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1.
Curr Issues Mol Biol ; 46(6): 5682-5700, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38921011

ABSTRACT

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731861

ABSTRACT

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.


Subject(s)
Extracellular Traps , Lactoferrin , Neural Cell Adhesion Molecules , Sialic Acids , Lactoferrin/pharmacology , Lactoferrin/metabolism , Humans , Extracellular Traps/metabolism , Extracellular Traps/drug effects , Neural Cell Adhesion Molecules/metabolism , Sialic Acids/metabolism , Neutrophils/metabolism , Neutrophils/drug effects , Heparin, Low-Molecular-Weight/pharmacology
3.
Phytochemistry ; 223: 114099, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38641143

ABSTRACT

Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal herb known as Sanqi or Tianqi in Asia and is commonly used worldwide. It is one of the main raw ingredients of Yunnan Baiyao, Fu fang dan shen di wan, and San qi shang yao pian. It is also a source of cardiotonic pill used to treat cardiovascular diseases in China, Korea, and Russia. Approximately 270 Panax notoginseng saponins have been isolated and identified as the major active components. Although the absorption and bioavailability of saponins are predominantly dependent on the gastrointestinal biotransformation capacity of an individual, minor saponins are better absorbed into the bloodstream and act as active substances than major saponins. Notably, minor saponins are absent or are present in minimal quantities under natural conditions. In this review, we focus on the strategies for the enrichment and production of minor saponins in P. notoginseng using physical, chemical, enzyme catalytic, and microbial methods. Moreover, pharmacological studies on minor saponins derived from P. notoginseng over the last decade are discussed. This review serves as a meaningful resource and guide, offering scholarly references for delving deeper into the exploration of the minor saponins in P. notoginseng.


Subject(s)
Drugs, Chinese Herbal , Panax notoginseng , Saponins , Saponins/chemistry , Panax notoginseng/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Molecular Structure
4.
Arch Microbiol ; 206(4): 176, 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38493413

ABSTRACT

The stems and leaves of Panax notoginseng contain high saponins, but they are often discarded as agricultural waste. In this study, the predominant ginsenosides Rg1, Rc, and Rb2, presented in the stems and leaves of ginseng plants, were biotransformed into value-added rare ginsenosides F1, compound Mc1 (C-Mc1), and Rd2, respectively. A fungal strain YMS6 (Penicillium sp.) was screened from the soil as a biocatalyst with high selectivity for the deglycosylation of major ginsenosides. Under the optimal fermentation conditions, the yields of F1, C-Mc1, and Rd2 were 97.95, 68.64, and 79.58%, respectively. This study provides a new microbial resource for the selective conversion of protopanaxadiol-type and protopanaxatriol-type major saponins into rare ginsenosides via the whole-cell biotransformation and offers a solution for the better utilization of P. notoginseng waste.


Subject(s)
Ginsenosides , Saponins , Agriculture , Biotransformation
5.
IEEE/ACM Trans Comput Biol Bioinform ; 20(3): 1876-1889, 2023.
Article in English | MEDLINE | ID: mdl-37015474

ABSTRACT

OBJECTIVE: Depression is accompanied by abnormalities in large-scale functional brain networks. This paper combined static and dynamic methods to analyze the abnormal topology and changes of functional connectivity network (FCN) of depression. METHODS: We collected resting-state EEG recordings from 27 depressed subjects and 28 normal subjects, then obtained 68 regions of interests (ROIs) by source localization. We took ROIs as the nodes and correlations as the edges to build FCNs and analyzed static network based on graph theory. We used a sliding window method followed by k-means clustering, states analyses and trend analysis of network metrics over time to study dynamic connectivity. RESULTS: The clustering coefficient (CC) and local efficiency in depression were increased, the characteristic path length and global efficiency were decreased, and local metrics had different manifestations in different resting state networks (RSNs); Depression had reduced connectivity in most RSNs, but increased connectivity in the default mode network, and there was a decoupling phenomenon between different RSNs; Depressed patients spent more time in sparsely connected states, their FCN's flexibility was less than normal subjects; The trend of CC over time was opposite between two groups. Most metrics in normal showed a relatively stronger correlation with time. SIGNIFICANCE: Our research may provide a deeper understanding of neurophysiological mechanisms of depression and new biomarkers for clinical diagnosis of depression.


Subject(s)
Brain Mapping , Depression , Humans , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Brain/physiology , Electroencephalography
6.
Microb Cell Fact ; 22(1): 46, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36890537

ABSTRACT

BACKGROUND: Resveratrol is a commercially available stilbenoid widely used as dietary supplements, functional food ingredients, and cosmetic ingredients due to its diverse physiological activities. The production of resveratrol in microorganisms provides an ideal source that reduces the cost of resveratrol, but the titer in Saccharomyces cerevisiae was still much lower than that in other hosts. RESULTS: To achieve enhanced production of resveratrol in S. cerevisiae, we constructed a biosynthetic pathway via combining phenylalanine and tyrosine pathways by introducing a bi-functional phenylalanine/tyrosine ammonia lyase from Rhodotorula toruloides. The combination of phenylalanine pathway with tyrosine pathway led to a 462% improvement of resveratrol production in yeast extract peptone dextrose (YPD) medium with 4% glucose, suggesting an alternative strategy for producing p-coumaric acid-derived compounds. Then the strains were further modified by integrating multi-copy biosynthetic pathway genes, improving metabolic flux to aromatic amino acids and malonyl-CoA, and deleting by-pathway genes, which resulted in 1155.0 mg/L resveratrol in shake flasks when cultured in YPD medium. Finally, a non-auxotrophic strain was tailored for resveratrol production in minimal medium without exogenous amino acid addition, and the highest resveratrol titer (4.1 g/L) ever reported was achieved in S. cerevisiae to our knowledge. CONCLUSIONS: This study demonstrates the advantage of employing a bi-functional phenylalanine/tyrosine ammonia lyase in the biosynthetic pathway of resveratrol, suggesting an effective alternative in the production of p-coumaric acid-derived compounds. Moreover, the enhanced production of resveratrol in S. cerevisiae lays a foundation for constructing cell factories for various stilbenoids.


Subject(s)
Saccharomyces cerevisiae , Tyrosine , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Resveratrol/metabolism , Tyrosine/metabolism , Phenylalanine/metabolism , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/metabolism , Metabolic Engineering/methods
7.
Microorganisms ; 11(1)2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36677495

ABSTRACT

Acetoin is an important four-carbon platform chemical with versatile applications. Optically pure (R)-acetoin is more valuable than the racemate as it can be applied in the asymmetric synthesis of optically active α-hydroxy ketone derivatives, pharmaceuticals, and liquid crystal composites. As a cytotoxic solvent, acetoin at high concentrations severely limits culture performance and impedes the acetoin yield of cell factories. In this study, putative genes that may improve the resistance to acetoin for Escherichia coli were screened. To obtain a high-producing strain, the identified acetoin-resistance gene was overexpressed, and the synthetic pathway of (R)-acetoin was strengthened by optimizing the copy number of the key genes. The engineered E. coli strain GXASR-49RSF produced 81.62 g/L (R)-acetoin with an enantiomeric purity of 96.5% in the fed-batch fermentation using non-food raw materials in a 3-L fermenter. Combining the systematic approach developed in this study with the use of low-cost feedstock showed great potential for (R)-acetoin production via this cost-effective biotechnological process.

8.
Microb Cell Fact ; 21(1): 230, 2022 Nov 05.
Article in English | MEDLINE | ID: mdl-36335407

ABSTRACT

BACKGROUND: Ginsenosides are Panax plant-derived triterpenoid with wide applications in cardiovascular protection and immunity-boosting. However, the saponins content of Panax plants is fairly low, making it time-consuming and unsustainable by direct extraction. Protopanaxadiol (PPD) is a common precursor of dammarane-type saponins, and its sufficient supply is necessary for the efficient synthesis of ginsenoside. RESULTS: In this study, a combinational strategy was used for the construction of an efficient yeast cell factory for PPD production. Firstly, a PPD-producing strain was successfully constructed by modular engineering in Saccharomyces cerevisiae BY4742 at the multi-copy sites. Then, the INO2 gene, encoding a transcriptional activator of the phospholipid biosynthesis, was fine-tuned to promote the endoplasmic reticulum (ER) proliferation and improve the catalytic efficiency of ER-localized enzymes. To increase the metabolic flux of PPD, dynamic control, based on a carbon-source regulated promoter PHXT1, was introduced to repress the competition of sterols. Furthermore, the global transcription factor UPC2-1 was introduced to sterol homeostasis and up-regulate the MVA pathway, and the resulting strain BY-V achieved a PPD production of 78.13 ± 0.38 mg/g DCW (563.60 ± 1.65 mg/L). Finally, sugarcane molasses was used as an inexpensive substrate for the first time in PPD synthesis. The PPD titers reached 1.55 ± 0.02 and 15.88 ± 0.65 g/L in shake flasks and a 5-L bioreactor, respectively. To the best of our knowledge, these results were new records on PPD production. CONCLUSION: The high-level of PPD production in this study and the successful comprehensive utilization of low-cost carbon source -sugarcane molassesindicate that the constructed yeast cell factory is an excellent candidate strain for the production of high-value-added PPD and its derivativeswith great industrial potential.


Subject(s)
Ginsenosides , Saccharum , Saponins , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharum/genetics , Saccharum/metabolism , Metabolic Engineering/methods , Molasses , Saponins/metabolism , Carbon/metabolism
9.
J Agric Food Chem ; 70(34): 10563-10570, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-35993186

ABSTRACT

Sclareol glycol is a key starting material with significant market interest for synthesizing high-value ambroxide, a sustainable substitute for ambergris in high-end fragrances. Sclareol glycol can be obtained by biotransformation of sclareol, a labdane-type diterpene, using Hyphozyma roseonigra. However, the pathway and mechanism of sclareol glycol biosynthesis remain unclear. In this study, the dynamic time course of sclareol biotransformation was explored by resting cell assays and several intermediates produced during biotransformation were detected. The results show that (1) sclareol glycol and sclareolide are not interconverted and are potentially synthesized via different metabolic pathways and (2) several putative intermediates resulting from biotransformation are featured with a labdane carbon backbone, including isomerized and oxidized analogues. A plausible transformation pathway of sclareol in H. roseonigra was proposed based on detected metabolites. This study sheds light on the biosynthetic mechanism of sclareol glycol and paves a way for the future biotechnological production of this promising compound.


Subject(s)
Ascomycota , Diterpenes , Ascomycota/metabolism , Biotransformation , Carbon/metabolism , Diterpenes/metabolism
10.
J Neural Eng ; 19(5)2022 10 07.
Article in English | MEDLINE | ID: mdl-36041420

ABSTRACT

Objective. Inferring the optimized and sparse network structure from the fully connected matrix is a key step in functional connectivity (FC) analysis. However, it is still an urgent problem to be solved, how to exclude the weak and spurious connections contained in functional networks objectively. Most existing binarization methods assume that the network has some certain constraint structures, which lead to changes in the original topology of the network.Approach. To solve this problem, we develop a Trade-off Model between Cost and Topology under Role Division (MCT), which consists of three crucial strategies, including modularity detection, definition of node role, and E-cost optimization algorithm. This algorithm weighs the physical cost and adaptive value of the network while preserving the network structure. Reliability and validity of MCT were evaluated by comparing different binarization methods (efficiency cost optimization, cluster-span threshold, threshold method, and MCT) on synthetic and real data sets.Main results. Experiment results demonstrated that the recovery rate of MCT for networks under noise interference is superior to other methods. In addition, brain networks filtered with MCT had higher network efficiency and shorter characteristic path length, which is more in line with the small world characteristics. Finally, applying MCT to resting-state electroencephalography data from patients with major depression reveals abnormal topology of the patients' connectivity networks, manifested as lower clustering coefficient (CC) and higher global efficiency (GE).Significance. This study provides an objective method for complex network analysis, which may contribute to the future of FC research.


Subject(s)
Brain Mapping , Magnetic Resonance Imaging , Brain , Brain Mapping/methods , Humans , Magnetic Resonance Imaging/methods , Neural Pathways , Reproducibility of Results
11.
Sci Data ; 9(1): 178, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35440583

ABSTRACT

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description.


Subject(s)
Mental Disorders , Artificial Intelligence , Electroencephalography , Humans , Mental Disorders/diagnosis , Mental Disorders/physiopathology
12.
ACS Synth Biol ; 11(2): 770-779, 2022 02 18.
Article in English | MEDLINE | ID: mdl-35107265

ABSTRACT

UDP-glycosyltransferase (UGT)-mediated glycosylation is a common modification in triterpene saponins, which exhibit a wide range of bioactivities and important pharmacological effects. However, few UGTs involved in saponin biosynthesis have been identified, limiting the biosynthesis of saponins. In this study, an efficient heterologous expression system was established for evaluating the UGT-mediated glycosylation process of triterpene saponins. Six UGTs (UGTPn17, UGTPn42, UGTPn35, UGTPn87, UGTPn19, and UGTPn12) from Panax notoginseng were predicted and found to be responsible for efficient and direct enzymatic biotransformation of 21 triterpenoid saponins via 26 various glycosylation reactions. Among them, UGTPn87 exhibited promiscuous sugar-donor specificity of UDP-glucose (UDP-Glc) and UDP-xylose (UDP-Xyl) by catalyzing the elongation of the second sugar chain at the C3 or/and C20 sites of protopanaxadiol-type saponins with a UDP-Glc or UDP-Xyl donor, as well as at the C20 site of protopanaxadiol-type saponins with a UDP-Glc donor. Two new saponins, Fd-Xyl and Fe-Xyl, were generated by catalyzing the C3-O-Glc xylosylations of notoginsenoside Fd and notoginsenoside Fe when incubated with UGTPn87. Moreover, the complete biosynthetic pathways of 17 saponins were elucidated, among which notoginsenoside L, vinaginsenoside R16, gypenoside LXXV, and gypenoside XVII were revealed in Panax for the first time. A yeast cell factory was constructed with a yield of Rh2 at 354.69 mg/L and a glycosylation ratio of 60.40% in flasks. Our results reveal the biosynthetic pathway of a group of saponins in P. notoginseng and provide a theoretical basis for producing rare and valuable saponins, promoting their industrial application in medicine and functional foods.


Subject(s)
Ginsenosides , Panax notoginseng , Panax , Saponins , Triterpenes , Ginsenosides/metabolism , Glycosyltransferases/metabolism , Panax/metabolism , Panax notoginseng/metabolism , Uridine Diphosphate/metabolism
13.
J Affect Disord ; 296: 622-634, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34688026

ABSTRACT

RATIONALE/IMPORTANCE: Researches have highlighted communication deficits between resting-state brain networks in major depressive disorder (MDD), as reflected in abnormal functional connectivity (FC). However, it is unclear whether impaired FC is associated with MDD pathology or is simply incidental to MDD symptoms. Moreover, there is no generalized theory to analyze the impact of treatment modalities on MDD. OBJECTIVES: To address the issues, we conducted a systematic review of 49 eligible papers to provide insight into the pathological mechanisms of MDD patients by summarizing resting-state FC alterations involving mood and cognitive abnormalities and the effects of medications on them. RESULTS: Mood disorders in MDD were characterized by abnormal FC between the amygdala, insula, anterior cingulate cortex (ACC), and prefrontal cortex (PFC). Cognitive impairment manifests as deficits in executive function, attention, memory, and rumination, primarily modulated by dysfunction between the fronto-parietal network and default mode network. Especially, we proposed the set of core abnormal FC (CA-FC) contributing to mood and cognitive impairment in MDD, currently including ACC-left precuneus/amygdala, rostral ACC-left dorsolateral PFC, left subgenual ACC-left cerebellar, left PFC- anterior subcallosal, and left precuneus-left pulvinar. After treatment, patients with normalized CA-FC showed remission of depressive symptoms. CONCLUSIONS: We propose a CA-FC set for possible causative principle of MDD, which unifies the FC results from specific, difficult-to-analyze conditions into one outcome set for screening. Furthermore, CA-FC varies from person to person, and the low success rate of a single treatment may be due to the inability to cover too many CA-FC.


Subject(s)
Depressive Disorder, Major , Antidepressive Agents/therapeutic use , Brain/diagnostic imaging , Brain Mapping , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Gyrus Cinguli , Humans , Magnetic Resonance Imaging
14.
Cancer Manag Res ; 13: 8575-8583, 2021.
Article in English | MEDLINE | ID: mdl-34815712

ABSTRACT

PURPOSE: Long non-coding RNA (lncRNA) DNAJC3 antisense RNA 1 (head to head) (DNAJC3-AS1) plays a key role in the progression of several cancers. However, its biological role in hepatocellular carcinoma (HCC) is still unclear. We aimed to investigate the role of DNAJC3-AS1 in the development of HCC and reveal the potential mechanisms. MATERIALS AND METHODS: Expression analysis of DNAJC3-AS1 and microRNA-27b (miR-27b) at both mature and premature levels was determined by RT-qPCR. HCC patients were followed up for 5 years to analyze the prognostic value of DNAJC3-AS1 for HCC. The direct interaction between DNAJC3-AS1 and premature miR-27b was analyzed with RNA pull-down assay. Subcellular analysis of DNAJC3-AS1 was explored by subcellular fractionation assay. DNAJC3-AS1 overexpression and knockdown were carried out to analyze the role of DNAJC3-AS1 in miR-27b maturation. Cell proliferation was analyzed by BrdU assay. RESULTS: DNAJC3-AS1 was overexpressed in HCC and predicts the poor survival. MiR-27b was downregulated at mature miRNA level, but upregulated at premature level. DNAJC3-AS1 directly interacted with premature miR-27b and was localized to both nuclear and cytoplasm. DNAJC3-AS1 overexpression upregulated premature miR-27b and downregulated mature miR-27b, while DNAJC3-AS1 knockdown led to the opposite results. DNAJC3-AS1 suppressed the role of miR-27b in inhibiting cell proliferation. CONCLUSION: DNAJC3-AS1 promotes HCC by sponging premature miR-27b and might be a biomarker and therapeutic target for HCC.

15.
Article in English | MEDLINE | ID: mdl-34166194

ABSTRACT

At present, most brain functional studies are based on traditional frequency bands to explore the abnormal functional connections and topological organization of patients with depression. However, they ignore the characteristic relationship of electroencephalogram (EEG) signals in the time domain. Therefore, this paper proposes a network decomposition model based on Improved Empirical Mode Decomposition (EMD), it is suitable for time-frequency analysis of brain functional network. On the one hand, it solves the problem of mode mixing on original EMD method, especially on high-density EEG data. On the other hand, by building brain function networks on different intrinsic mode function (IMF), we can perform time-frequency analysis of brain function connections. It provides a new insight for brain function connectivity analysis of major depressive disorder (MDD). Experimental results found that the IMFs waveform decomposed by Improved EMD was more stable and the difference between IMFs was obvious, it indicated that the mode mixing can be effectively solved. Besides, the analysis of the brain network, we found that the changes in MDD functional connectivity on different IMFs, it may be related to the pathological changes for MDD. More statistical results on three network metrics proved that there were significant differences between MDD and normal controls (NC) group. In addition, the aberrant brain network structure of MDDs was also confirmed in the hubs characteristic. These findings may provide potential biomarkers for the clinical diagnosis of MDD patients.


Subject(s)
Depressive Disorder, Major , Biomarkers , Brain , Electroencephalography , Humans
16.
Int J Cardiol ; 338: 185-195, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33731281

ABSTRACT

Myocardial ischemia/reperfusion (MI/R) may impair cardiac functions. Dexmedetomidine (DEX) is protective in various clinical cases. Therefore, this study investigated the role and mechanism of DEX in MI/R. The myocardial infarct size, apoptosis, and levels of myocardial enzymes, SOD, ROS, Ca2+, and inflammatory factors in DEX-treated MI/R rats were measured. Differentially expressed microRNAs (miRs) in DEX-treated MI/R rats were detected. miR-346-3p was intervened to assess the effects of DEX on MI/R rats. The targeted binding relationship between miR-346-3p and CaMKIId was predicted and verified. DEX effect on hypoxia/reoxygenation (H/R)-induced cell model was evaluated. The role of CaMKIId in DEX protection was assessed after CaMKIId overexpression in H/R cells. NF-κB pathway and NLRP3 inflammasome-related protein levels were detected. DEX alleviated the myocardial injury and Ca2+ overload in MI/R rats, as evidenced by reduced infarct size, apoptosis and levels of myocardial enzymes, ROS, Ca2+, and inflammatory factors. DEX promoted miR-346-3p expression in MI/R rats, and miR-346-3p knockdown reversed DEX protection on MI/R rats. miR-346-3p targeted CaMKIId. DEX improved H/R-induced cell injury and Ca2+ overload and inhibited NF-κB/NLRP3 inflammasome-related protein levels, which were all reversed by CaMKIId overexpression. DEX alleviated injury and Ca2+ overload in MI/R via regulating the miR-346-3p/CaMKIId axis and inhibiting the NF-κB/NLRP3 inflammasome pathway.


Subject(s)
Dexmedetomidine , MicroRNAs , Myocardial Reperfusion Injury , Animals , Apoptosis , Dexmedetomidine/pharmacology , MicroRNAs/genetics , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/genetics , Myocytes, Cardiac , Rats
17.
Front Bioeng Biotechnol ; 9: 792023, 2021.
Article in English | MEDLINE | ID: mdl-35145961

ABSTRACT

2,3,5,6-Tetramethylpyrazine (TMP) is an active pharmaceutical ingredient originally isolated from Ligusticum wallichii for curing cardiovascular and cerebrovascular diseases and is widely used as a popular flavoring additive in the food industry. Hence, there is a great interest in developing new strategies to produce this high-value compound in an ecological and economical way. Herein, a cost-competitive combinational approach was proposed to accomplish green and high-efficiency production of TMP. First, microbial cell factories were constructed to produce acetoin (3-hydroxy-2-butanone, AC), an endogenous precursor of TMP, by introducing a biosynthesis pathway coupled with an intracellular NAD+ regeneration system to the wild-type Escherichia coli. To further improve the production of (R)-AC, the metabolic pathways of by-products were impaired or blocked stepwise by gene manipulation, resulting in 40.84 g/L (R)-AC with a high optical purity of 99.42% in shake flasks. Thereafter, an optimal strain designated GXASR11 was used to convert the hydrolysates of inexpensive feedstocks into (R)-AC and achieved a titer of 86.04 g/L within 48 h in a 5-L fermenter under optimized fermentation conditions. To the best of our knowledge, this is the highest (R)-AC production with high optical purity (≥98%) produced from non-food raw materials using recombinant E. coli. The supernatant of fermentation broth was mixed with diammonium phosphate (DAP) to make a total volume of 20 ml and transferred to a high-pressure microreactor. Finally, 56.72 g/L TMP was obtained in 3 h via the condensation reaction with a high conversion rate (85.30%) under optimal reaction conditions. These results demonstrated a green and sustainable approach to efficiently produce high-valued TMP, which realized value addition of low-cost renewables.

18.
IEEE Trans Nanobioscience ; 19(3): 527-537, 2020 07.
Article in English | MEDLINE | ID: mdl-32340958

ABSTRACT

At present, depression has become a main health burden in the world. However, there are many problems with the diagnosis of depression, such as low patient cooperation, subjective bias and low accuracy. Therefore, reliable and objective evaluation method is needed to achieve effective depression detection. Electroencephalogram (EEG) and eye movements (EMs) data have been widely used for depression detection due to their advantages of easy recording and non-invasion. This research proposes a content based ensemble method (CBEM) to promote the depression detection accuracy, both static and dynamic CBEM were discussed. In the proposed model, EEG or EMs dataset was divided into subsets by the context of the experiments, and then a majority vote strategy was used to determine the subjects' label. The validation of the method is testified on two datasets which included free viewing eye tracking and resting-state EEG, and these two datasets have 36,34 subjects respectively. For these two datasets, CBEM achieves accuracies of 82.5% and 92.65% respectively. The results show that CBEM outperforms traditional classification methods. Our findings provide an effective solution for promoting the accuracy of depression identification, and provide an effective method for identificationof depression, which in the future could be used for the auxiliary diagnosis of depression.


Subject(s)
Depression/diagnosis , Electroencephalography/methods , Eye-Tracking Technology , Signal Processing, Computer-Assisted , Algorithms , Diagnosis, Computer-Assisted , Female , Humans , Machine Learning , Male
19.
Curr Top Med Chem ; 19(25): 2348-2356, 2019.
Article in English | MEDLINE | ID: mdl-31648637

ABSTRACT

Acetoin is an important four-carbon compound that has many applications in foods, chemical synthesis, cosmetics, cigarettes, soaps, and detergents. Its stereoisomer (S)-acetoin, a high-value chiral compound, can also be used to synthesize optically active drugs, which could enhance targeting properties and reduce side effects. Recently, considerable progress has been made in the development of biotechnological routes for (S)-acetoin production. In this review, various strategies for biological (S)- acetoin production are summarized, and their constraints and possible solutions are described. Furthermore, future prospects of biological production of (S)-acetoin are discussed.


Subject(s)
Acetoin/metabolism , Biological Products/metabolism , Acetoin/chemistry , Biological Products/chemistry , Molecular Conformation
20.
Exp Ther Med ; 17(1): 153-158, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30651776

ABSTRACT

The expression of ADAMTS-1 mRNA in myocardium of viral heart disease (VHD) mice was investigated to explore its role in myocardial fibrosis. A total of 150 purebred inbred Balb/c mice were used in this study. According to the principle of similar body weight, 50 mice were selected to make an acute viral myocarditis (VMC) animal model (acute VMC group), and 50 mice were selected to make a chronic VMC animal model (chronic VMC group), and the remaining 50 mice were selected as a control group. RT-qPCR was used to detect the relative expression of transforming growth factor-ß1 (TGF-ß1) mRNA and ADAMTS-1 mRNA in myocardial tissue of three groups of mice, and their relationship in myocardial fibrosis was analyzed. Compared with the control group, the collagen volume fraction (CVF) in the myocardial tissue of the acute VMC group was significantly increased, and the increase of CVF in the myocardial tissue of the chronic VMC group was the most significant (p<0.001). Compared with the control group, the relative expression of TGF-ß1 mRNA and ADAMTS-1 mRNA in myocardial tissue of the mice in the acute and chronic VMC group were significantly increased (p<0.001). The relative expression of TGF-ß1 mRNA and ADAMTS-1 mRNA in myocardial tissue of chronic VMC group was significantly higher than that of acute VMC group (p<0.001). Pearson's correlation test results showed that ADAMTS-1 mRNA was positively correlated with CVF and TGF-ß1 mRNA, and the correlation coefficients were (r=0.351, p<0.01, r=0.401, p<0.01). ADAMTS-1 is involved in the occurrence and development of myocardial fibrosis, and it is positively correlated with CVF and TGF-ß1. It may play a role in promoting myocardial fibrosis during the development of VHD. It can be used as a biological index for predicting myocardial fibrosis.

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