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1.
Microb Cell Fact ; 22(1): 113, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37312096

RESUMO

BACKGROUND: Compared with steviol glycosides, the taste of glucosylated steviol glycosides is better and more similar to that of sucrose. At present, cyclodextrin glucanotransferase (CGTase) is primarily used to catalyze the conversion of steviol glycosides to glucosylated steviol glycosides, with soluble starch serving as a glycosyl donor. The main disadvantages of enzymatic transglycosylation are the limited number of enzymes available, the low conversion rates that result in low yields, and the lack of selectivity in the degree of glycosylation of the products. In order to fill these gaps, the proteome of Alkalihalobacillus oshimensis (also named Bacillus oshimensis) was used for mining novel CGTases. RESULTS: Here, CGTase-15, a novel ß-CGTase with a wide pH adaptation range, was identified and characterized. The catalyzed product of CGTase-15 tasted better than that of the commercial enzyme (Toruzyme® 3.0 L). In addition, two amino acid sites, Y199 and G265, which play important roles in the conversion of steviol glycosides to glucosylated steviol glycosides were identified by site-directed mutagenesis. Compared with CGTase-15, CGTase-15-Y199F mutant significantly increased the conversion rate of rebaudioside A (RA) to glucosylated steviol glycosides. Compared with CGTase-15, the content of short-chain glycosylated steviol glycosides catalyzed by CGTase-15-G265A mutant was significantly increased. Moreover, the function of Y199 and G265 was verified in other CGTases. The above mutation pattern has also been applied to CGTase-13 (a CGTase discovered by our laboratory with great potential in the production of glycosylated steviol glycosides), confirming that the catalytic product of CGTase-13-Y189F/G255A mutant has a better taste than that of CGTase-13. CONCLUSIONS: This is the first report on the improvement of the sensory profiles of glycosylated steviol glycosides through site-directed mutagenesis of CGTase, which is significant for the production of glycosylated steviol glycosides.


Assuntos
Glucosídeos , Glicosilação
2.
Nanotechnology ; 34(45)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37524081

RESUMO

Blue phase liquid crystals (BPLCs) have significant potential in the field of liquid crystal displays (LCDs) and are proposed as potential next-generation of LCDs candidates. However, BPLCs do not emit light directly and need an extra backlight device. As a result, the blue phase liquid crystal display retains the disadvantages of low brightness and low energy efficiency, which remarkably limit its application. Recently, as a kind of novel fluorescent carbon nanomaterials, carbon dots (CDs) have captured considerable attention because of their excellent optical properties. Here, CDs were directly synthesized by a simple solvothermal method and introduced into BPLCs. By combining the excellent optical properties of CDs with the blue phase liquid crystal system, the photoluminescent blue phase liquid crystals (CDs-BPLCs) with self-photoluminescence are prepared. Meanwhile, the stability of BPLCs can be improved by CDs. Such CDs-BPLCs have enormous potential in the development of novel energy-saving display devices.

3.
Molecules ; 28(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36770912

RESUMO

The enzymatic transglycosylation of steviol glycosides can improve the edulcorant quality of steviol glycosides. Cyclodextrin glucanotransferase (CGTase) is one of the most popular glucanotransferases applied in this reaction. Herein, the CGTase-producing strain Alkalihalobacillus oshimensis CGMCC 23164 was isolated from Stevia planting soil. Using mass spectrometry-based secretome profiling, a high-efficiency CGTase that converted steviol glycosides to glucosylated steviol glycosides was identified and termed CGTase-13. CGTase-13 demonstrated optimal transglycosylation activity with 10 g/L steviol glycoside and 50 g/L soluble starch as substrates at <40 °C. Under the above conditions, the conversion rate of stevioside and rebaudioside A, two main components of steviol glycosides, reached 86.1% and 90.8%, respectively. To the best of our knowledge, this is the highest conversion rate reported to date. Compared with Toruzyme® 3.0 L, the commonly used commercial enzyme blends, glucosylated steviol glycosides produced using CGTase-13 exhibited weaker astringency and unpleasant taste, faster sweetness onset, and stronger sweetness intensity. Thus, CGTase provides a novel option for producing high-quality glucosylated steviol glycoside products and has great potential for industrial applications.


Assuntos
Diterpenos do Tipo Caurano , Stevia , Glucosídeos , Aditivos Alimentares , Glicosídeos
4.
Ann Surg ; 275(1): e99-e106, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32187028

RESUMO

OBJECTIVE: To assess the association between preoperative opioid exposure and readmissions following common surgery. SUMMARY BACKGROUND DATA: Preoperative opioid use is common, but its effect on opioid-related, pain-related, respiratory-related, and all-cause readmissions following surgery is unknown. METHODS: We analyzed claims data from a 20% national Medicare sample of patients ages ≥ 65 with Medicare Part D claims undergoing surgery between January 1, 2009 and November 30, 2016. We grouped patients by the dose, duration, recency, and continuity of preoperative opioid prescription fills. We used logistic regression to examine the association between prior opioid exposure and 30-day readmissions, adjusted for patient risk factors and procedure type. RESULTS: Of 373,991 patients, 168,579 (45%) filled a preoperative opioid prescription within 12 months of surgery, ranging from minimal to chronic high use. Preoperative opioid exposure was associated with higher rate of opioid-related readmissions, compared with naive patients [low: aOR=1.63, 95% CI=1.26-2.12; high: aOR=3.70, 95% CI=2.71-5.04]. Preoperative opioid exposure was also associated with higher risk of pain-related readmissions [low: aOR=1.27, 95% CI=1.23-1.32; high: aOR=1.62, 95% CI=1.53-1.71] and respiratory-related readmissions [low: aOR=1.10, 95% CI=1.05-1.16; high: aOR=1.44, 95% CI=1.34-1.55]. Low, moderate, and high chronic preoperative opioid exposures were predictive of all-cause readmissions (low: OR 1.09, 95% CI: 1.06-1.12); high: OR 1.23, 95% CI: 1.18-1.29). CONCLUSIONS: Higher levels of preoperative opioid exposure are associated with increased risk of readmissions after surgery. These findings emphasize the importance of screening patients for preoperative opioid exposure and creating risk mitigation strategies for patients.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Readmissão do Paciente/tendências , Cuidados Pré-Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Dor Pós-Operatória/epidemiologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
5.
World J Microbiol Biotechnol ; 39(2): 43, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36520300

RESUMO

Bifidobacterium pseudocatenulatum LI09 could prevent D-galactosamine-induced liver injury. Our previous study has preliminarily determined that different intestinal microbiota profiles existed in the LI09-treated rats. Due to the sample size limitation, some subsequent analyses could not be achieved. In the current study, we conducted different experiments and bioinformatic analyses to characterise the distinct intestinal bacterial microbiota profiles in the LI09-treated rats with liver injury (i.e., LI09 group). Partition around medoids clustering analysis determined two intestinal microbiota profiles (i.e., Cluster_1_LI09 and Cluster_2_LI09) in LI09 group. Compared with Cluster_2_LI09, Cluster_1_LI09 group was determined at less dysbiotic microbial status and with lower level of liver injury. The two microbiota profiles were determined with distinct representative amplicon sequence variants (ASVs), among which, ASV1_Akkermansia and ASV3_Bacteroides were most associated with Cluster_1_LI09 and Cluster_2_LI09, respectively. Multiple representative phylotypes in Cluster_1_LI09 negatively correlating with liver function variables were assigned to Parabacteroides, suggesting Parabacteroides could benefit LI09 on modulating the liver function. In addition, ASV310_Lachnospiraceae, ASV501_Muribaculaceae and ASV484_Lachnospiraceae were determined as network gatekeepers in Cluster_1_LI09 network. The relevant results suggest that some intestinal bacteria could assist LI09 in lowering the intestinal microbial dysbiosis in the rats with liver injury, and their clinical application deserves further investigation.


Assuntos
Bifidobacterium pseudocatenulatum , Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Microbiota , Ratos , Animais , Galactosamina/toxicidade , Fígado/microbiologia , Disbiose , Bactérias
6.
Can J Infect Dis Med Microbiol ; 2021: 9756586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211619

RESUMO

[This corrects the article DOI: 10.1155/2021/6632266.].

7.
Can J Infect Dis Med Microbiol ; 2021: 6632266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488888

RESUMO

In recent years, the relationship between intestinal microbiota (IM) and the pathogenesis of type 2 diabetes mellitus (T2DM) has attracted much attention. The beneficial effects of IM on the metabolic phenotype of the host are often considered to be mediated by short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate, the small-molecule metabolites derived from microbial fermentation of indigestible carbohydrates. SCFAs not only have an essential role in intestinal health but might also enter the systemic circulation as signaling molecules affecting the host's metabolism. In this review, we summarize the effects of SCFAs on glucose homeostasis and energy homeostasis and the mechanism through which SCFAs regulate the function of metabolically active organs (brain, liver, adipose tissue, skeletal muscle, and pancreas) and discuss the potential role of modulation of SCFAs as a therapeutic method for T2DM.

8.
Am J Transplant ; 20(3): 701-713, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31654553

RESUMO

Tacrolimus (TAC), the mainstay of maintenance immunosuppressive agents, plays a crucial role in new-onset diabetes after transplant (NODAT). Previous studies investigating the diabetogenic effects of TAC have focused on the ß cells of islets. In this study, we found that TAC contributed to NODAT through directly affecting hepatic metabolic homeostasis. In mice, TAC-induced hypoglycemia rather than hyperglycemia during starvation via suppressing gluconeogenetic genes, suggesting the limitation of fasting blood glucose in the diagnosis of NODAT. In addition, TAC caused hepatic insulin resistance and triglyceride accumulation through insulin receptor substrate (IRS)2/AKT and sterol regulatory element binding protein (SREBP1) signaling, respectively. Furthermore, we found a pivotal role of CREB-regulated transcription coactivator 2 (CRTC2) in TAC-induced metabolic disorders. The restoration of hepatic CRTC2 alleviated the metabolic disorders through its downstream molecules (eg, PCK1, IRS2, and SREBP1). Consistent with the findings from bench, low CRTC2 expression in graft hepatocytes was an independent risk factor for NODAT (odds ratio = 2.692, P = .023, n = 135). Integrating grafts' CRTC2 score into the clinical model could significantly increase the predictive capacity (areas under the receiver operating characteristic curve: 0.71 vs 0.79, P = .048). Taken together, in addition to its impact on pancreatic cells, TAC induces "hematogenous diabetes" via CRTC2 signaling. Liver-targeted management may be of help to prevent or heal TAC-associated diabetes.


Assuntos
Imunossupressores , Tacrolimo , Animais , Glucose , Homeostase , Fígado , Camundongos , Tacrolimo/efeitos adversos
9.
Environ Microbiol ; 22(1): 76-90, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31599077

RESUMO

Clearance and adaptation to reactive oxygen species (ROS) are crucial for cell survival. As in other eukaryotes, the Neurospora catalases are the main enzymes responsible for ROS clearance and their expression are tightly regulated by the growth and environmental conditions. The RNA polymerase II carboxyl terminal domain (RNAPII CTD) kinase complex (CTK complex) is known as a positive elongation factor for many inducible genes by releasing paused RNAPII near the transcription start site and promoting transcription elongation. However, here we show that deletion of CTK complex components in Neurospora led to high CAT-3 expression level and resistance to H2 O2 -induced ROS stress. The catalytic activity of CTK-1 is required for such a response. On the other hand, CTK-1 overexpression led to decreased expression of CAT-3. ChIP assays shows that CTK-1 phosphorylates the RNAPII CTD at Ser2 residues in the cat-3 ORF region during transcription elongation and deletion of CTK-1 led to dramatic decreases of SET-2 recruitment and H3K36me3 modification. As a result, histones at the cat-3 locus become hyperacetylated to promote its transcription. Together, these results demonstrate that the CTK complex is negative regulator of cat-3 expression by affecting its chromatin structure.


Assuntos
Catalase/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Neurospora/enzimologia , Neurospora/genética , Fosfotransferases/metabolismo , Cromatina/metabolismo , Histonas/metabolismo , Fosforilação , Sítio de Iniciação de Transcrição
10.
Brain Behav Immun ; 80: 633-643, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063846

RESUMO

OBJECTIVE: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated. METHODS: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients. RESULTS: The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698). CONCLUSIONS: Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.


Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Microbioma Gastrointestinal/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/microbiologia , Amnésia/diagnóstico , Amnésia/microbiologia , Área Sob a Curva , Povo Asiático , Biomarcadores , Encéfalo/fisiopatologia , China , Cognição , Disfunção Cognitiva/genética , Disfunção Cognitiva/microbiologia , Estudos de Coortes , Estudos Transversais , Fezes/microbiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , RNA Ribossômico 16S/genética
11.
Appl Microbiol Biotechnol ; 103(23-24): 9465-9477, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701197

RESUMO

Discovering sugar metabolism genes is of great interest for lignocellulosic biorefinery. Xylose isomerases (XIs) were commonly screened from metagenomes derived from bovine rumen, soil, and other sources. However, so far, XIs and other sugar-utilizing enzymes have not been discovered from fecal metagenomes. In this study, environmental DNA from the fecal samples collected from yellow cattle (Bos taurus) was sequenced and analyzed. In the whole 14.26 Gbp clean data, 92 putative XIs were annotated. After sequence analysis, seven putative XIs were heterologously expressed in Escherichia coli and characterized in vitro. The XIs 58444 and 58960 purified from E. coli exhibited 22% higher enzyme activity when compared with that of the native E. coli XI. The XI 58444, similar to the XI from Lachnospira multipara, exhibited a relatively stable activity profile across different pH conditions. Four XIs were further investigated in budding yeast Saccharomyces cerevisiae after codon optimization. Overexpression of the codon-optimized 58444 enabled S. cerevisiae to utilize 6.4 g/L xylose after 96 h without any other genetic manipulations, which is 56% higher than the control yeast strain overexpressing an optimized XI gene xylA*3 selected by three rounds of mutation. Our results provide evidence that a bovine fecal metagenome is a novel and valuable source of XIs and other industrial enzymes for biotechnology applications.


Assuntos
Aldose-Cetose Isomerases/genética , Aldose-Cetose Isomerases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Microbioma Gastrointestinal , Animais , Biotecnologia , Bovinos , Códon , Escherichia coli/genética , Fezes/microbiologia , Fermentação , Metagenoma , Mutação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Análise de Sequência de DNA
12.
Microb Cell Fact ; 17(1): 58, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29631591

RESUMO

BACKGROUND: Saccharomyces cerevisiae is widely studied for production of biofuels and biochemicals. To improve production efficiency under industrially relevant conditions, coordinated expression of multiple genes by manipulating promoter strengths is an efficient approach. It is known that gene expression is highly dependent on the practically used environmental conditions and is subject to dynamic changes. Therefore, investigating promoter activities of S. cerevisiae under different culture conditions in different time points, especially under stressful conditions is of great importance. RESULTS: In this study, the activities of various promoters in S. cerevisiae under stressful conditions and in the presence of xylose were characterized using yeast enhanced green fluorescent protein (yEGFP) as a reporter. The stresses include toxic levels of acetic acid and furfural, and high temperature, which are related to fermentation of lignocellulosic hydrolysates. In addition to investigating eight native promoters, the synthetic hybrid promoter P3xC-TEF1 was also evaluated. The results revealed that P TDH3 and the synthetic promoter P3xC-TEF1 showed the highest strengths under almost all the conditions. Importantly, these two promoters also exhibited high stabilities throughout the cultivation. However, the strengths of P ADH1 and P PGK1 , which are generally regarded as 'constitutive' promoters, decreased significantly under certain conditions, suggesting that cautions should be taken to use such constitutive promoters to drive gene expression under stressful conditions. Interestingly, P HSP12 and P HSP26 were able to response to both high temperature and acetic acid stress. Moreover, P HSP12 also led to moderate yEGFP expression when xylose was used as the sole carbon source, indicating that this promoter could be used for inducing proper gene expression for xylose utilization. CONCLUSION: The results here revealed dynamic changes of promoter activities in S. cerevisiae throughout batch fermentation in the presence of inhibitors as well as using xylose. These results provide insights in selection of promoters to construct S. cerevisiae strains for efficient bioproduction under practical conditions. Our results also encouraged applications of synthetic promoters with high stability for yeast strain development.


Assuntos
Regulação Fúngica da Expressão Gênica , Microbiologia Industrial , Regiões Promotoras Genéticas , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Ácido Acético/farmacologia , Biocombustíveis , Fermentação , Furaldeído/farmacologia , Proteínas de Fluorescência Verde/genética , Temperatura Alta , Saccharomyces cerevisiae/crescimento & desenvolvimento , Estresse Fisiológico , Xilose/química
13.
Mol Pharmacol ; 88(2): 326-34, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26013540

RESUMO

Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated kinase (ERK) 1/2 significantly decreased ABG-001-induced neurite outgrowth. Western blot analysis revealed that ABG-001 significantly induced phosphorylation of IGF-1 receptor, protein kinase B (Akt), ERK, and cAMP responsive element-binding protein (CREB). These effects were markedly reduced by addition of the corresponding inhibitors. We also found that ABG-001-induced neurite outgrowth was reduced by protein kinase C inhibitor as well as small-interfering RNA against the IGF-1 receptor. Furthermore, like ABG-001, IGF-1 also induced neurite outgrowth of PC12 cells, and low-dose nerve growth factor augmented the observed effects of ABG-001 on neurite outgrowth. These results suggest that ABG-001 targets the IGF-1 receptor and activates PI3K, mitogen-activated protein kinase, and their downstream signaling cascades to induce neurite outgrowth.


Assuntos
Hidroxibenzoatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Ratos
14.
Eng Life Sci ; 24(5): 2300016, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38708414

RESUMO

Non-alcoholic fatty liver disease (NAFLD) represents a growing global health concern that can lead to liver disease and cancer. It is characterized by an excessive accumulation of fat in the liver, unrelated to excessive alcohol consumption. Studies indicate that the gut microbiota-host crosstalk may play a causal role in NAFLD pathogenesis, with epigenetic modification serving as a key mechanism for regulating this interaction. In this review, we explore how the interplay between gut microbiota and the host epigenome impacts the development of NAFLD. Specifically, we discuss how gut microbiota-derived factors, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), can modulate the DNA methylation and histone acetylation of genes associated with NAFLD, subsequently affecting lipid metabolism and immune homeostasis. Although the current literature suggests a link between gut microbiota and NAFLD development, our understanding of the molecular mechanisms and signaling pathways underlying this crosstalk remains limited. Therefore, more comprehensive epigenomic and multi-omic studies, including broader clinical and animal experiments, are needed to further explore the mechanisms linking the gut microbiota to NAFLD-associated genes. These studies are anticipated to improve microbial markers based on epigenetic strategies and provide novel insights into the pathogenesis of NAFLD, ultimately addressing a significant unmet clinical need.

15.
Environ Sci Ecotechnol ; 21: 100428, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38800715

RESUMO

Micro/nanoplastics (MNPs) are detected in human liver, and pose significant risks to human health. Oral exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse liver. Similarly, nasal exposure to non-biodegradable plastics can cause airway dysbiosis in mice. However, the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly understood. Here we show the hepatotoxic effects of biodegradable polylactic acid (PLA) MNPs through multi-omics analysis of various biological samples from mice, including gut, fecal, nasal, lung, liver, and blood samples. Our results show that both foodborne and airborne PLA MNPs compromise liver function, disrupt serum antioxidant activity, and cause liver pathology. Specifically, foodborne MNPs lead to gut microbial dysbiosis, metabolic alterations in the gut and serum, and liver transcriptomic changes. Airborne MNPs affect nasal and lung microbiota, alter lung and serum metabolites, and disrupt liver transcriptomics. The gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure, while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP exposure. The relevant results suggest that foodborne PLA MNPs could affect the "gut microbiota-gut-liver" axis and induce hepatoxicity, while airborne PLA MNPs could disrupt the "airway microbiota-lung-liver" axis and cause hepatoxicity. These findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the environment. Our current study could be a starting point for biodegradable MNPs-induced hepatotoxicity. More research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

16.
Chemosphere ; 349: 140940, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101478

RESUMO

Microplastic (MP) and nanoplastic (NP) could cause gut microbiota alterations. Although micro/nanoplastic (MNP) degradation is attracting increasing scientific interest, the evaluation of MNP reduction in gut needs to be further investigated. This study aimed to determine whether partial reduction of polystyrene MNP in gut could affect the immunity, gut microbiota and metabolome of mice. Serum eotaxin/CCL11 was at a lower level in the mice exposed to 200 µg and 500 µg NP (i.e., 2NP and 5NP groups, respectively) compared to those exposed to 500 µg MP (i.e., 5 MP group), while serum IL-2 and IL-4 were both greater in the 5NP group compared to the 5 MP group. The gut bacterial alpha diversity, fungal diversity and evenness were all similar among the MNP and control groups. However, the gut fungal richness was greater in both the 5NP and 5 MP groups compared to the control group. The gut bacterial and fungal compositions were both different between the MNP and control groups. Multiple gut bacteria and fungi showed different levels between the 2NP and 5NP groups, as well as between the 2NP and 5 MP groups. Increased Staphylococcus and decreased Glomus were determined in the 2NP group compared to both the 5NP and 5 MP groups. A Lactobacillus phylotype was found as the sole gatekeeper in the bacterial network of the 2NP group, while a Bifidobacterium phylotype contributed most to the stability of the bacterial networks of both the 5NP and 5 MP groups. Multiple differential gut metabolic pathways were found between the 2NP and 5NP/5 MP groups, and mTOR signaling pathway was largely upregulated in the 2NP group compared to both the 5NP and 5 MP groups. The relevant results could help with the evaluation of partial reduction of MNP in gut.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Poliestirenos/farmacologia , Microplásticos , Plásticos/farmacologia , Metaboloma , Bactérias
17.
Int J Mol Sci ; 14(12): 24200-10, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24351811

RESUMO

A neuritogenic monoglyceride, 1-O-(myristoyl) glycerol (MG), was isolated from the head of Ilisha elongate using a PC12 cell bioassay system, and its chemical structure was elucidated using spectroscopic methods. MG significantly induced 42% of the neurite outgrowth of PC12 cells at a concentration of 10 µM. To study the structure-activity relationships of MG, a series of monoglycerides was designed and synthesised. Bioassay results indicated that the alkyl chain length plays a key role in the neuritogenic activity of the monoglycerides. The groups that link the propane-1,2-diol and alkyl chain were also investigated. An ester linkage, rather than an amido one, was found to be optimal for neuritogenic activity. Therefore, 1-O-(stearoyl) glycerol (SG), which induces 57% of the neurite outgrowth of PC12 cells at 10 µM, was determined to be a lead compound for neuritogenic activity. We then investigated the mechanism of action of neurite outgrowth induced by SG on PC12 cells using protein specific inhibitors and Western blot analysis. The mitogen-activated kinase/ERK kinase (MEK) inhibitor U0126 and the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 significantly decreased neurite outgrowth. At the same time, SG increased phosphorylation of CREB in protein level. Thus, SG-induced neuritogenic activity depends on the activation of the extracellular-regulated protein kinase (ERK), cAMP responsive element-binding protein (CREB) and PI3K signalling pathways in PC12 cells.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Monoglicerídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Butadienos/farmacologia , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Peixes/metabolismo , Monoglicerídeos/química , Monoglicerídeos/isolamento & purificação , Morfolinas/farmacologia , Nitrilas/farmacologia , Células PC12 , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Relação Estrutura-Atividade
18.
Chemosphere ; 310: 136764, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36216111

RESUMO

Microplastics (MP) and nanoplastics (NP) have been found in multiple environments and creatures. However, their effects on the airway microbiota still remain poorly understood. In this study, a series of bioinformatic and statistical analyses were carried out to explore the influence of airborne MP and NP on the nasal and lung microbiota in mice. Both MP and NP were capable of inducing nasal microbial dysbiosis, and MP had a stronger influence on the lung microbiota than NP. Multiple nasal and lung bacteria were associated with MP and NP groups, among which nasal Staphylococcus and lung Roseburia were most associated with MP group, while nasal Prevotella and lung unclassified_Muribaculaceae were most associated with NP group. The nasal Staphylococcus, lung Roseburia, lung Eggerthella and lung Corynebacterium were associated with both MP and NP groups, which were potential biomarkers of micro/nanoplastics-induced airway dysbiosis. SAR11_Clade_Ia and SAR11_Clade_II were associated with both nasal and lung microbiota in MP group, while no such bacterium was determined in NP group. The relevant results suggest that both airborne MP and NP could induce nasal and lung microbial dysbiosis, and the relevant preventative and curable strategies deserve further investigations.


Assuntos
Disbiose , Microplásticos , Camundongos , Animais , Disbiose/induzido quimicamente , Microplásticos/toxicidade , Poliestirenos , Plásticos/toxicidade , Pulmão
19.
J Hazard Mater ; 441: 129903, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36087528

RESUMO

Microplastics (MP) and nanoplastics (NP) exist in the disposable plastic take-away containers. This study aims to determine the gut and oral microbiota alterations in the individuals frequently and occasionally consuming take-away food in disposable plastic containers (TFDPC), and explore the effect of micro/nanoplastics (MNP) reduction on gut microbiota in mice. TFDPC consumption are associated with greater presences of gastrointestinal dysfunction and cough. Both occasional and frequent consumers have altered gut and oral microbiota, and their gut diversity and evenness are greater than those of non-TFDPC consuming cohort. Multiple gut and oral bacteria are associated with TFDPC consumers, among which intestinal Collinsella and oral Thiobacillus are most associated with the frequent consumers, while intestinal Faecalibacterium is most associated with the occasional consumers. Although some gut bacteria associated with the mice treated with 500 µg NP and 500 µg MP are decreased in the mice treated with 200 µg NP, the gut microbiota of the three MNP groups are all different from the control group. This study demonstrates that TFDPC induces gut and oral microbiota alterations in the consumers, and partial reduction of the size and amount of MNP cannot rectify the MNP-induced gut microbial dysbiosis.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Disbiose/induzido quimicamente , Camundongos , Microplásticos , Plásticos/toxicidade
20.
Biosensors (Basel) ; 12(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36140092

RESUMO

Through self-assembly, environmentally friendly cellulose nanocrystals (CNCs) can form films with a photonic crystal structure whose pitch size can be adjusted in a variety of ways at the fabrication stage. Moreover, the films exhibit response performance to multiple stimuli, which offers extensive applications. Poly(ethylene glycol) (PEG) and CNCs combine to form a smaller chiral nematic domain that develops a solid film with a uniform spiral structure when slowly dried. By changing the composition of CNCs and PEG, flexible and flat photonic composite films with uniform structural colors from blue to red are prepared. Benefiting from the change in pitch size by insertion and detachment of water molecules into the chiral nematic structure, CNCs films and CNC-PEG composite films exhibit a reversible structural color change in response to different humidity. In addition, the chiral nematic films formed by the combination of glycerol and CNCs have a reversible stimulation response to hydrochloric acid gas. Similarly, adjusting the ratio of glycerol can control the pitch size of the films and, thus, the reflective color. In summary, the pitch size of the photonic crystal structure of the films can be precisely tuned by regulating the additive ratio, and the two prepared films have reversible responses to humidity and hydrochloric acid gas, respectively. The CNC-based films show promise in the application of colorimetric biosensors.


Assuntos
Celulose , Glicerol , Celulose/química , Umidade , Ácido Clorídrico , Polietilenoglicóis , Água
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