Drug-resistant epilepsy associated with peripheral complement decreases and sex-specific cytokine imbalances: a pilot study

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 11, 2025

Drug-resistant epilepsy (DRE) presents significant challenges in treatment and management. While seizure-related alterations peripheral immune players are increasingly recognized, the involvement of complement system remains insufficiently explored DRE. We studied components their relationship to cytokine profiles serum samples from 46 DRE patients 45 matched healthy controls. examined relationships between these molecules clinical outcomes, including duration, intelligence scores, age. identified DRE-associated decreases, reduced levels C1q, Factor H, C4, C4b, C3, C3b/iC3b, as well elevated bFGF. females showed dysregulation classical pathway lower TNFα interleukin-8 compared females. males exhibited classical, lectin, terminal pathways, with trends increased CCL2 CCL5 males. Specific inflammatory markers (C2, IL-8, IL-9) correlated full-scale IQ scores patients. Our study reveals significantly circulating sex-specific imbalances. These findings suggest an underlying vulnerability that may be sex-dependent warrants further investigation

Language: Английский

---

Novel derivatives of brincidofovir and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine inhibit orthopoxviruses and human adenoviruses more potently than brincidofovir

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 10, 2025

Abstract Brincidofovir (BCV) and tecovirimat are the only two chemical drugs that have been approved to treat smallpox can be requested for monkeypox (Mpox) treatment through a single-patient Emergency Investigational New Drug (EIND) application. Disappointedly, efficacy of manifested in recent clinical trials is far from being satisfactory, while BCV still inconclusive. Given virus (MPXV), variola other emerging orthopoxviruses posing serious threats global health, it urgent develop better therapeutics. In this study, we tested antiviral effects three novel prodrugs, which were designed based on previously reported parent drugs, either (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine ((S)-HPMPC, cidofovir) or (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA). We found one (S)-HPMPA-based ODE-(S)-HPMPA formate, exhibited significantly anti-orthopoxvirus activity than both vitro vivo, also inhibited human adenovirus type 2 21 more efficiently BCV. Most strikingly, EC 50 90 formate against MPXV 40-fold lower those contrast, observed anti-herpes simplex 1 (HSV-1) activities prodrugs less effective cidofovir-based (BCV formate), especially vivo. Moreover, showed first time cytidine adenine analog combined therapies could provide mice with complete protection lethal challenges vaccinia HSV-1. Collectively, propose BCV/ODE-(S)-HPMPA combination worth further investigations their potential applications.

Language: Английский

---

Multiomics analysis unveils key biomarkers during dynamic progress of IAV infection in mice

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 22, 2025

Introduction Influenza infection is a significant threat to public health, and identifying dynamic biomarkers that influence disease progression crucial for effective intervention. Methods We conducted comprehensive evaluation of physiological pathological parameters in Balb/c mice infected with H1N1 influenza over 14-day period. employed the DIABLO multi-omics integration method analyze changes lung transcriptome, metabolome, serum metabolome from mild severe stages infection. Results Our analysis highlighted critical importance intervention within first 6 days post-infection prevent disease. identified several novel associated progression, including Ccl8, Pdcd1, Gzmk , kynurenine, L-glutamine, adipoyl-carnitine. Additionally, we developed serum-based scoring system. Discussion This study provides new insights into molecular mechanisms underlying identifies potential targets therapeutic The system serves as valuable tool early diagnosis prognosis influenza.

Language: Английский

---

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats

Pharmaceutical Biology, Journal Year: 2022, Volume and Issue: 60(1), P. 2229 - 2236

Published: Nov. 11, 2022

Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax C.A. Meyer (Araliaceae)].This study determined the underlying mechanisms treatment that acted on diabetes-injured lungs in diabetic rats.Streptozotocin (STZ)-induced rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, (20 mg/kg), insulin (15 U/kg to attain euglycaemic state) and (untreated). After for six weeks, oxidative stress assay; histological ultrastructure analyses; TNF-α, TGF-β, IL-1 IL-6 protein expression detection apoptosis performed.There decreased activity SOD (3.53-fold), CAT (2.55-fold) GSH (1.63-fold) increased levels NO (4.47-fold) MDA (3.86-fold) group from control. (2.4-fold), (1.9-fold) (1.29-fold) (1.76-fold) (1.51-fold) as compared with rats. The (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) TGF-β (2.39-fold) (2.43-fold), (2.27-fold), (1.68-fold) (2.3-fold) group. Diabetes rate (2.23-fold vs. control), (1.73-fold rats). ameliorated lung tissue injury.These findings indicate could be useful mitigating damage inflammatory infiltration lung.

Language: Английский

---

Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8669 - 8669

Published: Aug. 4, 2022

Dysregulation of renin−angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity mortality. This study sought investigate effect exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome 2 (SARS-CoV-2)-specific T-cells response in recovered patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang then stimulated a SARS-CoV-2 peptide pool. T-cell responses measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) intracellular cytokine staining (ICS) assays determined functional capability polarization. Additionally, relative level protein phosphorylation was phosphokinase array. Our results showed that treatment significantly increased magnitude SARS-CoV-2-specific PBMCs Moreover, levels numerous proteins implicated cardiovascular diseases, inflammation, viral significant increases presence II. The mitogenic stimulation after pool polarization toward Th1/Th17 Th17 phenotypes, respectively. Meanwhile, ELISA productions IL-1β IL-6 II-stimulated without affecting IL-10 level. To our knowledge, this is first demonstrate exaggerates response. Therefore, infection, may aggravate inflammatory change immune more profile against infection.

Language: Английский

---

Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Nov. 23, 2021

Abstract COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism basis for modern therapy is important. The aim was assessment gene expression levels, IL-6 , IL-6ST PIAS3 STAT3 miRNAs, miRNA-1, miRNA-106b, miRNA-155, patients with COPD. Induced sputum well PBMC were collected from 40 clinically verified according GOLD 2021 (A–D) classification control group (n = 20). levels miRNA analysed by qPCR. In induced IL6 significantly down-regulated compared ( p 0.0008), while IL6ST up-regulated 0.05). results also statistically significant 0.04) miRNA-155 0.03) higher current smokers ex-smokers. Higher exacerbation history without noted. Compared PB lymphocytes we observed 0.0003) 0.000001) miRNA-106b 0.000069 0.000016) lower 0.006), 0.002) miRNA-1 0.001). Differences IL-6/IL6ST/STAT3 pathway depending on smoking status suggest importance these genes pathogenesis may indicate their potential utility monitoring course disease.

Language: Английский

---

SpTNF regulates apoptosis and antimicrobial peptide synthesis in mud crab (Scylla paramamosain) during white spot syndrome virus infection

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 139, P. 108881 - 108881

Published: June 4, 2023

Language: Английский

---

Metabolic changes enhance necroptosis of type 2 diabetes mellitus mice infected with Mycobacterium tuberculosis

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(5), P. e1012148 - e1012148

Published: May 10, 2024

Previously, we found that Mycobacterium tuberculosis (Mtb) infection in type 2 diabetes mellitus (T2DM) mice enhances inflammatory cytokine production which drives pathological immune responses and mortality. In the current study, using a T2DM Mtb model, determined mechanisms make alveolar macrophages (AMs) more upon infection. Among various cell death pathways, necroptosis is major pathway involved by AMs. Anti-TNFR1 antibody treatment of -infected AMs from significantly reduced expression receptor interacting protein kinase 3 (RIPK3) mixed lineage domain-like (MLKL) (necroptosis markers) IL-6 production. Metabolic profile comparison nondiabetic control indicated 2-ketohexanoic acid deoxyadenosine monophosphate were abundant, acetylcholine pyridoxine (Vitamin B6) less abundant infected with . 2-Ketohexanoic enhanced TNFR1, RIPK3, MLKL lungs mice. contrast, inhibited Caspase (apoptosis marker) Our findings demonstrate metabolic changes enhance TNFR1-mediated AMs, leads to excess inflammation lung pathology.

Language: Английский

---

Poxvirus-encoded TNF receptor homolog dampens inflammation and protects from uncontrolled lung pathology during respiratory infection

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(43), P. 26885 - 26894

Published: Oct. 12, 2020

Significance Viruses have coevolved with their hosts and developed strategies to dampen, evade, or subvert the host immune response provide an advantage virus. We show that ectromelia virus (ECTV) encodes a TNF receptor (TNFR) homolog, which provides by dampening levels inflammation. Infection of ECTV-resistant mice mutant lacking viral TNFR (vTNFR) caused significant lung pathology death due secretion excessive other inflammatory cytokines. In vitro, recombinant vTNFR from ECTV orthopoxviruses bound membrane-associated down-regulated gene expression through reverse signaling. benefits enabling survival, potentially facilitating spread, should

Language: Английский

---

Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

Viruses, Journal Year: 2022, Volume and Issue: 14(1), P. 98 - 98

Published: Jan. 6, 2022

Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this diversity, genetic background has often been mentioned. In parallel, recent evidence also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed importance these two host-related in shaping immune response pneumoviral disease. We show prior gammaherpesvirus improves, background-dependent manner, system against subsequent lethal dose pneumovirus primary notably by inducing systematic expansion CD8

Language: Английский

---