This clinical trial will evaluate the safety, tolerability and efficacy of GLS-1027 in the prevention of severe pneumonitis caused by SARS-CoV-2 infection

Start Date07 May 2021

Sponsor / Collaborator

GeneOne Life Science, Inc.

NCT00760396 / CompletedPhase 1

A Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety and Pharmacokinetics of VGX-1027 in Healthy Subjects

The purpose of this study is to evaluate the safety profile, tolerability and pharmacokinetics following multiple oral doses of 40mg to 200mg VGX 1027 in healthy subjects administered for 5 days.

Start Date01 Sep 2008

Sponsor / Collaborator

VGX Pharmaceuticals LLC

[+1]

NCT00627120 / CompletedPhase 1

A Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety and Pharmacokinetics of VGX-1027 in Healthy Subjects

To assess the safety and tolerability of a single dose of VGX-1027 in the range of 1-800mg.

Start Date01 Feb 2008

Sponsor / Collaborator

VGX Pharmaceuticals LLC

[+1]

100 Clinical Results associated with p38 MAPK x NF-κB

100 Translational Medicine associated with p38 MAPK x NF-κB

0 Patents (Medical) associated with p38 MAPK x NF-κB

4,645

Literatures (Medical) associated with p38 MAPK x NF-κB

01 Jan 2025·Journal of Ethnopharmacology

Fei-yan-qing-hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways

Article

Author: Xu, Lirong ; Liu, Hui ; Wu, Xiao ; Tang, Chen-Chen ; Zhang, Wei ; Tang, Chenchen ; Zheng, Yuejuan ; Ye, Xiaolan ; Yang, Xiao-Dong ; Xu, Gui-Hua ; Duan, Nai-Fan ; Xu, Li-Rong ; Huang, Qilin ; Xu, Guihua ; Chen, Xuan ; Ye, Xiao-Lan ; Xu, Yan-Wu ; Hu, You ; Zheng, Yue-Yuan ; Xu, Yanwu ; Duan, Naifan ; Huang, Qi-Lin

ETHNOPHARMACOLOGICAL RELEVANCEFei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear.AIM OF THE STUDYThis study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms.MATERIALS AND METHODSThe protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA.RESULTSOur findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages.CONCLUSIONFYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

16 Dec 2024·Animal Biotechnology

Anti-inflammatory properties of Bacillus pumilus TS1 in lipopolysaccharide-induced inflammatory damage in broilers

Article

Author: Wan, Shuangshuang ; Li, Zixin ; Liu, Yinkun ; Liu, Sirui ; Li, Hao ; Tang, Shu

This study investigates whether Bacillus pumilus TS1 improves growth performance and alleviates inflammatory damage in broilers and explored its feasibility as an antibiotic alternative. We divided 240 one-day-old AA308 white-finned broilers into five groups (con, LPS, TS1L + LPS, TS1M + LPS and TS1H + LPS). The TS1L + LPS, TS1M + LPS and TS1H + LPS groups were fed TS1 for 15 days by gavage. The LPS, TS1L + LPS, TS1M + LPS and TS1H + LPS groups were injected intraperitoneally with 1 mg/kg LPS for three days. We investigated the probiotic and anti-inflammatory activities by measuring body weight, sequencing the intestinal flora and examining the structure of tissues by using pathological stain, real-time PCR, Western blotting and immunohistochemical detection. TS1 could improve growth performance and intestinal flora composition, also reduced different organ damage and inflammatory cytokine expression in serum and organs. The mechanism may involve upregulating HSP60 and HSP70 expression, targeting and regulating Nrf2 and P38 MAPK and modulating NF-κB and HO-1 expression at the transcriptional level in different organs. B. pumilus TS1 alleviated Inflammatory injury caused by LPS and attenuated the inflammatory response in broilers, and these effects were achieved through MAPK and Nrf2 regulation of HSPs/HO-1 in different organs. The above results suggested broilers fed with TS1 could release the LPS caused organ damage, and the most suggested dosage was 1.4 × 10⁸ CFU/mL.

01 Dec 2024·Molecular Biology Reports

Study on the mechanism of heterogeneous tumor-associated macrophages in three subtypes of breast cancer through the integration of single-cell RNA sequencing and in vitro experiments

Article

Author: Zhang, Shu ; Yuan, Yan ; Huang, Jian

BACKGROUNDTumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2.MATERIALS AND METHODSThis investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells.RESULTSOur findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-β1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance.CONCLUSIONOur study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.

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