Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2-3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced in-testinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12-/-mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Alzheimer's disease (AD) is the most common cause of dementia and is a growing public health challenge. Neuroinflammation has been proposed as a prominent pathological feature of AD and has traditionally been attributed to the innate immune system. However, emerging evidence highlights the involvement of adaptive immunity, particularly T and B lymphocytes, in the neuroinflammatory processes of AD. It remains unclear how adaptive immune responses, originally intended to protect the body, contribute to chronic inflammation and neuronal dysfunction in AD. Here, we review the roles of adaptive immunity, cellular composition, and niches and their contribution to AD development and progression. Notably, we synthesize the crosstalk between adaptive immunity and the innate immune system of the central nervous system (CNS), which is mainly mediated by glial cells and myeloid cells, and their interrelationships with amyloid-β (Aβ)/Tau pathology. We hypothesized that the alterations observed in innate immunity in AD mirror age-related immune alterations, whereas the dysregulation of adaptive immunity contributes more accurately to disease-specific immune responses. Targeting adaptive immunity in the context of neuroinflammation may provide new insights into potential therapeutic strategies designed to modulate immune responses, thereby facilitating the diagnosis, intervention, and treatment of AD.
Alzheimer Disease/metabolism* ; Humans ; Adaptive Immunity/physiology* ; Immunity, Innate/immunology* ; Animals ; Neuroinflammatory Diseases/immunology* ; Inflammation/immunology* ; Amyloid beta-Peptides/metabolism*

Objective To predict and validate the core targets of Sijunzi Decoction through network pharmacology and animal experiments,and to explore the mechanism of action of Sijunzi Decoction in inhibiting the occurrence of adenomas in chronic colorectal inflammation.Methods Based on TCMSP,GeneCards and OMIM databases,screen potential targets for active components of Sijunzi Decoction and gene targets related to disease and immunity,construct a potential target regulatory network for active components of Sijunzi Decoction,analyze relevant pathways and core targets through pathway enrichment and protein interaction networks,and explore potential targets of Sijunzi Decoction in inhibiting intestinal diseases.By intervening in the DSS induced chronic colorectal inflammation mouse model with Sijunzi Decoction,the protective effect of Sijunzi Decoction on chronic colorectal inflammation mice was confirmed through changes in intestinal phenotype and pathological staining in each group of mice.Finally,the transcriptional levels and protein expression levels of the core targets related to Sijunzi Decoction predicted based on network pharmacology were verified through qRT PCR and Western Blot,further validating the mechanism of Sijunzi Decoction's inhibitory effect on the occurrence of adenomas in mice with chronic colorectal inflammation.Results Network pharmacology analysis shows that Sijunzi Decoction is related to inflammatory,immune,and tumor related pathways,and 15 related core targets have been screened and predicted.After intervention with Sijunzi Decoction in DSS chronic colorectal inflammation model mice,it slowed down the inflammatory response of the colon and significantly improved the number and size of intestinal tumors.QRT PCR and Western Blot further confirmed that the mechanism of action of Sijunzi Decoction is related to the core targets of network pharmacology prediction,EGFR,MAPK8,and CASP3.Conclusion Sijunzi Decoction can inhibit the expression levels of EGFR,MAPK8,and CASP3,exerting the effect of inhibiting the occurrence of adenomas in chronic colorectal inflammation.This provides a new idea for further exploring the mechanism of Sijunzi Decoction's inhibition of the occurrence of adenomas in chronic colitis.

Objective To analyze the potential mechanism of action of Portulaca oleracea L.in the treatment of colorectal cancer(CRC)using network pharmacology and experimental verification.Methods With reference to TCMSP and ETCM databases,the effective ingredients and targets of Chinese medicine P.oleracea were obtained,and targets related to CRC were retrieved from Genecards,Drugbank and OMIM databases,which were imported into Venny database,String database and Cytoscape platform to construct the PPI proteins.The common core targets were analyzed for GO function and KEGG pathway enrichment using Metascape database and Microbiology Letter platform,and the active ingredients and key targets were molecularly docked using Autodock and Pymol software.To construct a CRC mouse model and give P.oleracea treatment,observe the histopathological changes of its colon,and validate the key targets using qRT-PCR experiments and Western blot experiments.In addition,quercetin,luteolin,and kaempferol were used to act on HCT116 cells to observe the effects on cell proliferation and calculate the IC50,which was further verified using qRT-PCR assay and Western blot assay.Results Network pharmacological yielded 11 active ingredients and 209 targets corresponding to the target of P.oleracea.Disease targets were 2667.By analyzing the results,it was predicted that the active ingredients such as quercetin,luteolin,and kaempferol were involved in biological processes such as cellular response to lipids through key targets such as IL6,TP53,and IL1β,which were closely related to pathways in cance.Molecular docking showed that quercetin,luteolin,and kaempferol had good affinity for IL6,TP53 and IL1β.In vivo experiments confirmed that P.oleracea significantly inhibited colon tumorigenesis in mice,and inhibited the levels of IL6,IL1β inflammatory factors and increased the expression level of P53 protein.In vitro experiments showed that quercetin,luteolin and kaempferol could inhibit the proliferation of HCT116 cells to different degrees,and luteolin could inhibit the expression of IL6 and IL1β and up-regulate the expression of P53.Conclusion Through network pharmacology,in vivo and in vitro experiments,the"multi-component-multi-target-multi-pathway"effect of P.oleracea in the treatment of CRC has been confirmed,which reveals that inhibition of inflammation and delay of inflammation-cancer transformation may be one of the potential therapeutic pathways,and provides a theoretical basis and research direction for further exploration of the mechanism and clinical application of P.oleracea.

Objective To analyze the potential mechanism of action of Portulaca oleracea L.in the treatment of colorectal cancer(CRC)using network pharmacology and experimental verification.Methods With reference to TCMSP and ETCM databases,the effective ingredients and targets of Chinese medicine P.oleracea were obtained,and targets related to CRC were retrieved from Genecards,Drugbank and OMIM databases,which were imported into Venny database,String database and Cytoscape platform to construct the PPI proteins.The common core targets were analyzed for GO function and KEGG pathway enrichment using Metascape database and Microbiology Letter platform,and the active ingredients and key targets were molecularly docked using Autodock and Pymol software.To construct a CRC mouse model and give P.oleracea treatment,observe the histopathological changes of its colon,and validate the key targets using qRT-PCR experiments and Western blot experiments.In addition,quercetin,luteolin,and kaempferol were used to act on HCT116 cells to observe the effects on cell proliferation and calculate the IC50,which was further verified using qRT-PCR assay and Western blot assay.Results Network pharmacological yielded 11 active ingredients and 209 targets corresponding to the target of P.oleracea.Disease targets were 2667.By analyzing the results,it was predicted that the active ingredients such as quercetin,luteolin,and kaempferol were involved in biological processes such as cellular response to lipids through key targets such as IL6,TP53,and IL1β,which were closely related to pathways in cance.Molecular docking showed that quercetin,luteolin,and kaempferol had good affinity for IL6,TP53 and IL1β.In vivo experiments confirmed that P.oleracea significantly inhibited colon tumorigenesis in mice,and inhibited the levels of IL6,IL1β inflammatory factors and increased the expression level of P53 protein.In vitro experiments showed that quercetin,luteolin and kaempferol could inhibit the proliferation of HCT116 cells to different degrees,and luteolin could inhibit the expression of IL6 and IL1β and up-regulate the expression of P53.Conclusion Through network pharmacology,in vivo and in vitro experiments,the"multi-component-multi-target-multi-pathway"effect of P.oleracea in the treatment of CRC has been confirmed,which reveals that inhibition of inflammation and delay of inflammation-cancer transformation may be one of the potential therapeutic pathways,and provides a theoretical basis and research direction for further exploration of the mechanism and clinical application of P.oleracea.

Objective:This study compares the magnetic resonance imaging (MRI) appearance of two types of breast tissue markers to investigate the appropriate clinical application of the markers.Methods:Breast MRI of 69 patients (78 masses) with breast tissue markers had been placed were analyzed retrospectively from November 2015 to August 2018 in our hospital. The sizes and shapes of breast tissue markers were assessed in axial fat-suppressed T2-weighted images, T1-weighted images and contrast-enhanced T1-weighed images.Results:The length of the coil nickel-free stainless steel markers were greater than ribbon titanium markers, with statistical difference in fat-suppressed T2-weighted images ( P=0.039). In contrast-enhanced T1-weighted images, all coil nickel-free stainless steel markers showed >6 mm diameter and round shape, and ribbon titanium markers showed >6 mm diameter ( n=20) or ≤6 mm diameter ( n=8), and round ( n=20), dot ( n=7) or band ( n=1) shapes. The categories of sizes and shapes in two types of breast tissue markers both had statistical significance ( P<0.001, P<0.001). Conclusions:Small breast lesions with breast tissue markers are not suitable for MRI evaluation. The artifact of ribbon titanium markers is smaller than coil nickel-free stainless steel markers, so they have less impact for lesions. The choice of the breast tissue markers and image evaluation methods should depend on the different clinical conditions.

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 lm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscrip-tomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

Objective To investigate the expression of hsa-miR-144 in esophageal squamous cell carcinoma, and its relationship with clinicopathological features and prognosis. Methods Reverse transcriptase polymerase chain reaction (RT-PCR) method was used to detect the hsa-miR-144 in 46 cases of esophageal squamous cell carcinoma and adjacent normal tissue. The expression of hsa-miR-144 in esophageal squamous cell carcinoma and its difference in the clinicopatho?logical characteristics including gender, age, and tumor size were investigated. The relationship between the expression of hsa-miR-144 and prognosis of patients with esophageal squamous cell carcinoma was analyzed. Kaplan-Meier method and Log-rank test were used to analyse the differences in survival rates in different pathological characteristics. Results The ex?pression level of hsa-miR-144 was lower in esophageal squamous cell carcinoma 0.97(0.22-24.48)×10-6 than that of adjacent normal tissue 8.60(0.09-258.20)×10-6, the difference was statistically significant (Z=2.221, P<0.05). The expression level of hsa-miR-144 was higher in esophageal squamous cell carcinoma with no lymph node metastasis than that in esophageal squa?mous cell carcinoma with lymph node metastasis (Z=2.758,P<0.05), and the expression level decreased with the increase in the pathological staging (Z=7.737,P<0.05). There were no significant differences in the expression levels of hsa-miR-144 between different gender, age, tumor size, tumor location, tumor differentiation and tumor invasion depth (all P>0.05). There was no correlation between the expression of hsa-miR-144 and prognosis in patients with esophageal squamous cell carcino?ma (rs=0.031, P=0.839). In the survival rate, there was no statistic significance between high expressive of hsa-miR-144 group and low expressive group (P=0.828). The survival rate was lower in patients with lymph node metastasis than that of pa?tients without lymph node metastasis. The survival rates were lower in patients with relatively deep invasion and higher patho?logic stage (P<0.05). Conclusion The expression of hsa-miR-144 is down regulated in esophageal squamous cell carcino?ma, and which is associated with lymph node metastasis and pathological staging of esophageal carcinoma. It shows that hsa-miR-144 may serve as an anti-oncogene in the occurrence and development of esophageal squamous cell carcinoma.

Carcinoma, Squamous Cell ; metabolism ; mortality ; Esophageal Neoplasms ; metabolism ; mortality ; Humans ; MicroRNAs ; metabolism ; Prognosis