Publications by authors named "Juan Guo"

241 Publications

Synthesis and evaluation of Grateloupia Livida polysaccharides-functionalized selenium nanoparticles.

Int J Biol Macromol 2021 Sep 18. Epub 2021 Sep 18.

College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China; The State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou, Hainan, China. Electronic address:

Grateloupia Livida polysaccharides-functionalized selenium nanoparticles (GLP-SeNPs) have been successfully prepared in a simple redox system of sodium selenite and ascorbic acid. The size, morphology, structure, stability and thermal behavior were analyzed by various characterization methods. These results showed that, GLP-SeNPs (particle size of 115.54 nm) prepared in optimal synthesis conditions (temperature of 45 °C, reaction time of 3 h, GLP concentration of 1.0 mg/mL and ascorbic acid concentration of 0.04 M) obtained by orthogonal experiments were uniform spherical and could be stable for 30 days at 4 °C. GLP-SeNPs exhibited significant scavenging ability on DPPH, ABTS, hydroxyl radical and superoxide anion radical when compared to GLP and NaSeO. GLP-SeNPs showed selective cytotoxicity toward various human cancer cells, but not normal cells. Besides, GLP-SeNPs exhibited low oral acute toxicity. Taken together, GLP-SeNPs might be used as potential diet nutritional supplement or anticancer agent.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.087DOI Listing
September 2021

HGF/c-MET pathway contributes to cisplatin-mediated PD-L1 expression in hepatocellular carcinoma.

Cell Biol Int 2021 Sep 5. Epub 2021 Sep 5.

Department of Pharmacology, Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, Kaifeng, China.

Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8  T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.
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http://dx.doi.org/10.1002/cbin.11697DOI Listing
September 2021

Dynamics of epigenetic regulator gene BCOR mutation and response predictive value for hypomethylating agents in patients with myelodysplastic syndrome.

Clin Epigenetics 2021 Aug 30;13(1):169. Epub 2021 Aug 30.

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Background: BCOR (BCL6 corepressor) is an epigenetic regulator gene involved in the specification of cell differentiation and body structure development. Recurrent somatic BCOR mutations have been identified in myelodysplastic syndrome (MDS). However, the clinical impact of BCOR mutations on MDS prognosis is controversial and the response of hypomethylating agents in MDS with BCOR mutations (BCOR) remains unknown.

Results: Among 676 MDS patients, 43 patients (6.4%) harbored BCOR mutations. A higher frequency of BCOR mutations (8.7%) was investigated in patients with normal chromosome, compared to 4.2% in patients with abnormal karyotype (p = 0.040). Compared to the BCOR patients, the BCOR patients showed a higher ratio of refractory anemia with excess blasts subset (p = 0.008). The most common comutations with BCOR genes were ASXL1 (p = 0.002), DNMT3A (p = 0.114) and TET2 (p = 0.148). When the hierarchy of somatic mutations was analyzed, BCOR mutations were below the known initial mutations (ASXL1 or TET2) but were above U2AF1 mutations. Transformation-free survival was significantly shorter in BCOR patients than that in BCOR patients (16 vs. 35 months; p = 0.035). RNA-sequencing was performed in bone marrow mononuclear cells from BCOR and BCOR patients and revealed 2030 upregulated and 772 downregulated genes. Importantly, HOXA6, HOXB7, and HOXB9 were significantly over-expressed in BCOR patients, compared to BCOR patients. Eight of 14 BCOR patients (57.1%) achieved complete remission (CR) with decitabine treatment, which was much higher than that in BCOR patients (28.7%, p = 0.036). Paired sequencing results (before and after decitabine) showed three of 6 CR patients lost the mutated BCOR. The median survival of CR patients with a BCOR was 40 months, which was significantly longer than that in patients with BCOR (20 months, p = 0.036). Notably, prolonged survival was observed in three BCOR CR patients even without any subsequent therapies.

Conclusions: BCOR mutations occur more frequently in CN MDS patients, predicting higher risk of leukemia transformation. BCOR patients showed a better response to decitabine and achieved longer post-CR survival.
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http://dx.doi.org/10.1186/s13148-021-01157-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404357PMC
August 2021

Activation of Orexinergic Neurons Inhibits the Anesthetic Effect of Desflurane on Consciousness State via Paraventricular Thalamic Nucleus in Rats.

Anesth Analg 2021 09;133(3):781-793

From the Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Background: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia.

Methods: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia.

Results: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia.

Conclusions: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.
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http://dx.doi.org/10.1213/ANE.0000000000005651DOI Listing
September 2021

Chemical-activity-based quality marker screening strategy for Viscum articulatum.

Biomed Chromatogr 2021 Aug 13:e5175. Epub 2021 Aug 13.

Academician Workstation, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Viscum articulatum Burm. f. is a parasitic plant rich in flavonoids, triterpenoids, and catechins and has a high nutritional value. It has been reported that consuming V. articulatum can prevent cardiac diseases. In this study, six bioactive compounds, including catechins, triterpenoids, and phenylpropanoid glycosides, were determined in alcohol extracts of the plant using HPLC. The anti-inflammatory and antioxidant activities of three catechins, two triterpenoids, and three combination drugs were measured in cardiomyocytes, and the results showed that the anti-inflammatory activity was significantly enhanced while retaining strong antioxidant activity when epicatechin and ursolic acid were used in combination. The main quality markers epicatechin and ursolic acid were screened based on the specificity of the genuine herb and a potent synergistic effect, and the lowest limitation contents of V. articulatum which could discriminate it from some other taxonomically similar materials were accordingly determined. This self-built lowest limitation content of the two screened quality markers could quickly and accurately reflect the efficacy in terms of chemical composition and reverse the disorderly market use of nongenuine herbs or confusing species for adulteration. This study is of some significance for market regulation, drug development, and clinical medication.
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http://dx.doi.org/10.1002/bmc.5175DOI Listing
August 2021

Effects of pulsed electromagnetic fields on tumor cell viability: a meta-analysis of in vitro randomized controlled experiments.

Electromagn Biol Med 2021 Jul 26:1-8. Epub 2021 Jul 26.

Department of Radiation Protection Medicine, Shaanxi Key Laboratory of Free Radical Biology and Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Faculty of Preventive Medicine, Air Force Medical University, Xi'an, Shaanxi Province, China.

Malignant tumor treatment remains a big challenge till now, and expanding literature indicated that pulsed electromagnetic fields (PEMF) is promising in tumor treatment with the advantage of safety and being economical, but it is still controversial on whether PEMF could affect the tumor cell viability. Therefore, we conducted the meta-analysis to evaluate effects of PEMF on tumor cell viability. The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published up to February 2021. Studies on the direct effects of PEMF on tumor cell viability, determined using colorimetric analysis, were included. Two authors extracted the data and completed the quality assessment. A meta-analysis was performed to calculate the absorbance values and 95% confidence intervals (CIs) using random-effects models. Seven studies, including 32 randomized controlled experiments, were analyzed. Compared with the control group, tumor cell viability in the PEMF exposure group was obviously lower (SMD, -0.67; 95% CI: -1.12 to -0.22). The subgroup meta-analysis results showed that PEMF significantly reduced epithelial cancer cell viability (SMD, -0.58; 95% CI: -0.92 to -0.23) but had no influence on stromal tumor cell viability (SMD, -0.93; 95% CI: -0.21 to 0.15). Our study demonstrated that PEMF could inhibit tumor cell proliferation to some extent, but the risk of bias and high heterogeneity (I > 75%) weakened the strength of the conclusions drawn from the analysis.
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http://dx.doi.org/10.1080/15368378.2021.1958341DOI Listing
July 2021

Fatty Acid Synthase-Suppressor Screening Identifies Sorting Nexin 8 as a Therapeutic Target for NAFLD.

Hepatology 2021 Jul 7. Epub 2021 Jul 7.

College of Life Sciences, Medical Science Research Center, Zhongnan Hospital, Wuhan University, Wuhan, China.

Background And Aims: NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration-approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of the most attractive targets for NAFLD treatment because of its robust rate-limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown.

Methods And Results: Through a systematic interactomics analysis of FASN-complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28-FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8-knockout mice compared to wild-type controls. Consistently, hepatocyte-specific overexpression of Snx8 in vivo markedly suppressed high-fat, high-cholesterol diet (HFHC)-induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression.

Conclusions: These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8-FASN axis is a promising strategy for NAFLD prevention and treatment.
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http://dx.doi.org/10.1002/hep.32045DOI Listing
July 2021

U2AF1 mutation promotes tumorigenicity through facilitating autophagy flux mediated by FOXO3a activation in myelodysplastic syndromes.

Cell Death Dis 2021 06 28;12(7):655. Epub 2021 Jun 28.

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Mutations in the U2 small nuclear RNA auxiliary factor 1 (U2AF1) gene are the common feature of a major subset in myelodysplastic syndromes (MDS). However, the genetic landscape and molecular pathogenesis of oncogenic U2AF1 mutation in MDS are not totally understood. We performed comprehensive analysis for prognostic significance of U2AF1 mutations in acute myeloid leukemia (AML) cohort based on The Cancer Genome Atlas (TCGA) database. Functional analysis of U2AF1 mutation was performed in vitro. Differentially expressed genes (DEGs) and significantly enriched pathways were identified by RNA sequencing. The forkhead box protein O3a (FOXO3a) was investigated to mediate the function of U2AF1 mutation in cell models using lentivirus. Chromatin immunoprecipitation, immunoblotting analyses, and immunofluorescence assays were also conducted. U2AF1 mutations were associated with poor prognosis in MDS and AML samples, which significantly inhibited cell proliferation and induced cellular apoptosis in cell models. Our data identified that U2AF1-mutant cell lines undergo FOXO3a-dependent apoptosis and NLRP3 inflammasome activation, which induces pyroptotic cell death. Particularly, an increase in the level of FOXO3a promoted the progression of MDS in association with restored autophagy program leading to NLRP3 inflammasome activation in response to U2AF1 mutation. Based on the result that U2AF1 mutation promoted the transcriptional activity of Bim through upregulating FOXO3a with transactivation of cell cycle regulators p21 and p27, FOXO3a, a potentially cancer-associated transcription factor, was identified as the key molecule on which these pathways converge. Overall, our studies provide new insights that U2AF1 mutation functions the crucial roles in mediating MDS disease progression via FOXO3a activation, and demonstrate novel targets of U2AF1 mutations to the pathogenesis of MDS.
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http://dx.doi.org/10.1038/s41419-021-03573-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238956PMC
June 2021

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state.

Biochem Biophys Res Commun 2021 Aug 2;565:21-28. Epub 2021 Jun 2.

School of Life Science and Technology, Shanghai Tech University, Shanghai, 201210, China. Electronic address:

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.079DOI Listing
August 2021

Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry.

J Ethnopharmacol 2021 Sep 24;277:114216. Epub 2021 May 24.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address:

Ethnopharmacological Relevance: Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever, and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum.

Aim Of The Study: The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification.

Materials And Methods: Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices.

Results: Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids (e.g., palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism.

Conclusion: The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum, which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine.
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http://dx.doi.org/10.1016/j.jep.2021.114216DOI Listing
September 2021

Hemodynamic testing using three-dimensional printing and computational fluid dynamics preoperatively may provide more information in mitral repair than traditional image dataset.

Ann Transl Med 2021 Apr;9(8):632

Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Mitral valve repair (MVR) has been considered superior to mitral replacement for degenerative MV disease and even rheumatic diseases. However, the repair rate varies widely depending on the medical center and the surgeons' experience. The aim of our study was to apply three-dimensional printing (3DP) and computational fluid dynamics (CFD) in surgical simulation to provide reference for surgical decision-making, especially for inexperienced surgeons.

Methods: Our study included retrospective and prospective cohorts. We first enrolled the retrospective cohort of 35 patients who were prepared to have MVR, aiming at exploring the feasibility of surgical simulation using 3DP and CFD. Three-dimensional transesophageal echocardiography (3D-TEE) and computed tomography angiography (CTA) were performed for all patients, and imaging data were fused to construct a 3D digital model. Next, the model was used to make the 3DP dynamic model and for CFD analysis. Mitral repair was simulated in both the 3DP dynamic model and CFD to predict surgical outcomes (grade of regurgitation and vena contracta width) and possible complications (systolic anterior motion, left ventricular outflow tract obstruction). Second, a prospective cohort of 20 patients was studied with 10 patients placed in a 3DP-guided group and 10 in an image-guided group. Rate of transformation to mitral replacement, surgery time, surgical outcomes, and surgical complications were compared between groups.

Results: Of the 35 patients retrospectively enrolled, 14 underwent MVR and 21 were transferred to mitral replacement. Surgical simulation for the 14 MVR patients showed high consistency with results. The result of surgical simulation for the 21 patients transferred to mitral replacement showed that 7 might have benefited from MVR. In the prospective cohort, the rate of transformation to mitral replacement and surgery time in the 3DP-guided group were significantly lower than those in the image-guided group.

Conclusions: 3DP and CFD models based on image data can be used for surgical simulation. These emerging technologies are now changing traditional models of diagnosis and treatment, and the role of imaging data will no longer be limited to diagnosis but will contribute more to assisting surgeons in choosing treatment strategies.
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http://dx.doi.org/10.21037/atm-20-7960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106081PMC
April 2021

The ERF-VII transcription factor SmERF73 coordinately regulates tanshinone biosynthesis in response to stress elicitors in Salvia miltiorrhiza.

New Phytol 2021 09 24;231(5):1940-1955. Epub 2021 Jun 24.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Here, we investigate the role of SmERF73, a group VII ETHYLENE RESPONSE FACTOR stress response transcription factor, in the regulation of post-modification of the skeleton precursors of diterpene tanshinones in Salvia miltiorrhiza. Most genes found to be involved in tanshinone biosynthesis are located on chromosome 6, and five of these genes comprise a large gene cluster in S. miltiorrhiza. We found that SmERF73 overexpression in S. miltiorrhiza coordinately up-regulated the transcription of seven tanshinone biosynthetic genes, four of which were located in the tanshinone gene cluster, consequently increasing tanshinone accumulation, while SmERF73 silencing reduced corresponding gene transcription and tanshinone accumulation. SmERF73 recognizes GCC-box promoter elements of four tanshinone-associated genes (DXR1, CPS1, KSL1 and CYP76AH3) and activates their expression. Moreover, SmERF73 and its targets were up-regulated by stress elicitors; SmERF73 appears to be at least partly mediated by the jasmonic acid (JA) signaling pathway via interaction with SmJAZ3. SmERF73 coordinately regulates tanshinone biosynthetic gene expression, suggesting a potential link between tanshinone production and plant stress responses.
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http://dx.doi.org/10.1111/nph.17463DOI Listing
September 2021

Recent progress and new perspectives for diterpenoid biosynthesis in medicinal plants.

Med Res Rev 2021 May 2. Epub 2021 May 2.

State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Diterpenoids, including more than 18,000 compounds, represent an important class of metabolites that encompass both phytohormones and some industrially relevant compounds. These molecules with complex, diverse structures and physiological activities, have high value in the pharmaceutical industry. Most medicinal diterpenoids are extracted from plants. Major advances in understanding the biosynthetic pathways of these active compounds are providing unprecedented opportunities for the industrial production of diterpenoids by metabolic engineering and synthetic biology. Here, we summarize recent developments in the field of diterpenoid biosynthesis from medicinal herbs. An overview of the pathways and known biosynthetic enzymes is presented. In particular, we look at the main findings from the past decade and review recent progress in the biosynthesis of different groups of ringed compounds. We also discuss diterpenoid production using synthetic biology and metabolic engineering strategies, and draw on new technologies and discoveries to bring together many components into a useful framework for diterpenoid production.
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http://dx.doi.org/10.1002/med.21816DOI Listing
May 2021

Pretreatment with metformin protects mice from whole-body irradiation.

J Radiat Res 2021 Jul;62(4):618-625

Department of Radiation Medical Protection, School of Military Preventive Medicine, Air Force Medical University, Xi'an 710032, China.

Metformin, a first-line oral drug for type II diabetes mellitus, not only reduces blood glucose levels, but also has many other biological effects. Recent studies have been conducted to determine the protective effect of metformin in irradiation injuries. However, the results are controversial and mainly focus on the time of metformin administration. In this study, we aimed to investigate the protective effect of metformin in BALB/c mice exposed to 6 Gy or 8 Gy of a 60Co source of γ-rays for total body irradiation (TBI). Survival outcomes were assessed following exposure to 8 Gy or 6 Gy TBI, and hematopoietic damage and intestinal injury were assessed after exposure to 6 Gy TBI. Metformin prolonged the survival of mice exposed to 8 Gy TBI and improved the survival rate of mice exposed to 6 Gy TBI only when administered before exposure to irradiation. Moreover, pretreatment with metformin reduced the frequency of micronuclei (MN) in the bone marrow of mice exposed to 6 Gy TBI. Pretreatment of metformin also protected the intestinal morphology of mice, reduced inflammatory response and decreased the number of apoptotic cells in intestine. In conclusion, we demonstrated that pretreatment with metformin could alleviate irradiation injury.
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http://dx.doi.org/10.1093/jrr/rrab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273805PMC
July 2021

A Follow-Up Investigation of Mental Health Among Discharged COVID-19 Patients in Wuhan, China.

Front Public Health 2021 12;9:640352. Epub 2021 Apr 12.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

To understand the mental health status and its risk factors among discharged COVID-19 patients during the first month of centralized quarantine and the subsequent home isolation. The scales of the Insomnia Severity Index (ISI), General Anxiety Disorder (GAD-7), and Patient Health Questionnaire (PHQ-9) were used to measure the symptoms of insomnia, anxiety, and depression in 782 COVID-19 patients during the first month of centralized quarantine (March 16 to 26, 2020) and then during home isolation (April 3 to 10, 2020). During the centralized quarantine, the prevalence rates of insomnia, anxiety, and depressive symptoms were 44.37, 31.59, and 27.62%, respectively, and those during the home isolation decreased significantly at 27.11, 17.26, and 16.11%, respectively. In both waves, women showed a higher prevalence of symptoms of poor mental health compared to men, and middle-aged (40-59 years old) and elderly (≥60 years old) showed a higher risk of symptoms of poor mental health compared to the younger. In addition, the severity of COVID-19 revealed no significant relationship to symptoms of poor mental health, whereas, the interaction analysis revealed that those with other underlying diseases showed more symptoms of poor mental health during the centralized quarantine and a greater decrease during the follow-up home isolation. The discharged COVID-19 patients suffered from mental health problems such as, insomnia, depression, and anxiety, and this was especially so for women, the middle-aged and elderly, and those with underlying diseases, but along with the rehabilitation and the environmental change from centralized quarantine to home isolation, all the mental symptoms were significantly alleviated. Based on a follow-up investigation, the current results provide critical evidence for mental health and early rehabilitation upon the discharged COVID-19 patients.
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http://dx.doi.org/10.3389/fpubh.2021.640352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071993PMC
May 2021

Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Modulate the Anesthetic Potency of Isoflurane in Mice.

Neurosci Bull 2021 Jul 13;37(7):934-946. Epub 2021 Apr 13.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.
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http://dx.doi.org/10.1007/s12264-021-00674-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275739PMC
July 2021

[Effect evaluation of bedside ultrasound monitoring of left ventricular functional parameters combined with clinical indicators on veno-arterial extracorporeal membrane oxygenation].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):329-333

Department of Ultrasonography, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. Corresponding author: Guo Ruiqiang, Email:

Objective: To explore the monitoring value of left ventricular functional parameters obtained by bedside ultrasound combined with clinically relevant indicators in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Methods: A retrospective study was conducted. A total of 24 patients receiving VA-ECMO adjuvant support in Renmin Hospital of Wuhan University from June 2018 to January 2020 were selected. The bedside ultrasound was performed on the first day of ECMO support, the day before weaning, the clinical indicators before weaning were obtained. The differences in clinical indicators and the left ventricular functional parameters between the two groups of whether weaning successfully were compared; univariate Logistic regression analysis was used to screen out the related factors affecting weaning.

Results: Sixteen patients were successful weaned and 8 patients failed. Compared with the weaning failure group, patients in the weaning success group required less continuous renal replacement therapy (CRRT, cases: 4 vs. 6, P < 0.05), mean arterial pressure (MAP) before weaning was higher [mmHg (1 mmHg = 0.133 kPa): 84.64±9.55 vs. 62.30±8.79, P < 0.05], and the pulse oxygen saturation (SpO) was also higher (0.966±0.670 vs. 0.866±0.061, P < 0.05), while vasoactive-inotropic score (VIS), serum creatinine (SCr) and serum lactic acid (Lac) were lower [VIS score: 7.27±1.42 vs. 16.93±8.52, SCr (μmol/L): 123.60±83.64 vs. 213.10±117.39, Lac (mmol/L): 1.94±0.91 vs. 5.62±5.48, all P < 0.05]. Univariate Logistic regression analysis showed that the MAP, VIS, SCr, Lac, SpO before weaning were the related factors affecting weaning [odds ratio (OR) were 0.306, -0.740, -0.011, -0.632, -4.069; 95% confidence interval (95%CI) were 1.065-1.732, 0.235-0.899, 0.979-0.999, 0.285-0.992 and 0.001-0.208; P values were 0.014, 0.022, 0.038, 0.047, 0.002]. In the weaning success group, left ventricular ejection fraction (LVEF), velocity of mitralannulus in systolic (LatSa), maximum flow velocity of aortic valve (AV-Vmax), velocity-time integral (VTI), left ventricular global longitudinal strain (LVGLS), left ventricular global longitudinal strain rate (LVGLSr) were all increased on the day before ECMO weaning compared with the first day of ECMO support [LVEF: 0.40±0.05 vs. 0.28±0.07, LatSa (cm/s): 6.81±0.91 vs. 4.62±1.02, AV-Vmax (cm/s): 104.81±33.98 vs. 64.44±16.85, VTI (cm): 14.56±3.11 vs. 7.96±1.98, LVGLS: (-8.95±2.59)% vs. (-5.26±1.28)%, LVGLSr (1/s): -0.48±0.11 vs. -0.29±0.09], whereas the ECMO flow was significantly reduced (L/min: 1.46±0.47 vs. 2.64±0.31), the differences were statistically significant (all P < 0.05). There was no significant difference in left ventricular functional parameters between the first day of ECMO support and the day before ECMO weaning in the weaning failure group. Compared with the weaning failure group, the weaning success group had higher LVEF, LatSa, AV-Vmax, VTI, LVGLS, LVGLSr on the day before ECMO weaning [LVEF: 0.40±0.05 vs. 0.26±0.07, LatSa (cm/s): 6.81±0.91 vs. 4.31±1.03, AV-Vmax (cm/s): 104.81±33.98 vs. 67.67±18.46, VTI (cm): 14.56±3.11 vs. 7.75±2.77, LVGLS: (-8.95±2.59)% vs. (-4.81±1.81)%, LVGLSr (1/s): -0.48±0.11 vs. -0.30±0.10, all P < 0.05] and lower ECMO flow (L/min: 1.46±0.47 vs. 2.20±0.62, P < 0.05).

Conclusions: Bedside echocardiographic left ventricular function parameters (LVEF, LatSa, AV-Vmax, VTI, LVGLS, LVGLSr) combined with clinical indicators (MAP, VIS, SCr, Lac, SpO) were helpful to evaluate the therapeutic effect of patients receiving VA-ECMO support and can provide important guiding value in the selection of VA-ECMO weaning timing and the judgment of prognosis.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201023-00684DOI Listing
March 2021

Circadian Rhythm Gene PER3 Negatively Regulates Stemness of Prostate Cancer Stem Cells via WNT/β-Catenin Signaling in Tumor Microenvironment.

Front Cell Dev Biol 2021 18;9:656981. Epub 2021 Mar 18.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Prostate cancer (PCa) cells are heterogeneous, containing a variety of cancer cells with phenotypical and functional discrepancies in the tumor microenvironment, where prostate cancer stem cells (PCSCs) play a vital role in PCa development. Our earlier studies have shown that ALDHCD44 (DP) PCa cells and the corresponding ALDHCD44 (DN) PCa cells manifest as PCSCs and non-PCSCs, respectively, but the underlying mechanisms regulating stemness of the PCSCs are not completely understood. To tackle this issue, we have performed RNA-Sequencing and bioinformatic analysis in DP (versus DN) cells in this study. We discovered that, PER3 (period circadian regulator 3), a circadian rhythm gene, is significantly downregulated in DP cells. Overexpression of PER3 in DP cells significantly suppressed their sphere- and colony-forming abilities as well as tumorigenicity in immunodeficient hosts. In contrast, knockdown of PER3 in DN cells dramatically promoted their colony-forming and tumor-initiating capacities. Clinically, PER3 is downregulated in human prostate cancer specimens and PER3 expression levels are highly correlated with the prognosis of the PCa patient. Mechanistically, we observed that low levels of PER3 stimulates the expression of BMAL1, leading to the phosphorylation of β-catenin and the activation of the WNT/β-catenin pathway. Together, our results indicate that PER3 negatively regulates stemness of PCSCs via WNT/β-catenin signaling in the tumor microenvironment, providing a novel strategy to treat PCa patients.
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http://dx.doi.org/10.3389/fcell.2021.656981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012816PMC
March 2021

Novel green synthesis and characterization of a chemotherapeutic supplement by silver nanoparticles containing Berberis thunbergii leaf for the treatment of human pancreatic cancer.

Biotechnol Appl Biochem 2021 Apr 3. Epub 2021 Apr 3.

Department of General Surgery, Qinghai Province People's Hospital, Xining, Qinghai, China.

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV-vis. and FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4-(dimethylamino)benzaldehyde,2,2-diphenyl-1- pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 μg/mL. To survey the anti-human pancreatic cancer activities of AgNO , B. thunbergii leaf aqueous extract, and AgNPs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti-human pancreatic cancer effects dose-dependently against PANC-1, AsPC-1, and MIA PaCa-2. The IC50 values of the AgNPs were 259, 268, and 141 μg/mL against PANC-1, AsPC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.
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http://dx.doi.org/10.1002/bab.2160DOI Listing
April 2021

Effects of alcohol intake on cognitive function and β-amyloid protein in APP/PS1 transgenic mice.

Food Chem Toxicol 2021 May 16;151:112105. Epub 2021 Mar 16.

School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China.

To investigate the effects of alcohol intake on cognitive function and β-amyloid protein (Aβ) in APP/PS1 double-transgenic mice with Alzheimer's disease (AD). Sixty APP/PS1 transgenic male mice were randomized into seven groups: control group, 0.5% alcohol group, 1% alcohol group, 2% alcohol group, 3% alcohol group, and 4% alcohol group, with 10 non-transgenic B6C3F1 mice of the same genetic background as the negative control group. All mice were pair-fed a liquid diet containing alcohol before assessment of learning and memory using the Y-maze test, and of Aβ content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of Aβ, Aβ, and β-amyloid precursor protein (β-APP) in the cerebral cortex. 3%, and 4% alcohol intake significantly impaired the learning and memory abilities. 2%, 3%, and 4% alcohol groups indicated a remarkable change in Aβ content, α-secretase and γ-secretase activities in the hippocampus, and β-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in Aβ content, β-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in α-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in Aβ content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of Aβ, Aβ and β-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of Aβ, Aβ, β-APP, and BACE1 activity in the hippocampus, and γ-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of α-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and γ-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of β-APP decomposition-related enzymes, increase Aβ content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of Aβ and slow down AD progression.
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http://dx.doi.org/10.1016/j.fct.2021.112105DOI Listing
May 2021

AHR signaling pathway reshapes the metabolism of AML/MDS cells and potentially leads to cytarabine resistance.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):492-500

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Emerging evidence suggests that aryl hydrocarbon receptor (AHR) promotes the initiation, invasion, progression, and metastasis of cancer cells. However, its effects in patients with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) remain undefined. In this study, we aimed to investigate the effects of AHR activation on malignant cells in patients with MDS/AML. We found that AHR was expressed aberrantly in patients with MDS/AML. Further studies demonstrated that inhibiting AHR decreased the mitochondrial dehydrogenase content and the mitochondrial membrane potential (MMP) in MDS/AML cells. Activating AHR with L-kynurenine (Kyn) increased AHR expression, which was accompanied by an increase in mitochondrial dehydrogenase content and MMP in MDS/AML cells. Moreover, the expression level of mitochondria-associated mitochondrial transcription factor A was increased after activating AHR with L-Kyn when compared with that in the control group but decreased after inhibiting the AHR signal. Activating AHR in MDS/AML cells enhanced the resistance to cytarabine. These findings indicated that activating the AHR signaling pathway reshaped the metabolism in MDS/AML cells, thus contributing to the resistance to cytarabine.
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http://dx.doi.org/10.1093/abbs/gmab017DOI Listing
March 2021

Cell-type-specific imaging of neurotransmission reveals a disrupted excitatory-inhibitory cortical network in isoflurane anaesthesia.

EBioMedicine 2021 Mar 7;65:103272. Epub 2021 Mar 7.

School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai 200030, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226000, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200030, China. Electronic address:

Background: Despite the fundamental clinical significance of general anaesthesia, the cortical mechanism underlying anaesthetic-induced loss of consciousness (aLOC) remains elusive.

Methods: Here, we measured the dynamics of two major cortical neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, through in vivo two-photon imaging and genetically encoded neurotransmitter sensors in a cell type-specific manner in the primary visual (V1) cortex.

Findings: We found a general decrease in cortical GABA transmission during aLOC. However, the glutamate transmission varies among different cortical cell types, where in it is almost preserved on pyramidal cells and is significantly reduced on inhibitory interneurons. Cortical interneurons expressing vasoactive intestinal peptide (VIP) and parvalbumin (PV) specialize in disinhibitory and inhibitory effects, respectively. During aLOC, VIP neuronal activity was delayed, and PV neuronal activity was dramatically inhibited and highly synchronized.

Interpretation: These data reveal that aLOC resembles a cortical state with a disrupted excitatory-inhibitory network and suggest that a functional inhibitory network is indispensable in the maintenance of consciousness.

Funding: This work was supported by the grants of the National Natural Science Foundation of China (grant nos. 81620108012 and 82030038 to H.D. and grant nos. 31922029, 61890951, and 61890950 to J.H.).
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http://dx.doi.org/10.1016/j.ebiom.2021.103272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941179PMC
March 2021

Bornyl Diphosphate Synthase From and Its Application for (+)-Borneol Biosynthesis in Yeast.

Front Bioeng Biotechnol 2021 11;9:631863. Epub 2021 Feb 11.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

(+)-Borneol is a desirable monoterpenoid with effective anti-inflammatory and analgesic effects that is known as soft gold. (+)-bornyl diphosphate synthase is the key enzyme in the (+)-borneol biosynthesis pathway. Despite several reported (+)-bornyl diphosphate synthase genes, relatively low (+)-borneol production hinders the attempts to synthesize it using microbial fermentation. Here, we identified the highly specific (+)-bornyl diphosphate synthase CbTPS1 from . An assay showed that (+)-borneol was the main product of CbTPS1 (88.70% of the total products), and the value was 5.11 ± 1.70 μM with a value of 0.01 s. Further, we reconstituted the (+)-borneol biosynthetic pathway in . After tailored truncation and adding Kozak sequences, the (+)-borneol yield was improved by 96.33-fold to 2.89 mg⋅L compared with the initial strain in shake flasks. This work is the first reported attempt to produce (+)-borneol by microbial fermentation. It lays a foundation for further pathway reconstruction and metabolic engineering production of this valuable natural monoterpenoid.
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http://dx.doi.org/10.3389/fbioe.2021.631863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905068PMC
February 2021

Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT/mTOR/NF-κB signaling in pressure overload-induced rats.

J Ethnopharmacol 2021 May 16;272:113920. Epub 2021 Feb 16.

School of Nursing, PR China. Electronic address:

Ethnopharmacological Relevance: Pinoresinol diglucoside (PDG), the active compound extracted from Eucommia ulmoides, Styrax sp. and Forsythia suspensa, plays the roles in regulating hypertension, inflammation and oxidative stress.

Aims: Considering that hypertension and inflammation has been proved to contribute to cardiac remodeling, we tested the effects of PDG on cardiac hypertrophy (CM).

Methods: Male Sprague Dawley (SD) rats were used to construct hypertrophic rats by partial abdominal aortic constriction (AAC)-surgery. PDG solution (2 mg/ml) was used to treat AAC-induced rats by intraperitoneal injection at low dose (L-PDG, 2.5 mg/kg per day), medium dose (M-PDG, 5 mg/kg per day), and high dose (H-PDG, 7.5 mg/kg per day) for 3 weeks post AAC-surgery. CM was evaluated by the ratio of left ventricular weight to body weight ratio (LVW/BW), left ventricular wall thickness by H&E staining, and collagen content deposit by Masson's staining. Further, isoproterenol (ISO) and phenylephrine (PE) were used to produce cellular models of CM in neonatal rat ventricular cardiomyocytes (NRVMs). PDG pre-treated NRVMs 2 h at low dose (L-PDG, 2.5 μg/ml), medium dose (M-PDG, 5 μg/ml), and high dose (H-PDG, 7.5 μg/ml) for 24 h with or without PE- and ISO-stimulation. CM was evaluated by the expressions of hypertrophic biomarkers. Next, the hypertrophic biomarkers and pro-inflammatory cytokines were measured using quantitative real-time PCR (qRT-PCR), the expressions of protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/transcription factor nuclear factor-kappa B (NF-kB) signaling pathway were determined by Western blotting.

Results: PDG treatment prevented cardiac histomorphology damages, decreased upregulations of hypertrophic biomarkers, and prevented fibrosis and inflammation after pressure overload resulting from AAC-surgery. Consistently, PDG remarkably inhibited the changes of cardiomyocyte hypertrophic biomarkers and inflammatory responses in cellular models of CM. Interestingly, PDG administration inhibited the activation of AKT/mTOR/NF-kB signaling pathway both in vivo and in vitro.

Conclusions: PDG prevents AAC-induced CM in vivo, PE- and ISO-induced CM in vitro. The AKT/mTOR/NF-kB signaling pathway could be the potential therapeutic target involved in the protection of PDG. These findings provide novel evidence that PDG might be a promising therapeutic strategy for CM.
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http://dx.doi.org/10.1016/j.jep.2021.113920DOI Listing
May 2021

Decitabine Induces Change of Biological Traits in Myelodysplastic Syndromes via FOXO1 Activation.

Front Genet 2020 27;11:603956. Epub 2021 Jan 27.

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Decitabine (DAC) is considered to be a profound global DNA demethylation, which can induce the re-expression of silenced tumor suppressor genes. Little is known about the function of tumor suppressor gene FOXO1 in myelodysplastic syndromes (MDS). To address this issue, the study firstly investigated differentially expressed genes (DEGs) for DAC treatment in MDS cell lines, then explored the role of FOXO1 through silencing its expression before DAC treatment in MDS. The results showed that FOXO1 exists in a hyperphosphorylated, inactive form in MDS-L cells. DAC treatment both induces FOXO1 expression and reactivates the protein in its low phosphorylation level. Additionally, the results also demonstrated that this FOXO1 activation is responsible for the DAC-induced apoptosis, cell cycle arrest, antigen differentiation, and immunoregulation in MDS-L cells. We also demonstrated DAC-induced FOXO1 activation upregulates anti-tumor immune response in higher-risk MDS specimens. Collectively, these results suggest that DAC induces FOXO1 activation, which plays an important role in anti-MDS tumors.
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http://dx.doi.org/10.3389/fgene.2020.603956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873873PMC
January 2021

Light-Responsive Nanofibrous Motor with Simultaneously Precise Locomotion and Reversible Deformation.

ACS Appl Mater Interfaces 2021 Feb 14;13(7):8985-8996. Epub 2021 Feb 14.

Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, Shaanxi, People's Republic of China.

Light-powered micromotors have drawn enormous attention because of their potential applications in cargo delivery, environmental monitoring, and noninvasive surgery. However, the existing micromotors still suffer from some challenges, including slow speed, poor controllability, single locomotion mode, and no deformation during movement. Herein, we employ a combined electrospinning with brushing of Chinese ink to simply fabricate a light-responsive gradient-structured poly(vinyl alcohol)/carbon (PVA/carbon) composite motor. Because of the surface deposition and ultrahigh loading amount of carbon nanoparticles (ca. 43%), the motor exhibits rapid (39 mm/s), direction-controlled, and multimodal locomotion (vertical movement, horizontal motion, rotation) under light irradiation. Simultaneously, gradient alignment structure of the PVA nanofibrous matrix endows the motor with controllable and reversible deformation during locomotion. We finally demonstrate the potential applications of the motors in leakage monitoring, object salvage, smart access, and intelligent assembly. The present work will inspire the design of novel photosensitive motors for applications in various fields, such as microrobots, environmental monitoring, and biomedicine.
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http://dx.doi.org/10.1021/acsami.0c22340DOI Listing
February 2021

Morphology display and hemodynamic testing using 3D printing may aid in the prediction of LVOT obstruction after mitral valve replacement.

Int J Cardiol 2021 05 31;331:296-306. Epub 2021 Jan 31.

Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address:

Aims: Left ventricular outflow tract(LVOT) obstruction after mitral valve replacement can be life-threatening once occur. We simulated mitral valve replacement preoperatively using dynamic, three-dimensional(3D) printed models to help predict LVOT obstruction in this study.

Methods: 56 patients who underwent mitral valve replacement were included. Prediction of LVOT obstruction in vitro was based on the data from 4 sources: digital, anatomical, flexible, and dynamic model. Digital 3D models were designed based on computed tomography (CT) image dataset and printed with photopolymer resin to create a 3D anatomical model, which contributed to the morphology display. Then, flexible models were made from specialized silicone, which is similar to cardiac tissue in terms of its softness and elasticity. Dynamic function was achieved by coupling flexible models to a mock circulatory system (MCS). Besides, surgery simulation and hemodynamic testing was done using dynamic 3D printed model and patients were regrouped based on hemodynamic change. Finally, different methods for prediction of LVOT obstruction as well as classification based on two-dimensional image data and dynamic model were compared with surgical results as golden standard.

Results: (1)Qualitatively, the prediction of LVOT obstruction using the dynamic 3D model was the most accurate and was consistent with clinical outcomes. In the four patients who developed LVOT obstruction after surgery, only two were at a high risk based on the other three models. (2)Quantitatively, the area of neo-LVOT predicted by the digital, anatomical, and flexible models was higher compared with the dynamic models and in-vivo after surgery. (3)Classification based on traditional criteria(two-dimensional image data) was different from surgical results. While the difference between dynamic model and surgical results was not statistically different.

Conclusions: After coupling the flexible model with the mock circulatory system, the dynamic 3D model predicted LVOT obstruction more accurately with hemodynamic testing compared with morphological evaluation. 3D printing can assist surgeons to better plan mitral valve replacement than traditional image data.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.029DOI Listing
May 2021

Integration Analysis of or Mutation With Bone Marrow Blast Can Improve Risk Stratification in the Patients With Lower Risk Myelodysplastic Syndrome.

Front Oncol 2020 13;10:610525. Epub 2021 Jan 13.

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Despite the improvements in prognostication of the revised International Prognostic Scoring System (IPSS-R) in myelodysplastic syndrome (MDS), there remain a portion of patients with lower risk (low/intermediate risk, LR) but poor prognostics. This study aimed to evaluate the relative contribution of mutational status when added to the IPSS-R, for estimating overall survival (OS) and progression-free survival (PFS) in patients with LR-MDS. We retrospectively analyzed clinical and laboratory variables of 328 patients diagnosed with MDS according to the FAB criteria. Twenty-nine-gene NGS assay was applied to bone marrow samples obtained at diagnosis. 233 (71.04%) patients were classified as LR-MDS. Univariate analysis showed association between inferior outcome (OS and PFS) and presence of (p = 0.0177, p = 0.0002), (p = 0.0250, p = 0.0387), and (p = 0.0227, p = 0.7995) mutations. Multivariable survival analysis revealed (p < 0.0001) and (p = 0.0215) mutations were independently prognostic for PFS in LR-MDS. Interestingly, bone marrow blast >1.5% could further predict disease progression of patients with LR-MDS (HR 8.06, 95%CI 2.95-22.04, p < 0.0001). Incorporation of , mutation and bone marrow blast in the IPSS-R can improve risk stratification in patients with LR-MDS. In summary, our result provided new risk factors for LR-MDS prognostics to identify candidates for early therapeutic intervention.
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http://dx.doi.org/10.3389/fonc.2020.610525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839382PMC
January 2021

Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.

Nat Commun 2021 01 29;12(1):685. Epub 2021 Jan 29.

State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.
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http://dx.doi.org/10.1038/s41467-021-20959-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846762PMC
January 2021

Analysis of the influencing factors related to liver and cardiac iron overload in MDS patients detected by MRI in the real world.

Hematology 2021 Dec;26(1):123-133

Department of Hematology, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Objectives: We aim to explore and analyze the related influencing factors of liver and cardiac iron overload in MDS patients detected by magnetic resonance imaging (MRI).

Methods: We have detected cardiac T2* and liver T2* by MRI in 105 MDS patients. Among them, 20 patients accepted MRI examination before and after iron chelation therapy (ICT). : We found that adjusted ferritin (ASF) was significantly correlated with liver T2* and cardiac T2*. RBC transfusion volume, brain natriuretic peptide (BNP) and age were the related factors of cardiac T2*, while RBC transfusion volume and erythropoietin (EPO) were related factors of liver T2*. After ICT, the changes of ASF and liver T2* were earlier than cardiac T2*. Chronic hepatitis but virus copy normal's has no significant effect on liver iron deposition.

Conclusion: These results showed special attention should be paid to these related influencing factors of liver and cardiac T2* expression when we evaluated iron overload and detected the efficacy of ICT in MDS patients.
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http://dx.doi.org/10.1080/16078454.2020.1866791DOI Listing
December 2021
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