 35% lard) until PN 60 and then fed with a normal diet until PN 120. At PN 120, the function of the cardiovascular and RAS was assessed (5-16 animals per group). Statistical analyses were performed with the Student's T-test or 2-way ANOVA. HF rats showed increased arterial pressure (+ 9%, P = .004). The HF animals showed an increased pressor response at the lower (50 ng/kg/iv; + 50%, P = .048) and higher (300 ng/kg/iv; + 32%, P = .033) dose of Angiotensin II (Ang II), compared with NF animals. A higher depressor response to enalapril (5 mg/kg/iv; -100%, P = .014) was observed in HF rats. Greater endogenous circulating Ang II (+ 16%, P = .010) and lower endogenous circulating Ang (1-7) (-28%, P = .005) were observed in HF animals. The Ang II type 1 receptor (AT1R) mRNA expression increased (+ 81%, P = .037) in the heart of HF animals; however, Ang II type 2 receptor (AT2R; -91%, P = .039) and MAS receptor (MASR; -67%, P = .022) mRNA expression were reduced. In the aorta, AT1R mRNA expression increased (+ 124%, P = .046) in HF animals, whereas MASR mRNA expression decreased (-70%, P = .035), compared with NF animals. RAS is disrupted in adult hypertensive rats exposed to an HF diet during peri-pubertal life.
Telomere length in patients with non-functional adrenal incidentalomas.
Endocr J
Nilufer Ozdemir, Seda Sabah Ozcan, Ayse Ece Turkmen +3 more
Telomeres maintain genomic integrity during cell replication by preventing chromosomal fusions. Beside genetic influences, telomere length is affected by environmental factors such as oxidative stress and inflammation. These mechanisms also contribute to metabolic syndrome components linked to cellular aging. We aim to evaluate whether telomere length is shortened in patients with non-functional adrenal incidentaloma (NFAI) compared to the control group. This study was designed as a prospective, single-center study. The total of 88 participants included were 44 patients aged between 40 and 60 years with NFAI in our endocrinology clinic and 44 control subjects. An Absolute Human Telomere Lengths Quantification qPCR Assay kit (Nucleotestbio, Budapest, Hungary) was used for analyses. There was no significant difference between the NFAI and control groups regarding age and sex distribution. Telomere length was significantly shorter in the NFAI group (NFAI group: 3.680 ± 1.970 kb; control group: 4.469 ± 1.672 kb; p = 0.046). While no significant difference was found in telomere lengths in subgroup analyses, patients with basal adrenocorticotropic hormone (ACTH) levels <15 pg/mL had significantly shorter telomeres than those with basal ACTH levels ≥15 pg/mL (p = 0.034). A strong positive correlation was observed only between telomere length and ACTH level (p = 0.001). This study demonstrated that telomere length is significantly shortened in NFAI patients. Here, we propose that the underlying cause of telomere length shortening in the NFAI group may be related to increased cardiovascular risk and an elevated inflammatory state, even in the presence of cortisol levels within the normal range.
BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers.
Pharmaceutics
Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Florin Eugen Constantinescu +7 more
Background/Objectives: BPC-157 (body protection compound 157) is a synthetic pentadecapeptide derived from a gastric protein fragment with reported cytoprotective and regenerative properties across multiple organ systems. Despite over three decades of preclinical research demonstrating consistent biological activity, its pharmaceutical development remains rudimentary, with no approved formulation, no validated dosing regimen, and no completed Phase II clinical trial. This review critically evaluates BPC-157 from a biopharmaceutical and drug development perspective, examining its physicochemical and pharmacokinetic properties, formulation challenges across routes of administration, the pharmacokinetic-pharmacodynamic disconnect that characterizes its preclinical profile, and the regulatory and translational barriers that currently preclude clinical advancement. Methods: A narrative review of the literature was conducted using PubMed/MEDLINE, Embase, and Cochrane Library from database inception to April 2026. Search terms included "BPC-157", "BPC157", "body protection compound 157", "pentadecapeptide", and "GEPPPGKPADDAGLV", each combined with "pharmacokinetics", "formulation", "biopharmaceutics", "drug delivery", "clinical trial", "toxicology", and "regulatory". Patent databases (Espacenet, Google Patents) and regulatory agency websites (FDA, EMA, WADA) were searched independently. Searches were supplemented by forward and backward citation tracking of key references. Articles were selected based on relevance to biopharmaceutical characterization, pharmacokinetics, formulation science, clinical evidence, and regulatory status; pharmacodynamic studies were included insofar as they inform translational development. Evidence was synthesized with emphasis on pharmaceutical characterization, formulation science, and translational feasibility; no formal quality assessment instrument was applied, consistent with the narrative review design. Results: BPC-157 exhibits unusual stability in gastric juice and demonstrates activity via oral, parenteral, and topical routes, yet its human pharmacokinetic profile remains critically undercharacterized despite a recently published formal preclinical ADME study in two species confirming a sub-30-min plasma half-life, linear dose-proportional kinetics, and intramuscular bioavailability of 14-51% depending on species. A plasma half-life of under 30 min-confirmed preclinically and in a preliminary two-subject human pilot-contrasts with prolonged biological effects lasting hours to days-a disconnect with significant implications for dosing strategy and formulation design. No pharmaceutical-grade formulation has been developed or validated. The peptide lacks bcs classification data, permeability characterization, and formal excipient compatibility studies. Available clinical data derive from fewer than 30 subjects across three uncontrolled pilot studies, none of which employed standardized pharmaceutical preparations. Conclusions: BPC-157 presents a compelling but pharmaceutically underdeveloped profile. The primary barrier to clinical translation is not the absence of biological activity, but the absence of fundamental pharmaceutical science: characterized formulations, validated pharmacokinetics, and a coherent drug development strategy. Addressing these biopharmaceutical gaps is a prerequisite for any meaningful clinical program.