Biapenem reduces sepsis mortality via barrier protective pathways against HMGB1-mediated septic responses

Kim, Jae Hong; Choo, Samyeol; Sim, Hyunchae; Baek, Moon‐Chang; Bae, Jong‐Sup

doi:10.1007/s43440-020-00212-0

Cited by 5 publications

(4 citation statements)

References 43 publications

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“… 2015 ; Kim et al. 2021 ). Furthermore, the inflammatory function of HMGB1 is mediated by its binding to cell surface receptors, and RAGE is one of its main receptors (Yao and Brownlee 2010 ; Tang et al.…”

Section: Discussionmentioning

confidence: 99%

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

Liu

Yuan

Tang

et al. 2023

Pharmaceutical Biology

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Context Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). Objective To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. Materials and methods Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d -LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. Results Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD ( p < 0.01). Discussion and conclusions DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.

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Section: Discussionmentioning

confidence: 99%

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

Liu

Yuan

Tang

et al. 2023

Pharmaceutical Biology

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“…Biapenem is an antibiotic that reduces HMGB1 release and septic mortality ( 150 ). Cilostazol is anti-platelet agent that inhibits HMGB1’s release in LPS-activated RAW 264.7 cells and increases the survival of septic mice ( 151 ).…”

Section: Hmgs In Sepsismentioning

confidence: 99%

High Mobility Group Proteins in Sepsis

Liang

2022

Front. Immunol.

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Sepsis, a systemic inflammatory response disease, is the most severe complication of infection and a deadly disease. High mobility group proteins (HMGs) are non-histone nuclear proteins binding nucleosomes and regulate chromosome architecture and gene transcription, which act as a potent pro-inflammatory cytokine involved in the delayed endotoxin lethality and systemic inflammatory response. HMGs increase in serum and tissues during infection, especially in sepsis. A growing number of studies have demonstrated HMGs are not only cytokines which can mediate inflammation, but also potential therapeutic targets in sepsis. To reduce sepsis-related mortality, a better understanding of HMGs is essential. In this review, we described the structure and function of HMGs, summarized the definition, epidemiology and pathophysiology of sepsis, and discussed the HMGs-related mechanisms in sepsis from the perspectives of non-coding RNAs (microRNA, long non-coding RNA, circular RNA), programmed cell death (apoptosis, necroptosis and pyroptosis), drugs and other pathophysiological aspects to provide new targets and ideas for the diagnosis and treatment of sepsis.

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“…В 2021 г. в работе J. Kim и соавт. [22] показали, что биапенем in vitro в культуре активированных липополисахаридом эпителиальных клеток человека (HUVEC) подавлял высвобождение белка HMGB1 на 60%. На модели сепсиса, вызванного перевязкой слепой кишки мышам, в группе с применением биапенема было установили снижение выхода HMGB1 на 54%, подавление гипер-проницаемости сосудов на 59%, уменьшение на 62% сосудистых нарушений, опосредованных HMGB1.…”

Section: обсуждение результатовunclassified

“…На модели сепсиса, вызванного перевязкой слепой кишки мышам, в группе с применением биапенема было установили снижение выхода HMGB1 на 54%, подавление гипер-проницаемости сосудов на 59%, уменьшение на 62% сосудистых нарушений, опосредованных HMGB1. Кроме того, регистрировали снижение смертности лабораторных животных на 50%, а гистологически определялась меньшая степень повреждения ткани лёгких, печени и почек [22].…”

Section: обсуждение результатовunclassified

Biapenem Activity Against Meropenem-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa

Gordina¹,

Божкова²,

Shabanova³

2022

A&Ch

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Currently, the diversity of resistant strains with a certain set of resistance mechanisms is growing, and the frequency of their distribution is increasing. One of the options for finding optimal ways to treat severe infections, including orthopedic infections caused by Klebsiella pneumoniae and Pseudomonas aeruginosa, is the use of new drugs with possible activity against resistant strains.The aim of the study is comparative evaluation of biapenem antibacterial activity against meropenem-resistant K.pneumoniae and P.aeruginosa.Materials and Methods. A total of 14 K.pneumoniae and 18 P.aeruginosa isolates were included in the study. The determination of sensitivity to biapenem and meropenem was carried out via determining the minimum inhibitory concentrations (MIC) for each microorganism by the method of serial dilutions in accordance with ISO 20776-1-2010. Carbapenemases genes (MBL:VIM-, IMP- and NDM-types; OXA-48; KPC) were detected by commercially available real-time PCR.Results. The highest MIC value of meropenem was registered in the carbapenemase-producing K.pneumoniae strain (NDM and OXA-48) and amounted to 512 mg/l, while the MIC value of biapenem in this isolate was 256 mg/l. The MIC50 of meropenem was determined to be 16 mg/l, while in case of biapenem it was 4 mg/l. MIC90 of meropenem against P.aeruginosa was 512 mg/l, of biapenem — 256 mg/l. Among all meropenem-resistant strains included in this study, 28.6% K.pneumoniae and 22.2% P.aeruginosa isolates showed sensitivity to biapenem, the rest were resistant to this drug or sensitive at increased exposure.Conclusion. Comparative analysis of the antibacterial activity against meropenem-resistant K.pneumoniae and P.aeruginosa showed that MIC50/90 of biapenem is several times lower than that of meropenem. Sensitivity to this drug was recorded in 25% of the studied isolates resistant to meropenem (4 — K.pneumoniae and 4 — P.aeruginosa), which increases the possibility of using this drug in the treatment of patients with orthopedic infections.

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Biapenem reduces sepsis mortality via barrier protective pathways against HMGB1-mediated septic responses

Cited by 5 publications

References 43 publications

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

High Mobility Group Proteins in Sepsis

Biapenem Activity Against Meropenem-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa

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