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Background: Destructions in the intestinal ecosystem are implicated with changes in slow transit constipation (STC), which is a kind of intractable constipation characterized by colonic motility disorder. However, the role of gut microbes in the pathophysiology of STC and deep relationships between the gut microbiota and fecal metabolites have not been understood. Methods: Fecal samples of 30 patients suffering from STC and 30 healthy subjects were performed 16S rDNA amplicon sequencing and metabolomics to obtain evidence of distinct phenotypes of fecal microorganisms and metabolites. The relationship between fecal microorganisms, metabolites, and clinical manifestations was explored according to the correlation analysis. Findings: The α-diversity of the STC group was changed to a certain degree, and the β-diversity was significantly different, which indicated that the composition of the gut microbiota of STC patients was inconsistent with healthy subjects. Different metabolites between STC and control group were involved in the process of bile acids and lipid metabolism. The colon histomorphology of STC patients was significantly disrupted, and TGR5 and FXR were significantly down-regulated. The differences in metabolites were related to changes in the abundance of specific bacteria and patients' intestinal dysfunction. Analysis of the fecal genomics and metabolomics enabled separation of the STC from controls based on random forest model prediction (STC vs control (14 gut microbiota and metabolite biomarker s) – Sensitivity: 1, Specificity: 0.877) Interpretation: Abnorma fecal microorganisms and metabolites related to bile acid metabolism is characteristic of STC, which provided a perspective for the diagnosis and intervention of STC. Funding: This work was supported by the National Key R&D Program of China (2018YFC1706506), Foundation of Tianjin Municipal Health Commission (No. ZC20097), Foundation of Tianjin Union Medical Center (No. 2020YJ017, 2017YJZD005), and National Natural Science Foundation of China (No. 82174374). Declaration of Interest: All authors declare that they do not have any competing interests. Ethical Approval: This study was conducted in Tianjin Union Medical Center, Tianjin, China. The samples and clinical data used in this study were obtained with approval of institutional review boards and under conditions of informed consent (China Clinical Trial Registry, ChiCTR2000033227).

There is increasing evidence showing that inflammation is associated with depression in humans. Hesperidin, a natural bioflavonoid, has performed excellent effects on depression. The aim of this research was to investigate the therapeutic effect of hesperidin on chronic unpredictable mild stress (CUMS)-induced rats. The sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT) were performed to measure the depression-related symptoms. The enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the prefrontal cortex (PFC) of rats and cellular supernatant. PCR and Western blot were used to monitor the differences of NLRP3, caspase-1, ASC activation in the levels of genes and proteins in the PFC of rats and microglia. The activation of microglia was determined using immunofluorescence staining and flow cytometry assay. Our results show that hesperidin treatment significantly relieved depressive like behaviors in CUMS rats. In addition, hesperidin decreased the expression levels of IL-1β, IL-6, TNF-α, NLRP3, caspase-1, and ASC in the PFC and microglia. This study investigated that hesperidin treatment ameliorated CUMS-induced depression by suppressing microglia and inflammation.

This study tested the hypothesis that heparanase (HPSE) is related to tumor metastasis and curcumin (CCM) inhibits tumor metastasis by down-regulating HPSE expression. MTT, Transwell assays, and RT-PCR were used to study the effects of CCM on the migration and invasion of CT26 cells and the expression of HPSE. CT26 cells were transfected with lentivirus to establish HPSE-overexpressing cells (OE) and corresponding negative control cells (NC). Signal pathways involved in down-regulating the expression of HPSE and inhibiting the migration and invasion of CT26 cells by CCM were screened by the liquid crystal chip. HPSE promoted CT26 cells migration and invasion, and CCM inhibited the proliferation and metastasis of CT26 cells. The results of RT-PCR indicated that CCM down-regulated HPSE expression. Liquid phase microarray showed that CCM inhibited the phosphorylation of P38 and STAT5 in CT26 cells and NC cells. In contrast, the inhibitory function of CCM was markedly enhanced when HPSE was overexpressed (P < 0.05). In short, HPSE is closely related to metastasis of colon cancer cells. CCM inhibits colon cancer cell migration and invasion by inhibiting HPSE expression, which may be related to P38 MAPK and JAK/STAT5 signal pathways.

Today, cancers pose a major public health burden. Although a myriad of cancer treatments are available, only a few have achieved clinical efficacy. This is partly attributed to cancers capability to evade host immunity by converting dendritic cells (DCs) from potent stimulators to negative modulators of immunity. Dendritic cell-based immunotherapy attempts to resolve this problem by manipulating the functional characteristics of DCs. Plant-derived polysaccharides (PDPs) can stimulate the maturation of DCs conferring on them the capacity to present internalised tumorigenic antigens to naïve T cells and subsequently priming T cells to eliminate tumours. PDPs have been used as immune modulators and later as anti-cancer agents by Traditional Chinese Medicine practitioners for centuries. They are abundant in nature and form a large group of heterogeneous though structurally related macromolecules that exhibit diverse immunological properties. They can induce antigen pulsed DCs to acquire functional characteristics in vitro which can subsequently be re-introduced into cancer patients. They can also be used as adjuvants in DC-based vaccines or independently for their intrinsic anti-tumour activities. Clinically, some in vitro generated DCs have been shown to be both safe and immunogenic although their clinical application is limited in part by unsatisfactory functional maturation as well as impaired migration to draining lymph nodes where T cells reside. We review the relative potencies of individual PDPs to induce both phenotypic and functional maturation in DCs, their relative abilities to activate anti-cancer immunity, the possible mechanisms by which they act and also the challenges surrounding their clinical application.

Delvestidine (DLTD) is a monomeric compound isolated from Aconitum leucostomum Worosch, a widely used medicine for local treatment of rheumatoid arthritis (RA). Studies have shown that Aconitum leucostomum Worosch. can inhibit maturation of bone marrow-derived dendritic cells (BMDCs). Further, microRNAs (miRNAs) have regulatory effects on DC maturity and function. However, the mechanism underlying DLTD effects on DC maturity and RA remains to be elucidated. This study investigated whether DLTD-mediated inhibition of DC maturation is regulated by miRNAs. LPS-induced mature BMDCs were treated with DLTD for 48 h. CD80 and CD86 expression on BMDCs was detected by flow cytometry, and levels of inflammatory factors IL-6, IL-23, IL-1β, and TNF-α were detected by ELISA and PCR. Further, gene expression and miRNA expression profiles were investigated by bioinformatics analysis and verified by PCR. DLTD was found to inhibit CD80 and CD86 expression on the surface of BMDCs and secretion of inflammatory factors IL-6, IL-23, IL-1β, and TNF-α. In total, 54 differentially expressed miRNAs were detected, including 29 up-regulated and 25 down-regulated miRNAs after DLTD treatment. Analysis of biological information revealed that the differentially expressed target genes mainly regulated biological processes, including cell differentiation, cell cycle, and protein kinase complexes. Additionally, miR-511-3p downstream targets Calcr, Fzd10, and Eps8, were closely related to BMDCs maturation. DLTD may induce BMDCs maturity through regulation of miRNAs that affect Calcr, Fzd10, and Eps8 gene signals.

Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode, and Berberis, has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.