Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.

Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic Bacillus amyloliquefaciens has been shown to alleviate the pathological injuries in mice infected with Schistosoma japonicum by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in S. japonicum-infected mice treated with B. amyloliquefaciens. The results revealed that intervention with B. amyloliquefaciens altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of xfp/xpk and genes translated to urease was significantly restored. Further analysis showed that Limosilactobacillus reuteri was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by S. japonicum infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by B. amyloliquefaciens might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica. IMPORTANCE: Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.

Caprini risk assessment model combined with D-dimer to predict the occurrence of deep vein thrombosis and guide intervention after laparoscopic radical resection of colorectal cancer.

BACKGROUND: To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery. METHODS: A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization. RESULTS: A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38-8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209-31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69-0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555-0.921, P < 0.01), the cut-off value is 0.835 µg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754-0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 µg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 µg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered. CONCLUSIONS: The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.

Exploring the Plasticity of Diet on Gut Microbiota and Its Correlation with Gut Health.

Dietary habits have been proven to help alter the composition of gut microbiota, and exploring the impact of nutritional patterns on gut microbiota changes can help protect gut health. However, few studies have focused on the dietary impact on the gut microbiota over an experimental timeframe. In this study, 16S rRNA gene sequencing was employed to investigate the gut microbiota of mice under different dietary patterns, including AIN-93G diet (Control), high protein diet (HPD), high fiber diet (HFD), and switch diet (Switch). The alpha diversity of the HPD group significantly decreased, but HFD can restore this decline. During HPD, some genera were significantly upregulated (e.g., Feacalibaculum) and downregulated (e.g., Parabacteroides). However, after receiving HFD, other genera were upregulated (e.g., Akkermansia) and downregulated (e.g., Lactobacillus). In addition, the interaction between pathogenic bacteria was more pronounced during HPD, while the main effect was probiotics during HFD. In conclusion, the plasticity exhibited by the gut microbiota was subject to dietary influences, wherein disparate dietary regimens hold pivotal significance in upholding the well-being of the host. Therefore, our findings provide new ideas and references for the relationship between diets and gut microbiota.

Bacillus amyloliquefaciens alleviates the pathological injuries in mice infected with Schistosoma japonicum by modulating intestinal microbiome.

Schistosoma japonicum causes serious pathological organ damage and alteration of the intestinal microbiome in the mammalian host, threatening the health of millions of people in China. Bacillus amyloliquefaciens has been reported to be able to alleviate the damage to the gut and liver and maintain the homeostasis of the intestinal microenvironment. However, it was unclear whether B. amyloliquefaciens could alleviate the hepatic and intestinal symptoms caused by S. japonicum. In this study, the intragastric administration of B. amyloliquefaciens was performed to treat S. japonicum-infected mice during the acute phase. Histopathological analysis and 16S rRNA gene sequencing were used to evaluate the pathological damage and changes in the intestinal microbiome. The results of the study showed that B. amyloliquefaciens treatment significantly reduced the degree of granuloma and fibrosis in infected mice. Additionally, recovery of diversity in the intestinal microbiome, decrease in the relative abundance of potential pathogenic bacteria such as Escherichia-Shigella, and reshaping of the interactive network between genera in the intestine were also observed after treatment with B. amyloliquefaciens. Our findings indicated that treatment with B. amyloliquefaciens effectively alleviated the pathological injuries of the liver and intestine in mice infected with S. japonicum by modulating the intestinal microbiome, implying that this probiotic can function as an effective therapeutic agent against schistosomiasis. We hope our study will provide auxiliary strategies and methods for the early prevention of schistosomiasis japonica.

Ecological and dynamic analysis of gut microbiota in the early stage of azomethane-dextran sodium sulfate model in mice.

The success rate of azomethane-dextran sodium sulfate (AOM-DSS) model in mice has been a long-standing problem. Treatment of AOM and the first round DSS induces acute colitis and is of great significance for the success of AOM-DSS model. In this study, we focused on the role of gut microbiota in the early stage of AOM-DSS model. Few mice with obvious weight loss and high disease-activity score survived from double strike of AOM and the first round DSS. Different ecological dynamics of gut microbiota were observed in AOM-DSS treated mice. Pseudescherichia, Turicibacter, and Clostridium_XVIII were of significance in the model, uncontrolled proliferation of which accompanied with rapid deterioration and death of mice. Akkermansia and Ruthenibacterium were significantly enriched in the alive AOM-DSS treated mice. Decrease of Ligilactobacillus, Lactobacillus, and Limosilactobacillus were observed in AOM-DSS model, but significant drop of these genera could be lethal. Millionella was the only hub genus of gut microbiota network in dead mice, which indicated dysbiosis of the intestinal flora and fragility of microbial network. Our results will provide a better understanding for the role of gut microbiota in the early stage of AOM-DSS model and help improve the success rate of model construction.

A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma.

BACKGROUND: The prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients remains poor due to the lack of therapeutic options. However, few studies have investigated the factors contributing to the prognosis of WT Bf-CM patients. METHODS: In this paper, we proposed and validated a novel 7-RNA based signature to predict the prognosis of WT Bf-CM by analyzing the information from TCGA database. RESULTS: Dependence of this signature to other clinical factors were verified and a nomogram was also drawn to promote its application in clinical practice. Functional analysis suggested that the predictive function of this signature might attribute to the prediction of the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group, which have been demonstrated to be linked to malignancy of cancer. Moreover, functional analysis and therapy response analysis supported that the prognosis is highly related to PI3K/Akt/mTOR pathway among WT Bf-CM patients. CONCLUSION: Collectively, this study will provide a preliminary bioinformatics evidence for the molecular mechanism and potential drug targets that could improving WT Bf-CM prognosis.

Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer.

Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.

Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases.

Microglia are macrophages that reside in the central nervous system (CNS) and belong to the innate immune system. Moreover, they are crucially involved in CNS development, maturation, and aging; further, they are closely associated with neurons. In normal conditions, microglia remain in a static state. Upon trauma or lesion occurrence, microglia can be activated and subsequently polarized into the pro-inflammatory or anti-inflammatory phenotype. The phenotypic transition is regulated by numerous modulators. This review focus on the literature regarding the modulators and signaling pathways involved in regulating the microglial phenotypic transition, which are rarely mentioned in other reviews. Hence, this review provides molecular insights into the microglial phenotypic transition, which could be a potential therapeutic target for neuroinflammation.

Lung microbiome alterations in NSCLC patients.

Lung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.

Systematic Investigation of DNA Methylation Associated With Platinum Chemotherapy Resistance Across 13 Cancer Types.

Background: Platinum resistance poses a significant problem for oncology clinicians. As a result, the role of epigenetics and DNA methylation in platinum-based chemoresistance has gained increasing attention from researchers in recent years. A systematic investigation of aberrant methylation patterns related to platinum resistance across various cancer types is urgently needed. Methods: We analyzed the platinum chemotherapy response-related methylation patterns from different perspectives of 618 patients across 13 cancer types and integrated transcriptional and clinical data. Spearman's test was used to evaluate the correlation between methylation and gene expression. Cox analysis, the Kaplan-Meier method, and log-rank tests were performed to identify potential risk biomarkers based on differentially methylated positions (DMPs) and compare survival based on DMP values. Support vector machines and receiver operating characteristic curves were used to identify the platinum-response predictive DMPs. Results: A total of 3,703 DMPs (p value < 0.001 and absolute delta beta >0.10) were identified, and the DMP numbers of each cancer type varied. A total of 39.83% of DMPs were hypermethylated and 60.17% were hypomethylated in platinum-resistant patients. Among them, 405 DMPs (Benjamini and Hochberg adjusted p value < 0.05) were found to be associated with prognosis in tumor patients treated with platinum-based regimens, and 664 DMPs displayed the potential to predict platinum chemotherapy response. In addition, we defined six DNA DMPs consisting of four gene members (mesothelin, protein kinase cAMP-dependent type II regulatory subunit beta, msh homeobox 1, and par-6 family cell polarity regulator alpha) that may have favorable prognostic and predictive values for platinum chemotherapy. Conclusion: The methylation-transcription axis exists and participates in the complex biological mechanism of platinum resistance in various cancers. Six DMPs and four associated genes may have the potential to serve as promising epigenetic biomarkers for platinum-based chemotherapy and guide clinical selection of optimal treatment.

Long Non-Coding RNA in Drug Resistance of Non-Small Cell Lung Cancer: A Mini Review.

Lung cancer is one of main causes of cancer mortality and 83% of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Patients with NSCLC usually have a poor prognosis and one of the leading causes is drug resistance. With the progress of drug therapy, the emergence and development of drug resistance affected the prognosis of patients severely. Accumulating evidence reveals that long non-coding RNAs (lncRNAs), as "dark matters" of the human genome, is of great significance to drug resistance in NSCLC. Herein, we review the role of lncRNAs in drug resistance in NSCLC.