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Glucagon-like peptide-1 receptor agonists for weight management in mental illness: a network meta-analysis.
Transl Psychiatry
Taro Kishi, Toshikazu Ikuta, Kenji Sakuma +4 more
This network meta-analysis involved nine randomized controlled trials, comprising 595 participants (average age = 37.8 years, 55.3% female, 83.9% schizophrenia spectrum disorders), evaluating the comparative risk-benefit profiles of glucagon-like peptide-1 receptor agonists in individuals with obesity comorbid with mental illness.
Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.
BMJ
Kailei Nong, Qingyang Shi, Xinran Xie +26 more
To provide an up-to-date evidence summary about the comparative benefits and harms of drugs for adults with overweight or obesity to inform decision making for policymakers, payers, clinicians, and patients.
Could the cognitive benefits of amyloid-beta clearance grow in time for Alzheimer's disease?
Transl Psychiatry
Chen-Yang He, Xuan-Yue Wang, Jin Fan +3 more
Alzheimer's disease (AD) is characterized histologically by amyloid-β (Aβ) deposition in the brain. Immunotherapies targeting Aβ clearance have become a leading treatment strategy. Although these therapies effectively reduce cerebral Aβ burden, their cognitive benefits remain modest during the trial period. This review systematically assesses the extent of Aβ clearance by immunotherapies and its related cognitive outcomes, focusing on whether cognitive benefits increase over time. We refine a model of the "lag effect" between plaque clearance and cognitive benefit, which is potentially influenced by clearance rate, treatment duration, disease stage, genetic factors, and aging. We also discuss the underlying biological mechanisms and potential neuroprotective targets. Future research should prioritize long-term studies, early intervention, personalized therapies, and combination approaches addressing multiple pathological pathways. Given limited short-term cognitive gains, optimizing outcomes will require tailoring treatments to individual patient factors-including genetics, disease progression, and aging-to minimize side effects and enhance long-term cognitive function.
Eight Weeks of MitoQ Supplementation Does Not Alter Kidney Function or Urinary Kidney Injury Biomarkers in Middle-Aged and Older Adults.
Am J Physiol Renal Physiol
Nina L Stute, Jake P Muma, Zach J Hutchison +7 more
Introduction: Several human trials have used the mitochondrial antioxidant mitoquinol mesylate (MitoQ). There are no apparent negative consequences on the kidneys following an acute high dose of MitoQ in young adults, however it remains unclear whether chronic MitoQ influences kidney function. Therefore, we examined whether eight weeks MitoQ supplementation (20mg/day) impacts kidney function and kidney injury biomarkers using a randomized, placebo-controlled, crossover study in middle-aged and older adults (n=30, 8 males/22 females, 57±8 years). Methods: Participants completed four visits (pre- and post-placebo; pre- and post-MitoQ) where we collected serum samples (creatinine and cystatin c) and 24-hr urine samples to assess general kidney function (estimated glomerular filtration rate [eGFR] and creatinine clearance), and kidney injury markers (neutrophil gelatinase-associated lipocalin; NGAL, kidney injury molecule-1; KIM-1, nephrin, tissue inhibitor of metalloproteinase-2; TIMP-2, and insulin-like growth factor binding protein-7; IGFBP7). We used mixed-effects models to examine time, condition, and interaction effects. Results: We observed no alterations in glomerular filtration measures (ps ≥ 0.309), or kidney injury markers when indexed to flow rate, osmolality, or creatinine (ps ≥ 0.198). For example, TIMP-2 × IGFBP7 was not different between groups (pre placebo: 114 ± 162, post placebo: 138 ± 161; pre MitoQ: 162 ± 238, post MitoQ: 127 ± 137 ng2/min; interaction p = 0.754). Conclusion: Eight weeks of MitoQ supplementation doesn't appear to benefit or harm kidney function or kidney injury markers in middle-aged and older adults.
Maternal oxytocin mitigates offspring autism-like phenotypes and oxytocin system alterations through improved maternal care.
Sci Rep
Fatemeh Barzi, Monireh Mansouri, Mohammadreza Bigdeli +1 more
Maternal care is crucial for normal neurodevelopment. Disruptions in early caregiver-infant interactions, potentially linked to modern lifestyles, may contribute to the rising prevalence of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Given the reported deficits in the oxytocinergic system in both ASD and impaired mother-child interactions, this study investigated: (1) whether inadequate maternal care induced by early-life maternal separation (MS) in female rats leads to autism-like phenotypes in their offspring, and (2) whether improving maternal care with oxytocin (OXT) can ameliorate these outcomes. Female rat pups underwent MS (3 h/day from postnatal day (PND) 1-14). As adults, they were mated and assigned to MS+Saline, MS + OXT (0.8 IU/kg intranasal, PND1-14), or control groups. Maternal behavior was assessed. Their male offspring were evaluated during adolescence for social and repetitive behaviors, and their brains were analyzed for hypothalamic OXT and hippocampal Oxytocin Receptors (OXTRs) expression. Dams with a MS history exhibited impaired maternal care, characterized by reduced nursing and increased harmful behaviors. OXT treatment significantly improved maternal care in these dams. The offspring of MS+Saline dams displayed core autism-like phenotypes, including social deficits and increased repetitive behaviors, alongside reduced OXT expression in the hypothalamus and OXTR expression in the hippocampus. Crucially, these behavioral and neurobiological abnormalities were ameliorated in the offspring of OXT-treated MS dams. This study demonstrates that impaired maternal care, resulting from early-life stress, can induce autism-like abnormalities in offspring. OXT administration to dams effectively improves maternal behavior and mitigates the development of these abnormalities, highlighting the maternal environment as a key modifiable factor. Our findings provide a compelling preclinical framework supporting the potential of early interventions focused on the parent-child environment to mitigate neurodevelopmental risk.
Real-World vs. Randomized Trial Evidence for Incretin-Based Therapies: A Narrative Review.
J Diabetes
Zachary Bloomgarden
Incretin-based therapies have transformed the management of obesity and type 2 diabetes (T2D). Pivotal randomized controlled trials (RCTs) report substantial weight loss and glycemic improvements; the extent to which these translate to clinical populations remains uncertain. Seven 2026-published RCT meta-analyses (comprising 127 RCTs and 58 976 participants) were compared with 26 real-world studies identified through structured PubMed search. Primary outcomes were body weight loss and HbA1c reduction; secondary outcomes included major adverse cardiovascular events (MACE), neurological end-points, and safety. The comparison is descriptive. For T2D, real-world semaglutide achieved 4.7-10.5 kg weight loss (6-12 months) and 1.0-1.3 percentage-point HbA1c reductions, lower than RCT meta-analytic estimates (tirzepatide mean difference [MD] -9.55% vs. placebo). Without diabetes, real-world persister analyses (SHAPE study: semaglutide -14.1%, tirzepatide -16.5%) approximated per-protocol RCT estimates (semaglutide -14.9%, tirzepatide 15 mg -20.9%), whereas intention-to-treat real-world estimates were substantially lower. Just 13% of semaglutide users reached 2.4 mg and 25.9% of tirzepatide users reached 15 mg. Real-world cardiovascular data showed 20%-46% MACE reductions, broadly consistent with the RCT reduction. Differences between T2D and non-T2D populations likely reflect channeling bias and differential follow-up. Real-world incretin-based therapy effectiveness is broadly consistent with RCT efficacy when dose attainment is accounted for. High discontinuation rates (20%-50% within 1 year) and prior GLP-1 RA exposure track with the observed efficacy gap. Clinicians can expect RCT-level outcomes in patients who tolerate and persist with target doses. Head-to-head cardiovascular outcome trials comparing tirzepatide and semaglutide in non-diabetic populations are needed.
Acute Left Heart Failure in Twin Pregnancies: Clinical Characteristics and Outcomes-A 10‑Year Retrospective Analysis of 24 Cases.
J Clin Hypertens (Greenwich)
Qianqian Xiang, Yuan Wei, Yangyu Zhao
This retrospective study evaluated the clinical characteristics, management, and maternal-neonatal outcomes of 24 twin pregnancies complicated by acute left heart failure (ALHF) delivered at Peking University Third Hospital from January 2015 to December 2025. Patients were stratified by timing of onset (antenatal vs. postnatal). The mean maternal age was 33.8 years, and 70.8% had preeclampsia. ALHF occurred antenatally in 9 cases (37.5%) and postnatally in 15 cases (62.5%). Dyspnea was the most common initial symptom (79.2%). The mean left ventricular end‑diastolic diameter was 50.6 ± 3.7 mm, and the median NT‑proBNP level was 1406.0 pg/ml (IQR: 1146.5-2053.5 pg/ml). All patients received multidisciplinary care and diuretics, with 37.5% requiring intensive care. Full cardiac recovery by 6 weeks postpartum was achieved in 87.5% of patients. The preterm birth rate was 87.5%, and the perinatal mortality rate was 10.4%. Compared with the postnatal‑onset group, the antenatal‑onset group had significantly higher NT‑proBNP levels at disease onset or diagnosis (2388.5 vs. 1257.0 pg/ml, p = 0.018), longer hospital stay (11 vs. 8 days, p = 0.019), earlier gestational age at delivery (30 vs. 36 weeks, p = 0.002), and higher rates of neonatal intensive care unit admission (92.3% vs. 40.0%, p = 0.01) and perinatal mortality (27.8% vs. 0, p = 0.016). In conclusion, ALHF in twin pregnancies predominantly occurs postnatally and is frequently associated with preeclampsia; maternal outcomes are favorable with multidisciplinary care, whereas neonatal outcomes were poorer in the antenatal-onset group, likely reflecting medically indicated early preterm delivery in the setting of maternal decompensation.
Immunoadsorption and subsequent immunoglobulin G replacement (IA/IG) in patients with dilated cardiomyopathy: a systematic review and meta-analysis.
Front Cardiovasc Med
Xiao Xia, Yuhao Yao, Jun Li +6 more
Dilated cardiomyopathy (DCM) is a refractory cardiac disease with significant morbidity and mortality. Although immune adsorption combined with immunoglobulin G replacement therapy (IA/IG) has shown potential in treating DCM, only small-scale clinical trials have been reported. Its efficacy and safety characteristics still need to be further systematically evaluated.
Enterohepatic Circulation of Polystyrene Nanoplastics Promotes Intestinal Inflammation by Impairing Enteric Neurons.
ACS Nano
Xiaochang Wang, Quanlin Wang, Wenqi Jiang +3 more
Microplastics (MPs) are emerging contaminants of increasing concern, yet their in vivo fate and mechanisms of intestinal toxicity remain poorly defined. Here, we demonstrate that polystyrene nanoplastics (PS-NPs) undergo a previously overlooked enterohepatic recirculation pathway that markedly enhances their intestinal retention. Using oral exposure and a Zombie mouse model with intravenous PS-NPs delivery, we show that systemically absorbed PS-NPs are efficiently captured by the liver, concentrated in the gallbladder, and subsequently reintroduced into the intestine via bile. Chronic PS-NPs exposure caused pronounced epithelial injury, including goblet cell loss, tight-junction disruption, and robust cytokine-mediated inflammation. Multiomics analyses revealed gut microbial dysbiosis, extensive shifts in metabolite profiles, and enrichment of neuroactive signaling pathways, suggesting microbiome-metabolite contributions to toxicity. We further identified significant enteric neurotoxicity characterized by reduced expression of vasoactive intestinal peptide, increased expression of tyrosine hydroxylase, and downregulation of the mechanosensitive PIEZO1 channel. Together, these findings establish hepatobiliary recycling as a key driver of intestinal PS-NPs accumulation and demonstrate that epithelial damage, microbiome-metabolite imbalance, and enteric nervous system dysfunction collectively mediate PS-NPs-induced gut pathology. This work provides mechanistic insights essential for evaluating the health risks of environmental PS-NPs exposure.
Ectopic ACTH Production in Medullary Thyroid Carcinoma-A Study of Two Cases.
Case Rep Endocrinol
Robert Bränström, Fredric Hedberg, Monique Huisman +6 more
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from thyroid parafollicular C-cells, accounting for 1-2% of all thyroid cancers. An exceedingly rare manifestation of MTC is ectopic adrenocorticotropic hormone (ACTH) production, causing Cushing's syndrome and complicating management. This report presents two cases of MTC with ectopic ACTH production, highlighting diagnostic challenges, therapeutic strategies, and clinical outcomes. A comprehensive literature review on this rare paraneoplastic syndrome is included and supplements the case findings. Case 1 involves a 49-year-old man presenting with abdominal pain, weight loss, and pulmonary nodules, diagnosed with MTC and ectopic ACTH-related Cushing's syndrome. Surgical resection and targeted therapy with selpercatinib improved cortisol levels but were complicated by adverse drug reactions. Case 2 details a 65-year-old woman with severe hypercortisolism and locally advanced MTC. Selpercatinib successfully reduced hormone levels and achieved partial tumor regression. Both cases underscore the critical role of tyrosine kinase inhibitors (TKIs) in controlling tumor progression, and paraneoplastic hormone production is exemplified in both cases, as treatment initiation was followed by a biochemical response with declining levels of ACTH, cortisol, and calcitonin. Ectopic ACTH production in MTC is a rare but clinically significant entity associated with aggressive disease. Early recognition, comprehensive biochemical and imaging evaluations, and a multidisciplinary approach are pivotal for optimal management. The advent of targeted therapies, such as selpercatinib, has transformed the therapeutic landscape, offering improved control of both tumor burden and hormone excess. This report highlights the importance of integrating genomic insights and precision medicine in addressing these complex cases.
GABA neurons in the sublaterodorsal tegmental nucleus suppress wakefulness in healthy and narcoleptic mice.
PLoS Biol
HanHee Lee, Jimmy J Fraigne, John H Peever
The sleep-wake cycle is generated by competing neural circuits that control the oscillation between wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. While the sublaterodorsal tegmental nucleus (SLD) is recognized for its role in REM sleep generation, the functional contribution of its GABAergic neurons (SLDGABA) to sleep-wake regulation remains poorly understood. Here, we found that SLDGABA neurons function as a suppressor of wakefulness in both healthy (i.e., orexin+/+) and narcoleptic (i.e., orexin-/-) mice. In healthy mice, optogenetic silencing of SLDGABA neurons rapidly induced robust wakefulness, while enhancing cortical and motor activity. Conversely, optogenetic activation of these neurons suppressed wakefulness and promoted NREM sleep. We found traces of SLDGABA axonal projections to wake-promoting brain regions, providing an anatomical basis for their wake-suppressing effects. Importantly, we discovered that SLDGABA neurons play a pathological role in narcolepsy: their activation in orexin-deficient narcoleptic mice triggered characteristic sleep attacks-rapid intrusions of NREM sleep during active wakefulness-while silencing these neurons rescued animals from both sleep attacks and cataplexy. Collectively, these findings establish SLDGABA neurons as a key regulator of arousal state transitions and identify them as a novel therapeutic target for the treatment of narcolepsy.
Functional diversity of cathelicidin peptides in the frog lung: An integrated transcriptomic and functional analysis.
Comp Biochem Physiol C Toxicol Pharmacol
Pawarit Khamlaiwong, Chutima Karnmongkol, Rujiraphorn Musigapan +4 more
Amphibians have evolved sophisticated innate immune mechanisms shaped by dual aquatic-terrestrial lifestyles, yet the pulmonary cathelicidin repertoire remains incompletely characterized. This study investigated the diversity, and comparative activity profiles of lung-expressed cathelicidin in the tiger frog (Hoplobatrachus rugulosus) through an integrated transcriptomic and biochemical approach. RNA sequencing of lung tissue identified four cathelicidin paralogs-Hr-CATH1 to Hr-CATH4 (AS34, SN34, AR37 and DL37)- representing the complete cathelicidin complement co-expressed in this tissue, including both previously reported sequences and paralogs not yet functionally characterized. RT-qPCR analysis confirmed the expression of all four transcripts and revealed distinct expression patterns among the paralogs. Bioinformatic analysis revealed conserved signal peptide and cathelin-like pro-regions, alongside divergent mature peptide domains, resulting in substantial variation in physicochemical properties, from highly cationic (AS34, +9) to anionic (DL37, -4). Circular dichroism spectroscopy showed membrane-induced α-helical adoption across all peptides. Biological activity assays demonstrated that AS34 exhibited potent broad-spectrum antimicrobial potency consistent with membrane disruption and DNA binding, whereas SN34 displayed moderate selective activity and AR37 and DL37 lacked direct antimicrobial effects. Notably, all four peptides suppressed lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages. AS34 further downregulated pro-inflammatory gene expression (TNF-α, IL-1β, IL-6, iNOS, COX-2). All peptides established low to moderate hemolytic efficacy at high concentration. Collectively, these findings suggest functional diversity among lung-expressed cathelicidins contributing to a multifaceted pulmonary defense in H. rugulosus, and position AS34 as a promising scaffold for developing novel antimicrobial and anti-inflammatory therapeutics.
Brain Neuromodulation via Endoscopic Gastric Implant Improves Glycemic Control in Insulin-Dependent Type-2 Diabetes: First-in-Human Feasibility and Autonomic Response Study.
J Laparoendosc Adv Surg Tech A
Valerio Cigaina, Alfredo Saggioro, Paolo Fabris +1 more
A miniaturized, self-powered Brain NeuroModulator (BNM) device, endoscopically implanted under neuroleptanalgesia in the submucosal layer of the proximal lesser gastric curvature, has the potential to consistently increase parasympathetic tone as measured by heart rate variability (HRV).
Role of GLP-1 receptor agonists in the prevention and treatment of obesity-related cancer.
Intern Emerg Med
Giovanna Muscogiuri, Guendalina Del Vecchio, Luca Colangeli +3 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become pivotal in treating type 2 diabetes and obesity due to their ability to improve glycemic control and promote weight loss. Beyond their metabolic benefits, emerging evidence suggests that GLP-1 RAs may exert anticancer effects by modulating critical biological pathways involved in tumorigenesis, including insulin signaling, inflammation, and cellular proliferation. Current evidence derived from observational and secondary analyses suggests potential protective effects of GLP-1 RAs against several cancers-including prostate, breast, pancreatic, gynecological, glioma, and oral squamous cell cancer through both weight-dependent and independent mechanisms, but the absence of large-scale randomized controlled trials (RCTs) with cancer-specific endpoints remains a critical limitation. Moreover, safety concerns remain a major challenge. Although rodent studies raised concerns regarding medullary thyroid carcinoma, human data have not substantiated a significant risk. Similarly, initial signals of pancreatitis and pancreatic cancer risk have been largely attenuated by subsequent rigorous analyses. Common side effects, such as gastrointestinal discomfort, are usually manageable and transient, but rare adverse events warrant vigilance, particularly in vulnerable patient populations. GLP-1 RAs show emerging signals for cancer prevention and treatment, but their therapeutic application in oncology should proceed cautiously. Future research must prioritize well-designed, adequately powered cancer-focused RCTs that evaluate both efficacy and safety over extended periods.
GLP-1 medications: use and interest in a representative survey of Finns.
Int J Obes (Lond)
Piia Tuuli Jallinoja, Kirsi H Pietiläinen, Virginia W Chang
GLP-1-based medications have rapidly reshaped the landscape of obesity treatment. Semaglutide was approved for obesity treatment in 2021 in the US and 2022 in Europe, sparking global interest, and the GLP-1/GIP dual-agonist tirzepatide has demonstrated even greater efficacy. However, survey-based data on who uses or considers these medications-particularly across socioeconomic groups, BMI categories, and weight management experiences-remain limited.
Elamipretide in pediatric Barth syndrome: from heart failure to school return.
Orphanet J Rare Dis
Pascal Amedro, Mathieu Andrianoely, Pauline Gohier +16 more
Barth syndrome (BTHS) is a rare X-linked mitochondrial disorder characterized by cardiomyopathy, neutropenia, and skeletal myopathy. Elamipretide is a mitochondria-targeting peptide that stabilizes cardiolipin and improves mitochondrial function. While use of this treatment in infants with BTHS has been reported in the United States, no cases have been described outside the US or in older children.
Spontaneous aging of mature amyloids alters structural stability, cytotoxicity, and susceptibility to biological clearance.
Cell Death Discov
Maksim I Sulatsky, Olga V Stepanenko, Arina A Kayda +3 more
Accumulation of amyloid fibrils is a key factor in the pathogenesis of progressive diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's disease, as well as systemic amyloidosis. Although amyloid deposits are known to persist in vivo for years or even decades, it remains unclear how the structure and biological properties of mature fibrils evolve during prolonged post-assembly residence. Here, we addressed this question using a simplified cell-free aqueous model designed to isolate the intrinsic time-dependent behavior of mature amyloid aggregates from the complexity of the biological milieu. Specifically, we investigated the long-term evolution of two polymorphs of lysozyme amyloid fibrils as model systems with distinct clustering propensities that mimic the diversity of amyloid deposits. We challenge the assumption of amyloid stability by demonstrating their spontaneous degradation over 16 months at physiological temperature, a process we define as amyloid "aging". This process is characterized by aggregate declustering, fibril shortening, and progressive depolymerization into monomeric subunits, accompanied by a pronounced reduction in intrinsic toxicity across multiple human cell lines. Notably, "aged" fibrils were disassembled and degraded more efficiently than freshly prepared aggregates by the molecular chaperone α-B-crystallin and immune-associated proteases, including matrix metalloproteinase-9 and cathepsins B and D. However, this enhanced degradation revealed a paradox: accelerated processing of "aged" amyloids did not always reduce cytotoxicity and, in some cases, even exacerbated it, consistent with the generation of biologically active fibril-derived species rather than their complete conversion into non-toxic monomers. We provide the first systematic evidence that mature amyloids are dynamic structures undergoing spontaneous degradation that fundamentally alters their cytotoxicity and susceptibility to biological clearance. Our results introduce amyloid aging as a previously underappreciated dimension of amyloid biology and emphasize the need to account for fibril "age" when evaluating pathogenic potential and developing anti-amyloid therapeutic strategies.Spontaneous "aging" of amyloid fibrils leads to suprastructural remodeling: declustering, fibril shortening, and attenuated cytotoxicity. While "aged" aggregates are degraded more efficiently by immune-associated proteases and α-B-crystallin than "fresh" fibrils, this enhanced degradation does not reduce cytotoxicity and, in some cases, exacerbates it, highlighting the complex interplay between aggregate maturity and biological outcomes.
Noninvasive Cardiac Output Monitoring Combined With Critical Care Ultrasound for Postoperative Volume Management in Cardiac Surgery Patients: A Randomized Controlled Trial.
J Surg Res
Yunzhu Xu, Lu Zhang, Xian Pan +2 more
Postoperative hemodynamic instability and low cardiac output syndrome are common complications following cardiac surgery. Conventional volume management guided by central venous pressure and mean arterial pressure has well-documented limitations. Noninvasive cardiac output monitoring (NICOM) and critical care ultrasound (CCUS) provide complementary, real-time hemodynamic and volumetric assessments. This randomized controlled trial evaluated whether NICOM+CCUS-guided fluid management improves clinical outcomes in cardiac surgery patients with postoperative hemodynamic instability.
Mechanisms of systolic heart failure in PP2CxPP5 double transgenic mice.
Naunyn Schmiedebergs Arch Pharmacol
Rebecca Schwarz, Katarina Hadova, Jan Klimas +3 more
The function importance of serine threonine phosphatases (PP) in the heart is still subject of investigations. For instance, PP5 and PP2C occur in the human heart. It is unclear how they interact in the human heart. In order to obtain a model system, we have crossbred mice with heart-specific overexpression of PP2C or PP5 to obtain wild-type mice (WT), PP2C transgenic mice (PP2C-TG), PP5 transgenic mice (PP5-TG), and PP2CxPP5 double transgenic mice (DT). Moreover, while PP2C-TG and PP5-TG did not show any increase in relative heart weight, it was increased in DT. In histology, DT showed cardiac fibrosis based on Masson/Goldner staining compared to WT. Basal ejection fraction was reduced in PP5-TG by 25%, by 29% in PP2C-TG, and by 38% of WT values in DT. This went hand in hand with a diminished phosphorylation of phospholamban at serine-16, the phosphorylation site for the cAMP-dependent protein kinase (PKA), after perfusion of isolated hearts with isoprenaline. DT and PP2C-TG sustained ischemia and reperfusion of isolated hearts worse than WT or PP5-TG. Expression of atrial natriuretic factor (ANF, marker of hypertrophy), of collagen 1a (fibrosis marker) and nuclear factor kappa B (marker of inflammation) in DT were augmented versus WT (ANF: 5.14 ± 0.75 vs. 1.00 ± 0.33; Col1a1: 1.82 ± 0.09 vs. 1.00 ± 0.10; Nfkb1: 1.33 ± 0.03 vs 1.00 ± 0.04; n = 6-10; p < 0.05). In summary, cardiac co-overexpression of two PPs, namely, PP2C and PP5, was detrimental to cardiac function. The underlying (patho)mechanism for this may involve dephosphorylation of Ca2+ regulatory proteins but also accompanying fibrosis and inflammation.
Semaglutide Modulates Visceral Adipose Tissue Lipid Metabolism in Type 2 Diabetic Mice: A Lipidomics Study.
Front Biosci (Landmark Ed)
Xinlei Chen, Bingrou Tu, Zhaoyuan Li +3 more
Type 2 diabetes mellitus (T2DM) is a major public health challenge. This study aimed to explore the molecular mechanisms underlying the effects of semaglutide on lipid metabolism in visceral white adipose tissue in a mouse model of T2DM.