Regulatory effect of Ganoderma lucidum and its active components on gut flora in diseases.

Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers.

PBX3 as a biomarker for the early diagnosis and prediction of prognosis of glioma.

BACKGROUND: Increasing evidence have elucidated that PBX3 played a crucial role in cancer initiation and progression. PBX3 was differentially expressed in many cancer types. However, PBX3 potential involvement in gliomas remains to be explored. METHODS: The expression level of PBX3 in glioma tissues and glioma cells, and its correlation with clinical features were analyzed by data from TCGA, GEPIA, CGGA and CCLE. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. We also analyzed the correlation between PBX3 expression level and survival outcome and survival time of LGG and GBM patients by using linear regression equation. GSEA was used to generate an ordered list of all genes related to PBX3 expression and screening of genes co-expressed with PBX3 mRNA by "limma" package. RESULTS: The results showed that PBX3 was highly expressed in gliomas and its expression increased with the increase of malignancy. Survival analysis found that PBX3 is more valuable in predicting the OS and PFI of LGG patients than that of GBM. For further study, TCGA and CGGA data were downloaded for univariate Cox analysis and multivariate Cox analysis which showed that the expression of PBX3 was independent influencing factors for poor prognosis of LGG patients. Meanwhile, Receiver operating characteristic (ROC) curve showed that PBX3 was a predictor of overall survival rate and progression-free survival rate of LGG. Linear regression model analysis indicated that the higher expression of PBX3 the higher the risk of death of LGG patients, and the higher expression of PBX3 the higher the risk of disease progression of LGG patients. Next, TCGA data were downloaded for GSEA and Co-expression analyses, which was performed to study the function of PBX3. CONCLUSION: PBX3 may be involved in the occurrence and development of glioma, and has potential reference value for the early diagnosis and prediction of prognosis of glioma.

Inhibition of Alzheimer's disease by 4-octyl itaconate revealed by RNA-seq transcriptome analysis.

AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.

A composition of ursolic acid derivatives from Ludwigia hyssopifolia induces apoptosis in throat cancer cells via the Akt/mTOR and mitochondrial signaling pathways and by modulating endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia hyssopifolia (LH), an ethnopharmacological herb used in Guangxi Zhuang medicine, is known for its extensive therapeutic use in treating throat disorders. The anti-laryngeal-cancer benefits of the ethyl acetate and petroleum ether fractions of the ethanolic extracts of LH have been shown in our prior cell-based research. Nevertheless, the specific impacts and underlying processes by which LH combats throat cancer effects have not been fully understood. AIM OF THE STUDY: This study involved the extraction of a composition containing two derivatives of ursolic acid from LH (LH-CUAD). The present study aimed to assess the anti-throat-cancer effects of these derivatives and the underlying mechanisms through in vitro and in vivo experiments. MATERIALS AND METHODS: Solvent extraction, fractionation, chromatography, and semipreparative high-performance liquid chromatography were used for the extraction, purification, and analysis of LH-CUAD. The in vitro and in vivo anti-throat-cancer effects of LH-CUAD were investigated using the throat cancer cell lines Hep-2 and FaDu as well as Hep-2 tumor-bearing nude mice. RESULTS: LH-CUAD significantly inhibited the proliferation and migration of throat cancer cells without any prominent toxicity. The Hoechst 33258 staining, Annexin V-FITC/PI double-staining assays, and flow cytometry confirmed that LH-CUAD could induce throat cancer cell death from early to late apoptosis in vitro. LH-CUAD exhibited significant antitumor activity and low toxicity in a xenograft model, and induced throat cancer cells apoptosis in vivo. The apoptotic effects of LH-CUAD therapy were validated using Western blotting, which demonstrated the activation of a caspase cascade response triggered by an imbalance between the endoplasmic reticulum and mitochondria. In addition, it was observed that LH-CUAD exhibited inhibitory effects on Akt and mTOR phosphorylation, hence promoting apoptosis. CONCLUSIONS: LH-CUAD induces apoptosis in both in vivo and in vitro models of throat cancer. This effect is achieved by activating the mitochondrial pathway, inhibiting the Akt/mTOR pathway and initiating endoplasmic reticulum stress. The findings of this study suggest that LH-CUAD has the potential to offer a novel approach to the clinical management of throat cancer.

Integrative proteomics and m6A microarray analyses of the signatures induced by METTL3 reveals prognostically significant in gastric cancer by affecting cellular metabolism.

METTL3-mediated RNA N6-methyladenosine (m6A) is the most prevalent modification that participates in tumor initiation and progression via governing the expression of their target genes in cancers. However, its role in tumor cell metabolism remains poorly characterized. In this study, m6A microarray and quantitative proteomics were employed to explore the potential effect and mechanism of METTL3 on the metabolism in GC cells. Our results showed that METTL3 induced significant alterations in the protein and m6A modification profile in GC cells. Gene Ontology (GO) enrichment indicated that down-regulated proteins were significantly enriched in intracellular mitochondrial oxidative phosphorylation (OXPHOS). Moreover, the protein-protein Interaction (PPI) network analysis found that these differentially expressed proteins were significantly associated with OXPHOS. A prognostic model was subsequently constructed based on the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, and the high-risk group exhibited a worse prognosis in GC patients. Meanwhile, Gene Set Enrichment Analysis (GSEA) demonstrated significant enrichment in the energy metabolism signaling pathway. Then, combined with the results of the m6A microarray analysis, the intersection molecules of DEPs and differential methylation genes (DMGs) were significantly correlated with the molecules of OXPHOS. Besides, there were significant differences in prognosis and GSEA enrichment between the two clusters of GC patients classified according to the consensus clustering algorithm. Finally, highly expressed and highly methylated molecules regulated by METTL3 were analyzed and three (AVEN, DAZAP2, DNAJB1) genes were identified to be significantly associated with poor prognosis in GC patients. These results signified that METTL3-regulated DEPs in GC cells were significantly associated with OXPHOS. After combined with m6A microarray analysis, the results suggested that these proteins might be implicated in cell energy metabolism through m6A modifications thus influencing the prognosis of GC patients. Overall, our study revealed that METTL3 is involved in cell metabolism through an m6A-dependent mechanism in GC cells, and indicated a potential biomarker for prognostic prediction in GC.

Models for Predicting Response to Immunotherapy and Prognosis in Patients with Gastric Cancer: DNA Damage Response Genes.

Objective: DNA damage response (DDR) is a complex system that maintains genetic integrity and the stable replication and transmission of genetic material. m6A modifies DDR-related gene expression and affects the balance of DNA damage response in tumor cells. In this study, a risk model based on m6A-modified DDR-related gene was established to evaluate its role in patients with gastric cancer. Methods: We downloaded 639 DNA damage response genes from the Gene Set Enrichment Analysis (GSEA) database and constructed risk score models using typed differential genes. We used Kaplan-Meier curves and risk curves to verify the clinical relevance of the model, which was then validated with the univariate and multifactorial Cox analysis, ROC, C-index, and nomogram, and finally this model was used to evaluate the correlation of the risk score model with immune microenvironment, microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoints. Results: In this study, 337 samples in The Cancer Genome Atlas (TCGA) database were used as training set to construct a DDR-related gene model, and GSE84437 was used as external data set for verification. We found that the prognosis and immunotherapy effect of gastric cancer patients in the low-risk group were significantly better than those in the high-risk group. Conclusion: We screened eight DDR-related genes (ZBTB7A, POLQ, CHEK1, NPDC1, RAMP1, AXIN2, SFRP2, and APOD) to establish a risk model, which can predict the prognosis of gastric cancer patients and guide the clinical implementation of immunotherapy.

S100A9­containing serum exosomes obtained from patients with burn injuries promote myocardial cell pyroptosis through NLRP3.

S100 calcium-binding protein A9 (S100A9) is highly expressed in the serum exosomes of patients with burn injuries. The present study aimed to investigate the underlying mechanisms of burn injury-associated exosomes in the regulation of myocardial cell pyroptosis. Reverse transcription-quantitative PCR and western blotting were used to examine relative mRNA and protein levels. The morphology of exosomes was visualized using transmission electron microscopy. The expression levels of IL-1ß and IL-18 in cells were examined using ELISA kits. Finally, cell pyroptosis was examined using flow cytometry. When AC16 cells were treated with the serum exosomes obtained from patients with burn injuries, pyroptosis was significantly promoted and the expression levels of IL-1ß and IL-18 were increased. NLR family pyrin domain containing 3 (NLRP3), S100A9, caspase-1 and Gasdermin D (GSDMD)-N expression levels were also upregulated. However, these were significantly reversed by anti-S100A9 antibodies. Thereafter, CY-09, an NLRP3 inhibitor, was revealed to restore the increase in pyroptosis and IL-18, IL-1ß, caspase-1, NLRP3 and GSDMD-N expression levels caused by recombinant S100A9 to be similar to the control. These findings suggested that burn injury-associated exosomes containing S100A9 can affect AC16 cell pyroptosis through NLRP3.

Identification and Validation of METTL3-Related Molecules for Predicting Prognosis and Efficacy of Immunotherapy in Gastric Cancer Based on m6A Methylome and Transcriptome Sequencing Analysis.

Abnormal N6-methyladenosine (m6A) modification levels caused by METTL3 have been identified to be a critical regulator in human cancers, and its roles in the immune microenvironment and the relationship between targeted therapy and immunotherapy sensitivity in gastric cancer (GC) remain poorly understood. In this study, we assessed the transcriptome-wide m6A methylation profile after METTL3 overexpression by m6A sequencing and RNA sequencing in BGC-823 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of core targets of METTL3. Eighteen methylation core molecules were identified in GC patients by combining transcriptome and methylome sequencing. GC patients can be separated into two subtypes based on the expression of 18 methylation core molecules. Furthermore, subgroup analysis showed that patients with different subtypes had a different OS, PFS, stage, grade, and TMB. Gene set enrichment analysis (GSEA) showed that immune-related pathways were enriched among subtype A. The ESTIMATE analysis suggested that the extent of infiltration of immune cells was different in two subtypes of GC patients. Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA) database also showed that there were significant differences in the efficacy of immunotherapy among different types of GC patients. Altogether, our results reveal that METTL3-mediated m6A methylation modification is associated with the immune microenvironment and the effects of immunotherapy in GC patients. Our findings provide novel insights for clinicians in the diagnosis and optimal treatment of GC patients.

m7G-Related DNA Damage Repair Genes are Potential Biomarkers for Predicting Prognosis and Immunotherapy Effectiveness in Colon Cancer Patients.

Objective: m7G is a post-transcriptional modification modality, however, limited research has been conducted on its role in colon cancer. DNA damage repair (DDR) is an important factor that contributes to colon cancer development, growth and chemoresistance. This study aimed to explore whether m7G-related DNA damage repair genes may be used as biomarkers to predict the prognosis of colon cancer patients. Methods: We use non-negative matrix factorization (NMF) to type CRC patients into. Risk models were constructed using different expression genes in two clusters. We assessed the reliability of risk models with DCA curves, and a Nomogram. Meanwhile, The receiver operating characteristic and C-index curves were used to compare the predictive significance of the constructed risk models with other studies. In additional, we examined the significance of risk models on patients' immunity microenvironment and response to immune therapy. Finally, we used a series of cellular experiments to validate the effect of model genes on the malignant progression of CRC cells. Results: Twenty-eight m7G genes were obtained from the GSEA database. Multivariate Cox and LASSO Cox regression analysis was performed and eleven m7G-related DDR genes were identified for constructing the risk model. Survival and stage of CRC patients were worser in the high-risk group than in the low-risk group for both the training and test sets. Additionally, the different immune microenvironment status of patients in the high- and low-risk groups, suggesting that patients in the low-risk group may be more sensitive to immunotherapy, particularly immune checkpoint inhibitors. Finally, we found that depletion of ATP2A1, one of the risk genes in our model, influence the biologic behaviour of CRC cells significantly. Conclusion: The m7G-related DDR genes can be used as important markers for predicting patient prognosis and immunotherapy response. Our data suggest that ATP2A1 may promote the proliferation of colon cancer cells. These findings may provide new therapeutic targets for the treatment of colon cancer.

Role of TGM2 in T­cell lymphoblastic lymphoma via regulation of IL­6/JAK/STAT3 signalling.

Transglutaminase 2 (TGM2) is a Ca2+­dependent enzyme that is closely associated with cancer progression; however, the function of TGM2 in T­cell lymphoma remains unclear. In the present study, TGM2 was identified as an upregulated gene by bioinformatics analysis of the microarray datasets GSE132550 and GSE143382 from the Gene Expression Omnibus database. The effects and mechanisms of TGM2 on T­cell lymphoma cells were evaluated using the Cell Counting Kit­8, colony formation assay, 5­ethynyl­2'­deoxyuridine (EdU) assay, flow cytometry, reverse transcription­quantitative polymerase chain reaction, western blotting and gene set enrichment analysis (GSEA). TGM2 expression was shown to be elevated in formalin­fixed paraffin­embedded skin biopsies from patients with T­cell lymphoma relative to skin tissue from healthy cases. TGM2 expression was also increased in T­cell lymphoma cell lines compared with that in CD4+ T cells. Transfection with TGM2 small interfering RNAs (siRNAs) decreased the number of EdU­positive cells, and the viability and colony formation of T­cell lymphoma cells. Furthermore, TGM2 siRNAs enhanced the apoptosis of T­cell lymphoma cells potentially via cleavage of caspase­3 and poly ADP­ribose polymerase. GSEA identified the IL­6/JAK/STAT3 pathway as a potential downstream signalling pathway of TGM2. Notably, the effects of TGM2 siRNAs on T­cell lymphoma cells were attenuated by IL­6 and accelerated by IL­6/JAK/STAT3 inhibitor AG490. These findings indicated that TGM2 siRNAs inhibited the proliferation of T­cell lymphoma cells by regulating the IL­6/JAK/STAT3 signalling pathway; therefore, TGM2 may function as a potential therapeutic target for T­cell lymphoma.

3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model.

3,4-Dihydroxyphenylethanol (DOPET) is a polyphenol found in olive oil. The present study evaluated the protective role of DOPET on LPS provoked septic cardiac injury in a murine model. Four groups were used in the study (n = 3): control, LPS, DOPET alone, and DOPET + LPS. LPS (15 mg/kg; i.p.); they were used to induce cardiac sepsis. The cardiac markers like LDH, CK-MB, and troponin-T, as well as inflammatory cytokines like TNF-α and IL-6 were measured in the serum. The antioxidants and oxidative stress parameters were measured in cardiac tissues. RT-PCR and western blot methods were done to evaluate the expression of inflammatory mediators and apoptotic markers. DOPET significantly decreased the cardiac markers (LDH, CK-MB, and troponin-T) and TNF-α and IL-6 level in the serum. DOPET effectively reduced the levels of MDA and NO in LPS intoxicated rats. DOPET also increased the levels of antioxidants like SOD, CAT, GPx, and GSH in LPS intoxicated rats. The mRNA levels of TNF-α, IL-6, and NF-κB were significantly downregulated by DOPET in cardiac tissues of LPS rats. The protein expression of Bcl-2 was upregulated, and Bax and caspase-3 were downregulated by DOPET. DOPET effectively attenuates LPS-induced cardiac dysfunction through its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Associations Between Serum Zinc Levels and Alanine Aminotransferase Elevation in Adults.

Recent findings showed that zinc might be linked to alanine aminotransferase (ALT) elevation. This analysis aimed to explore the association between serum zinc levels and ALT elevation in adults. Data on serum zinc and ALT levels from adults aged 20 years and older who participated in the 2011-2016 National Health and Nutrition Examination Surveys were analyzed (N = 4138). Individuals with excessive alcohol consumption and hepatitis B or C infection were excluded. ALT elevation was defined as any value above normal of ALT (> 33 IU/L for males and > 25 IU/L for females). The multivariate logistic model and restricted cubic splines were adopted to assess the non-linear relationship. In a fully adjusted model, the odds ratio and 95% confidence interval of ALT elevation for quartile 4 (Q4) vs. quartile 1 (Q1) of serum zinc levels were 1.68 and 1.29-2.20 (per quartile: 1.20 (1.10-1.31)). In subgroup analysis, the association between serum zinc levels and ALT elevation was found in females (Q4 vs Q1: 1.95 (1.20-3.15)), obese individuals (Q4 vs Q1: 1.80 (1.19-2.74)), and young adults (Q4 vs Q1: 1.72 (1.09-2.72)), while the association was not evident in males, non-obese individuals, and adults older than 50 years old. A linear dose-response relationship between serum zinc levels and ALT elevation was found (Pfor non-linearity = 0.77). In conclusion, serum zinc was positively associated with ALT elevation in adults, and the association was mainly observed in females, obese individuals, and young adults.

PRDM14 mediates chemosensitivity and glycolysis in drug­resistant A549/cisplatin cells and their progenitor A549 human lung adenocarcinoma cells.

Recent studies have reported that aberrant PR domain zinc finger protein 14 (PRDM14) expression is associated with the therapeutic sensitivity of cancer cells to drugs. However, its role in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to determine the functions of knockdown or overexpression of PRDM14 in the chemosensitivity and glycolysis of LUAD cells. PRDM14 expression was analyzed in lung cancer tissues from patients resistant and sensitive to cisplatin (DDP), as well as in LUAD cell lines A549 and DDP­resistant A549 (A549/DDP) using reverse transcription quantitative­PCR and western blotting. Additionally, apoptosis was analyzed by flow cytometry, and flow cytometry and biochemical analysis was used to analyze glycolysis, indicated by glucose uptake and lactate release. The results of the present study demonstrated that PRDM14 expression was upregulated in patients with DDP­resistant LUAD and DDP­resistant cell lines. Overexpression of PRDM14 suppressed the sensitivity of A549 cells to DDP and silencing of PRDM14 using shRNA targeting PRDM14 promoted the sensitivity of A549/DDP cells to DDP, compared with that in the respective control groups. In mice with xenograft tumors, knockdown of PRDM14 using shRNA targeting PRDM14 inhibited the A549/DDP cell­derived tumor growth compared with scramble shRNA. The results of the glycolysis assays demonstrated that PRDM14 silencing inhibited glucose uptake, lactate release and glucose transporter 1 expression in A549/DDP cells compared with those in the control cells. PRDM14 overexpression relieved the inhibitory effects of 3­bromopyruvate, a potent glycolytic inhibitor for glycolysis, on glucose uptake and lactate release in A549 cells compared with those in the control cells. Therefore, the results of the present study suggested that PRDM14 may inhibit the chemosensitivity and promote glycolysis in human LUAD cells.

Long Non-Coding RNA Taurine Upregulated Gene 1 Targets miR-185 to Regulate Cell Proliferation and Glycolysis in Acute Myeloid Leukemia Cells in vitro.

BACKGROUND: Acute myeloid leukemia (AML) is a group of malignant hematopoietic system diseases. Taurine-upregulated gene 1 (TUG1) is a long non-coding RNA that has been associated with human cancers, including AML. However, the role and molecular mechanisms of TUG1 in AML remains to be defined. METHODS: Expression of TUG1 and miR-185 was detected using RT-qPCR. Cell viability and apoptotic rate were measured by MTT assay and flow cytometry, respectively. Glycolysis was determined by commercial glucose and lactate assay kits and Western blot. The target binding between TUG1 and miR-185 was predicted on Starbase online database and confirmed by luciferase reporter assay and RNA immunoprecipitation. RESULTS: TUG1 was upregulated and miR-185 was downregulated in the peripheral blood mononuclear cells of AML specimens and cells (HL-60, KG-1, MOLM-14, and MOLM-13). Both TUG1 knockdown and miR-185 overexpression via transfection could suppress cell viability, glucose consumption, lactate production, and hexokinase 2 expression, but promote apoptotic rate in HL-60 and KG-1 cells. Notably, TUG1 functioned as a sponge of miR-185 by target binding. Moreover, downregulation of miR-185 could partially overturn the effect of TUG1 knockdown on cell proliferation and glycolysis in HL-60 and KG-1 cells. CONCLUSION: Expression of TUG1 was upregulated in AML patients and cells, and its knockdown repressed cell proliferation and glycolysis in AML cells in vitro by targeting miR-185.

Chemokine C-C motif ligand 2 suppressed the growth of human brain astrocytes under Ischemic/hypoxic conditions via regulating ERK1/2 pathway.

PRIMARY OBJECTIVE: Chemokine C-C motif ligand 2 (CCL2) plays a critical role in inflammation-related diseases in the central nervous system (CNS). However, the role of CCL2 in ischemic stroke remains unclear. RESEARCH DESIGN: To investigate the role of CCL2 in ischemic stroke, we performed oxygen-glucose deprivation (OGD) on human brain astrocytes. METHODS AND PROCEDURES: To assess cell proliferation, the CCK-8 assay was performed. Cell apoptosis was determined using flow cytometry. qRT-PCR and western blotting were utilized to measure gene expression. MAIN OUTCOMES AND RESULTS: Our results suggest that CCL2 and its receptor CCR2 are upregulated in OGD cells. Moreover, a CCL2 antibody significantly alleviated the ischemic/hypoxic-induced suppression of growth in human brain astrocytes. Human recombinant protein, CCL2, inhibited the growth of human brain astrocytes under normoxia conditions. These results demonstrate that CCL2 upregulation suppresses the recovery of human brain astrocytes under ischemic/hypoxic conditions. This effect was abolished by the ERK inhibitor PD98059. Therefore, CCL2/CCR2 activation may suppress the growth of human brain astrocytes through enhancing the activity of ERK1/2. CONCLUSIONS: Our results not only developed a deeper understanding of the role of CCL2 in human brain astrocytes but also provided novel insight into potential treatments for ischemic stroke.

P4HB modulates epithelial-mesenchymal transition and the ß-catenin/Snail pathway influencing chemoresistance in liver cancer cells.

The aim of the present study was to investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) in the chemoresistance of liver cancer. Drug-resistant liver cancer cell lines, such as HepG2/adriamycin (ADR) cells, were treated and screened using adriamycin. Gene interference was used to silence the expression of P4HB in liver cancer cells. Cell viability, invasiveness and migration were assessed using CCK8, Transwell and wound healing assays, respectively. In addition, changes to key genes and proteins in the epithelial-mesenchymal transition (EMT) and ß-catenin/Snail pathway were analyzed using reverse transcription-quantitative PCR and western blotting. Drug-resistant HepG2/ADR cells were successfully cultivated; the IC50 to ADR for HepG2/ADR and HepG2 cell lines was 4.85 and 0.61 µM, respectively. HepG2/ADR cells exhibited higher invasion and migration abilities compared with HepG2 cells (P<0.05). E-cadherin mRNA and protein expression levels in HepG2/ADR cells were decreased significantly, whereas P4HB, N-cadherin and vimentin mRNA and protein levels were significantly increased compared with HepG2 cells (all P<0.05). Knockdown of P4HB significantly decreased cell viability and the invasion and migration ability of HepG2/ADR cells. In addition, P4HB knockdown enhanced E-cadherin mRNA and protein expression levels, whereas N-cadherin, vimentin, total ß-catenin, nuclear ß-catenin and Snail mRNA and protein levels were significantly decreased (all P<0.05). Overall, the present study demonstrated that EMT and ß-catenin/Snail pathway influence P4HB modulation in liver cancer chemoresistance.

The Photoreceptor Components FaWC1 and FaWC2 of Fusarium asiaticum Cooperatively Regulate Light Responses but Play Independent Roles in Virulence Expression.

Fusarium asiaticum belongs to one of the phylogenetical subgroups of the F. graminearum species complex and is epidemically predominant in the East Asia area. The life cycle of F. asiaticum is significantly regulated by light. In this study, the fungal blue light receptor white collar complex (WCC), including FaWC1 and FaWC2, were characterized in F. asiaticum. The knockout mutants ΔFawc1 and ΔFawc2 were generated by replacing the target genes via homologous recombination events. The two mutants showed similar defects in light-induced carotenoid biosynthesis, UV-C resistance, sexual fruiting body development, and the expression of the light-responsive marker genes, while in contrast, all these light responses were characteristics in wild-type (WT) and their complementation strains, indicating that FaWC1 and FaWC2 are involved in the light sensing of F. asiaticum. Unexpectedly, however, the functions of Fawc1 and Fawc2 diverged in regulating virulence, as the ΔFawc1 was avirulent to the tested host plant materials, but ΔFawc2 was equivalent to WT in virulence. Moreover, functional analysis of FaWC1 by partial disruption revealed that its light-oxygen-voltage (LOV) domain was required for light sensing but dispensable for virulence, and its Zinc-finger domain was required for virulence expression but not for light signal transduction. Collectively, these results suggest that the conserved fungal blue light receptor WCC not only endows F. asiaticum with light-sensing ability to achieve adaptation to environment, but it also regulates virulence expression by the individual component FaWC1 in a light-independent manner, and the latter function opens a way for investigating the pathogenicity mechanisms of this important crop disease agent.

Identify Molecular Mechanisms of Jiangzhi Decoction on Nonalcoholic Fatty Liver Disease by Network Pharmacology Analysis and Experimental Validation.

BACKGROUND: Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against nonalcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study is aimed at identifying the core molecular mechanisms of JZD against NAFLD. METHODS: The active ingredients were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Traditional Chinese Medicine Integrated Database (TCMID). The targets of those ingredients were identified using ChemMapper database based on 3D structure similarity. NAFLD-related genes were searched from DisGeNET database and Gene Expression Omnibus (GEO) database. Then, we performed protein-protein interaction (PPI) analysis, functional enrichment analysis, and constructed pathway networks of "herbs-active ingredients-candidate targets" and identified the core molecular mechanisms and key active ingredients in the network. Also, molecular docking was carried out to predict the ligands of candidate targets using SwissDock. Finally, the human hepatic L02 cell line was used to establish the NAFLD model in vitro. The effect and key molecules were validated by Oil Red O staining, biochemical assays, and quantitative real-time PCR (qRT-PCR). RESULTS: We found 147 active ingredients in JZD, 1285 targets of active ingredients, 401 NAFLD-related genes, and 59 overlapped candidate targets of JZD against NAFLD. 22 core targets were obtained by PPI analysis. Finally, nuclear receptor transcription and lipid metabolism regulation were found as the core molecular mechanisms of JZD against NAFLD by functional enrichment analysis. The candidate targets PPARα and LXRα were both docked with hyperin as the most favorable interaction, and HNF4α was docked with linolenic acid ethyl ester. According to in vitro experiments, it was found that JZD had an inhibitory effect on lipid accumulation and regulatory effects on cholesterol and triglycerides. Compared with OA group, the mRNA expression levels of PPARα and HNF4α were significantly upregulated in JZD group (P < 0.05), and LXRα was significantly downregulated (P < 0.001). CONCLUSION: JZD might alleviate hepatocyte steatosis by regulating some key molecules related to nuclear receptor transcription and lipid metabolism, such as PPARα, LXRα, and HNF4α. Our study will provide the scientific evidences of the clinical efficacy of JZD against NAFLD.

Surveillance and analysis of viral hepatitis among train attendants in Jiangxi province in 2013-2015 / 中华实验和临床病毒学杂志

Objective@#To understand and analyze the prevalence of viral hepatitis in railway passenger occupational population in Jiangxi province, and to explore its epidemiological characteristics, so as to provide basis for the prevention and control of viral hepatitis in railway occupational population in the future.@*Methods@#The test results of anti-hepatitis A virus (HAV)-IgM, anti-HAV-IgG, hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs), anti-hepatitis C virus (HCV), anti-hepatitis E virus (HEV)-IgM and anti-HEV-IgG in some passenger train attendants of Nanchang Railway Bureau from 2013 to 2015 were collected and analyzed by SPSS 19.0 and Excel 2007 software.@*Results@#The positive rate of anti-HAV-IgG was 90.6%-98.7% from 2013 to 2015, the positive rate of HBsAg was 6.6%-15.1%, the positive rate of anti-HCV was 0.2%-1.4%, the positive rate of anti-HEV-IgG was 16.1%-24.9%; the positive rate of anti-HEV-IgG was significantly different between men and women, and the positive rate of anti-HEV-IgG was 29.5%, 30.5%, 22.5% between 2013 and 2015. The positive rate of male was higher than that of female (22.3, 22.5, 13.8) (χ2=3.934, P=0.047; χ2 =4.363, P=0.037; χ2=6.755, P=0.009), and there was no significant difference between male and female in the surveillance results of other types of viral hepatitis.@*Conclusions@#The positive rate of intestinal transmitted hepatitis was high in the population and low in the acute phase. The positive rate of anti-HCV was low in the population with extraintestinal transmitted hepatitis. The positive rate of HBsAg was high in the population with extraintestinal transmitted hepatitis.

Ultrasonic monitoring of carotid blood flow in interposed abdominal pulling-pressing cardiopulmonary resuscitation / 中华危重病急救医学

OBJECTIVE@#To explore the difference in ultrasonic monitoring in carotid blood flow, resuscitation effects and prognosis between interposed abdominal pulling-pressing cardiopulmonary resuscitation (IAPP-CPR) and standard cardiopulmonary resuscitation (STD-CPR).@*METHODS@#Seventy-five cardiac arrest (CA) patients admitted to emergency department of Shijingshan Teaching Hospital of Capital Medical University from June 2015 to December 2017 were enrolled. The patients were divided into STD-CPR group and IAPP-CPR group according to the treatment orders of them and the desire of relatives. All patients were given persistent external compression, airway open, tube intubation, and mechanical ventilation, vasoactive drugs application, defibrillation if required. STD-CPR group was operated according to the 2015 American Heart Association (AHA) CPR guidelines. On the basis of the standard CPR, IAPP-CPR group was recovered using abdominal lifting and compressing CPR instrument to press down to lift the upper abdomen continuously, when the chest compressing relaxed (frequency 100 times/min, down and lift time ratio 1:1, compressing strength 50 kg, lifting strength 30 kg). The patients' gender, age and CA etiology were recorded in the two groups. The vital signs and blood flow of carotid artery were monitored with ultrasonic Doppler during the CPR. The return of spontaneous circulation (ROSC) rate and 48-hour survival rate were observed in patients. The influence factors of ROSC were screened by Logistic regression analysis.@*RESULTS@#The data of 75 patients with CA were enrolled finally, with STD-CPR group of 38 patients and IAPP-CPR group of 37 patients. There were no significant differences in patients' gender, age or CA etiology between the two groups. Comparing with STD-CPR group, the peak blood flow velocity of carotid artery in IAPP-CPR group was speeded up significantly (cm/s: 107.16±13.75 vs. 78.99±14.77, P < 0.01), the overall blood flow volume of carotid artery was increased significantly (mL/min: 989.06±115.88 vs. 751.62±118.92, P < 0.01), but there was no significant difference in inner diameter of carotid artery between the two groups (mm: 4.55±0.25 vs. 4.61±0.21, P > 0.05). During the CPR, the mean arterial pressure (MAP) and the transcutaneous oxygen saturation (SpO2) in IAPP-CPR group were significantly higher than those of STD-CPR group, but no significant difference was found in heart rate between the two groups. Four patients in STD-CPR group got ROSC, and 3 survived over 48 hours (1 myocardial infarction patient died of ventricular fibrillation) while 6 patients in IAPP-CPR group got ROSC and survived over 48 hours. There was no significant difference in ROSC rate or 48-hour survival rate between the two groups, but data of IAPP-CPR group was slightly higher than that of STD-CPR group [ROSC rate: 16.22% (6/37) vs. 10.53% (4/38), 48-hour survival rate: 16.22% (6/37) vs. 7.89% (3/38), both P > 0.05]. Multivariate Logistic regression analysis showed that the higher the MAP during CPR, the greater the possibility of ROSC was [odds ratio (OR) = 1.361, 95% confidence interval (95%CI) = 1.182-1.669, P = 0.030].@*CONCLUSIONS@#IAPP-CPR was superior to traditional STD-CPR in improving arterial blood flow and resuscitation effect, but no superiority was found in ROSC rate and survival rate, which may be relate to the small number of patients that included in this study. More clinic trials are needed.