Berberine (BBR) is an effective cholesterol-lowering drug. Although gut microbiota has been implicated in the pharmacological activities of BBR, little evidence exists on the specific species of gut ...microbiota involved in its therapeutic effects, nor on linking gut bacteria to its recognized hypercholesterolemia-alleviating mechanism–upregulation of the low-density lipoprotein receptor (LDLR) in the liver. The present study was performed to identify the specific species of gut microbiota involved in the anti-hyperlipdemic effect of BBR, and interpret its mechanism through linking the gut microbiota and LDLR. The BBR-enriched gut bacterial species were identified by whole genome shotgun sequencing. Pure cultured B. producta was orally administered to C57BL/6 mice to evaluate its anti-hyperlipdemic effect. The LDLR-upregulating effect of B. producta was evaluated both in vitro and in vivo. Orally administration of BBR (200 mg/kg) decreased serum and liver lipid levels in HFD-induced hyperlipidemic mice. Microbiome analysis indicated that Blautia was closely associated with BBR’s lipid-modulating activities. Further analysis revealed that BBR selectively promoted the growth of Blautia producta. Orally treatment of HFD mice with live B. producta reduced obesity and alleviated hyperlipidemia. Notably, the B. producta significantly increased LDLR expression in the liver, and its spent culture supernatant upregulated the LDLR level and promoted LDL uptake by HepG2 cells. Simultaneously, B. producta also linked butyrate-producing and bile salt hydrolase (BSH)-inhibiting effect of BBR. The gut microbiota, especially B. producta, may confers the hypercholesterolemia-alleviating effects of berberine. B. producta represents a novel probiotic that may be used for the treatment of dyslipidemia.
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•A novel and easy one-step method for the synthesis of the aryl- and ferrocenyl-based carbazole derivatives was developed.•The ferrocenyl-based chemosensor displayed reversible ...fluorescent “turn on” response toward Hg2+ in aqueous environment.•The ferrocenyl-based probe could perform naked-eye detection of Cu2+ in aqueous environment.•The ferrocenyl-based chemosensor can be used for determination of Hg2+ in living cells.
Ferrocenyl-based carbazole derivative has been synthesized by a simple one-step reaction and characterized by 1H NMR, 13C NMR, ESI-MS and X-ray analysis. Meanwhile, The newly synthesized receptor 1 displayed reversible fluorescent “turn on” response toward Hg2+ with good quantum yield in aqueous environment. The color of the solution containing receptor 1 changed from colorless to yellow upon the addition of Cu2+ ions. Therefore, receptor 1 can act as a fluorescent chemosensor for Hg2+ and a naked-eye probe for Cu2+ in aqueous environment. Quantification of absorption titration analysis shows that the detection limit was 6.15×10−7M for 1-Cu2+ and 3.16×10−7M for 1-Hg2+, respectively. Finally, the receptor 1 has been used successfully for determination of Hg2+ in living cells.
This work performed a large scale assessment for organophosphorus pesticides (OPPs) degradation activity of 121
(
.)
strains. Six
strains (P9, IMAU80110, IMAU40100, IMAU10585, IMAU10209, and ...IMAU80070) were found to possess high capacity of degrading three commonly used OPPs, namely dimethoate, phorate, and omethoate; and they were selected for more detailed characterization. Moreover, the three OPPs were mainly detected in the culture supernatants but not in the cell extracts, further confirming that the OPPs were degraded rather than absorbed by the cells. Among the six selected strains, P9 was most tolerant to gastrointestinal juices and bile. We thus used ultra-high performance liquid chromatography electron spray ionization coupled with time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) to generate the metabolomic profiles of the strain P9 growing in MRS medium with and without containing phorate. By using orthogonal partial least squares discriminant analysis, we identified some potential phorate-derived degradative products. This work has identified novel lactic acid bacteria resources for application in pesticide degradation. Our results also shed light on the phorate degradation mechanism by
P9.
Porcine epidemic diarrhea virus (PEDV) is deadly for suckling piglets and is a significant threat to most pig farms. Alpiniae oxyphyllae fructus polysaccharide 3 (AOFP3) shows antiviral activity ...against PEDV. However, the anti-PEDV mechanism of AOFP3 is unknown. Entering the host cell is important for viral infection, and many drugs play antiviral roles by inhibiting this process. To understand the antiviral mechanism of AOFP3 against PEDV, the effect of AOFP3 on PEDV entering IPEC-J2 cells was investigated in the present study. Real-time PCR and immunofluorescence were used to study the effect of AOFP3 on PEDV binding and penetrating IPEC-J2 cells. The effect of PEDV on AOFP3 attachment to IPEC-J2 cells was also investigated. Afterward, the effect of AOFP3 on PEDV spike (S) protein binding to porcine aminopeptidase was tested by using coimmunoprecipitation, and the effect of AOFP3 on the cholesterol level of IPEC-J2 cells was detected. The results showed that AOFP3 competitively inhibited PEDV adsorption on IPEC-J2 cells by blocking PEDV S protein binding to porcine aminopeptidase in IPEC-J2 cells. Furthermore, AOFP3 decreased PEDV penetration into host cells by decreasing the cholesterol level in IPEC-J2 cells.
•AOFP3 inhibits PEDV entering IPEC-J2 cell.•AOFP3 competitively inhibited PEDV adsorbing on IPEC-J2 cells.•AOFP3 blocked PEDV S protein binding to porcine aminopeptidase of IPEC-J2 cell.•AOFP3 decreased the cholesterol level in IPEC-J2 cell.
Increasing evidence indicates that microRNAs (miRNAs) play critical roles in osteosarcoma (OS) occurrence and development. MicroRNA-874 (miR-874) has proven to be dysregulated in several human ...cancers. However, the biological function and underlying molecular mechanism of miR-874 in OS remain unclear. In this study, we aimed to investigate the biological role and potential mechanism of miR-874 in OS. Here, we found that miR-874 expression was significantly decreased in OS cell lines and tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and its expression was correlated with tumor-node-metastasis (TNM) stage, tumor size, and lymph node metastasis (all P < 0.01). Functional study revealed that overexpression of miR-874 in OS cells could remarkably inhibit proliferation, migration, and invasion and induce cell apoptosis. In addition, E2F transcription factor 3 (E2F3) was confirmed as a target of miR-874 in OS cells. E2F3 mRNA expression was upregulated and was inversely correlated with the level of miR-874 in OS tissues. Importantly, downregulation of E2F3 mimicked the effect of overexpression miR-874 in OS cells, and E2F3 overexpression partially attenuated the tumor-suppressive effects of miR-874 in OS cells. Taken together, these findings suggested that miR-874 might suppress the growth and metastasis of OS cells partially by targeting E2F3.
Porcine epidemic diarrhea virus (PEDV) is a deadly pathogen that still plagues suckling piglets. However, there is still no anti-PEDV drug available in clinics. To develop potential anti-PEDV drugs, ...the antiviral activity of Alpiniae oxyphyllae fructus polysaccharide 3 (AOFP3) against PEDV infection in IPEC-J2 cells were assessed in our present study. The structural characterization of AOFP3 was studied by using HPAEC, GC–MS, FT-IR and NMR techniques. At the same time, the anti-PEDV activity of AOFP3 was investigated by performing RT-qPCR, Western blot and immunofluorescence assays. The results showed that AOFP3 (44.4 kDa) was composed of glucose and galacturonic acid at a molar ratio of 77.54:22.46 and consisted of →4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, T-α-D-Glcp-(1→ and →4)-α-D-GalAp-(1→. AOFP3 significantly decreased PEDV titer in IPEC-J2 cells and prevented cellular damage of IPEC-J2 cells caused by PEDV infection. Furthermore, AOFP3 showed an antioxidative activity in inhibiting PEDV reproduction. Therefore, AOFP3 was expected to be a material of anti-PEDV drug.
•Structure of Alpiniae oxyphyllae fructus polysaccharides 3 was first reported.•Antiviral activity of AOFP3 against PEDV was first studied.•AOFP3 showed anti-oxidative ability in inhibiting PEDV reproduction.•Anti-oxidative ability of AOFP3 played a vital role in its inhibiting PEDV effect.
This study aimed to characterize the structural features of a novel water-soluble polysaccharide (AOHP) extracted from
Hance and to verify its regulating effect on mouse immunity. Cellulose DEAE-52 ...and Sephadex G-100 columns were used to obtain purified AOHP. Techniques including NMR, methylation, monosaccharide composition, FT-IR, and molecular weight determination were applied to investigate the physicochemical properties and structural characterization of AOHP. Then, the influence of AOHP on mice was studied. After oral administration of AOHP, organ indexes, serum biochemistry indexes, and cytokines in the spleens of the mice were analysed. The results showed that AOHP was composed of T-α-D-Glc
, (1,4)-α-D-Glc
and (1,4,6)-α-D-Glc
with a number-average molecular weight of 26.0 kDa and a weight-average molecular weight of 52.8 kDa. Additionally, the innate immune statuses of the mice were improved by treatment with AOHP, while no obvious damage was identified. To conclude, the immunomodulatory activity and biological safety make AOHP a viable candidate as an ingredient for healthcare drugs.
The aim of this study is to explore the characterization of Amomum longiligulare T.L. Wu fruits polysaccharide (ALP) and their immune enhancement effects. Two homogeneous polysaccharides (ALP1 and ...ALP2) were isolated from the fruits. The structural characterization results showed that ALP1 (26.10 kDa) and ALP2 (64.10 kDa) were both mainly composed of glucose. Furthermore, ALP1 was consisted of (1,2)-α-D-Glcp, (1,2,3)-α-D-Glcp and T-α-D-Glcp, while ALP2 was consisted of T-α-D-Glcp, (1,3)-α-D-Glcp and (1,3,6)-α-D-Glcp. Afterwards, the immune enhancement effects of two polysaccharides were evaluated by determining their effects on immunogenicities of infectious bursal disease virus (IBDV) VP2 protein. Chickens were immunized with IBDV VP2 protein accompanied with ALP1/ALP2. And the results indicated both ALP1 and ALP2 promoted the weights and bursa of fabricius indexes of chickens. In addition, both two polysaccharides increased specific IBDV antibody levels, while ALP1 possessed higher immune enhancement ability and was expected to be an adjuvant for IBDV VP2 protein.
•Polysaccharides from Amomum longiligulare T.L. Wu dry fruits were first reported.•Two polysaccharides (ALP1 and ALP2) were obtained from the dry fruits.•The structural characterizations of ALP1 and ALP2 were first reported.•Immune enhancement abilities of ALP1 and ALP2 were first reported.•Both of ALP1 and ALP2 showed adjuvant effects on IBDV VP2 protein.
RBM5 (RNA-binding motif protein 5), a nuclear RNA binding protein, is known to trigger apoptosis and induce cell cycle arrest by regulating the activity of the tumor suppressor protein p53. However, ...its expression and function in spinal cord injury (SCI) are still unknown. To investigate whether RBM5 is involved in central nervous system injury and repair, we performed an acute SCI model in adult rats in this study. Our results showed RBM5 was unregulated significantly after SCI, which was accompanied with an increase in the levels of apoptotic proteins such as p53, Bax, and active caspase-3. Immunofluorescent labeling also showed that traumatic SCI induced RBM5 location changes and co-localization with active caspase-3 in neurons. To further probe the role of RBM5, a neuronal cell line PC12 was employed to establish an apoptotic model. Knockdown of RBM5 apparently decreased the level of p53 as well as active caspase-3, demonstrating its pro-apoptotic role in neurons by regulating expressions of p53 and caspase-3. Taken together, our findings indicate that RBM5 promotes neuronal apoptosis through modulating p53 signaling pathway following SCI.
Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered ...significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-β-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-β-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair.
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