Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

BACKGROUND: This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. METHODS: Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. RESULTS: After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. CONCLUSION: L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing.

Aims: Epilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats. Materials and methods and results: A temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1ß, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-ß1 increased. 16S rDNA sequencing revealed that the ANOSIM index differed significantly between the groups. At the genus level, Helicobacter, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 were significantly reduced in the model group. CBD intervention attenuated the intervention effects of Li-pilocarpine. Roseburia, Eubacterium_xylanophilum_group, and Ruminococcus_2 were strongly positively correlated with proinflammatory cytokine levels. CBD reversed dysregulated metabolites, including glycerophosphocholine and 4-ethylbenzoic acid. Conclusion: CBD could alleviate the dysbiosis of gut microbiota and metabolic disorders of epileptic rats. CBD attenuated Epilepsy in rats might be related to gut microbial abundance and metabolite levels. Significance and impact of study: The study may provide a reliable scientific clue to explore the regulatory pathway of CBD in alleviating Epilepsy.

Applications and influencing factors of the biochar-persulfate based advanced oxidation processes for the remediation of groundwater and soil contaminated with organic compounds.

Biochar (BC) is a low-cost material rich in carbon, which is being used increasingly as a catalyst in persulfate-based advanced oxidation processes (PS-AOPs) for the remediation of groundwater and soil contaminated with organic compounds. In this work, a general summary of preparation methods and applications of various BC (i.e., pristine BC, magnetic BC, and chemically modified BC) in PS-AOPs is presented. Different influence factors (e.g., pH, anions, natural organic matter) for the degradation of organic compounds are discussed. Meanwhile, the influence of external energy (e.g., solar irradiation, UV-Vis, ultrasonic) is also mentioned. Furthermore, the advantage of different BC in PS-AOPs are compared. Finally, potential problems, challenges, and prospects in the application of biochar-persulfate based advanced oxidation processes (BCPS-AOPs) are discussed in the conclusion and perspective.

Construction of a Prognostic Gene Signature Associated with Immune Infiltration in Glioma: A Comprehensive Analysis Based on the CGGA.

BACKGROUND: Tumor microenvironment (TME) is closely related to the progression of glioma and the therapeutic effect of drugs on this cancer. The aim of this study was to develop a signature associated with the tumor immune microenvironment using machine learning. METHODS: We downloaded the transcriptomic and clinical data of glioma patients from the Chinese Glioma Genome Atlas (CGGA) databases (mRNAseq_693). The single-sample Gene Set Enrichment Analysis (ssGSEA) database was used to quantify the relative abundance of immune cells. We divided patients into two different infiltration groups via unsupervised clustering analysis of immune cells and then selected differentially expressed genes (DEGs) between the two groups. Survival-related genes were determined using Cox regression analysis. We next randomly divided patients into a training set and a testing set at a ratio of 7 : 3. By integrating the DEGs into least absolute shrinkage and selection operator (LASSO) regression analysis in the training set, we were able to construct a 15-gene signature, which was validated in the testing and total sets. We further validated the signature in the mRNAseq_325 dataset of CGGA. RESULTS: We identified 74 DEGs associated with tumor immune infiltration, 70 of which were significantly associated with overall survival (OS). An immune-related gene signature was established, consisting of 15 key genes: adenosine triphosphate (ATP)-binding cassette subfamily C member 3 (ABCC3), collagen type IV alpha 1 chain (COL4A1), podoplanin (PDPN), annexin A1 (ANXA1), COL4A2, insulin-like growth factor binding protein 2 (IGFBP2), serpin family A member 3 (SERPINA3), CXXC-type zinc finger protein 11 (CXXC11), junctophilin 3 (JPH3), secretogranin III (SCG3), secreted protein acidic and rich in cysteine (SPARC)-related modular calcium-binding protein 1 (SMOC1), Cluster of Differentiation 14 (CD14), COL1A1, S100 calcium-binding protein A4 (S100A4), and transforming growth factor beta 1 (TGF-ß1). The OS of patients in the high-risk group was worse than that of patients in the low-risk group. GSEA showed that interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT3) signaling, interferon gamma (IFN-γ) response, angiogenesis, and coagulation were more highly enriched in the high-risk group and that oxidative phosphorylation was more highly enriched in the low-risk group. CONCLUSION: We constructed a stable gene signature associated with immune infiltration to predict the survival rates of glioma patients.

Toward Understanding Non-coding RNA Roles in Intracranial Aneurysms and Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a common and frequently life-threatening cerebrovascular disease, which is mostly related with a ruptured intracranial aneurysm. Its complications include rebleeding, early brain injury, cerebral vasospasm, delayed cerebral ischemia, chronic hydrocephalus, and also non neurological problems. Non-coding RNAs (ncRNAs), comprising of microRNAs (miRNAs), small interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs), play an important role in intracranial aneurysms and SAH. Here, we review the non-coding RNAs expression profile and their related mechanisms in intracranial aneurysms and SAH. Moreover, we suggest that these non-coding RNAs function as novel molecular biomarkers to predict intracranial aneurysms and SAH, and may yield new therapies after SAH in the future.

14-3-3ε functions as an oncogene in SGC7901 gastric cancer cells through involvement of cyclin E and p27kip1.

Investigation into the highly conserved 14­3­3ε protein has become increasingly important in cell biology due to its involvement in cell survival signaling, cell cycle control and apoptosis. The 14­3­3ε protein has been found to exert an impact on the development of various tumor types. However, the functional role and the possible mechanism of 14­3­3ε in gastric cancer remains to be elucidated. A previous study by our group indicated a negative correlation between 14­3­3ε expression levels and gastric cancer tissue differentiation and a positive correlation between 14­3­3ε expression levels and tumor infiltration, lymph node metastasis and tumor, nodes and metastasis staging. In the present study, 14­3­3ε suppression in the SGC7901 gastric cancer cell line was demonstrated to inhibit cell proliferation in vitro and tumor growth in vivo and the cell cycle­associated proteins cyclin E and p27kip1 may have contributed to this antitumor effect. The present study showed for the first time that reducing the expression of 14­3­3ε may inhibit the proliferation and progression of gastric cancer and inhibition of this protein may provide a potential strategy for gastric cancer therapy in the future.

Identification of stromal differentially expressed proteins in the colon carcinoma by quantitative proteomics.

Tumor microenvironment plays very important roles in the carcinogenesis. A variety of stromal cells in the microenvironment have been modified to support the unique needs of the malignant state. This study was to discover stromal differentially expressed proteins (DEPs) that were involved in colon carcinoma carcinogenesis. Laser capture microdissection (LCM) was captured and isolated the stromal cells from colon adenocarcinoma (CAC) and non-neoplastic colon mucosa (NNCM) tissues, respectively. Seventy DEPs were identified between the pooled LCM-enriched CAC and NNCM stroma samples by iTRAQ-based quantitative proteomics. Gene Ontology (GO) relationship analysis revealed that DEPs were hierarchically grouped into 10 clusters, and were involved in multiple biological functions that were altered during carcinogenesis, including extracellular matrix organization, cytoskeleton, transport, metabolism, inflammatory response, protein polymerization, and cell motility. Pathway network analysis revealed 6 networks and 56 network eligible proteins with Ingenuity pathway analysis. Four significant networks functioned in digestive system development and its function, inflammatory disease, and developmental disorder. Eight DEPs (DCN, FN1, PKM2, HSP90B1, S100A9, MYH9, TUBB, and YWHAZ) were validated by Western blotting, and four DEPs (DCN, FN1, PKM2, and HSP90B1) were validated by immunohistochemical analysis. It is the first report of stromal DEPs between CAC and NNCM tissues. It will be helpful to recognize the roles of stromas in the colon carcinoma microenvironment, and improve the understanding of carcinogenesis in colon carcinoma. The present data suggest that DCN, FN1, PKM2, HSP90B1, S100A9, MYH9, TUBB, and YWHAZ might be the potential targets for colon cancer prevention and therapy.