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1.
Nat Commun ; 12(1): 790, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542233

RESUMO

Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2-C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine.


Assuntos
Proteínas de Bactérias/metabolismo , Flavonas/metabolismo , Flavonóis/metabolismo , Microbioma Gastrointestinal/fisiologia , Oxirredutases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/ultraestrutura , Clostridiales/enzimologia , Clostridiales/genética , Cristalografia por Raios X , Oxirredutases/genética , Oxirredutases/isolamento & purificação , Oxirredutases/ultraestrutura , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura
2.
Nat Chem ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603222

RESUMO

Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis.

3.
J Reprod Immunol ; 144: 103281, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33549904

RESUMO

MiR-126-3p is a prototype of an endothelial miRNA and has protective effects on endothelial cells. However, little is known about the effects of miR-126-3p on placental trophoblasts. In the present study, we tested the hypothesis that aberrant miR-126-3p expression is present in preeclamptic placenta which contributes to increased inflammatory response in trophoblasts. Placentas were obtained immediately after delivery from normotensive and preeclamptic pregnancies. Villous tissue was either fixed with formalin or used for trophoblast isolation. Trophoblast miR-126-3p expression was assessed by in situ hybridization of formalin-fixed tissue sections and by RT-PCR in cultured syncytiotrophoblasts. Culture medium was collected for measurement of IL-6, TNFα, and 8-Isoprostane production by ELISA and total cellular protein was collected for evaluation of HIF1α expression by Western blot. Effects of overexpression of miR-126-3p in trophoblasts on cytokine production were tested by transfection of pre-mir-126, a precursor of miR-126, into primary isolated trophoblasts. We found that downregulation of miR-126-3p expression was associated with increased IL-6 and TNFα production in trophoblasts from preeclamptic placentas vs. normal placentas. Moreover, transient overexpression of miR-126-3p significantly reduced IL-6 and TNFα production in trophoblasts from both normal and preeclamptic placentas. We further found that increase in miR-126-3p expression not only suppressed hypoxia-induced increases in IL-6 and TNFα production, but also attenuated hypoxia-induced increases in HIF1α expression and 8-Isoprostane production in trophoblasts cultured under hypoxic condition. These results provide plausible evidence that downregulation of miR-126-3p expression reduces anti-inflammatory and anti-oxidative stress activities in placental trophoblasts in preeclampsia.

4.
Ecotoxicology ; 30(2): 373-380, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33511510

RESUMO

The existing methods of measuring combined toxicity of heavy metal mixtures in environment do not fully consider three major factors (i.e., number of heavy metal species, aquatic biota, all investigated sites as an entity). Herein, a new method named joint probabilistic risk (JPR) method is proposed for evaluating the combined toxicity of heavy metal mixtures to aquatic biota. In this new method, the above three factors are fully taken into account. In order to evaluate the feasibility of the new method, the Pearl River Estuary (PRE) is selected as a case study. Concentrations of heavy metals (Cd, Pb, Cr, Ni, Cu, and Zn) in surface sediments of PRE are investigated and toxic equivalent factors (TEFs) of these heavy metals are calculated. Based on TEFs, sedimental concentrations of heavy metals of PRE are converted to Cd toxic equivalent concentration (Cdeq), while the Cd toxicity data (Cdto) are extracted from the literature. The probability density curves for Cdeq and Cdto are constructed and the overlap area is quantified as 0.2497. This indicates that the surface sediments of PRE have a 24.97% probability of toxic effect towards aquatic biota. Finally, this new method is validated by two indirect methods of mERMq and mPELq.

5.
Neurology ; 96(9): e1278-e1289, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33472914

RESUMO

OBJECTIVE: To test the hypothesis that brain injury is more common and varied in patients receiving extracorporeal membrane oxygenation (ECMO) than radiographically observed, we described neuropathology findings of ECMO decedents and associated clinical factors from 3 institutions. METHODS: We conducted a retrospective multicenter observational study of brain autopsies from adult ECMO recipients. Pathology findings were examined for correlation with demographics, clinical data, ECMO characteristics, and outcomes. RESULTS: Forty-three decedents (n = 13 female, median age 47 years) received autopsies after undergoing ECMO for acute respiratory distress syndrome (n = 14), cardiogenic shock (n = 14), and cardiac arrest (n = 15). Median duration of ECMO was 140 hours, most decedents (n = 40) received anticoagulants; 60% (n = 26) underwent venoarterial ECMO, and 40% (n = 17) underwent venovenous ECMO. Neuropathology was found in 35 decedents (81%), including microhemorrhages (37%), macrohemorrhages (35%), infarctions (47%), and hypoxic-ischemic brain injury (n = 17, 40%). Most pathology occurred in frontal neocortices (n = 43 occurrences), basal ganglia (n = 33), and cerebellum (n = 26). Decedents with hemorrhage were older (median age 57 vs 38 years, p = 0.01); those with hypoxic brain injury had higher Sequential Organ Failure Assessment scores (8.0 vs 2.0, p = 0.04); and those with infarction had lower peak Paco2 (53 vs 61 mm Hg, p = 0.04). Six of 9 patients with normal neuroimaging results were found to have pathology on autopsy. The majority underwent withdrawal of life-sustaining therapy (n = 32, 74%), and 2 of 8 patients with normal brain autopsy underwent withdrawal of life-sustaining therapy for suspected neurologic injury. CONCLUSION: Neuropathological findings after ECMO are common, varied, and associated with various clinical factors. Further study on underlying mechanisms is warranted and may guide ECMO management.

7.
JAMA Netw Open ; 3(12): e2028086, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33289845

RESUMO

Importance: Axillary lymph node metastasis (ALNM) status, typically estimated using an invasive procedure with a high false-negative rate, strongly affects the prognosis of recurrence in breast cancer. However, preoperative noninvasive tools to accurately predict ALNM status and disease-free survival (DFS) are lacking. Objective: To develop and validate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of ALNM and to assess individual DFS in patients with early-stage breast cancer. Design, Setting, and Participants: This retrospective prognostic study included patients with histologically confirmed early-stage breast cancer diagnosed at 4 hospitals in China from July 3, 2007, to September 21, 2019, randomly divided (7:3) into development and vaidation cohorts. All patients underwent preoperative MRI scans, were treated with surgery and sentinel lymph node biopsy or ALN dissection, and were pathologically examined to determine the ALNM status. Data analysis was conducted from February 15, 2019, to March 20, 2020. Exposure: Clinical and DCE-MRI radiomic signatures. Main Outcomes and Measures: The primary end points were ALNM and DFS. Results: This study included 1214 women (median [IQR] age, 47 [42-55] years), split into development (849 [69.9%]) and validation (365 [30.1%]) cohorts. The radiomic signature identified ALNM in the development and validation cohorts with areas under the curve (AUCs) of 0.88 and 0.85, respectively, and the clinical-radiomic nomogram accurately predicted ALNM in the development and validation cohorts (AUC, 0.92 and 0.90, respectively) based on a least absolute shrinkage and selection operator (LASSO)-logistic regression model. The radiomic signature predicted 3-year DFS in the development and validation cohorts (AUC, 0.81 and 0.73, respectively), and the clinical-radiomic nomogram could discriminate high-risk from low-risk patients in the development cohort (hazard ratio [HR], 0.04; 95% CI, 0.01-0.11; P < .001) and the validation cohort (HR, 0.04; 95% CI, 0.004-0.32; P < .001) based on a random forest-Cox regression model. The clinical-radiomic nomogram was associated with 3-year DFS in the development and validation cohorts (AUC, 0.89 and 0.90, respectively). The decision curve analysis demonstrated that the clinical-radiomic nomogram displayed better clinical predictive usefulness than the clinical or radiomic signature alone. Conclusions and Relevance: This study described the application of MRI-based machine learning in patients with breast cancer, presenting novel individualized clinical decision nomograms that could be used to predict ALNM status and DFS. The clinical-radiomic nomograms were useful in clinical decision-making associated with personalized selection of surgical interventions and therapeutic regimens for patients with early-stage breast cancer.

8.
Sensors (Basel) ; 20(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33322029

RESUMO

Due to deep learning's accurate cognition of the street environment, the convolutional neural network has achieved dramatic development in the application of street scenes. Considering the needs of autonomous driving and assisted driving, in a general way, computer vision technology is used to find obstacles to avoid collisions, which has made semantic segmentation a research priority in recent years. However, semantic segmentation has been constantly facing new challenges for quite a long time. Complex network depth information, large datasets, real-time requirements, etc., are typical problems that need to be solved urgently in the realization of autonomous driving technology. In order to address these problems, we propose an improved lightweight real-time semantic segmentation network, which is based on an efficient image cascading network (ICNet) architecture, using multi-scale branches and a cascaded feature fusion unit to extract rich multi-level features. In this paper, a spatial information network is designed to transmit more prior knowledge of spatial location and edge information. During the course of the training phase, we append an external loss function to enhance the learning process of the deep learning network system as well. This lightweight network can quickly perceive obstacles and detect roads in the drivable area from images to satisfy autonomous driving characteristics. The proposed model shows substantial performance on the Cityscapes dataset. With the premise of ensuring real-time performance, several sets of experimental comparisons illustrate that SP-ICNet enhances the accuracy of road obstacle detection and provides nearly ideal prediction outputs. Compared to the current popular semantic segmentation network, this study also demonstrates the effectiveness of our lightweight network for road obstacle detection in autonomous driving.

9.
Laryngoscope ; 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33378575

RESUMO

OBJECTIVES: Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. MATERIALS AND METHODS: From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. RESULTS: Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. CONCLUSIONS: TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2020.

11.
Front Bioeng Biotechnol ; 8: 560726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195125

RESUMO

The sustainable production of chemicals from non-petrochemical sources is one of the greatest challenges of our time. CO2 release from industrial activity is not environmentally friendly yet provides an inexpensive feedstock for chemical production. One means of addressing this problem is using acetogenic bacteria to produce chemicals from CO2, waste streams, or renewable resources. Acetogens are attractive hosts for chemical production for many reasons: they can utilize a variety of feedstocks that are renewable or currently waste streams, can capture waste carbon sources and covert them to products, and can produce a variety of chemicals with greater carbon efficiency over traditional fermentation technologies. Here we investigated the metabolism of Clostridium ljungdahlii, a model acetogen, to probe carbon and electron partitioning and understand what mechanisms drive product formation in this organism. We utilized CRISPR/Cas9 and an inducible riboswitch to target enzymes involved in fermentation product formation. We focused on the genes encoding phosphotransacetylase (pta), aldehyde ferredoxin oxidoreductases (aor1 and aor2), and bifunctional alcohol/aldehyde dehydrogenases (adhE1 and adhE2) and performed growth studies under a variety of conditions to probe the role of those enzymes in the metabolism. Finally, we demonstrated a switch from acetogenic to ethanologenic metabolism by these manipulations, providing an engineered bacterium with greater application potential in biorefinery industry.

12.
Med Sci Monit ; 26: e925068, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33177483

RESUMO

BACKGROUND Rifaximin is an antimicrobial agent used to treat inflammatory bowel disease (IBD). Vitamin D3 can control IBD due to its effects on inflammatory cytokines. The purpose of this study was to assess the effect of vitamin D3 on the intestinal flora of a dextran sulfate sodium (DSS)-induced mouse model treated with rifaximin. MATERIAL AND METHODS The mouse model of IBD was developed using DSS (4%) administered via the drinking water. Twenty-four male C57BL6 mice were divided into the control group with a normal diet (N=6), the DSS group with a normal diet (N=6), the DSS group with a normal diet treated with rifaximin (N=6), and the DSS group with a normal diet treated with rifaximin and vitamin D3 (N=6). After 14 days, the colonic tissue was studied histologically. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1ß (IL-1ß) and enzyme-linked immunosorbent assay (ELISA) were used to measure the level of IL-6 and P65, and phospho-p65 was measured by western blot. 16S rRNA gene sequencing was used to analyze fecal samples. RESULTS In the DSS mouse model of IBD, rifaximin reduced the inflammation severity of the colon and reduced the expression of phospho-p65, p65, TNF-alpha, and IL-6. In the DSS+rifaximin+vitamin D3 group, the therapeutic influences of rifaximin, in terms of weight loss and colonic disease activity, were significantly reduced, and the gut microbiota of the mice were completely changed in composition and diversity. CONCLUSIONS In a mouse model of IBD, treatment with vitamin D3 significantly increased the metabolism of rifaximin and reduced its therapeutic effects.

14.
BMC Nephrol ; 21(1): 514, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243164

RESUMO

BACKGROUND: A renal biopsy is needed to define active inflammatory infiltration and guide therapeutic management in drug-induced acute tubulointerstitial nephritis (D-ATIN). However, factors such as various contraindications, refusal of informed consent and limited technical support may stop the biopsy process. It is thus of great importance to explore approaches that could deduce probable pathologic changes. METHODS: A total of 81 biopsy-proven D-ATIN patients were enrolled from a prospective cohort of ATIN patients at Peking University First Hospital. The systemic inflammation score (SIS) was developed based on the CRP and ESR levels at biopsy, and patients were divided into high-SIS, median-SIS, and low-SIS groups. The demographic data, clinicopathologic features, and renal outcomes were compared. RESULTS: The SIS was positively correlated with inflammatory cell infiltration and was inversely correlated with interstitial fibrosis. The number of interstitial inflammatory cells increased significantly with increasing SISs. The proportions of neutrophils and plasma cells were the highest in the high-SIS group compared with the other two groups. Prednisone (30-40 mg/day) was prescribed in all patients. The high-SIS group tended to have more favorable renal restoration than the other two groups. By 12 months postbiopsy, a decreased eGFR (< 60 mL/min/1.73 m2) was observed in 66.7% of medium-SIS patients, 32.4% of high-SIS patients, and 30.4% of low-SIS patients. CONCLUSION: The SIS was positively correlated with active tubulointerstitial inflammation and therefore could help to aid therapeutic decisions in D-ATIN.

15.
Cancer Cell Int ; 20: 517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33100909

RESUMO

Background: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments. Methods: Differentially expressed miRNAs and mRNAs were screened from six pairs of primary OC tissues and metastatic tissues using a miRStar™ Human Cancer Focus miRNA and Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFß2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFß2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells. Results: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFß2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFß2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFß2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFß2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFß2 overexpression rescued the cell activities. Conclusions: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFß2 expression, thereby inhibiting the growth and metastasis of OC.

16.
Can Respir J ; 2020: 2379814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082890

RESUMO

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.

17.
Nat Chem Biol ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116303
18.
Placenta ; 103: 43-49, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33070036

RESUMO

INTRODUCTION: N6-methyladenosine (m6A) has been recognized as one of the most abundant and functionally relevant modifications of RNAs and plays critical roles in biological and pathological processes. Placental trophoblast dysfunction significantly contributes to the pathogenesis of preeclampsia. The present study aimed to determine if altered m6A expression occurs in placental trophoblasts in preeclampsia. Expression of m6A methyltransferase (methyltransferase like 3 (METTL3)), m6A demethylases (fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)), and m6A reader protein, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2), were also examined. METHODS: A total of 43 placentas (20 normal term, 5 normotensive preterm, and 18 preeclamptic) were used in the study. Expression of m6A, METTL3, FTO, ALKBH5, and hnRNPC1/C2 were examined by immunostaining in villous tissue sections and/or by Western blot of total cellular protein in trophoblasts isolated from normotensive and preeclamptic placentas. Total RNA extracted from trophoblasts was used to measure m6A RNA methylation. Effects of METTL3 on m6A RNA methylation and hnRNPC1/C2 expression were assessed by transfection of METTL3 siRNA in trophoblasts from preeclamptic placentas. RESULTS: Expression of m6A and m6A RNA methylation were significantly increased in trophoblasts from preeclamptic vs. normotensive placentas, p < 0.05. Expression of METTL3 and hnRNPC1/C2, but not FTO and ALKBH5, was significantly upregulated in trophoblasts from preeclamptic vs. normotensive placentas, p < 0.01. Transfection of METTL3 siRNA significantly reduced the level of m6A RNA methylation and hnRNPC1/C2 expression in trophoblasts from preeclamptic placentas, p < 0.05. CONCLUSION: The finding of increased METTL3 expression and m6A RNA methylation associated with increased hnRNPC1/C2 expression provides a new posttranscriptional mechanism that aberrant m6A modification may contribute to trophoblast dysfunction in preeclampsia.

19.
Appl Microbiol Biotechnol ; 104(21): 9109-9124, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32974742

RESUMO

As natural metabolites, organic acids have been widely applied in food, pharmaceutical, and bio-based materials industries. Particularly, the short-chain organic acids, including C2, C3, C4, C5, and C6 organic acids, are necessary intermediate metabolites in cells and are also alternatives to some commercial chemical products. As the necessary metabolites in cells, most major short-chain organic acids can be produced through microbial fermentation. Specifically, with the development of synthetic biology, metabolic engineering could endow cells with the ability to produce more short-chain organic acid products including propionic acid, pyruvate, lactic acid, 3-hydroxypropionic acid, malic acid, succinic acid, fumaric acid, butyric acid, itaconic acid, α-ketoglutaric acid, glutaric acid, citric acid, gluconic acid, muconic acid, adipic acid, xylonic acid, and so on. The recent advances in the biological production of short-chain organic acids, as well as the challenges and perspectives, are summarized in this review to promote the generation of microbial cell factories for the production of short-chain organic acids.Key points• Outlines the production strategy of short-chain organic acids• Provide guidance for efficient synthesis of short-chain organic acids• Impacts the necessary factor of acid resistance on the successful production of host cells.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32774418

RESUMO

Electroacupuncture (EA) is reported to possess anti-inflammatory properties and has beneficial effects on acute respiratory distress syndrome (ARDS). However, the underlying mechanisms of the effects of EA on ARDS remain unclear. This study aims to investigate the protective effect of EA on LPS-induced ARDS. In this study, Sprague-Dawley male rats were treated with EA at Hegu (LI4) for 45 minutes before LPS instillation (0.4 mg/kg, 100 ul). H&E staining, wet-to-dry weight (W/D) ratio, PaO2, and protein content in BALF were employed to determine the function of lung tissues. Inflammatory cytokines in serum and BALF were detected by enzyme-linked immunoassay assay (ELISA). The levels of oxidative stress markers were detected to determine the oxidative stress status. Cell apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and western blot. Here, we found that EA pretreatment effectively alleviated lung pathological damage. Moreover, EA suppressed the oxidative stress damage by upregulating glutathione and superoxide dismutase and downregulating malondialdehyde. EA pretreatment also regulated apoptosis-related proteins, such as Bax and Bcl-2. We found that peroxisome proliferators-activated receptors γ (PPARγ) play a critical role during ARDS, EA up-regulated the expression of PPARγ, which inhibited the activation of nuclear factor-kappa B (NF-κB) and decreased the inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α). When rats were treated with GW9662, a selective PPARγ antagonist, these effects of EA were reversed. Our study demonstrated that EA pretreatment had a beneficial effect on LPS-induced ARDS in rats by anti-inflammatory, antioxidative, and antiapoptotic properties which was regulated via PPARγ/NF-κB signaling pathway.

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