Search Results (1,984)

Class B scavenger receptor BI splice variants (SR-BI) and BII (SR-BII) internalize lipoproteins but also bind and internalize bacteria. Their individual roles in sepsis are unknown. We overexpressed human SR-BI or BII in transgenic mice, primarily in the liver, but also in the kidney and in bone marrow-derived macrophages, and then performed cecal ligation and puncture (CLP) surgery. SR-BI and BII transgenic mice had significantly worse survival compared to WT mice. Twenty-four hours after CLP, liver injury markers and histological damage were elevated in both SR-BI and BII transgenic mice, whereas kidney damage was similar. Systemic inflammatory cytokines were markedly increased in SR-BI and BII transgenic mice; parallel increases were seen in liver mRNA expression, but not in the kidney. The highest degree of neutrophil infiltration was observed in the liver of SR-BI. Human SR-BI and BII dramatically decreased bacterial accumulation in the liver. Green fluorescent protein-labeled E. coli were efficiently phagocytosed in hepatic macrophages of SR-BI and BII transgenic mice; phagocytosis was more prominent in SR-BII transgenic mice. Finally, human SR-BI overexpression reduced systemic HDL-C levels, eliminated adrenal cortex lipid droplets, and dampened the systemic increase of corticosterone after CLP. Supplementation with glucocorticoid and mineralocorticoid improved survival in SR-BI but not in SR-BII transgenic mice after CLP. In summary, our findings suggest human SR-BI and BII overexpression contributes to higher mortality after CLP by different mechanisms: excessive inflammatory response due to adrenal insufficiency (SR-BI) or hyperactive phagocytosis (SR-BII) in the liver. Full article

Fibromyalgia, a syndrome characterized by hyperalgesia and ‘negative emotionality’, and major depressive disorder (MDD) demonstrate substantial overlaps in clinical, neurobiological, and therapeutic domains. Currently, treatment options for fibromyalgia remain limited; however, the epidemiology of this syndrome continues to grow worldwide. The use of animal models is indispensable for developing new treatment strategies for fibromyalgia. Meanwhile, the choice of animal paradigms is limited. Here, we used the ultrasound exposure of emotional stress on CBA, BALB/c, and C57BL/6 mouse strains to model this condition and to identify new molecular targets of fibromyalgia treatment. We exposed young male mice of three common strains to a three-week ultrasound stress (US) comprising emotionally negative and neutral frequencies of 20–25 kHz and 25–45 kHz, resulting in the development of altered pain sensitivity and signs of ‘negative emotionality’. Specifically, mice were studied for timid-like/aggressive behaviors and the tail flick response. Serum levels of corticosterone, cortisol, β-Endorphin, and brain-derived neurotrophic factor (BDNF), as well as brain gene expression of interleukin-33 (Il-33), Bdnf, and its receptor Trkb were investigated. Among the stressed mouse strains, C57BL/6 mice displayed augmented pain sensitivity, allodynia, and suppressed dominant behavior, whereas CBA and BALB/c mice demonstrated opposing changes. Glucocorticoid levels were increased in all stressed groups. Stressed C57BL/6 mice showed downregulated gene and protein expression of functionally inter-related BDNF and IL-33 molecules in the hippocampus, amygdala, and striatum, significantly correlating with behavioral outcomes, as well as lowered blood levels of β-Endorphin and elevated cortisol concentrations. Altogether, our study identified the BDNF/IL-33 regulatory pathway as a molecular correlate of fibromyalgia, and the use of US-exposed young C57BL/6 mice as a potential model that recapitulates this syndrome. Full article

Background/Objectives: Hospitalisations in systemic lupus erythematosus (SLE) reflect disease severity, accumulated damage, and the burden of comorbidity, remaining a major determinant of healthcare utilisation. Recent evidence suggests a shift from flare-driven admissions toward complications related to infections, comorbidities, and long-term treatment effects. We aimed to analyse the causes, characteristics, and outcomes of hospital admissions in patients with systemic lupus erythematosus (SLE) over a 30-year period in a tertiary referral centre in Catalonia (Spain) and to evaluate changes over time and prognostic factors associated with adverse outcomes. Methods: A retrospective observational study was conducted including all SLE patients admitted to the Department of Autoimmune Diseases at Hospital Clínic de Barcelona between June 1995 and December 2024. Admissions lasting less than 48 h or lacking clinical documentation were excluded. Variables analysed included demographics, disease duration, comorbidities, cause of admission, treatments, and outcomes. A composite outcome was defined as intensive care unit (ICU) admission, 30-day readmission, or prolonged hospital stay. Statistical analyses included univariate and multivariate regression models. Results: Among the 1216 hospital admissions, SLE flares and infections were the most frequent causes. Over the study period, admissions due to infections increased significantly and, in the last five years, exceeded those related to disease flares (33.7% vs. 26.1%). Patients hospitalized for flares were younger and had a shorter disease duration, whereas infection-related admissions were more common among older patients, those with overlap syndromes, and those with higher damage scores. Vascular events and SLE flares were independently associated with poorer outcomes. Although antimalarial use increased over time, it remained suboptimal, largely due to drug toxicity and newly diagnosed cases (from 45.2% to 69.7%; p < 0.001). Treatment strategies also evolved, with a shift toward lower glucocorticoid doses (from 14.5% to 38.3%; p < 0.001), and mycophenolate mofetil replacing cyclophosphamide as the preferred immunosuppressive agent. Conclusions: Hospitalisation patterns in SLE have shifted over time, with infections emerging as the leading cause of admission. This trend reflects an evolving patient profile characterized by older age, greater accumulated damage, comorbidities, and increased exposure to immunosuppressive therapies. These findings underscore the need for optimized infection prevention strategies and individualized treatment approaches to improve outcomes in contemporary SLE care. Full article

Background: Immune-mediated hypophysitis comprises a heterogeneous group of inflammatory pituitary disorders, including primary lymphocytic hypophysitis, immune checkpoint inhibitor (ICI)-induced hypophysitis, IgG4-related hypophysitis, and paraneoplastic autoimmune hypophysitis. Although these entities share immune-mediated mechanisms, they differ substantially in clinical presentation, imaging features, and therapeutic implications. Methods: This narrative review synthesizes current evidence on the pathophysiology, clinical manifestations, radiological characteristics, diagnostic approach, and management of immune-mediated hypophysitis, with particular emphasis on etiological heterogeneity. Results: Hypopituitarism—particularly ACTH deficiency—is the most frequent and clinically relevant manifestation, as secondary adrenal insufficiency may be life-threatening if not promptly recognized and treated. It is often accompanied by headache, arginine vasopressin deficiency, or mass effect depending on the subtype. Magnetic resonance imaging typically shows symmetrical pituitary enlargement and stalk thickening in inflammatory forms, although findings vary according to etiology and may be minimal in certain subtypes such as PD-1/PD-L1 inhibitor-associated hypophysitis. Distinct clinical phenotypes are observed across subtypes, particularly in ICI-induced hypophysitis and IgG4-related disease. Diagnosis relies on the integration of endocrine, radiological, and clinical features, supported by clinicoradiological scoring systems in selected cases. Management is primarily based on prompt hormone replacement, with selective use of glucocorticoids or immunosuppressive therapies depending on disease severity and underlying etiology. Conclusions: Immune-mediated hypophysitis represents a clinically relevant and increasingly recognized spectrum of disorders requiring a multidisciplinary and etiology-specific approach. Early recognition is essential to prevent life-threatening endocrine complications. Advances in the understanding of immunopathogenic mechanisms and the identification of reliable biomarkers may enable earlier diagnosis and more personalized therapeutic strategies. Full article

Introduction: Gastric cancer is a prevalent and aggressive malignancy driven by complex signaling networks. Estrogen receptor-α36 (ER-α36), a membrane-localized receptor, mediates non-genomic signaling and promotes tumor progression. ER-α36 can interact with epidermal growth factor receptor (EGFR) to activate downstream mitogen-activated protein kinase (MAPK) signaling, but the detailed mechanism in gastric cancer remains unclear. This study aimed to explore whether ER-α36 promotes gastric cancer progression by regulating serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated Erk1/2 activation. Methods: We collected 53 human gastric adenocarcinoma specimens and detected ER-α36 expression by immunohistochemistry. Bioinformatics analysis was used to identify ER-α36-related kinases. Gastric cancer cell lines (SGC7901, HGC27, NCI-N87, and MFC) were used for in vitro studies. Western blotting, qRT-PCR, immunofluorescence, co-immunoprecipitation (Co-IP), wound healing, MTT, and Transwell invasion analyses, and nude mouse orthotopic tumor models were applied to investigate the function and mechanism of the ER-α36/SGK1/Erk1/2 axis. Results: ER-α36 was positively expressed in 62.3% of gastric adenocarcinoma tissues and was associated with poor differentiation and prognosis. SGK1 was identified as a key kinase downstream of ER-α36. ER-α36, SGK1, and p-Erk1/2 were co-upregulated in gastric cancer tissues and cells. ER-α36 regulated Raf/MEK1/2/Erk1/2 phosphorylation in an SGK1-dependent manner. EGF-induced Erk1/2 activation required both ER-α36 and SGK1. Overexpression of ER-α36 promoted the proliferation, migration, and invasion of gastric cancer cells, while SGK1 knockdown abolished these oncogenic effects. In vivo experiments confirmed that ER-α36 promoted gastric tumor growth and EGFR/Erk signaling, which was attenuated by SGK1 knockdown. Conclusions: ER-α36 contributes to the malignant progression of gastric adenocarcinoma by activating the Erk1/2 pathway through SGK1. The ER-α36–SGK1–Erk1/2 axis may serve as a novel therapeutic target for gastric cancer. Full article

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet’s syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included “VEXAS” and “treatment.” Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-α inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome. Full article

Impacted mandibular third-molar surgery commonly causes early postoperative pain, swelling, and trismus. This randomized, controlled, three-arm parallel trial evaluated whether intra-alveolar corticosteroid delivery via an absorbable gelatin sponge improves postoperative recovery compared with a saline control. Fifty-five patients were assessed for eligibility; 37 healthy adults (18–35 years) undergoing standardized mandibular third-molar extraction were randomized to dexamethasone 8 mg (Decort^®), methylprednisolone 40 mg (Prednol^®), or control (saline), all applied intra-alveolarly using a gelatin sponge carrier. Doses were selected using standard systemic glucocorticoid equivalence tables as a pragmatic potency reference, acknowledging unknown intra-alveolar pharmacokinetics/bioavailability. The prespecified primary endpoint (used for sample size planning) was postoperative Day 1 VAS pain; key secondary endpoints were Day 1 analgesic consumption and Day 3 facial swelling. Pain (VAS), analgesic use, trismus, and facial swelling (tragus–pogonion, tragus–labial commissure, and angulus–canthus distances) were assessed on postoperative Days 1, 2, 3, and 7 by a blinded evaluator. Two participants in the methylprednisolone group did not attend postoperative visits. To address potential attrition bias, an Intention-to-Treat (ITT) sensitivity analysis using conservative control-median imputation was performed alongside the available-case analyses. A global False Discovery Rate (FDR) correction was also applied to control for multiplicity. In both analyses, the steroid groups showed lower Day 1 pain scores than the control group. Methylprednisolone was associated with lower Day 3 swelling values than control for the tragus–pogonion and angulus–canthus measurements. These findings should be interpreted as preliminary, given the small sample size, linear swelling measurements, and lack of blinding verification. Full article

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which B-cell dysregulation plays a central pathogenic role beyond autoantibody production. Advances in B-cell biology have led to the development of targeted therapies, including inhibition of the B-cell activating factor (BAFF) pathway. Belimumab, a monoclonal antibody that neutralizes soluble BAFF, modulates B-cell survival signals upstream, promoting progressive immunologic remodeling rather than rapid depletion. This review integrates current knowledge on BAFF-dependent B-cell biology with mechanistic, pharmacokinetic, and clinical data to provide a comprehensive framework for understanding belimumab’s effects in SLE and lupus nephritis (LN). Belimumab preferentially reduces transitional and naïve B cells, while memory B cells show a relative transient increase followed by a gradual return to baseline levels, reflecting redistribution rather than expansion, and long-lived plasma cells are largely unaffected. These effects result in progressive remodeling of B-cell compartment dynamics and contribute to broader modulation of adaptive immune amplification pathways. Pharmacokinetic data support a threshold-based model of BAFF neutralization, with exposure influenced by disease-related factors such as proteinuria in LN. Clinical response is primarily determined by baseline disease biology, with greater benefit observed in patients with serologically active disease and less established organ involvement. Across clinical trials and real-world studies, belimumab reduces disease activity and flares, enables glucocorticoid tapering, and slows organ damage accrual. In LN, it improves renal outcomes and reduces the risk of kidney-related events. Collectively, these findings support belimumab as a disease-modifying therapy in SLE. Further research is needed to refine patient selection and optimize treatment sequencing and combination strategies. Full article

Background: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis primarily affecting small and medium-sized vessels. The typical presentation commonly includes upper and/or lower respiratory tract and renal involvement. GPA has a particularly strong association with proteinase-3 (PR3) ANCA. Though well defined, GPA may be clinically difficult to recognize, particularly in early disease. Initial presentations may include nonspecific symptoms, including but not limited to fatigue, fever, and sinus congestion or sinusitis, which may be mistaken for infection. Though initial ANCA testing is useful, it is not definitive as early stages of disease may be negative, thus delaying diagnosis; Clinical Significance: This case highlights the importance of including GPA in the differential diagnosis of patients with unremitting upper or lower respiratory and constitutional symptoms despite negative ANCA testing. Though atypical, GPA cases may lack renal involvement and even have negative ANCA serologies, leading to a delay in diagnosis and increased morbidity. ANCA positivity can be as low as 60% in limited GPA cases, and less than 20% of individuals have renal involvement at presentation. If GPA suspicion is high, repeat testing and biopsy are warranted; Case Presentation: A woman in her 50s initially presented to the emergency department with recurrent/persistent fever with nonspecific sinus symptoms that remained unresolved despite multiple outpatient treatments and tests. Infectious work-up was negative. She was found to have multiple pulmonary nodules on various scans. Initial testing on admission was unremarkable or nondiagnostic, including anti-neutrophil cytoplasmic antibody (ANCA) serologies. The patient’s hospital course was complicated by acute hypoxic respiratory failure with distributive shock during bronchoscopy. Repeat serological testing was positive for PR3-ANCA, and lung biopsy demonstrated necrotizing granulomatous vasculitis consistent with a diagnosis of granulomatosis with polyangiitis (GPA). The patient demonstrated clinical improvement with avacopan, glucocorticoids, and rituximab; Conclusions: The diagnosis of GPA should be suspected in all patients with nonspecific constitutional symptoms along with clinical evidence of upper/lower respiratory tract involvement, regardless of renal function. Physicians with a strong suspicion of an autoimmune disease, such as GPA, should utilize a thorough clinical history, physical exam, and other labs in the setting of a negative autoimmune marker and/or negative imaging. Clinical judgment is required to not rule out GPA despite a negative workup when other more serious causes have been excluded, as the diagnosis may be life-threatening. Full article

Canine atopic dermatitis is a hereditary chronic inflammatory and pruritic skin disease, which is mediated by T cells and requires long-term, individualized management. In recent years, numerous studies have described a wide range of therapeutic approaches for canine atopic dermatitis, including fast-acting symptomatic treatments, long-term immune-modulating interventions, and strategies to support skin barrier function and microbial balance. This review summarizes the principal treatment modalities currently available, including glucocorticoids, cyclosporine A, mycophenolate, Janus kinase inhibitors, lokivetmab, and allergen-specific immunotherapy, as well as complementary strategies aimed at restoring skin barrier integrity. Emphasis is placed on the importance of a multimodal and personalized approach to optimize long-term disease control and improve quality of life in affected dogs. Providing an integrated overview of current evidence, this article aims to guide clinicians in making informed, evidence-based decisions and to support the safe and effective management of canine atopic dermatitis. Full article

This case highlights a novel genotype–phenotype correlation in the field of endocrinology. Specific endocrine and imaging assessment, in addition to next-generation sequencing (NGS), was performed on the Illumina MiSeq platform, using a TruSight One Sequencing Panel kit for genomic analysis of coding regions of 4813 genes. A 54-year-old female was confirmed with a papillary thyroid carcinoma after total thyroidectomy and underwent radioiodine ablative therapy. Three years later, a left femoral enchondroma of almost 3 cm was identified at computed tomography (CT) scan and magnetic resonance imaging (MRI). She experienced hypertension (in addition to obesity, dyslipidaemia and impaired glucose tolerance) and was later confirmed with ACTH-independent cortisol excess [lack of cortisol suppression at 1 mg dexamethasone testing of 13.9 (normal < 1.8 µg/dL)], noting bilateral adrenal tumors, of 4.7 cm (right), respectively, and of 1.6 cm (left) at CT. Right laparoscopic adrenalectomy was performed with post-operative adrenal insufficiency, requiring glucocorticoid replacement and stopping the anti-hypertensive medication. Pathology report confirmed an adrenocortical adenoma (a Ki67 proliferation index of 2%). Noting the unusual association of the mentioned conditions, NGS was performed in the peripheral blood and identified a heterozygote missense variant of the APC gene (c.5759G>A, p.Arg1920Gln), a heterozygote missense variant of the MSH6 gene (c.2092C>G, p.Gln698Glu), and an incidental additional finding: a heterozygote stop gain pathogenic variant of the CACNA1S gene (c.2707C>T, p.Arg903*). The first two are currently classified as variants of uncertain significance. Whether the co-presence of a triple mutation may change the clinical picture and the life-long outcomes across reciprocal influence is still an open matter. Further research will point out the clinical implications of this genotype–phenotype association, which, to our best knowledge, has not been previously reported. Full article

In vertebrates, corticosterone and cortisol are glucocorticoid (GC) steroid hormones central to the vertebrate stress response, but their relative contribution depends on context and life history. We used water-borne hormone sampling in lesser sirens, Siren intermedia, to examine whether corticosterone or cortisol predominates in stress responses and evaluated whether dermal secretions reliably track acute corticosterone changes. First, we measured corticosterone via dermal swabbing over a 2 h period following a hand-restraint stressor. Dermal corticosterone did not increase relative to pre-stressor baseline levels during the 2 h sampling period, suggesting that dermal measurements may not reflect acute circulating GC changes. We then measured cortisol and corticosterone across the GC profile (baseline, stressed, and recovery) using water-borne sampling techniques in juveniles. Cortisol release rates were significantly higher than corticosterone and were elevated during the recovery phase relative to baseline (p = 0.08), whereas stressed samples did not differ from baseline. Additionally, cortisol release rates were positively associated with temperature, while no effect of temperature was detected on corticosterone. Although cortisol and corticosterone were strongly correlated, cortisol responded to environmental temperatures and was repeatable, whereas corticosterone was not. Finally, we validated the use of water-borne sampling techniques to measure cortisol and corticosterone in S. intermedia. Cortisol was higher in juvenile sirens, highlighting that each GC may play functionally distinct roles across contexts. Together, these findings indicate that cortisol is the more environmentally responsive GC in juvenile S. intermedia and that water-borne sampling provides a more reliable method for assessing acute stress physiology in this species. Full article

Glucocorticoid-induced hypertension affects over 30% of treated patients, yet its underlying mechanisms remain unclear, particularly how glucocorticoids regulate renin within the renin-angiotensin-aldosterone system (RAAS). Modeling these dynamics is difficult because only four dose-response measurements are available at a single 24-h timepoint (36 observations total), while the system depends on roughly eleven biochemical parameters spanning minutes-long receptor interactions to days-long protein secretion. Classical parameter estimation becomes unreliable in this extremely underdetermined setting, and purely data-driven methods offer limited biological interpretability. In this paper, we introduce a physics-informed neural network (PINN) framework that integrates ELISA measurements from As4.1 juxtaglomerular cells, ordinary differential equations describing glucocorticoid receptor signaling and renin transcription, and automatic differentiation to enforce mechanistic constraints. By systematically tuning synthetic-data weights (SW in {0.2, 0.3, 0.5}), we identify an intermediate value of SW = 0.3 that provides the best overall balance between predictive accuracy, accepted ensemble size, and biologically plausible parameter estimates among the tested configurations. The framework uses adaptive constraint scheduling with a plateau ramp to reduce premature convergence and introduces calibrated plausibility thresholds reflecting experimental noise. The accepted PINN ensemble (n = 5, 50% success rate) achieved R² = 0.803, compared with 0.759 for the SW = 0.5 baseline and −0.220 for the ODE-only baseline, with RMSE = 0.024. Key learned parameters (IC₅₀ = 2.925 ± 0.012 mg/dL, Hill = 1.950 ± 0.009) are biologically plausible within the model assumptions, and the best single accepted model attained R² = 0.891. Information criteria favored the PINN over the ODE model, with improvements of approximately 77× (AIC) and 5.9× (BIC). Despite training on a single timepoint, the PINN also infers full 48-h trajectories and reproduces non-monotonic dose-response behavior. This work presents, to our knowledge, the first PINN framework for glucocorticoid-mediated renin regulation and should be interpreted as a proof-of-concept approach for integrating sparse biomedical data with mechanistic constraints. The inferred parameters and temporal dynamics are best viewed as model-dependent, hypothesis-generating estimates rather than validated biological quantities. Full article

Maternal nutrition during late gestation is critical for fetal development, neonatal resilience, and postnatal adaptation in beef cattle. This study aimed to evaluate the effects of nutritional restriction and supplementation of hydroxytyrosol (HT) in late pregnancy on behavioural, circadian, stress-related, and inflammatory responses in cows and their restricted nursed offspring. Pregnant cows were allocated to a 2 × 2 factorial experimental design (feeding level: T100% vs. T60% of nutrient requirements; HT: 0 vs. 180 mg/kg of diet). Cow behaviours were recorded during meals (from week −12 prepartum to term), and calf activities, body temperature, and mother–offspring interactions were assessed at 5 weeks postpartum. Nutritional restriction accelerated feed intake in cows and increased stress-related behaviours, while HT partially mitigated these effects. Molecular analyses in blood samples revealed dynamic prepartum upregulation of glucocorticoid-receptor NR3C1 in week −6, and downregulation of circadian (BMAL1, PER1, CRY1) gene expression in week 5 after parturition, both in T60%-HT cows. In calves, maternal HT supplementation promoted active exploratory behaviour, and counteracted behavioural and circadian (CRY1 and PER1) and inflammatory markers (IL8) gene expression resulting from prenatal nutrient restriction, leading to behavioural profiles and blood gene expression comparable to those observed in calves born to adequately fed dams. Full article

SUMOylation may be involved in preeclampsia (PE) progression. We aimed to investigate the roles of SUMOylation in PE and its underlying mechanism using animal and cell models. A rat PE model was established by dexamethasone (DEX) treatment from pregnancy day 7.5–17.5. HTR8 and BeWo trophoblasts were used as cell models. Placental RNA-seq analysis coupled with Western blotting showed upregulated SUMOylation in placentas of DEX-treated rats. SUMOylation inhibitor TAK-981 treatment robustly alleviated PE-like features including reduced blood pressure and improved renal injury, fetal weight, spiral artery remodeling and placental blood flow in DEX-treated rats. DEX increased SUMOylation in HTR8 and BeWo cells. TAK-981 reversed DEX-induced dysfunction in HTR8 and BeWo cells, such as migration, invasion and syncytialization. Mass spectrum analysis of SUMO1 immunoprecipitation coupled with functional validation showed that SUMOylated proteins related to oxidative stress caused by DEX were reversed by TAK-981 in cultured trophoblasts. TAK-981 mitigated placental oxidative stress in DEX-treated rats. GEO database combined with Western blotting showed upregulated SUMOylation in human placentas with PE. Our findings indicate that protein SUMOylation is one of the key events in PE, particularly in that associated with high glucocorticoid exposure. Targeting placental SUMOylation might be a promising therapeutic strategy for PE. Full article