Objective To analyze the diversity and composition of gut microbiota in individuals with circadian rhythm disruption and their correlation with cognition.Methods Night shift workers and regular shift workers were subjected from our hospital during August 2022 and October 2024.The participants with circadian rhythm disorders were assigned into an experimental group(n=24),and those with normal circadian rhythms were into a control group(n=24).Their height,weight,age,gender,body mass index(BMI)and fresh fecal samples were collected,and Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were used to evaluate their mental status.Metagenomics,Alpha and Beta diversity analyses,Linear Discriminant Analysis Effect Size(LEfSe),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to investigate the diversity and function characteristics of gut microbiota in the participants.Results There were no statistical differences between the 2 groups in baseline data,such as height,weight,gender,age,and BMI(P>0.05).Alpha diversity analysis indicated that no statistical differences were observed in the ACE,Chao1,Shannon,or Simpson indices between the 2 groups,while beta diversity analysis revealed significant differences(P<0.01),suggesting different structure of gut microbiota between them.In the experimental group,the abundance of Faecalibacterium prausnitzii and Agathobacter rectalis was decreased,while that of Escherichia coli and Phocaeicola vulgaratus was increased,with significant differences when compared with the control group(P<0.05).Additionally,KEGG functional analysis showed that the experimental group had obviously higher expression levels in Th17 cell differentiation and the IL-17 signaling pathway than the control group(P<0.05).Agathobacter rectalis and Faecalibacterium prausnitzii were positively correlated with MoCA score and MMSE score(P<0.05,P<0.01).Agathobacter rectalis was negatively correlated with the IL-17 signaling pathway and Th17 cell differentiation.Conclusion Individuals with circadian rhythm disorders have significant changes in the structure and function of gut microbiota when compared to those with normal circadian rhythms.Agathobacter rectalis may be involved in the regulation of the IL-17 signaling pathway and differentiation of Th17 cells,thereby possibly impacting the increases of cognitive score related to circadian rhythm disorders.

Objective To explore the underlying mechanisms by which time-restricted feeding(TRF)attenuates dextran sodium sulfate(DSS)-induced colitis in mice via modulation of regenerating islet-derived protein 3 gamma(Reg3γ)expression and gut microbiota.Methods Six-week-old C57BL/6 mice were stratified by body weight and randomized into ad libitum feeding(AL)and TRF groups(n=7).The AL mice were given unrestricted food access,whereas the TRF mice were allowed feeding only during 00:00 and 08:00 daily,for totally 4 weeks.Mouse colitis model was induced at the fourth week by adding 2.5%dextran sodium sulfate(DSS)in drinking water for 6 d.Disease severity and the effects of TRF were assessed with disease activity index(DAI)scoring,colon length measurement,HE staining and histopathological scoring,and mRNA expression levels of regenerating islet-derived 3 gamma(Reg3g)and inflammatory cytokines in colonic tissues.Another 14 mice were randomized into AL plus antibiotic cocktail(AL+ABX)and TRF plus antibiotic cocktail(TRF+ABX)groups,with 7 animals in each group.ABX was administered to deplete gut microbiota and evaluate the microbiota dependence of TRF in attenuating colitis.Fecal samples from AL and TRF mice were analyzed by 16S ribosomal RNA sequencing(16S rRNA-seq),and serum lipopolysaccharide(LPS)level was measured.The colonic epithelial cells were collected for RNA-seq.Results After modeling,the AL mice exhibited typical colitis symptoms,such as weight loss,diarrhea,and hematochezia.TRF intervention significantly attenuated these above symptoms,with lower DAI scores from day 4 post-modeling(P<0.001),reduced colon shortening(P<0.01),preserved tissue architecture,and decreased inflammation.RT-qPCR analysis showed that TRF down-regulated colonic mRNA expression levels of Reg3g and pro-inflammatory cytokines(IL-1 β,IL-6,TNF-α)(P<0.05)while up-regulated that of anti-inflammatory factor IL-10(P<0.000 1)when compared with the corresponding levels in AL mice.ABX treatment led no significant differences between the AL+ABX and TRF+ABX groups in term of DAI score,colon length,or histopathology.Obviously down-regulated Reg3g was observed in the TRF+ABX group than the AL+ABX group(P<0.05),whereas L-1β,IL-6,TNF-α and IL-10 showed no notable changes.16S rRNA-seq revealed that TRF markedly reshaped gut microbiota composition,with increased Gram-positive bacterial abundance,reduced Gram-negative bacteria,with concomitant lower serum LPS level(P<0.001).RNA-seq also indicated significant suppression of NF-κB and other inflammation-related signaling pathways in the TRF group.Conclusion TRF attenuates DSS-induced colitis in mice by downr-egulating Reg3γ expression,reshaping gut microbiota,and reducing serum LPS level,and thereby suppressing NF-κB-mediated inflammatory signaling pathways.

Objective: To explore the anti-proliferation and apoptosis-inducing effects of decitabine combined with paclitaxel on paclitaxel-resistant MCF-7 cells. Methods:Cell counting kit-8 (CCK-8) assays were used to determine the proliferation inhibition of drugs at different concentrations in 24, 48 and 72h. The group was treated with decitabine, paclitaxel and the combination of the two drugs, respectively. The cell apoptosis rate was determined by flow cytometry after the treatment with the drugs at different concentra-tions in 48h. Results:The results of CCK-8 showed the combination group significantly inhibited the cell proliferation when compared with the single drug use group(P<0. 05), and the anti-proliferation value was in a dose-dependent manner in all groups. The apopto-sis values after the treatment with decitabine, paclitaxel and the combination in 48h was(20. 4 ± 1. 98)%,(21. 8 ± 3. 34)% and(70. 8 ± 8. 23)%,respectively. Conclusion:The proliferation inhibition and apoptosis induction are both increased significantly in the com-bination group. Synergistic effect of decitabine and paclitaxel is found in multidrug resistant breast cancer cell line MCF-7 in vitro.