Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Expression of PNNs and the functional changes of GABA-ergic neurons in the medial prefrontal cortex in a rat model of depression

Objective:To investigate the effects of chronic unpredictable mild stress(CUMS)on perineuronal nets(PNNs)andγ-aminobutyric acid(GABA)-ergic neurons in the medial prefrontal cortex(mPFC)of adult rats.Methods:28 rats were randomly divided into two groups.The model group adopted CUMS to establish a depression model,and the control group did not give any treatment.The density of PNNs and the percentage of PNNs positive(PNNs^(+))and parvalbumin positive(PV^(+))neurons in total PV^(+)neurons in the mPFC were detected by immunofluorescence.The protein expression of main components of PNNs,Aggrecan and Brevican,and GABA main synthase glutamic acid decarboxylase 67(GAD67)in the mPFC were detected by Western blot.Results:The density of PNNs and the percentage of PNNs^(+)and PV^(+)neurons in total PV^(+)neurons in the mPFC in the model group were decreased compared with the control group(P<0.05);The expression levels of PNNs component proteins Aggrecan and Brevican,and GABA main synthase GAD67 were also decreased in the model group(P<0.01).Conclusion:The levels of PNNs and GABA synthase GAD67 in the mPFC of rats were decreased after chronic unpredictable mild stress.

Network pharmacological study of Qingfei Paidu Decoction intervening on cytokine storm mechanism of COVID-19

Objective:To explore the possible mechanism of Qingfei Paibu Decoction in the treatment of COVID-19 from the perspective of cytokine storm by network pharmacology.Methods: The TCMSP and SymMap databases were used to screen out the active components and targets of Qingfei Paibu Decoction;The GeneCards database was used to screen the predicted targets of COVID-19;Two targets were mapped;The STRING database and Cytoscape3.7.2 software were used to construct the network diagram of active drag-ingredient-target and screen out the core components and targets;The GO enrichment analysis and KEGG pathway enrichment analysis were carried out by OmicShare cloud platform and David respectively.Results:A total of 52 potential targets of Qingfei Paibu Decoction for the treatment of COVID-19 were obtained, among which 17 were core targets related to inflammation, mainly including cytokines such as IL, IFN, TNF and chemokines. And 26 core components were obtained, including quercetin, luteolin, kaempferol, naringenin, and baicalein;The GO enrichment results showed 224 biological processes, 15 molecular functions and 33 cell components related to inflammation;There were 5 inflammatory signaling pathways in KEGG enrichment results, including TNF signaling pathway, Nod-like receptor signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway and cytokine receptor interaction. Conclusion: Qingfei Paibu Decoction can inhibit cytokine storms by acting on multiple targets and pathways with multiple components and thus treat COVID-19.

Effects of stress of different duration on depression-like behavior and expression of CB1 and GluA1 in medial prefrontal cortex of rats

Objective:To explore the changes of cannabinoid receptor(CB1)and AMPA receptor subunit GluA1 in the medial prefrontal cortex(mPFC)of depression model rats induced by chronic unpredictable mild stress(CUMS).Methods:30 rats were randomly divided into three groups.The three-week model group was given a three-week CUMS model,the four-week model group was given a four-week CUMS model,and the control group was given no treatment.The behavior of rats were detected in each group,and the expression of CB1 and GluA1 protein in synaptosomes in mPFC brain region was detected by Western blot.Results:Compared with the control group,the surcose preference decreased,the feeding latency increased in the novel inhibition feeding test,and the immobility time increased in the forced swimming test in the four-week model group.However,after three weeks of CUMS,there was no obvious change in the behavior of rats compared with the control group,suggesting that four-week model of CUMS was successful.CUMS can reduce the expression level of CB1 and GluA1 protein in synaptosomes of mPFC brain area in four-week model group(P<0.05),but there was no significant difference between three-week model group and control group.Conclusion:Four-week CUMS was more likely to lead to depressive-like behavior in rats,which may be closely related to the expression of CB1 and GluA1 in mPFC.

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

The acidic tumor microenvironment provides an energy source driving malignant tumor progression.Adaptation of cells to an acidic environment leads to the emergence of cancer stem cells.The expression of the vitamin D receptor(VDR)is closely related to the initiation and development of colorectal carcinoma(CRC),but its regulatory mechanism in CRC stem cells is still unclear.Our study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta(PPARD)expression.Overexpression of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in acidosis.The nuclear export signal in VDR was sensitive to acidosis,and VDR was exported from the nucleus.Chromatin immunoprecipitation(ChIP)and assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)analyses showed that VDR transcriptionally repressed SRY-box 2(SOX2)by binding to the vitamin D response elements in the promoter of SOX2,impairing tumor growth and drug resistance.We demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in vivo.These findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling,resulting in a lack of efficacy of vitamin D in antineoplastic process.