Allicin suppressed <i>Escherichia coli</i>-induced urinary tract infections by a novel MALT1/NF-κB pathway

Chang, Zhenglin; An, Lingyue; He, Zhican; Zhang, Yuyan; Li, Shujue; Lei, Min; Xu, Peng; Lai, Yongchang; Jiang, Zheng; Huang, Yapeng; Duan, Xiaolu

doi:10.1039/d1fo03853b

Cited by 8 publications

(12 citation statements)

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“…According to previous studies, MALT1 is a vital regulator of the NF-κB pathway ( Schaefer, 2020 ). MALT1, together with the caspase recruitment domain-containing (CARD) family and B-cell lymphoma 10 (BCL10), forms the CARD-BCL10-MALT1 (CBM) complex that mediates the activation of the NF-κB transcription factor in various pathological conditions, including malignancies, allergic response, and infection ( McAuley et al, 2019 ; Alfano et al, 2020 ; Chang et al, 2022 ). However, the interaction between MALT1 and the NF-κB pathway in sepsis has yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

et al. 2023

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ObjectiveMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates the inflammatory immune response and organ dysfunction, which are closely implicated in sepsis pathogenesis and progression. This study aimed to explore the role of MALT1 in sepsis-induced organ injury, immune cell dysregulation, and inflammatory storms.MethodsSeptic mice were constructed by intraperitoneal injection of lipopolysaccharide, followed by overexpression or knockdown of MALT1 by tail vein injection of the corresponding lentivirus. Mouse naïve CD4+ T cells and bone marrow-derived macrophages were treated with MALT1 overexpression/knockdown lentivirus plus lipopolysaccharide.ResultsIn the lungs, livers, and kidneys of septic mice, MALT1 overexpression exaggerated their injuries, as shown by hematoxylin and eosin staining (all p < 0.05), elevated cell apoptosis, as reflected by the TUNEL assay and cleaved caspase-3 expression (p < 0.05 in the lungs and kidneys), and promoted macrophage infiltration, as illustrated by CD68 immunofluorescence (p < 0.05 in the lungs and kidneys). Meanwhile, in the blood, MALT1 overexpression reduced T-helper (Th)1/Th2 cells, increased Th17/regulatory T-cell ratios (both p < 0.05), promoted systematic inflammation, as revealed by tumor necrosis factor-α, interleukin-6, interleukin-1β, and C-reactive protein (all p < 0.05), elevated oxidative stress, as shown by nitric oxide (p < 0.05), superoxide dismutase, and malondialdehyde (p < 0.05), and enhanced liver and kidney dysfunction, as revealed by an automatic animal biochemistry analyzer (all p < 0.05 except for aspartate aminotransferase). However, MALT1 knockdown exerted the opposite effect as MALT1 overexpression. Ex vivo experiments revealed that MALT1 overexpression promoted the polarization of M1 macrophages and naïve CD4+ T cells toward Th2 and Th17 cells (all p < 0.05), while MALT1 knockdown attenuated these effects (all p < 0.05). Mechanistically, MALT1 positively regulated the nuclear factor-κB (NF-κB) pathway both in vivo and ex vivo (p < 0.05).ConclusionMucosa-associated lymphoid tissue lymphoma translocation protein 1 amplifies multiple organ injury, inflammation, oxidative stress, and imbalance of macrophages and CD4+ T cells by activating the NF-κB pathway in sepsis.

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Section: Discussionmentioning

confidence: 99%

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

et al. 2023

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“…Both principal components 1 and 2 were selected as signature scores. Finally, the scores were defined using a method similar to Genomic Grade Index ( 21 , 22 ):…”

Section: Methodsmentioning

confidence: 99%

“…Three bladder samples of carcinomas and adjacent normal tissues were obtained from BLCA patients who underwent surgery at Guangzhou Medical University’s Second Affiliated Hospital (GZhmu2.cohort) without preoperative immunotherapy or chemotherapy. RNA extraction and qRT-PCR were conducted as previously described ( 22 , 23 ). The PCR primers are described in Supplementary Table 2 .…”

Section: Methodsmentioning

confidence: 99%

“…All images were observed by a tissue scanner (PathScope 4s, DigiPath, NV, USA) to observe the inflammatory and immune histological changes of bladder tissues. The corresponding score system was performed as previously described ( 22 , 23 ).…”

Section: Methodsmentioning

confidence: 99%

“…The primary antibodies: CD247 (1:200), TLR2 (1:200), c-MYC (1:500), IL10 (1:200), and FN1 (1:200) were obtained from Proteintech (Rosemont, IL, USA) and were applied for IHC. IHC was conducted as previously described ( 22 , 23 ). For each IHC-tissue section, five random visual fields were selected for determination.…”

Section: Methodsmentioning

confidence: 99%

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Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients

Chang

Li²,

Zhang³

et al. 2022

Front. Immunol.

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Due to the molecular heterogeneity, most bladder cancer (BLCA) patients show no pathological responses to immunotherapy and chemotherapy yet suffer from their toxicity. This study identified and validated three distinct and stable molecular clusters of BLCA in cross-platform databases based on personalized immune and inflammatory characteristics. H&E-stained histopathology images confirmed the distinct infiltration of immune and inflammatory cells among clusters. Cluster-A was characterized by a favorable prognosis and low immune and inflammatory infiltration but showed the highest abundance of prognosis-related favorable immune cell and inflammatory activity. Cluster-B featured the worst prognosis and high immune infiltration, but numerous unfavorable immune cells exist. Cluster-C had a favorable prognosis and the highest immune and inflammatory infiltration. Based on machine learning, a highly precise predictive model (immune and inflammatory responses signature, IIRS), including FN1, IL10, MYC, CD247, and TLR2, was developed and validated to identify the high IIRS-score group that had a poor prognosis and advanced clinical characteristics. Compared to other published models, IIRS showed the highest AUC in 5 years of overall survival (OS) and a favorable predictive value in predicting 1- and 3- year OS. Moreover, IIRS showed an excellent performance in predicting immunotherapy and chemotherapy’s response. According to immunohistochemistry and qRT-PCR, IIRS genes were differentially expressed between tumor tissues with corresponding normal or adjacent tissues. Finally, immunohistochemical and H&E-stained analyses were performed on the bladder tissues of 13 BLCA patients to further demonstrate that the IIRS score is a valid substitute for IIR patterns and can contribute to identifying patients with poor clinical and histopathology characteristics. In conclusion, we established a novel IIRS depicting an IIR pattern that could independently predict OS and acts as a highly precise predictive biomarker for advanced clinical characters and the responses to immunotherapy and chemotherapy.

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The levels of immunosuppressive checkpoint protein PD‐L1 and tumor‐infiltrating lymphocytes were integrated to reveal the glioma tumor microenvironment

Zhang,

Liu,

Liu

et al. 2023

Environmental Toxicology

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In spite of significant strides in the realm of cancer biology and therapeutic interventions, the clinical prognosis for patients afflicted with glioblastoma (GBM) remains distressingly dismal. The tumor immune microenvironment (TIME), a crucial player in the progression, treatment response, and prognostic trajectory of glioma, warrants thorough exploration. Within this intricate microcosm, the immunosuppressive checkpoint protein PD‐L1 and tumor‐infiltrating lymphocytes (TILs) emerge as pivotal constituents, underscoring their potential role in deciphering glioma biology and informing treatment strategies. However, prognostic models based on the association between PD‐L1 expression and TIL infiltration in the tumor immune microenvironment have not been established. The aim of this study was to explore TIME genes associated with PD‐L1 expression and TIL invasion and to construct a risk score for predicting the overall survival (OS) of GBM patients based on these genes. The samples were separately classified according to the PD‐L1 expression level and TIL score and TIME‐related genes were identified using differential expression and weighted gene co‐expression network analysis. The DEGs were subjected to least absolute contraction and selection operator (LASSO) ‐Cox regression to construct TIME associated risk score (TIMErisk). A TIMErisk was developed based on STEAP3 and CXCL13 genes. The STLEAP3 was demonstrated to be involved in glioma progression. The results showed that the patients in the high TIMErisk group had poor OS compared with subjects in the low TIMErisk group. The biological phenotypes associated with TIMErisk were analyzed in terms of functional enrichment, tumor immune profile, and tumor mutation profile. The results on tumor immune dysfunction and exclusion dysfunction (TIDE) score and immune surface score (IPS) showed that GBM patients with different TIME risks had different responses to immunotherapy. Tumor purity analysis indicated that PD‐L1 and TIL scores were positively correlated with TIMErisk score and negatively correlated with tumor purity. These results show that the TIMErisk‐based prognostic model had high predictive value for the prognosis and immune characteristics of GBM patients. Immunohistochemical staining images of patients in the high and low TIMErisk groups were analyzed, showing that the degree of immune cell infiltration was higher in the high TIMErisk group relative to the low TIMErisk group. The present study provides a basis for understanding glioma tumor microenvironment and a foundation for conducting comprehensive immunogenomic analysis.

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Allicin suppressed Escherichia coli-induced urinary tract infections by a novel MALT1/NF-κB pathway

Abstract: Escherichia coli (E. coli) strains cause the majority of urinary tract infections (UTIs) and are resistant to various antibiotics. Therefore, it is imperative to explore novel host-target therapies. As a...

Cited by 8 publications

References 51 publications

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients

The levels of immunosuppressive checkpoint protein PD‐L1 and tumor‐infiltrating lymphocytes were integrated to reveal the glioma tumor microenvironment

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