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1.
Biotechnol Adv ; 72: 108352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574900

RESUMO

Nitrilases represent a distinct class of enzymes that play a pivotal role in catalyzing the hydrolysis of nitrile compounds, leading to the formation of corresponding carboxylic acids. These enzymatic entities have garnered significant attention across a spectrum of industries, encompassing pharmaceuticals, agrochemicals, and fine chemicals. Moreover, their significance has been accentuated by mounting environmental pressures, propelling them into the forefront of biodegradation and bioremediation endeavors. Nevertheless, the natural nitrilases exhibit intrinsic limitations such as low thermal stability, narrow substrate selectivity, and inadaptability to varying environmental conditions. In the past decade, substantial efforts have been made in elucidating the structural underpinnings and catalytic mechanisms of nitrilase, providing basis for engineering of nitrilases. Significant breakthroughs have been made in the regulation of nitrilases with ideal catalytic properties and application of the enzymes for industrial productions. This review endeavors to provide a comprehensive discourse and summary of recent research advancements related to nitrilases, with a particular emphasis on the elucidation of the structural attributes, catalytic mechanisms, catalytic characteristics, and strategies for improving catalytic performance of nitrilases. Moreover, the exploration extends to the domain of process engineering and the multifarious applications of nitrilases. Furthermore, the future development trend of nitrilases is prospected, providing important guidance for research and application in the related fields.


Assuntos
Aminoidrolases , Nitrilas , Aminoidrolases/genética , Aminoidrolases/química , Catálise , Biodegradação Ambiental
2.
Cancer Lett ; 588: 216806, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38467179

RESUMO

The aim of this study was to investigate the underlying molecular mechanism behind the promotion of cell survival under conditions of glucose deprivation by l-lactate. To accomplish this, we performed tissue microarray and immunohistochemistry staining to analyze the correlation between the abundance of pan-Lysine lactylation and prognosis. In vivo evaluations of tumor growth were conducted using the KPC and nude mice xenograft tumor model. For mechanistic studies, multi-omics analysis, RNA interference, and site-directed mutagenesis techniques were utilized. Our findings robustly confirmed that l-lactate promotes cell survival under glucose deprivation conditions, primarily by relying on GLS1-mediated glutaminolysis to support mitochondrial respiration. Mechanistically, we discovered that l-lactate enhances the NMNAT1-mediated NAD+ salvage pathway while concurrently inactivating p-38 MAPK signaling and suppressing DDIT3 transcription. Notably, Pan-Kla abundance was significantly upregulated in patients with Pancreatic adenocarcinoma (PAAD) and associated with poor prognosis. We identified the 128th Lysine residue of NMNAT1 as a critical site for lactylation and revealed EP300 as a key lactyltransferase responsible for catalyzing lactylation. Importantly, we elucidated that lactylation of NMNAT1 enhances its nuclear localization and maintains enzymatic activity, thereby supporting the nuclear NAD+ salvage pathway and facilitating cancer growth. Finally, we demonstrated that the NMNAT1-dependent NAD+ salvage pathway promotes cell survival under glucose deprivation conditions and is reliant on the activity of Sirt1. Collectively, our study has unraveled a novel molecular mechanism by which l-lactate promotes cell survival under glucose deprivation conditions, presenting a promising strategy for targeting lactate and NAD+ metabolism in the treatment of PAAD.


Assuntos
Adenocarcinoma , Nicotinamida-Nucleotídeo Adenililtransferase , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Ácido Láctico , NAD/metabolismo , Glucose , Camundongos Nus , Lisina , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Nicotinamida-Nucleotídeo Adenililtransferase/metabolismo
3.
Bioresour Technol ; 395: 130391, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307483

RESUMO

In response to the persistent expansion of global resource demands, considerable attention has been directed toward the synthetic microbial consortia (SMC) within the domain of microbial engineering, aiming to address the sustainable management and valorization of biomass wastes. This comprehensive review systematically encapsulates the most recent advancements in research and technological applications concerning the utilization of SMC for biomass waste treatment. The construction strategies of SMC are briefly outlined, and the diverse applications of SMC in biomass wastes treatment are explored, with particular emphasis on its potential advantages in waste degradation, hazardous substances control, and high value-added products conversion. Finally, recommendations for the future development of SMC technology are proposed, and prospects for its sustainable application are discussed.


Assuntos
Consórcios Microbianos , Tecnologia , Biomassa
4.
Curr Res Food Sci ; 8: 100699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420347

RESUMO

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very important role in the synthesis of human and animal cartilage. GLC is commonly used in the treatment of mild to moderate osteoarthritis and has good anti-inflammatory and antioxidant properties. In this study, alcoholic injury models were constructed in mice and human normal hepatocyte L02 cells to explore the protective effect and mechanism of GLC on ALD. Mice were given GLC by gavage for 30 days. Liver injury models of both mice and L02 cells were produced by ethanol. Detecting the levels of liver injury biomarkers, lipid metabolism, oxidative stress biomarkers, and inflammatory factors through different reagent kits. Exploring oxidative and inflammatory pathways in mouse liver tissue through Western blot and RT-PCR. The results showed that GLC can significantly inhibit the abnormal increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), and can significantly improve the level of high-density lipoprotein cholesterol (HDL-C). In addition, GLC intervention significantly improved alcohol induced hepatic oxidative stress by reducing the levels of malondialdehyde (MDA) and, increasing the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the liver. Further mechanisms suggest that GLC can inhibit the expression of ethanol metabolism enzyme cytochrome P4502E1 (CYP2E1), activate the antioxidant pathway Keap1/Nrf2/HO-1, down-regulate the phosphorylation of MAPK and NF-κB signaling pathways, and thus reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Therefore, GLC may be a significant candidate functional food for attenuating alcohol induced acute liver injury.

5.
Adv Sci (Weinh) ; 11(4): e2306044, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38032137

RESUMO

The assembly line biosynthesis of the powerful anticancer-antiviral didemnin cyclic peptides is proposed to follow a prodrug release mechanism in Tristella bacteria. This strategy commences with the formation of N-terminal prodrug scaffolds and culminates in their cleavage during the cellular export of the mature products. In this study, a comprehensive exploration of the genetic and biochemical aspects of the enzymes responsible for both the assembly and cleavage of the acylated peptide prodrug scaffolds is provided. This process involves the assembly of N-acyl-polyglutamine moieties orchestrated by the nonribosomal peptide synthetase DidA and the cleavage of these components at the post-assembly stage by DidK, a transmembrane CAAX hydrolase homolog. The findings not only shed light on the complex prodrug mechanism that underlies the synthesis and secretion of didemnin compounds but also offer novel insights into the expanded role of CAAX hydrolases in microbes. Furthermore, this knowledge can be leveraged for the strategic design of genome mining approaches aimed at discovering new bioactive natural products that employ similar prodrug biochemical strategies.


Assuntos
Depsipeptídeos , Pró-Fármacos , Peptídeo Hidrolases , Endopeptidases , Pró-Fármacos/farmacologia
6.
ISME Commun ; 3(1): 123, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993728

RESUMO

Amphibian skin harbors microorganisms that are associated with the fungal pathogen Batrachochytrium dendrobatidis (Bd), which causes chytridiomycosis, one of the most significant wildlife diseases known. This pathogen originated in Asia, where diverse Bd lineages exist; hence, native amphibian hosts have co-existed with Bd over long time periods. Determining the nuances of this co-existence is crucial for understanding the prevalence and spread of Bd from a microbial context. However, associations of Bd with the natural skin microbiome remain poorly understood for Asian hosts, especially in relation to skin-associated fungi. We used 16 S rRNA and fungal internal transcribed spacer (ITS) gene sequencing to characterize the skin microbiome of four native Asian amphibian species and examined the relationships between Bd infection and their skin bacterial and fungal communities; we also analyzed the correlates of the putative anti-Bd bacteria. We show that both skin bacterial and fungal community structure and composition had significant associations with infection status (Bd presence/absence) and infection intensity (frequency of Bd sequence reads). We also found that the putative anti-Bd bacterial richness was correlated with Bd infection status and infection intensity, and observed that the relative abundance of anti-Bd bacteria roughly correspond with changes in both Bd prevalence and mean infection intensity in populations. Additionally, the microbial co-occurrence network of infected frogs was significantly different from that of uninfected frogs that were characterized by more keystone nodes (connectors) and larger proportions in correlations between bacteria, suggesting stronger inter-module bacterial interactions. These results indicate that the mutual effects between Bd and skin-associated microbiome, including the interplay between bacteria and fungi, might vary with Bd infection in susceptible amphibian species. This knowledge will help in understanding the dynamics of Bd from a microbial perspective, potentially contributing to mitigate chytridiomycosis in other regions of the world.

7.
Bioresour Technol ; 385: 129467, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37429549

RESUMO

Thermophilic composting (TC) can effectively shorten maturity period with satisfactory sanitation. However, the higher energy consumption and lower composts quality limited its widespread application. In this study, hyperthermophilic pretreatment (HP) was introduced as a novel approach within TC, and its effects on humification process and bacterial community during food waste TC was investigated from multiple perspectives. Results showed that a 4-hour pretreatment at 90 °C increased the germination index and humic acid/fulvic acid by 25.52% and 83.08%, respectively. Microbial analysis demonstrated that HP stimulated the potential functional thermophilic microbes, and significantly up-regulated the genes related to amino acid biosynthesis. Further network and correlation analysis suggested that pH was the key factor affecting bacterial communities, and higher HP temperatures help to restore bacterial cooperation and showed higher humification degree. In summary, this study contributed to a better understanding of the mechanism towards the accelerated humification by HP.


Assuntos
Compostagem , Eliminação de Resíduos , Solo , Alimentos , Bactérias/genética , Archaea , Substâncias Húmicas/análise , Esterco/microbiologia
8.
Heliyon ; 9(1): e12378, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36820187

RESUMO

Pancreatic cancer (PC) is one of the most fatal malignant tumors, and is commonly diagnosed at an advanced stage with no effective therapy. Metabolism-related genes (MRGs) and immune-related genes (IRGs) play considerable roles in the tumor microenvironment. Therefore, an effective prediction model based on MRGs and IRGs could aid in the prognosis of PC. In this study, differential expression analysis was performed to gain 25 intersectional genes from 857 differentially expressed MRGs (DEMRGs), and 1353 differentially expressed IRGs, from The Cancer Genome Atlas database of PC. Cox and Lasso regression were applied and a five-DEMRGs prognostic model constructed. Survival analysis, ROC values, risk curve and validation analysis showed that the model could independently predict PC prognosis. In addition, the correlation analysis suggested that the five-DEMRGs prognostic model could reflect the status of the immune microenvironment, including Tregs, M1 macrophages and Mast cell resting. Therefore, our study provides new underlying predictive biomarkers and associated immunotherapy targets.

9.
Phytomedicine ; 107: 154428, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36115171

RESUMO

BACKGROUND: 24-epibrassinolide (EBR) is a ubiquitous steroidal phytohormone with anticancer activity. Yet the cytotoxic effects and mechanism of EBR on hepatocarcinoma (HCC) cells remain elusive. METHODS: Cell counting kit-8 (CCK-8) assay was performed to evaluate cell viability. Real-time cell analysis (RTCA) technology and colony formation assays were used to evaluate cell proliferation. The apoptosis ratio was measured by flow cytometry. Seahorse XFe96 was applied to detect the effects of EBR on cellular bioenergetics. RNA-seq analysis was performed to investigate differences in gene expression profiles. Western blot and qRT-PCR were used to detect the changes in target molecules. RESULTS: EBR induced apoptosis and caused energy restriction in HCC, both of which were related to insulin-like growth factor-binding protein 1 (IGFBP1). EBR rapidly and massively induced IGBFP1, part of which was transcribed by activating transcription factor-4 (ATF4). The accumulation of secreted and cellular IGFBP1 had different important roles, in which secreted IGFBP1 affected cell energy metabolism by inhibiting the phosphorylation of Akt, while intracellular IGFBP1 acted as a pro-survival factor to resist apoptosis. Interestingly, the extracellular signal-regulated kinase (ERK) inhibitor SCH772984 and MAP/ERK kinase (MEK) inhibitor PD98059 not only attenuated the EBR-induced IGFBP1 expression but also the basal expression of IGFBP1. Thus, the treatment of cells with these inhibitors further enhances the cytotoxicity of EBR. CONCLUSION: Taken together, these findings suggested that EBR can be considered as a potential therapeutic compound for HCC due to its pro-apoptosis, restriction of energy metabolism, and other anti-cancer properties. Meanwhile, the high expression of IGFBP1 induced by EBR in HCC contributes to our understanding of the role of IGFBP1 in drug resistance.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Somatomedinas , Fatores Ativadores da Transcrição/farmacologia , Apoptose , Brassinosteroides , Proliferação de Células , MAP Quinases Reguladas por Sinal Extracelular , Quinases de Proteína Quinase Ativadas por Mitógeno , Reguladores de Crescimento de Plantas/farmacologia , Somatomedinas/farmacologia , Esteroides Heterocíclicos
10.
Metabolites ; 12(9)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36144271

RESUMO

Alcoholic liver disease (ALD) is a primary cause of mortality and morbidity worldwide. Oxidative stress and inflammation are important pathogenic factors contributing to ALD. We investigated the protective mechanism of galacto-oligosaccharide (GOS) against ALD through their antioxidant and anti-inflammatory activities by performing in vivo and in vitro experiments. Western blot and RT‒PCR results indicated that the expression of cytochrome P450 protein 2E1 (CYP2E1) in liver tissues and L02 cells was reduced in the GOS-treated mice compared with the model group. In addition, GOS prominently reduced the expression of Kelch-like ECH-associated protein 1 (Keap1), increased the expression of the nuclear factor erythroid-2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) proteins, and enhanced the antioxidant capacity. In addition, GOS decreased inflammation by reducing inflammatory factor levels and inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Based on these results, GOS may be a prospective functional food for the prevention and treatment of ALD.

11.
Biomed Pharmacother ; 154: 113577, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35988420

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is primarily caused by abnormal lipid metabolism and the accumulation of triglycerides in the liver. NAFLD is also associated with hepatic steatosis and nutritional and energy imbalances and is a chronic liver disease associated with a number of factors. Nuclear receptors play a key role in balancing energy and nutrient metabolism, and the peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR) regulate lipid metabolism genes, controlling hepatocyte lipid utilization and regulating bile acid (BA) synthesis and transport. They play an important role in lipid metabolism and BA homeostasis. At present, PPARα and FXR are the most promising targets for the treatment of NAFLD among nuclear receptors. This review focuses on the crosstalk mechanisms and transcriptional regulation of PPARα and FXR in the pathogenesis of NAFLD and summarizes PPARα and FXR drugs in clinical trials, laying a theoretical foundation for the targeted treatment of NAFLD and the development of novel therapeutic strategies.


Assuntos
Hepatopatia Gordurosa não Alcoólica , PPAR alfa/metabolismo , Proteínas de Ligação a RNA/metabolismo , Hepatócitos/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
12.
Int J Mol Sci ; 23(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36012464

RESUMO

The global prevalence of nonalcoholic fatty liver disease (NAFLD) continues to rise, yet effective treatments are lacking due to the complex pathogenesis of this disease. Although recent research has provided evidence for the "multiple strikes" theory, the classic "two strikes" theory has not been overturned. Therefore, there is a crucial need to identify multiple targets in NAFLD pathogenesis for the development of diagnostic markers and targeted therapeutics. Since its discovery, the mechanistic target of rapamycin (mTOR) has been recognized as the central node of a network that regulates cell growth and development and is closely related to liver lipid metabolism and other processes. This paper will explore the mechanisms by which mTOR regulates lipid metabolism (SREBPs), insulin resistance (Foxo1, Lipin1), oxidative stress (PIG3, p53, JNK), intestinal microbiota (TLRs), autophagy, inflammation, genetic polymorphisms, and epigenetics in NAFLD. The specific influence of mTOR on NAFLD was hypothesized to be divided into micro regulation (the mechanism of mTOR's influence on NAFLD factors) and macro mediation (the relationship between various influencing factors) to summarize the influence of mTOR on the developmental process of NAFLD, and prove the importance of mTOR as an influencing factor of NAFLD regarding multiple aspects. The effects of crosstalk between mTOR and its upstream regulators, Notch, Hedgehog, and Hippo, on the occurrence and development of NAFLD-associated hepatocellular carcinoma are also summarized. This analysis will hopefully support the development of diagnostic markers and new therapeutic targets in NAFLD.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
13.
Mar Drugs ; 20(5)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35621961

RESUMO

Marine crustacean waste has not been fully utilized and is a rich source of chitin. Enzymatic degradation has attracted the wide attention of researchers due to its unique biocatalytic ability to protect the environment. Chitosan (CTS) and its derivative chitosan oligosaccharides (COSs) with various biological activities can be obtained by the enzymatic degradation of chitin. Many studies have shown that chitosan and its derivatives, chitosan oligosaccharides (COSs), have beneficial properties, including lipid-lowering, anti-inflammatory and antitumor activities, and have important application value in the medical treatment field, the food industry and agriculture. In this review, we describe the classification, biochemical characteristics and catalytic mechanisms of the major degrading enzymes: chitinases, chitin deacetylases (CDAs) and chitosanases. We also introduced the technology for enzymatic design and modification and proposed the current problems and development trends of enzymatic degradation of chitin polysaccharides. The discussion on the characteristics and catalytic mechanism of chitosan-degrading enzymes will help to develop new types of hydrolases by various biotechnology methods and promote their application in chitosan.


Assuntos
Quitinases , Quitosana , Animais , Quitina/química , Quitinases/metabolismo , Quitosana/química , Crustáceos/metabolismo , Oligossacarídeos/química
14.
Phytomedicine ; 102: 154164, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35597026

RESUMO

BACKGROUND: Many extracts and purified alkaloids of M. cordata (Papaveraceae family) have been reported to display promising anti-tumor effects by inhibiting cancer cell growth and inducing apoptosis in many cancer types. However, no evidence currently exists for anti-pancreatic cancer activity of alkaloids extracted from M. cordata, including a novel alkaloid named 6­methoxy dihydrosphingosine (6-Methoxydihydroavicine, 6-ME) derived from M. cordata fruits. PURPOSE: The aim of this study was to investigate the anti-tumor effects of 6-ME on PC cells and the underlying mechanism. METHODS: CCK-8, RTCA, and colony-formation assays were used to analyze PC cell growth. Cell death ratios, changes in MMP and ROS levels were measured by flow cytometry within corresponding detection kits. A Seahorse XFe96 was employed to examine the effects of 6-ME on cellular bioenergetics. Western blot and q-RT-PCR were conducted to detect changes in target molecules. RESULTS: 6-ME effectively reduced the growth of PC cells and promoted PCD by activating RIPK1, caspases, and GSDME. Specifically, 6-ME treatment caused a disruption of OAA metabolism and increased ROS production, thereby affecting mitochondrial homeostasis and reducing aerobic glycolysis. These responses resulted in mitophagy and RIPK1-mediated cell death. CONCLUSION: 6-ME exhibited specific anti-tumor effects through interrupting OAA metabolic homeostasis to trigger ROS/RIPK1-dependent cell death and mitochondrial dysfunction, suggesting that 6-ME could be considered as a highly promising compound for PC intervention.


Assuntos
Alcaloides , Antineoplásicos , Caspases , Equol/análogos & derivados , Ácido Oxaloacético , Neoplasias Pancreáticas , Espécies Reativas de Oxigênio , Proteína Serina-Treonina Quinases de Interação com Receptores , Alcaloides/farmacologia , Antineoplásicos/farmacologia , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Equol/farmacologia , Humanos , Ácido Oxaloacético/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Papaveraceae/química , Espécies Reativas de Oxigênio/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
15.
Front Microbiol ; 13: 823254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359710

RESUMO

The symbiosis between a host and its microbiome is essential for host fitness, and this association is a consequence of the host's physiology and habitat. Sinocyclocheilus, the largest cavefish diversification of the world, an emerging multi-species model system for evolutionary novelty, provides an excellent opportunity for examining correlates of host evolutionary history, habitat, and gut-microbial community diversity. From the diversification-scale patterns of habitat occupation, major phylogenetic clades (A-D), geographic distribution, and knowledge from captive-maintained Sinocyclocheilus populations, we hypothesize habitat to be the major determinant of microbiome diversity, with phylogeny playing a lesser role. For this, we subject environmental water samples and fecal samples (representative of gut-microbiome) from 24 Sinocyclocheilus species, both from the wild and after being in captivity for 6 months, to bacterial 16S rRNA gene profiling using Illumina sequencing. We see significant differences in the gut microbiota structure of Sinocyclocheilus, reflective of the three habitat types; gut microbiomes too, were influenced by host-related factors. There is no significant association between the gut microbiomes and host phylogeny. However, there is some microbiome related structure at the clade level, with the most geographically distant clades (A and D) being the most distinct, and the two overlapping clades (B and C) showing similarities. Microbes inhabiting water were not a cause for significant differences in fish-gut microbiota, but water quality parameters were. Transferring from wild to captivity, the fish microbiomes changed significantly and became homogenized, signifying plastic changes and highlighting the importance of environmental factors (habitat) in microbiome community assembly. The core microbiome of this group, at higher taxonomic scale, resembled that of other teleost fishes. Our results suggest that divergent natural environments giving rise to evolutionary novelties underlying host adaptations, also includes the microbiome of these fishes.

16.
Cancer Cell Int ; 22(1): 143, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366902

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a severe malignant with a 5-year survival rate of approximately 9%. Oleanolic acid is a well-known natural triterpenoid which exhibits pharmacological activities. We previously synthesized a series of oleanolic acid derivatives and evaluated the tumor-suppressive activity of olean-28,13ß-lactam (B28) in prostate cancer. However, the detailed mechanism remains to be understood. METHODS: The anti-tumor activity of B28 in PAAD was confirmed by RTCA, colony formation assay and flow cytometry. GO and KEGG enrichment analyses were performed to analyze the differentially expressed genes (DEGs) obtained by RNA sequencing. The effects of B28 on cell bioenergetics were evaluated by seahorse analyzer. Lenti-virus packaged plasmids were performed to knockdown or overexpress target genes. Alteration of mitochondrial membrane potential, ROS and GSH/GSSG were measured by corresponding detection kits according to the manufacturer's protocol. RESULTS: We evaluated and confirmed the promising anti-tumor activity of B28 in vitro. RNA-seq profile indicated that multiple metabolic pathways were interrupted in B28 treated PAAD cells. Next, we demonstrated that B28 induces cellular bioenergetics crisis to inhibit PAAD cells growth and induce cell death. We further validated that cell cycle arrest, inhibition of cell growth, cell apoptosis and cell bioenergetics disruption were functionally rescued by ROS scavenger NAC. Mechanistically, we found glutamine metabolism was inhibited due to B28 administration. Moreover, we validated that down-regulation of GLS1 contributes to ROS generation and bioenergetics interruption induced by B28. Furthermore, we elucidated that YTHDF1-GLS1 axis is the potential downstream target of B28 to induce PAAD cell metabolic crisis and cell death. Finally, we also confirmed the anti-tumor activity of B28 in vivo. CONCLUSIONS: Current study demonstrates B28 disrupts YTDFH1-GLS1 axis to induce ROS-dependent cell bioenergetics crisis and cell death which finally suppress PAAD cell growth, indicating that this synthesized olean-28,13ß-lactam maybe a potent agent for PAAD intervention.

17.
Mar Drugs ; 20(1)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35049924

RESUMO

Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have two kinds of active groups, amino and hydroxyl groups, which can form a variety of derivatives, and the properties of these derivatives can be further improved. In this review, the key structures of chitosan oligosaccharides and recent studies on chitosan oligosaccharide derivatives, including their synthesis methods, are described. Finally, the antimicrobial and antitumor applications of chitosan oligosaccharides and their derivatives are discussed.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Organismos Aquáticos , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Animais , Antibacterianos/química , Antineoplásicos/química , Quitosana/química , Oligossacarídeos/química , Relação Estrutura-Atividade
18.
Bioprocess Biosyst Eng ; 45(4): 689-700, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35038012

RESUMO

This study investigated the effects of different bulking agents (i.e., sawdust, wheat straw, rice straw, and corncob) on bacterial structure and functions for organic degradation during food waste in-situ rapid biological reduction (IRBR) inoculated with microbial agent. Results showed that the highest organic degradation (409.5 g/kg total solid) and volatile solids removal efficiency (41.0%) were achieved when wheat straw was used, largely because the degradation of readily degradable substrates and cellulose was promoted by this bulking agent. Compared with other three bulking agents, the utilization of wheat straw was conducive to construct a more suitable environmental condition (moisture content of 18.0-28.2%, pH of 4.91-5.87) for organic degradation during IRBR process, by virtue of its excellent structural and physiochemical properties. Microbial community analysis suggested that the high-moisture environment in rice straw treatment promoted the growth of Staphylococcus and inhibited the activity of the inoculum. By contrast, lowest bacterial richness was observed in corncob treatment due to the faster water loss. Compared with these two bulking agents, sawdust and wheat straw treatment led to a more stable bacterial community structure, and the inoculated Bacillus gradually became the dominant genus (36.6-57.8%) in wheat straw treatment. Predicted metagenomics analysis showed that wheat straw treatment exhibited the highest carbohydrate metabolism activity which improved the pyruvate, amino sugar and nucleotide sugar metabolism, and thereby promoted the organic degradation and humic substrate production. These results indicated that wheat straw was a more desirable bulking agent, and revealed the potential microbial organics degradation mechanism in IRBR process.


Assuntos
Microbiota , Eliminação de Resíduos , Bactérias , Alimentos , Eliminação de Resíduos/métodos , Triticum
19.
Bioresour Technol ; 346: 126603, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953987

RESUMO

In this study, a community-scale in-situ rapid biological reduction (IRBR) system was applied to achieve the rapid disposal and resource recovery of food waste (FW). A total of 5263 kg FW was processed in the 35 days of stably operation, during which 84.37% total mass reduction and 43.30% volatile solid removal were achieved, and the odor had been effectively controlled. Microbial sequencing results showed that aerobic and facultative thermophilic bacteria were major bacterial community, and vigorous metabolism of both carbohydrate and amino acid were maintained during the IRBR process. The final products have the potential to be recycled as organic fertilizers or bio-solid fuel to realize resource recovery. The results of economic analysis showed that the IRBR system had lower FW disposal costs due to the high automation. These results suggested that the IRBR system was an environmentally friendly, economical and practical method for the FW rapid treatment.


Assuntos
Eliminação de Resíduos , Anaerobiose , Alimentos
20.
ACS Appl Mater Interfaces ; 13(43): 51736-51745, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34668690

RESUMO

Optical security involving the use of light to achieve distinctive vision effects has become a widely used approach for anticounterfeiting. Holographic multiplexing has attracted considerable interest in multiplexing security due to its high degree of freedom for manipulating the optical parameters of incident laser beams. However, the complex and time-consuming fabrication process of metasurface-based holograms and the sophisticated nature of holographic imaging systems have hindered the practical application of holographic multiplexing in anticounterfeiting. Combining holography with shape memory polymers to construct reconfigurable holograms provides a simple and efficient way for holographic multiplexing. This paper proposes a reconfigurable four-level amplitude hologram fabricated on a heat-shrinkable shape memory polymer using spatially modulated femtosecond laser pulses. Simply by triggering the shape recovery of the polymer through heating, the amplitude modulation of light by the hologram is reconfigured through the shrinking of processed microcrater pixels with three diameters, which enables variation to be achieved in reconstructed holographic images. Examples of holographic multiplexing and data encryption are used to validate the proposed method. The proposed economic and simple approach for holographic multiplexing provides an integrated and single-material solution to packaging and optical security, which has extensive potential in anticounterfeiting and optical encryption.

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