Type 2 diabetes mellitus (T2DM) is one of the most risk factors threatening human health. Although genetic and environmental factors contribute to the development of T2DM, gut microbiota has also ...been found to be involved. Gut microbiota-derived metabolites are a key factor in host-microbe crosstalk, and have been revealed to play a central role in the physiology and physiopathology of T2DM. In this review, we provide a timely and comprehensive summary of the microbial metabolites that are protective or causative for T2DM, including some amino acids-derived metabolites, short-chain fatty acids, trimethylamine N-oxide, and bile acids. The mechanisms by which metabolites affect T2DM have been elaborated. Knowing more about these processes will increase our understanding of the causal relationship between gut microbiota and T2DM. Moreover, some frontier therapies that target gut microbes and their metabolites to improve T2DM, including dietary intervention, fecal microbiota transplantation, probiotics, prebiotics or synbiotics intervention, and drugging microbial metabolism, have been critically discussed. This review may provide novel insights for the development of targeted and personalized treatments for T2DM based on gut microbial metabolites. More high-quality clinical trials are needed to accelerate the clinical translation of gut-targeted therapies for T2DM.
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•The key role of gut microbial metabolites in T2DM was comprehensively reviewed.•Graphically displayed the mechanisms by which microbial metabolites affect T2DM.•Targeting gut microbial metabolites provides a new strategy for treating T2DM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Increasing evidence indicates that the ability of cancer cells to convey biological information to recipient cells within the tumor microenvironment (TME) is crucial for tumor progression. ...Microvesicles (MVs) are heterogenous vesicles formed by budding of the cellular membrane, which are secreted in larger amounts by cancer cells than normal cells. Recently, several reports have also disclosed that MVs function as important mediators of intercellular communication between cancerous and stromal cells within the TME, orchestrating complex pathophysiological processes. Chemokines are a family of small inflammatory cytokines that are able to induce chemotaxis in responsive cells. MVs which selective incorporate chemokines as their molecular cargos may play important regulatory roles in oncogenic processes including tumor proliferation, apoptosis, angiogenesis, metastasis, chemoresistance and immunomodulation, et al. Therefore, it is important to explore the association of MVs and chemokines in TME, identify the potential prognostic marker of tumor, and develop more effective treatment strategies. Here we review the relevant literature regarding the role of MVs and chemokines in TME.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. ...Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Senkyunolide I (SI) is a natural phthalide that has drawn increasing interest for its potential as a cardio-cerebral vascular drug candidate. In this paper, the botanical sources, phytochemical ...characteristics, chemical and biological transformations, pharmacological and pharmacokinetic properties, and drug-likeness of SI are reviewed through a comprehensive literature survey, in order to provide support for its further research and applications. In general, SI is mainly distributed in Umbelliferae plants, and it is relatively stable to heat, acid, and oxygen, with good blood-brain barrier (BBB) permeability. Substantial studies have established reliable methods for the isolation, purification, and content determination of SI. Its pharmacological effects include analgesic, anti-inflammatory, antioxidant, anti-thrombotic, anti-tumor effects, alleviating ischemia-reperfusion injury, etc. Pharmacokinetic parameters indicate that its metabolic pathway is mainly phase Ⅱ metabolism, and it is rapidly absorbed in vivo and widely distributed in the kidneys, liver, and lungs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Exploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into ...diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis-mediated aerobic glycolysis pathway.
PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral ...arteries. The present study was performed to determine the function of miR-29b (microRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin β1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE.
The match of rotor and stator blades significantly affects the flow field structure and flow-induced pressure pulsation characteristics inside the pump. In order to study the effects of the rotor and ...stator matching mode on the complex flow field and pressure pulsation of a centrifugal pump with a vaned diffuser, this paper designs three different vaned diffusers (DY5, DY8 and DY9) and uses the DDES (Delayed Detached Eddy Simulation) numerical method combined with structured grids to simulate the unsteady flow phenomena of the model pump under rated conditions. The results show that, under different rotor and stator matching modes, the pressure pulsation spectrum is dominated by the blade passing frequency and its harmonics. The matching mode of the rotor and stator significantly affects the time–frequency domain characteristics of the pressure pulsation inside the pump, and it is observed that the pressure pulsation energy of vaned diffusers with more blades is significantly smaller than that of fewer-blade vaned diffusers in comparison to the energy of the pressure pulsation at the blade passing frequency and within the 10–1500 Hz frequency band. Combined with the distribution characteristics of the complex flow field inside the pump, it can be found that increasing the number of vaned diffuser blades can reduce the energy of flow-induced pressure pulsation, improve the distribution of high-energy vortices in the interaction zone and stabilize the flow inside the centrifugal pump effectively.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pre‐eclampsia is thought to be a systemic disease of maternal endothelial cell dysfunctions. miRNAs regulate various basic biological functions in cells, including stem cells. Mesenchymal stem cells ...exist in almost all tissues and are the key cellular source for tissue repair and regeneration. Our aims are to investigate whether miRNAs regulate MSCs in fetal–maternal interfaces to influence the pathogenesis of pre‐eclampsia. The differential expression of miRNAs in decidua‐derived mesenchymal stem cells of all patients with severe pre‐eclampsia (n = 20) and normal groups (n = 20) was first screened by microarray analysis and validated by quantitative real‐time PCR analysis. The integrated bioinformatics analysis showed that miR‐16 showed the highest number of connections in the miRNA GO network and the miRNA gene network. Moreover, over‐expressed miR‐16 inhibited the proliferation and migration of decidua‐derived mesenchymal stem cells and induced cell‐cycle arrest by targeting cyclin E1. Interestingly, over‐expression of miR‐16 by decidua‐derived mesenchymal stem cells reduced the ability of human umbilical vein endothelial cells to form blood vessels and reduced the migration of trophoblast cells. Furthermore, decidua‐derived mesenchymal stem cell‐expressed endothelial growth factor VEGF‐A was involved in migration of trophoblast cells and human umbilical vein endothelial cells as well as tube and network formation. Importantly, the levels of cyclin E1 and VEGF‐A were negatively correlated with the level of miR‐16 expression in decidua‐derived mesenchymal stem cells from the patients with severe pre‐eclampsia. Together, these data suggest that the alteration of miR‐16 expression in decidua‐derived mesenchymal stem cells may be involved in the development of pre‐eclampsia.
The differential expression of miRNAs in decidua‐derived mesenchymal stem cells from normal and pre‐eclampsia groups was analysed using microarrays and bioinformatics. Over‐expressed miR‐16 inhibited the proliferation and migration of dMSCs and induced cell cycle arrest by targeting CCNE1. miR‐16‐over‐expressed dMSCs reduced the ability of HUVEC to form blood vessels and the migration of the trophoblast cells
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The bearing fault diagnosis based on instantaneous angular speed (IAS) has been developed rapidly. However, it is difficult to identify the weak fault of bearings by using the variable reluctance ...sensor (VRS) as an encoder because of the lack of the high-frequency information in the modulation frequency of IAS. To overcome this shortcoming, a novel method based on the raw signal of the VRS is proposed for bearing diagnosis in this paper. The mechanism of bearing local fault signal response is analyzed by establishing the bearing outer ring fault model and the sensor signal response model, which are explored and verified by the fault simulation experiments. The results show that the gearwheel tooth-pass frequency is modulated by the outer ring fault characteristic frequency, and the defect size can be estimated by the double peaks in the high-frequency band. Moreover, compared with the acceleration signals, the defect size estimations based on the VRS are closer to the actual defect size, which verifies the effectiveness of the proposed method.
Globally, metabolic diseases are becoming a major public health problem. Herbal medicines are medicinal materials or preparations derived from plants and are widely used in the treatment of metabolic ...diseases due to their good curative effects and minimal side effects. Recent studies have shown that gut microbiota plays an important role in the herbal treatment of metabolic diseases. However, the mechanisms involved are still not fully understood. This review provides a timely and comprehensive summary of the interactions between herbal medicines and gut microbiota in metabolic diseases. Mechanisms by which herbal medicines treat metabolic diseases include their effects on the gut microbial composition, the intestinal barrier, inflammation, and microbial metabolites (e.g., short-chain fatty acids and bile acids). Herbal medicines can increase the abundance of beneficial bacteria (e.g.,
and
), reduce the abundance of harmful bacteria (e.g.,
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), protect the intestinal barrier, and alleviate inflammation. In turn, gut microbes can metabolize herbal compounds and thereby increase their bioavailability and bioactivity, in addition to reducing their toxicity. These findings suggest that the therapeutic effects of herbal medicines on metabolic diseases are closely related to their interactions with the gut microbiota. In addition, some methods, and techniques for studying the bidirectional interaction between herbal medicines and gut microbiota are proposed and discussed. The information presented in this review will help with a better understanding of the therapeutic mechanisms of herbal medicines and the key role of gut microbiota.
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