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Anshen Decoction Improves Synaptic Plasticity and Memory in Insomnia Rats by Regulating Hippocampal Mitochondrial Dysfunction via the AMPK/PGC-1α Pathway.
Comb Chem High Throughput Screen
Tiantian Tan, Biyong Liu, Shaojie Wan +8 more
This study investigated the effects of Anshen Decoction (ASD) on heart-kidney disharmony insomnia, focusing on the AMPK/PGC-1α pathway.
Refractory hyponatremia after traumatic brain injury unmasks adrenal insufficiency in a patient with remote steroid use.
CEN Case Rep
Toshikazu Ozeki, Seiya Ito, Yuna Muto +7 more
A man in his early 60 s developed persistent hyponatremia following lumbar spine surgery complicated by traumatic brain injury with subarachnoid hemorrhage. Initial evaluation demonstrated hypotonic hyponatremia with inappropriately concentrated urine, consistent with the syndrome of inappropriate antidiuretic hormone secretio. Standard therapy including hypertonic saline and oral sodium supplementation resulted in only transient improvement. Given a history of secondary adrenal insufficiency due to long-term topical corticosteroid use, adrenal function was reassessed. An adrenocorticotropic hormone stimulation test confirmed secondary adrenal insufficiency. Initiation of hydrocortisone therapy led to sustained normalization of serum sodium. This case highlights the diagnostic difficulty of post-TBI hyponatremia and underscores the importance of considering adrenal insufficiency, even years after apparent recovery from steroid-induced hypothalamic-pituitary-adrenal axis suppression.
Integrated bioinformatics analysis and experimental validation reveal circFoxO1 as a regulator of pathological cardiac hypertrophy.
3 Biotech
Huicong Yang, Jie Lin, Yongqing Yang +6 more
Pathological Cardiac Hypertrophy (CHT) is a maladaptive response that can lead to heart failure and increase the risk of severe cardiovascular events. However, the molecular mechanisms underlying CHT remain incompletely understood, and effective targeted therapies are still limited in clinical practice. Circular RNAs (circRNAs) emerge as important epigenetic regulators in cardiovascular biology, yet their roles in CHT remain insufficiently characterized. In this study, we combined transcriptomic analysis with in vitro and in vivo experimental models to identify functional circRNAs associated with CHT. Differential expression analysis of the GSE148602 dataset, coupled with machine-learning-assisted prioritization, highlighted circFoxO1 as a potential regulator. Angiotensin II (AngII)-induced hypertrophy models were established in HL-1 cardiomyocytes and C57BL/6 mice, revealing significant downregulation of circFoxO1 under hypertrophic conditions. Gain-of-function experiments demonstrated that circFoxO1 overexpression reduced the expression of classical hypertrophic markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), and alleviated AngII-induced cardiomyocyte enlargement. Mechanistic analyses further suggested that circFoxO1 may influence hypertrophic responses through the canonical Wnt/β-catenin signaling pathway, as circFoxO1 overexpression restored Wnt3a and β-catenin expression levels, whereas pharmacological inhibition with FH535 attenuated its antihypertrophic effect. Collectively, these findings indicate that circFoxO1 may modulate AngII-induced CHT and provide additional insight into circRNA-mediated regulatory mechanisms during pathological cardiac remodeling.
The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients.
Schizophr Bull
Riddhita De, Yasser Amin Alfatwa, Pruntha Kanagasundaram +8 more
Antipsychotic use in severe mental illnesses (SMI) is associated with metabolic dysregulation, including antipsychotic-induced weight gain (AIWG), type 2 diabetes (T2D), and dyslipidemia. In the case of non-response to metformin which is currently recommended for AIWG mitigation, no clear alternatives exist. Semaglutide, a weekly injectable glucagon like peptide-1 receptor agonist, represents a promising option. However, effectiveness and safety data in SMI are lacking. With initiation of semaglutide, we hypothesized weight loss, improvements in metabolic indices, and good tolerability.
Weight Changes With Lower Doses of Semaglutide in Clinical Practice: Findings From the Chinese HARMONY Cohort.
Diabetes Obes Metab
Shuang Liu, Baige Cao, Chuwen Lin +5 more
To evaluate 24-week weight changes with lower-dose semaglutide in routine care among Chinese adults with obesity and to examine whether diabetes and ectopic fat in the liver and pancreas are associated with heterogeneity in weight-loss response.
The Effect of Semaglutide on Quality of Life in Adults With Overweight or Obesity: A Brief Systematic Review and Meta-Analysis.
Diabetes Obes Metab
Naseem Eisa, Mira Khoury
Semaglutide 2.4 mg causes substantial weight loss, but its average effect on patient-reported physical function requires interpretation against clinically meaningful thresholds and routine clinical expectations. This systematic review and meta-analysis aimed to evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on patient-reported physical functioning and weight-related quality-of-life outcomes in adults with overweight or obesity.
GLP-1 Receptor Agonists in Aesthetic Surgery: A Narrative Review on Perioperative Safety, Sarcopenic Morphologies, and Adapted Body Contouring Strategies.
Aesthetic Plast Surg
Mario Venza, Isabella Venza
GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity and for weight management in individuals seeking aesthetic improvement. Their pharmacologic effects (delayed gastric emptying and reduced appetite) and the rapidity of weight loss may create perioperative and morphologic challenges for aesthetic and body contouring surgery.
Tirzepatide monotherapy in Chinese patients with early type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial (SURPASS-CN-MONO).
Med
Yaqi Yin, Jianhua Ma, Dexue Liu +8 more
We report findings from the Chinese SURPASS-CN-MONO trial (ClinicalTrials.gov: NCT05963022) of tirzepatide monotherapy.
SURMOUNT-REAL UK: A Pragmatic Randomized Clinical Trial to Assess the Effectiveness of Tirzepatide in Adults With Obesity.
Obesity (Silver Spring)
Martin K Rutter, Julie Mount, J Martin Gibson +12 more
SURMOUNT-REAL UK will evaluate the effectiveness of tirzepatide when offered in addition to standard-of-care (SoC) in adults with Class I obesity (BMI ≥ 30 and ≤ 34.9 kg/m2) and without diabetes in a UK primary care setting.
Temporal Trends and Clinical Characteristics of Incretin-Based Therapy Use in Women With Polycystic Ovary Syndrome: A Real-World Cohort Study From a Polish Private Healthcare Network.
Diabetes Obes Metab
Artur Dziewierz, Natalia Kulicka, Kaja Stolarska +4 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the dual GIP/GLP-1 receptor agonist tirzepatide are increasingly used for weight and cardiometabolic management, but real-world prescribing patterns in women with polycystic ovary syndrome (PCOS) remain poorly characterised.
Safety profile of teprotumumab-trbw, the first and only medicine approved by the FDA for the treatment of thyroid eye disease.
Expert Opin Drug Saf
Terry J Smith
Teprotumumab (Tepezza), a monoclonal antibody targeting the insulin-like growth factor 1 receptor (IGF-IR), was approved in January 2020 by the US Food and Drug Administration for treatment of thyroid-associated ophthalmopathy (TAO). The drug was found to be effective and generally well-tolerated in two registered clinical trials and subsequent post-marketing trials.
L-carnosine alleviates wooden breast myopathy in broilers fed oxidized soybean oil: Focus on antioxidant defense, calcium homeostasis, and satellite cell function.
Anim Nutr
Baohua Dong, Doudou Wang, Xiao'e Xiang +5 more
Feeding oxidized soybean oil (OSO) can disrupt the redox homeostasis in broilers and increase the incidence and severity of wooden breast (WB) myopathy. The antioxidant activity of L-carnosine (LC) has been demonstrated to help alleviate oxidative stress generated during metabolic processes. Therefore, the effects of dietary LC supplementation on WB myopathy were investigated in this study. One hundred and twenty-six 21-d-old white-feathered broilers (1.017 ± 0.039 kg) were randomly allocated into three groups (7 replicates per group with 6 broilers per replicate): fresh soybean oil group (CON), OSO group (OSO), and OSO + 800 mg/kg LC (OSO + LC), for a 21-d trial. Compared with the CON group, broilers in the OSO group showed an increased feed-to-gain ratio, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) contents, and decreased LC content in the pectoralis major (PM) muscle (P < 0.05). Concurrently, disrupted muscle calcium homeostasis was observed in the OSO group, characterized by significant upregulation of calcium-regulating proteins such as MCU, RYR, and NCX, together with downregulation of SERCA in the PM muscle (P < 0.05). Upregulation of MYOD and PAX7 along with downregulation of MYF6 was observed in the OSO group compared to the CON group (P < 0.05). Furthermore, the OSO group showed a 33.34% higher incidence of WB and increased muscle collagen deposition than the CON group (P < 0.05). Compared with the OSO group, broilers in the OSO + LC group exhibited reduced levels of oxidative stress markers (ROS, MDA, and protein carbonyls) and increased levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and LC in the PM muscle (P < 0.05). Muscle calcium homeostasis was rebalanced in the OSO + LC group through downregulation of IP3R, MCU, NCX, RYR, and PMCA, combined with upregulation of SERCA (P < 0.05). Moreover, the numbers of MYOD+ and PAX7+ cells in PM muscle of the OSO + LC group were lower than those of the OSO group (P < 0.05). Collagen deposition in the OSO + LC group was significantly reduced (P < 0.001) along with a decreasing trend in WB incidence compared to the OSO group (P = 0.043). The results indicate that OSO induces WB myopathy through oxidative stress, while LC effectively mitigates its adverse effects.
Unraveling the emerging role of glial heterogeneity in neuropathic pain: from pathological mechanisms to therapeutic Frontiers.
Front Neurol
Zhiwei Li, Jiafeng Lu, Zhonghua Chen
Neuropathic pain (NP) arises from injury or dysfunction within the somatosensory nervous system and represents a major clinical challenge due to its complex and multifactorial pathogenesis. Emerging evidence underscores that the onset and maintenance of NP are not solely governed by neuronal mechanisms but are critically shaped by the persistent activation and inherent heterogeneity of glial cells. Glial heterogeneity encompasses diverse molecular phenotypes, functional states, and distinct spatial distributions. Within the central nervous system (CNS), microglia and astrocytes undergo dynamic phenotypic transitions, contributing to both neurotoxic and neuroprotective effects by modulating neuroinflammatory cascades. In the peripheral nervous system, satellite glial cells actively sensitize sensory neurons through enhanced intercellular communication and the release of specific mediators, thereby facilitating the development and persistence of NP. The coordinated actions of heterogeneous glial populations drive key pathological processes-including synaptic remodeling, sustained neuroinflammation, and dysregulation of ion channels-ultimately promoting peripheral and central sensitization. Importantly, emerging therapeutic strategies targeting distinct glial subpopulations or their specific activation states, such as P2X4 receptor antagonists or NF-κB inhibitors, have shown promise beyond conventional neuron-centric approaches. This review synthesizes current insights into glial heterogeneity in NP, addressing a critical gap in the literature and providing a framework for advancing mechanism-based clinical interventions.
Pseudothrombocytopenia: a Case of Maternal-Induced Neonatal Platelet Phagocytosis and Platelet Satellitism Phenomenon.
Clin Lab
Suning Wang, Fucun Ma, Lei Shang +1 more
The phenomena of platelet phagocytosis and platelet satellitism (PS) are rare in vitro observations, with an estimated occurrence of 0.008%. These phenomena can be identified in blood smears utilizing ethylenediaminetetraacetic acid (EDTA) as an anticoagulant, manifesting as neutrophils engulfing platelets and platelets clustering around neutrophils to form satellite-like structures. These occurrences may result in pseudothrombocytopenia (PTCP), potentially complicating clinical diagnosis and treatment decisions.
MCC links Wnt/PCP signaling to endothelial polarity and vascular remodeling.
Angiogenesis
Valentin Delobel, Béatrice Jaspard, Malvina Salami +7 more
Vascular remodeling is crucial for establishing a functional vasculature and maintaining organ homeostasis. In the central nervous system (CNS), Wnt signaling plays a critical role in guiding endothelial cell (EC) behavior during vascular development and specialization. While canonical Wnt/β-catenin signaling regulates endothelial specification and blood-brain barrier formation, the non-canonical Wnt/Planar Cell Polarity (PCP) pathway orchestrates vascular remodeling and flow adaptation. However, how PCP signaling is transduced into intracellular polarity control remains unknown. Here, we identify MCC (Mutated in Colorectal Cancer) as a key regulator of endothelial polarity and migration downstream of the Wnt/PCP signaling pathway. Mechanistically, MCC interacts with the centriolar satellite protein CEP131 and promotes its turnover through proteasome- and autophagy-dependent pathways, thereby maintaining centrosome-associated organization required for directional polarity. MCC depletion disrupts directional polarity while preserving and enhancing flow-induced cytoskeletal elongation, revealing a functional dissociation between alignment and front-rear polarization. In vivo, endothelial-specific deletion of Mcc in the postnatal retina impairs vascular remodeling, reduces endothelial proliferation, and disrupts polarity at the angiogenic front. Notably, normalization of vascular density and regression by captopril does not restore polarity, indicating a cell-intrinsic role for MCC in endothelial organization. Together, these findings uncover an MCC-CEP131 axis linking Wnt/PCP signaling to centrosome-associated proteostasis and identify MCC as a key coordinator of endothelial polarity during vascular remodeling.
Thymosin α1 combined with immune checkpoint inhibitors: synergistic remodeling of the tumor immune microenvironment to enhance clinical efficacy and safety.
Front Immunol
Haiyv Guo, Ruichao Li
Although immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of solid tumors, their clinical utility remains constrained by several challenges, including tumor heterogeneity, immunosuppressive tumor microenvironments, and immune-related adverse events (irAEs), which collectively limit overall response rates. Thymosin α1 (Tα1), a pleiotropic immunomodulator, not only enhances immune competence and regulates excessive immune activation but also exerts direct antitumor effects. Given these immunoregulatory and antitumor properties, a growing body of preclinical and clinical studies has investigated the combination of Tα1 with ICIs, demonstrating its potential to augment the efficacy of ICIs and mitigate their limitations. In this review, we summarize and discuss the biological characteristics of Tα1 and current evidence regarding the synergistic effects of Tα1 combined with ICIs. Preliminary findings suggest that this combination exhibits promising clinical efficacy with manageable safety profiles in cancer therapy. Nevertheless, large-scale and long-term clinical studies are warranted to further validate its sustained clinical benefits.
A protease-sensing circuit links neutrophil inflammation to virulence regulation in Streptococcus pyogenes.
bioRxiv
Stephanie Guerra, Ananya Dash, Doris L LaRock +1 more
Streptococcus pyogenes (Group A Streptococcus) causes infections with a disproportionately hyperinflammatory response from the host, such as scarlet fever, necrotizing fasciitis, and toxic shock syndrome. Inflammation is specifically driven by S. pyogenes virulence factors, including the protease SpeB, but how inflammation impacts SpeB expression in return during disease is unknown. In this study, we identify a novel interaction between NETosis, a form of inflammatory cell death for neutrophils, and the induction of speB. Specifically, while the cathelicidin peptide LL-37 can repress speB through the two-component regulatory system CovRS, neutrophil proteases released during NETosis relieve repression of speB by degrading another repressor of speB, the bacterial protein Vfr. Furthermore, at high cell densities, SpeB autoregulates its expression through similar degradation of Vfr. Abrogating the formation of NETs or depleting neutrophils resulted in speB repression in vivo, showing the mutual host and pathogen counterattacks collectively lead to the pathological exacerbations characteristic of disease.
Synergistic antibacterial effect of CATH-2 and D-amino acids against mastitis causing gram-positive bacteria.
Front Cell Infect Microbiol
Edwin J A Veldhuizen, Sasja T van der Velden, David Alons +5 more
To effectively treat bacterial diseases caused by antibiotic-resistant strains, new antimicrobial agents are needed to overcome this resistance. This study explored whether the combination of the antimicrobial peptide CATH-2 with positively charged D-amino acids can be used as a potential alternative to antibiotics for treatment of mastitis in cows.
A-Intercalated Cell Dysfunction Disrupts Renal Epithelial-Immune Balance and Impairs Host Defense During UTI.
Am J Physiol Renal Physiol
Forough Chelangarimiyandoab, Kristina MacNaughton, Grace Essuman +1 more
Intercalated cells (ICs) of the renal collecting duct are traditionally recognized for their role in acid-base homeostasis, but growing evidence suggests they also participate in innate immune defense. Although ICs have been implicated in renal antimicrobial function, their specific role in coordinating immune responses during urinary tract infection (UTI) remains unclear. Using Ae1 R607H knock-in mice, a distal renal tubular acidosis (dRTA) model with A-intercalated cell (A-IC) dysfunction, we examined the renal response to uropathogenic Escherichia coli (UPEC). Mice with A-IC dysfunction exhibited higher bacterial loads 24 h post-infection and increased renal expression of antimicrobial peptides lipocalin-2 (Lcn2), galectin-3 (Lgals3), and cathelicidin-related antimicrobial peptide (Camp). Pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) were elevated at both transcript and protein levels, whereas tumor necrosis factor-α (TNF-α) increased only at the protein level. Interleukin-10 (IL-10) showed a modest rise in mRNA. Chemokines C-X-C motif chemokine ligand 2 (Cxcl2) and C-C motif chemokine ligand 2 (Ccl2) were also upregulated, accompanied by excessive neutrophil infiltration and a marked shift in renal myeloid-cell composition. A-IC dysfunction therefore correlates with higher bacterial load, exaggerated inflammation and impaired immune resolution. These findings identify A-ICs as essential epithelial immunomodulators that integrate antimicrobial defense, cytokine regulation, and immune-cell recruitment during UTI.
Comparative Effectiveness and Safety of Once-Weekly Injectable Semaglutide Versus Dulaglutide in Individuals with Type 2 Diabetes Managed in UK Primary Care: A Population-Based Cohort Study.
Lancet Reg Health Eur
Franziska S Ulrich, Morten Frost Nielsen, Nicola Napoli +1 more
The SUSTAIN-7 trial demonstrated greater HbA1c and bodyweight reductions with once-weekly semaglutide versus dulaglutide in type 2 diabetes, but strict eligibility criteria limit external validity. We evaluated the comparative real-world effectiveness and safety of these agents in UK primary care.