Publications by authors named "Feng Feng"

623 Publications

A Comprehensive Nomogram Combining CT Imaging with Clinical Features for Prediction of Lymph Node Metastasis in Stage I-IIIB Non-small Cell Lung Cancer.

Ther Innov Regul Sci 2021 Oct 26. Epub 2021 Oct 26.

Department of Radiology, Affiliated Tumor Hospital of Nantong University, No. 30 Tongyangbei Road, Tongzhou District, Nantong, 226361, China.

Objective: The status of lymph node metastasis (LNM) is highly correlated with the recurrence and survival outcomes of patients with lung cancer. Thus, a tool that predicts LNM could benefit patient treatment and prognosis. The present study established a new radiomic model by combining computed tomography (CT) radiomic features and clinical parameters to predict the LNM status in patients with non-small cell lung cancer (NSCLC).

Methods: Demographic parameters and clinical laboratory values were analyzed in 217 patients with stage I-IIIB NSCLC; 107 of the patients received CT scanning and radiomic characteristics were used for LNM assessment (76 in the training cohort and 31 in the validation cohort). The minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) regression model were used to select the most predictive features on the basis of the 76 patients in the training set. The value of the area under the receiver operator characteristic (ROC) curve (AUC) was adopted to determine the correlation between LN status and the radiomics signature in training cohorts and then validated in the 31 patients of validation set. The radiomics nomogram was analyzed using univariate and multivariate logistic regression. Decision curve analysis (DCA) was performed to evaluate the clinical utility of this model.

Results: This was a retrospective study. Five radiomic characteristics were significantly correlated with LNM in the two cohorts (P < 0.05). The radiomic nomogram that incorporated the above radiomic characteristics, the RDW, and the CT-based LN status had satisfactory discrimination and calibration in the training (AUC, 0.79; 95% CI 0.69-0.89) and validation cohorts (AUC, 0.70; 95% CI 0.50-0.89).The DCA showed that the developed nomogram had promising clinical utility.

Conclusions: The developed nomogram, combined with preoperative radiomics evidence, the RDW, and the CT-based LN status, has the potential to preoperatively predict LNM with high accuracy and can facilitate the prediction of LN status for NSCLC patients.
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http://dx.doi.org/10.1007/s43441-021-00345-1DOI Listing
October 2021

Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

Front Aging Neurosci 2021 5;13:705030. Epub 2021 Oct 5.

State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.

: Hippocampal atrophy is a characteristic of Alzheimer's disease (AD). However, alterations in structural connectivity (number of connecting fibers) between the hippocampus and whole brain regions due to hippocampal atrophy remain largely unknown in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI). : We collected high-resolution structural MRI (sMRI) and diffusion tensor imaging (DTI) data from 36 AD patients, 30 aMCI patients, and 41 normal control (NC) subjects. First, the volume and structural connectivity of the bilateral hippocampi were compared among the three groups. Second, correlations between volume and structural connectivity in the ipsilateral hippocampus were further analyzed. Finally, classification ability by hippocampal volume, its structural connectivity, and their combination were evaluated. : Although the volume and structural connectivity of the bilateral hippocampi were decreased in patients with AD and aMCI, only hippocampal volume correlated with neuropsychological test scores. However, positive correlations between hippocampal volume and ipsilateral structural connectivity were displayed in patients with AD and aMCI. Furthermore, classification accuracy (ACC) was higher in AD vs. aMCI and aMCI vs. NC by the combination of hippocampal volume and structural connectivity than by a single parameter. The highest values of the area under the receiver operating characteristic (ROC) curve (AUC) in every two groups were all obtained by combining hippocampal volume and structural connectivity. : Our results showed that the combination of hippocampal volume and structural connectivity (number of connecting fibers) is a new perspective for the discrimination of AD and aMCI.
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http://dx.doi.org/10.3389/fnagi.2021.705030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524052PMC
October 2021

Blinking Acoustic Nanodroplets Enable Fast Super-resolution Ultrasound Imaging.

ACS Nano 2021 Oct 14. Epub 2021 Oct 14.

State Key Laboratory of Membrane Biology, National Biomedical Imaging Center, Peking-Tsinghua Center for Life Sciences, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.

The advent of localization-based super-resolution ultrasound (SRUS) imaging creates a vista for precision vasculature and hemodynamic measurements in brain science, cardiovascular diseases, and cancer. As blinking fluorophores are crucial to super-resolution optical imaging, blinking acoustic contrast agents enabling ultrasound localization microscopy have been highly sought, but only with limited success. Here we report on the discovery and characterization of a type of blinking acoustic nanodroplets (BANDs) ideal for SRUS. BANDs of 200-500 nm diameters comprise a perfluorocarbon-filled core and a shell of DSPC, Pluronic F68, and DSPE-PEG2000. When driven by clinically safe acoustic pulses (MI < 1.9) provided by a diagnostic ultrasound transducer, BANDs underwent reversible vaporization and reliquefaction, manifesting as "blinks", at rates of up to 5 kHz. By sparse activation of perfluorohexane-filled BANDs-C at high concentrations, only 100 frames of ultrasound imaging were sufficient to reconstruct super-resolution images of a no-flow tube through either cumulative localization or temporal radiality autocorrelation. Furthermore, the use of high-density BANDs-C (1 × 10/mL) with a 1:9 admixture of perfluorohexane and perfluorobutane supported the fast SRUS imaging of muscle vasculature in live animals, at 64 μm resolution requiring only 100 frames per layer. We anticipate that the BANDs developed here will greatly boost the application of SRUS in both basic science and clinical settings.
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http://dx.doi.org/10.1021/acsnano.1c07896DOI Listing
October 2021

Potential Application of MR-MR-US Fusion Imaging Navigation with Needle Tail Intelligent Positioning in Guiding Puncture in Percutaneous Transforaminal Endoscopic Discectomy.

Ultrasound Med Biol 2021 Sep 27. Epub 2021 Sep 27.

Department of Spine Surgery, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, Guangzhou, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, China. Electronic address:

This study sought to investigate the feasibility of using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) fusion imaging navigation (FIN) with needle tail intelligent positioning (NTIP) to guide puncture in percutaneous transforaminal endoscopic discectomy (PTED). First, in a pig experiment, we found that puncture errors in lumbar intervertebral foramen (LIF) puncture using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) FIN with NTIP for experienced and novice operators were 2.00 ± 1.00 and 2.57 ± 0.98 mm, respectively (p = 0.231), suggesting this technique was minimally dependent on experience. Then, two experienced surgeons agreed (inter-observer agreement к=0.801) that the quality of MR-MR fusion images was good or sufficient. Finally, we performed PTED in eight patients using MR-MR-US FIN with NTIP, and no significant complications were reported during LIF puncture. Overall, MR-MR-US FIN with NTIP may be a potential application for guiding puncture in PTED, but more clinical studies with a larger sample size are required to further evaluate the advantages of MR-MR-US FIN with NTIP.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.08.011DOI Listing
September 2021

Effects of stewing with tea polyphenol on the gel properties, microstructure, and secondary structure of boiled egg white.

J Food Sci 2021 Oct 25;86(10):4262-4274. Epub 2021 Sep 25.

Jiangxi Key Laboratory of Natural Products and Functional Food, Jiangxi Agricultural University, Nanchang, China.

This study aimed to investigatethe mechanism of stewing with tea polyphenols (TP) on the properties of boiled egg white gel (BEWG). The results indicated that, during the stewing process, soluble protein and hardness showed an overall increasing trend, while surface hydrophobicity showed a decreasing trend with blue-shift. The free sulfhydryl group showed that TP could promote the formation of disulfide bonds, and the position of immobilized water at T showed a decreasing trend. Environmental scanning electron microscopy and SDS-PAGE showed that the protein gel aggregation degree increased. Moreover, Fourier transform infrared spectrometry showed that protein polarity increased and that α-helices, β-turn, intramolecular β-sheets, as well as intermolecular antiparallel β-sheets showed an increasing trend. Generally, TP strengthened protein aggregation by promoting the formation of disulfide and hydrogen bonds, thus enhancing the gel strength of BEWG. Moreover, the secondary structure of proteins became more stable under the action of TP, and the higher the concentration of TP, the greater the effect on BEWG. PRACTICAL APPLICATION: TP, an ideal, cheap, and safe natural food additive, can be applied to the processing of egg products because the addition of TP can significantly improve the gel strength of egg white.
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http://dx.doi.org/10.1111/1750-3841.15919DOI Listing
October 2021

Effects of ApoE genotype on clinical phenotypes in early-onset and late-onset Alzheimer's disease in China: Data from the PUMCH dementia cohort.

Brain Behav 2021 Sep 23:e2373. Epub 2021 Sep 23.

Neurology Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing, China.

Introduction: To investigate the heterogeneous effect of Apolipoprotein E (ApoE) genotype on clinical phenotypes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively.

Methods: 785 probable AD patients were enrolled from the dementia cohort of Peking Union Medical College Hospital (PUMCH), China. There were 386 EOAD and 399 LOAD cases. All individuals finished history inquiry, neurological examination, blood biochemical test, neuropsychological screening test, electroencephalography, brain CT/MRI, and ApoE genotyping. Some participants had neuropsychological domain assessment (n = 317), MRI morphometry (n = 130), CSF testing of Aβ42, p-tau, t-tau (n = 144), or DNA sequencing (n = 690). The variables were compared mainly between ɛ4 carriers and non-carriers in EOAD and LOAD, respectively.

Results: In LOAD, ɛ4 carriers showed female predominance; worse performance in trail making test, delayed recall of auditory verbal learning test (AVLT) and rey complex figure; smaller hippocampal, parahippocampal, and entorhinal volume, as compared to ɛ4 non-carriers. In EOAD, ɛ4 carriers had lower scores in AVLT, episodic memory and modified Luria's tapping task; but less cortical atrophy in entorhinal, middle cingulate, inferior frontal, and parieto-occipital regions, in comparison to ɛ4 non-carriers. 6.2% (43/690) subjects harbored potential causative mutations in APP, PSEN1, and PSEN2. In both EOAD and LOAD, no differences were observed between ɛ4 carriers and non-carriers in CSF levels of Aβ42, p-tau, t-tau, or mutation frequency.

Conclusions: ApoE exerts a heterogeneous effect on clinical phenotypes in EOAD and LOAD, which might be related to the different genetic and pathological basis underlying them.
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http://dx.doi.org/10.1002/brb3.2373DOI Listing
September 2021

The Association Between Perivascular Spaces and Cerebral Blood Flow, Brain Volume, and Cardiovascular Risk.

Front Aging Neurosci 2021 31;13:599724. Epub 2021 Aug 31.

Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Basal ganglia perivascular spaces are associated with cognitive decline and cardiovascular risk factors. There is a lack of studies on the cardiovascular risk burden of basal ganglia perivascular spaces (BG-PVS) and their relationship with gray matter volume (GMV) and GM cerebral blood flow (CBF) in the aging brain. Here, we investigated these two issues in a large sample of cognitively intact older adults. A total of 734 volunteers were recruited. MRI was performed with 3.0 T using a pseudo-continuous arterial spin labeling (pCASL) sequence and a sagittal isotropic T1-weighted sequence for CBF and GMV analysis. The images obtained from 406 participants were analyzed to investigate the relationship between the severity of BG-PVS and GMV/CBF. False discovery rate-corrected -values ( ) of <0.05 were considered significant. The images obtained from 254 participants were used to study the relationship between the severity of BG-PVS and cardiovascular risk burden. BG-PVS were rated using a 5-grade score. The severity of BG-PVS was classified as mild (grade <3) and severe (grade ≥3). Cardiovascular risk burden was assessed with the Framingham General Cardiovascular Risk Score (FGCRS). Severe basal ganglia perivascular spaces were associated with significantly smaller GMV and CBF in multiple cortical regions ( <0.05), and were associated with significantly larger volume in the bilateral caudate nucleus, pallidum, and putamen ( <0.05). The participants with severe BG-PVS were more likely to have a higher cardiovascular risk burden than the participants with mild BG-PVS (60.71% vs. 42.93%; =0.02). In cognitively intact older adults, severe BG-PVS are associated with smaller cortical GMV and CBF, larger subcortical GMV, and higher cardiovascular risk burden.
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http://dx.doi.org/10.3389/fnagi.2021.599724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438293PMC
August 2021

[Application Progress of Arterial Spin Labeling Magnetic Resonance Imaging in Renal Perfusion Analysis].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Aug;43(4):642-648

Department of Vascular Surgery,Beijing 100730,China.

Arterial spin labeling is a noninvasive,quantitative method for perfusion imaging,which does not need any contrast media.This technique has been used in the renal perfusion analysis.In this article,we briefly introduced this technique and summarized its application in healthy volunteers,acute kidney injury,chronic kidney diseases,renovascular diseases,renal tumors,and renal transplantation.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12684DOI Listing
August 2021

The fluorescence imaging and precise suppression of bacterial infections in chronic wounds by porphyrin-based metal-organic framework nanorods.

J Mater Chem B 2021 Oct 6;9(38):8048-8055. Epub 2021 Oct 6.

Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410004, China.

Nano-antibacterial agents can play a critical role in chronic wound management. However, the design of an intelligent nanosystem that can provide both a visual warning of infection and precise sterilization remains a hurdle. Herein, a rod-like porphyrin-based metal-organic framework theranostic nanosystem (Zn-TCPP nanorods) is fabricated coordination chelation between tetrakis(4-carboxylphenyl)porphyrin and zinc ions. This system can show significant fluorescence activation in response to the local elevated pH shown by chronic wounds, a main indicator of wound infection. Meanwhile, under the guidance of fluorescence imaging, the highly spatiotemporally precise photodynamic inactivation of microorganisms can be carried out without the destruction of surrounding normal cells and nascent cells. The results demonstrated that the Zn-TCPP nanorods were a highly sensitive and reversible probe for sensing alkaline pH levels. Alterations in the fluorescence of the Zn-TCPP nanorods can accurately indicate the infection status and heterogeneity of infection within the wound bed. Under specific light irradiation, the Zn-TCPP nanorods can exterminate 97% of the generation of reactive oxygen species (ROS). Assays of extensive wounds demonstrate that the precise fluorescence-imaging-guided suppression of bacterial infection can significantly reduce the mouse mortality rate and accelerate wound healing. This system provides the opportunity for "precision medicine" relating to chronic wounds and some large-area wounds.
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http://dx.doi.org/10.1039/d1tb01649kDOI Listing
October 2021

Computational design of binder as the LC3-p62 protein-protein interaction.

Bioorg Chem 2021 Oct 13;115:105241. Epub 2021 Aug 13.

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Cellular autophagy is an intracellular degradation pathway, which transports damaged, deformed, senescent or non-functional proteins and organelles to lysosome for digestion and degradation. Cellular autophagy is deeply evolutionarily conservedfromyeasttomammaliancells, and many homologous proteins of the autophahgy regulators are found in several species. This physiological process maintains the steady state of cells. Furtheremore, autophagy dysfunction is closely related to various diseases, such as neurodegenerative diseases, inflammation-related diseases, cardiovascular diseases, metabolic diseases, etc. The LC3 and p62 protein protein interaction (PPI) promotes the formation of autophagosomes and delivers polyubiquitinated "cargoes" to autophagic degradation. Therefore, LC3-p62 PPI plays an integral role in the formation of autophagosomes and effectively inhibits autophagy. However, there are still few studies on the LC3-p62 PPI inhibitors for its unclear molecular mechanism. Furthermore, most of these inhibitors are macromolecules with poorly active, and small molecules are particularly scarce. In this article, the computation method was used to identify the hot spot and design peptides as the binder of LC3-p62 PPI. Findings from this work provide a reference for the follow-up research of discovering small molecule inhibitors targeting LC3-p62 PPI.
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http://dx.doi.org/10.1016/j.bioorg.2021.105241DOI Listing
October 2021

A label-free fluorescence nanosensor based on nitrogen and phosphorus co-doped carbon quantum dots for ultra-sensitive detection of new coccine in food samples.

Food Chem 2022 Jan 10;368:130829. Epub 2021 Aug 10.

Shanxi Datong University, Datong 037009, PR China. Electronic address:

In this paper, an innovative method for the sensitive detection of new coccine using N, P-doped carbon quantum dots (N,P-CQDs) as fluorescent nanosensor is reported for the first time. The sensing mechanism is based on the fluorescence quenching of N,P-CQDs by new coccine through inner filter effect (IFE). N,P-CQDs were prepared by simple hydrothermal treatment of citric acid, phosphoric acid and ethylenediamine. Under the optimal conditions, the new coccine has two good linear responses in the concentration range of 0.2-100 and 100-200 μM, and the detection limits are as low as 24.8 and 9.4 nM, respectively. Our developed nanosensor has been successfully used for the determination of new coccine in food samples with good precision and high accuracy. This work highlights the economic, rapid, simple, selective and ultra-sensitive for new coccine detection, and opens up a new way for the monitoring of new coccine in actual food samples.
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http://dx.doi.org/10.1016/j.foodchem.2021.130829DOI Listing
January 2022

Time of symptoms beyond the bulbar region predicts survival in bulbar onset amyotrophic lateral sclerosis.

Neurol Sci 2021 Aug 12. Epub 2021 Aug 12.

Medical School of Chinese PLA, Beijing, China.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Spreading pattern and time interval of spreading are getting more and more attention. The aim of present study was to investigate spreading pattern in bulbar onset ALS patients and to explore the relationship between time interval of spreading and survival.

Methods: ALS patients with bulbar onset diagnosed at Chinese PLA General Hospital from January 2015 to December 2018 were recruited. Clinical features including gender, onset age, diagnostic delay, the second involved region (SIR), time of symptoms beyond the bulbar region, forced vital capacity (FVC), ALSFRS-R score, electromyography results, and survival time were retrospectively collected.

Results: A total of 96 bulbar onset ALS patients were collected. Overall patients showed female predominance. Median age at onset was 56 years. Median diagnostic delay was 8.5 months. Median time of symptoms beyond the bulbar region (TBBR) was 7 months. Median ALSFRS-R score at baseline was 40. Fifty-six (58.3%) patients' SIR were upper limb, 6 (6.3%) patients' SIR were lower limb, 3 (3.1%) patients' SIR were upper and lower limbs, and 5 (5.2%) patients' SIR were thoracic region. Twenty-six (27.1%) patients did not report SIR. The median survival time of patients with TBBR ≥ 7 months was significantly longer than that with TBBR < 7 month. Multivariate Cox regression showed that onset age and TBBR were prognostic factors.

Conclusions: In bulbar onset ALS patients, cervical region is the second most common SIR. TBBR is an independent prognostic factor.
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http://dx.doi.org/10.1007/s10072-021-05556-wDOI Listing
August 2021

Nocturnal blood pressure rise as a predictor of cognitive impairment among the elderly: a retrospective cohort study.

BMC Geriatr 2021 08 11;21(1):462. Epub 2021 Aug 11.

Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR China.

Background: This study investigated the different blood pressure patterns that were evaluated by ambulatory blood pressure monitoring (ABPM) among elderly patients and explored the effect of pressure patterns on cognitive impairment and mortality.

Methods: A total of 305 elderly participants aged ≥65 years were divided into the cognitive impairment group (CI, n = 130) and the non-cognitive impairment group (NCI, n = 175) according to the MMSE score. All participants underwent ABPM to evaluate possible hypertensive disorder and cerebral MRI for the evaluation of cerebral small vessel disease. Follow-up was performed by telephone or medical records. The primary outcome was all-cause mortality. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE).

Results: Among 305 participants, 130 (42.6%) were identified with cognitive impairment (CI), with average systolic blood pressure (BP) of 127 mmHg and diastolic BP of 66 mmHg. According to ABPM, only 13.1% had a dipper pattern, 45.6% had a nocturnal BP rise, while 41.3% had a non-dipper pattern. Compared with NCI patients, the CI group had significantly higher night-time systolic BP (130.0 ± 18.2 vs. 123.9 ± 15.1, p = 0.011), and more participants had nocturnal BP rise (52.3% vs. 40.6%, p = 0.042). Nocturnal BP rise was associated with greater white matter hyperintensities (WMH) (p = 0.013). After 2.03 years of follow-up, there were 35 all-cause deaths and 33 cases of major adverse cardiac and cerebrovascular events (MACCE). CI was independently associated with all-cause mortality during long-term observation (p < 0.01). Nocturnal BP rise had no significant predictive ability for all-cause mortality in elderly patients (p = 0.178).

Conclusions: Nocturnal BP rise contributed to greater cognitive impairment in elderly patients. Not nocturnal BP rise, but CI could significantly increase all-cause mortality. Controlling BP based on ABPM is critical for preventing the progression of cognitive dysfunction.
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http://dx.doi.org/10.1186/s12877-021-02406-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359081PMC
August 2021

Genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis patients with TARDBP mutations.

Brain Behav 2021 08 1;11(8):e2312. Epub 2021 Aug 1.

Department of Neurology, First Medical Center, Chinese PLA General Hospital, Beijing, China.

Objectives: To investigate the genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis (SALS) patients with TARDBP mutations, we carried out a genetic analysis in a cohort of 391 SALS patients and explored the clinical manifestations of patients with TARDBP variants.

Materials And Methods: The coding region of all five coding exons of TARDBP, exons 2-6, were sequenced for mutations in 391 Chinese SALS patients. The clinical features of patients with TARDBP mutations were described and compared with cases in literatures.

Results: Two missense mutations in TARDBP gene, c.1132A > G (p.N378D) and c.1147A > G (p.I383V), were detected in three cases, showing a low frequency (0.77%, 3/391) of TARDBP missense mutations in Chinese SALS patients. Based on a retrospective analysis of literatures, p.N378D mutation mainly presents a phenotype of early onset, whereas p.I383V mutation presents pure ALS or ALS alongside semantic variant primary progressive aphasia (svPPA), a type of frontotemporal dementia (FTD).

Conclusions: Our results demonstrate that TARDBP mutation is a rare cause of Chinese SALS patients and expand the spectrum of phenotype. It is implied that genetic analysis of SALS patients plays a crucial role in uncovering the cause of disease, especially for cases developing early onset or alongside FTD.
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http://dx.doi.org/10.1002/brb3.2312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413724PMC
August 2021

Inhibition of the unfolded protein response reduces arrhythmia risk after myocardial infarction.

J Clin Invest 2021 Sep;131(18)

Division of Cardiology, Department of Medicine, the Lillehei Heart Institute and.

Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels. When activated, the protein kinase-like ER kinase (PERK) branch of the UPR reduces protein translation and abundance. We hypothesized that PERK inhibition could prevent ion channel downregulation and reduce arrhythmia risk after myocardial infarct (MI). MI induced in mice by coronary artery ligation resulted in reduced ion channel levels, ventricular tachycardia (VT), and prolonged corrected intervals between the Q and T waves on the ECGs (QTc). Protein levels of major cardiac ion channels were decreased. MI cardiomyocytes showed significantly prolonged action potential duration and decreased maximum upstroke velocity. Cardiac-specific PERK KO reduced electrical remodeling in response to MI, with shortened QTc intervals, fewer VT episodes, and higher survival rates. Pharmacological PERK inhibition had similar effects. In conclusion, we found that activated PERK during MI contributed to arrhythmia risk by the downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmia risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmia mechanism and that maintenance of ion channel levels is antiarrhythmic.
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http://dx.doi.org/10.1172/JCI147836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439592PMC
September 2021

Design, Bio-evaluation and Molecular Dynamics Simulation of Novel GSK-3β Inhibitors.

Mol Inform 2021 Jul 29. Epub 2021 Jul 29.

School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.

Glycogen synthase kinase 3 beta (GSK-3β) is considered as a promising drug target for the treatment of Alzheimer's disease (AD). In the present study, two compound libraries were selected for virtual screening based on pharmacophore models of GSK-3β to discover new inhibitors. Nine potential hits were retained for biological investigation and four of these compounds showed GSK-3β inhibitory activity (with the IC values in sub-micromolar range on GSK-3β). Compounds 6 and 9 have good safety. They do not have any significant in vitro cytotoxicity against PC12 and SH-SY5Y neuroblastoma cells at concentrations up to 90 μM. Based on the inhibitory activity and druggability properties, compound 8 is the preferred molecule, and it is a promising lead for the development of the GSK-3β inhibitors for reducing the abnormal hyperphosphorylation of tau protein and relieving AD.
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http://dx.doi.org/10.1002/minf.202060031DOI Listing
July 2021

The role of metabolites of steviol glycosides and their glucosylated derivatives against diabetes-related metabolic disorders.

Food Funct 2021 Sep 20;12(18):8248-8259. Epub 2021 Sep 20.

School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.

Diabetes mellitus (DM), characterized by abnormal carbohydrate, lipid, and protein metabolism, is a metabolic disorder caused by a shortage of insulin secretion or decreased sensitivity of target cells to insulin. In addition to changes in lifestyle, a low-calorie diet is recommended to reduce the development of DM. Steviol glycosides (SGs), as natural sweeteners, have gained attention as sucrose alternatives because of their advantages of high sweetness and being low calorie. Most SGs with multiple bioactivities are beneficial to regulate physiological functions. Though SGs have been widely applied in food industry, there is little data on their glucosylated derivatives that are glucosylated steviol glycosides (GSGs). In this review, we have discussed the metabolic fate of GSGs in contrast to SGs, and the molecular mechanisms of glycoside metabolites against diabetes-related metabolic disorders are also summarized. SGs are generally extracted from the leaf, while GSGs are mainly manufactured using enzymes that transfer glucose units from a starch source to SGs. Results from this study suggest that SGs and GSGs share same bioactive metabolites, steviol and steviol glucuronide (SVG), which exhibit anti-hyperglycemic effects by activating glucose-induced insulin secretion to enhance pancreatic β-cell function. In addition, steviol and SVG have been found to ameliorate the inflammatory response, lipid imbalance, myocardial fibrosis and renal functions to modulate diabetes-related metabolic disorders. Therefore, both SGs and GSGs may be used as potential sucrose alternatives and/or pharmacological alternatives for preventing and treating metabolic disorders.
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http://dx.doi.org/10.1039/d1fo01370jDOI Listing
September 2021

Altered cerebral perfusion and microstructure in advanced Parkinson's disease and their associations with clinical features.

Neurol Res 2021 Jul 27:1-10. Epub 2021 Jul 27.

Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Objective: To explore the whole cerebral perfusion and microstructure alteration patterns in Parkinson's disease (PD) and the associations of these patterns with clinical features.

Methods: Forty-one subjects [20 PD patients and 21 healthy controls (HCs)] underwent arterial spin labeling (ASL), diffusion tensor imaging (DTI) and 3D T1-weighted imaging (T1WI) MRI. The cerebral blood flow (CBF) of the whole brain and the fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) of subcortical and cerebellar regions were measured and compared between groups. Pearson's correlation was calculated between MRI measurements and clinical features [Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS III, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and olfactory test scores].

Results: Compared to HCs, PD patients showed lower CBF in the frontal, parietal and temporal lobes but higher CBF in bilateral hippocampi, red nuclei, right substantia nigra, thalamus and most cerebellar regions. The MD in the right thalamus and several regions in the cerebellum increased in PD compared to HCs. In PD patients, the total UPDRS, UPDRS III, MoCA, MMSE and olfactory test scores were related to FA or CBF in cerebellum. (all p < 0.05).

Conclusion: Hypoperfusion in cortical regions, together with hyperperfusion in subcortical and cerebellar regions may be the characteristic perfusion pattern in advanced PD patients. The microstructures of the right thalamus and cerebellum were changed in PD patients. The cognitive, motor and olfactory performance of PD patients is closely related to the perfusion and microstructure of the brain, especially the cerebellum.
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http://dx.doi.org/10.1080/01616412.2021.1954842DOI Listing
July 2021

Forsythiaside B inhibits myocardial fibrosis via down regulating TGF-β1/Smad signaling pathway.

Eur J Pharmacol 2021 Oct 17;908:174354. Epub 2021 Jul 17.

Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. Electronic address:

Forsythiaside B is the major ingredient of Callicarpa kwangtungensis Chun, and has been proven to protect myocardium from ischemia-reperfusion injury to achieve myocardial protection. However, the effect of forsythiaside B on adverse myocardial fibrosis remains unclear. In the present study, the myocardial fibrosis animal models were established induced by isoproterenol (ISO) to investigate whether forsythiaside B exhibited antifibrotic actions. Forsythiaside B was found to significantly improve the cardiac ejection fraction and fractional shortening rate of myocardial fibrosis mice compared with the normal saline group. In addition, forsythiaside B could lower the level of TGF-β1, the expression of α-SMA and collagen III. Forsythiaside B down-regulated the expression of Smad4 and the phosphorylation level of Smad3, which indicates that forsythiaside B could suppress myocardial fibrosis by inhibiting the TGF-β1/Smad signaling pathway. These results demonstrated that forsythiaside B could prevent myocardial fibrosis in ISO-induced mice, and may be a potentially rational therapeutic approach for the treatment of myocardial fibrosis.
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http://dx.doi.org/10.1016/j.ejphar.2021.174354DOI Listing
October 2021

Iatrogenic fracture during shoulder dislocation reduction: characteristics, management and outcomes.

Eur J Med Res 2021 Jul 12;26(1):73. Epub 2021 Jul 12.

Department of Orthopedics, Renmin Hospital of Wuhan University, #238 Jiefang Road, Wuhan, 430060, Hubei, People's Republic of China.

Background: Shoulder dislocation and the cases of iatrogenic fractures during manual reduction are becoming increasingly common. The aim of this study was to investigate the characteristics, management, and patient outcomes of iatrogenic proximal humeral fracture during the manual reduction of shoulder dislocation.

Methods: A retrospective and multi-center study was performed to identify all patients presenting with shoulder dislocation from January 2010 to January 2020. The sex and age of patients, associated injuries, first-time or habitual shoulder dislocation, type of anesthesia, time from injury to revision surgery, and functional outcomes were analyzed.

Results: A total of 359 patients with a mean age of 62.1 ± 7.3 years (range 29-86 years) were included. Twenty-one patients (female/male ratio 17:4) with an average age of 66.3 ± 9.7 years (range 48-86 years) were identified with a post-reduction iatrogenic fracture. Female cases with greater tuberosity fractures (GTF) were more likely than male cases to have iatrogenic fractures during reduction (P = 0.035). Women aged 60 years or older experienced more iatrogenic fractures during manual reduction (P = 0.026). Closed reduction under conscious sedation was more likely than that under general anesthesia to have iatrogenic fractures (P = 0.000). A total of 21 patients underwent open reduction and internal fixation (ORIF) when iatrogenic fractures occurred. The mean follow-up period was 19.7 ± 6.7 months (range 12-36 months). The mean Neer scores were 80.5 ± 7.6 (range 62-93), and the mean visual analog score (VAS) was 3.3 ± 1.5 (range 1-6). Significant differences were observed in the Neer score and VAS with the time (more or less 8 h) from injury to revision surgery (P < 0.05).

Conclusion: A high risk of iatrogenic proximal humeral fracture is present in shoulder dislocation with GTF in senile females without general anesthesia. ORIF performed in a timely manner may help improve functional outcomes in the case of iatrogenic injury.
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http://dx.doi.org/10.1186/s40001-021-00545-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274043PMC
July 2021

[Determination of 16 mycotoxins in drug and food homologous products by ultra performance liquid chromatography-tandem mass spectrometry combined with accelerated solvent extraction and QuEChERS].

Se Pu 2020 Jul;38(7):782-790

Chinese Academy of Inspection and Quarantine, Beijing 100176, China.

A method was developed for the simultaneous determination of 16 mycotoxins in drug and food homologous products by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combined with accelerated solvent extraction (ASE) and QuEChERS. The target mycotoxins in drug and food homologous products were extracted by ASE. After concentration, the extracts were purified by QuEChERS. Then, the target compounds were analyzed by UPLC-MS/MS in both positive and negative electrospray ionization and MRM modes. Aflatoxin B1 and fumonisin B1 were quantified by the internal standard method, and the remaining mycotoxins were quantified by the matrix-matched external standard method. The proposed method showed a good linear relationship, with correlation coefficients greater than 0.99. The limits of detection (LODs) and limits of quantification (LOQs) of the 16 mycotoxins ranged from 0.008 μg/kg to 0.3 μg/kg and from 0.03 μg/kg to 1.0 μg/kg, respectively. The blank samples were spiked at three levels, and the recoveries ranged from 70.8% to 118%, with the RSDs being 2.5% to 10.2%. The developed method was successfully applied to mycotoxin analysis in 30 scutellaria, puerarin and sea buckthorn samples bought from local markets. Different levels of mycotoxins were detected in some of the products. The proposed method is simple, rapid and sensitive, and it can be applied to the simultaneous determination of multi-mycotoxins in drug and food homologous products.
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http://dx.doi.org/10.3724/SP.J.1123.2019.10034DOI Listing
July 2020

Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE/GSK3β inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine.

Eur J Med Chem 2021 Nov 22;223:113663. Epub 2021 Jun 22.

Department of Pharmaceutical Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3β (Glycogen synthase kinase 3β) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3β inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD.
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http://dx.doi.org/10.1016/j.ejmech.2021.113663DOI Listing
November 2021

Neuroprotective Effects of Rhynchophylline Against Aβ-Induced Oxidative Stress, Neurodegeneration, and Memory Impairment Via Nrf2-ARE Activation.

Neurochem Res 2021 Sep 25;46(9):2439-2450. Epub 2021 Jun 25.

Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.

Extensive studies have shown that oxidative stress is a crucial pathogenic factor in Alzheimer's disease (AD). Nuclear factor E2-related factor 2 (Nrf2) is a master cytoprotective regulator against oxidative stress, and thus represents an attractive therapeutic target in AD. The goal of our study is to investigate the contribution of Nrf2 in Rhynchophylline (Rhy)-induced neuroprotection in AD. The data showed that intraperitoneal administration of Rhy (10 or 20 mg/kg) could ameliorate Aβ-induced cognitive impairment, evidenced by performance improvement in memory tests. The result of Antioxidant response element (ARE)-luciferase activity assay indicated that Rhy treatment improved ARE promoter activity. The results of reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assessment in the frontal cortex and hippocampus showed that Rhy treatment could attenuate Aβ-induced oxidative stress to some extent, evidenced by reversion of these cytokines compared to Aβ + Veh group. Rhy treatment also restored expression of Nrf2 and its downstream protein heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (NOQ1), and recombinant glutamate cysteine ligase, modifier subunit (GCLM) in the frontal cortex and hippocampus of Aβ-treated mice. In addition, to investigate whether activation of Nrf2-mediated pathway is responsible for the neuroprotection of Rhy, Nrf2 siRNA was used in human neuroblastoma cells (SH-SY5Y). Interestingly, the results showed that the protective effects of Rhy, including anti-oxidative, anti-apoptosis and elevation of Nrf2 and its downstream proteins, were abolished in Nrf2 siRNA-transfected cells. These findings indicate that Rhynchophylline is protective against Aβ-induced neurotoxicity via Nrf2-ARE activation, and suggest that Rhy may serve as a potential candidate and promising Nrf2 activator for management of AD.
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http://dx.doi.org/10.1007/s11064-021-03343-9DOI Listing
September 2021

Naphtho-γ-pyrone Dimers from an Endozoic and the Effects of Coisolated Monomers in Combination with Cisplatin on a Cisplatin-Resistant A549 Cell Line.

J Nat Prod 2021 07 22;84(7):1889-1897. Epub 2021 Jun 22.

Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, People's Republic of China.

Chemotherapy resistance is one of the main causes of lung cancer treatment failure, and a combination regimen may be an effective way to overcome this. Here we report 5 new (-, , and ) and 15 known polyketides, isolated from an endozoic . The structures of the new compounds were determined by the interpretation of IR, HRESIMS, NMR, and ECD spectra. The ESI-MS/MS fragmentation of the isolated naphtho-γ-pyrone isomers in positive mode is discussed. The effects of isolated compounds in combination with cisplatin (DDP) on a DDP-resistant A549 cell line (A459/DDP) are investigated. The most active compound, , could reduce the ratio of GSH/GSSG, promote the generation of intracellular ROS, and cooperate with DDP to down-regulated levels of Nrf2, Akt, HO-1, and NQO1, suggesting that inhibition of Nrf2 and Akt pathways might be involved in the combined effect of and DDP in A549/DDP cells.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01262DOI Listing
July 2021

Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications.

J Allergy Clin Immunol 2021 Jun 17. Epub 2021 Jun 17.

Pulmonary Center and Section of Pulmonary, Allergy, Sleep & Critical Care, Department of Medicine, Boston University School of Medicine, Boston, Mass. Electronic address:

Background: Noninfectious complications are the greatest cause of morbidity and mortality in common variable immunodeficiency (CVID), but their pathogenesis remains poorly defined.

Objective: Using high-throughput approaches, we aimed to identify, correlate, and determine the significance of immunologic features of CVID with noninfectious complications (CVIDc).

Methods: We simultaneously applied proteomics, RNA sequencing, and mass cytometry to a large cohort with primary antibody deficiency.

Results: CVIDc is differentiated from uncomplicated CVID, other forms of primary antibody deficiency, and healthy controls by a distinct plasma proteomic profile. In addition to confirming previously reported elevations of 4-1BB, IL-6, IL-18, and IFN-γ, we found elevations of colony-stimulating factor 1, IL-12p40, IL-18R, oncostatin M, TNF, and vascular endothelial growth factor A to differentiate CVIDc. This cytokine dysregulation correlated with deficiency of LPS-specific antibodies and increased soluble CD14, suggesting microbial translocation. Indicating potential significance of reduced LPS-specific antibodies and resultant microbial-induced inflammation, CVIDc had altered LPS-induced gene expression matching plasma proteomics and corresponding with increased CD14CD16 monocytes, memory T cells, and tissue inflammation ameliorated by T-cell-targeted therapy. Unsupervised machine learning accurately differentiated subjects with CVIDc and supported cytokine dysregulation, antibody deficit, and T-cell activation as defining and convergent features.

Conclusions: Our data expand understanding of CVIDc proteomics, establish its link with deficiency of IgA and LPS-specific antibodies, and implicate altered LPS-induced gene expression and elevated monocytes and T cells in this cytokine dysregulation. This work indicates that CVIDc results when insufficient antibody neutralization of pathogen-associated molecular patterns, like LPS, occurs in those with a heightened response to these inflammatory mediators, suggesting a 2-hit model of pathogenesis requiring further exploration.
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http://dx.doi.org/10.1016/j.jaci.2021.06.008DOI Listing
June 2021

An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury.

Bioact Mater 2021 Dec 28;6(12):4816-4829. Epub 2021 May 28.

MOE Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou, 510632, China.

The harsh local micro-environment following spinal cord injury (SCI) remains a great challenge for neural regeneration. Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern. Herein, a hybrid hydrogel was developed using Fmoc-grafted chitosan (FC) and Fmoc peptide (FI). Dynamic reversible π-π stacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties, as characterized by visual appearances and rheological tests. Furthermore, the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin (Cur), which was named as FC/FI-Cur hydrogel. studies confirmed that with the support of FC/FI-Cur hydrogel, neurite outgrowth was promoted, and Schwann cell (SC) migration away from dorsal root ganglia (DRG) spheres with enhanced myelination was substantiated. The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells. In addition, endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves. These outcomes favored functional recovery, as evidenced by improved hind limbs movement and enhanced electrophysiological properties. Thus, our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175285PMC
December 2021

Matrix Stiffness Induces Pericyte-Fibroblast Transition Through YAP Activation.

Front Pharmacol 2021 31;12:698275. Epub 2021 May 31.

State Key Laboratory for Structural Chemistry of Unstable and Stable Species, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.

Vascular pericytes, important mural cells that retain progenitor cell properties and protect vascular integrity in healthy tissues, are often associated with tumor development, but their functions in cancer invasion remain elusive. One prominent outcome of tumor occurrence is that the microenvironment of the lesion often stiffens, which could change resident cell behavior. Here, we found pericytes are matrix stiffness-responsive and mechanical stimuli induce pericyte-fibroblast transition (PFT). Soft PA gels that mimic the stiffness of healthy tissues retain the identity and behavior of pericytes, whereas stiff PA gels that reflect the stiffness of tumorous tissues promote PFT and the mobility and invasiveness of the cells. Matrix stiffness-induced PFT depends on the activation of YAP (Yes-associated protein), a transcription factor, which, upon receiving mechanical signals, transfers from cytoplasm to nucleus to mediate cell transcriptional activities. Our result reveals a mechanism through which vascular pericytes convert to fibroblasts and migrate away from vasculatures to help tumor development, and thus targeting matrix stiffness-induced PFT may offer a new perspective to the treatment of cancer metastasis.
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http://dx.doi.org/10.3389/fphar.2021.698275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202079PMC
May 2021

Digestive promoting effect and mechanism of Jiao Sanxian in rats.

J Ethnopharmacol 2021 Oct 12;278:114334. Epub 2021 Jun 12.

Department of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: Jiao Sanxian, a customary term for the three Traditional Chinese Medicines of charred hawthorn (Crataegi Fructus), charred malt (Hordei Fructus Germinatus) and Liu Shenqu (Massa Medicata Fermentata), is a classic prescription for the treatment of functional dyspepsia (FD). This prescription is called "Jiao Sanxian" in China because people believe that it is a miracle medicine for enhancing digestion and improving stagnation of digestive system. Even though Jiao Sanxian is widely used in clinical treatment, the underlying mechanism has not been clarified to date.

Aim Of The Study: The present study is aimed to explore the efficacy and mechanism of Jiao Sanxian in improving the symptoms of FD in rats by using multiple pharmacological methods.

Materials And Methods: The Sprague Dawley (SD) rats were divided into control, model, Jiao Sanxian decoction low-dosage (JSXD LD), Jiao Sanxian decoction medium-dosage (JSXD MD), and Jiao Sanxian decoction high-dosage (JSXD HD) group at random. A FD model was established with reserpine, and animals were given intragastric administration. During this period, weight and food intake of animals were recorded. Samples of rat gastric antrum, spleen, and duodenum were collected for pathological staining and immunohistochemical determination of Ghrelin protein expression after 19 days of treatment. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of related brain gut peptides in serum. Moreover, 16S rRNA sequencing was used to valuate the influence of intestinal flora structure of the cecal contents of experimental rats. And plasma metabolomics by Ultra Performance Liquid Chromatography coupled with Quadrupole-Time-of-Flight mass spectrometry (UPLC-Q/TOF-MS) were performed to further reveal the mechanism of action.

Results: Jiao Sanxian decoction (JSXD) group with different dosage could increase body weight and food intake, improve histopathological changes, and alter disordered brain gut peptides in FD rats. 16S rRNA sequencing results described that JSXD improved the disorder of structural composition, biodiversity and function of gut microbiota in FD rats. Metabolomics illustrated 26 metabolites with JSXD treatment underwent continuous changes, which revealed JSXD might exert digestive effect by ameliorating abnormal metabolic pathways. The most relevant metabolic pathways were arachidonic acid metabolism, pyruvate metabolism, glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism.

Conclusions: JSXD can improve functional dyspepsia in rats and the mechanism is related to regulate secretion of brain gut peptides, significantly improve the disorder of intestinal flora and ameliorated multi-metabolic pathways.
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http://dx.doi.org/10.1016/j.jep.2021.114334DOI Listing
October 2021

Neuroprotective Activities of Constituents from Phyllosticta capitalensis, an Endophyte Fungus of Loropetalum chinense var. rubrum.

Chem Biodivers 2021 Aug 22;18(8):e2100314. Epub 2021 Jun 22.

Department of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, P. R. China.

One new dioxolanone derivative, guignardianone G (1) and twelve known compounds (2-13) were isolated from the 95 % ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Among these known compounds, isoaltenuene (3), brassicasterol (7), 5,6-epoxyergosterol (8), citreoanthrasteroid A (9), demethylincisterol A (10), and chaxine C (11) were reported from Phyllosticta sp. for the first time. The structure of 1 was elucidated by 1D- and 2D-NMR experiments and HR-ESI-MS data analysis, and its absolute configuration was established through the comprehensive use of the methods of modified Mosher methods, calculations of ECD spectra and optical rotation values. The neuroprotective activity of compounds (1-9, 11-13) were evaluated on PC12 cells damage induced by glutamate, and compounds 9 and 12 showed potential neuroprotective activities with half effective concentration (EC ) of 24.2 and 33.9 μM, respectively.
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http://dx.doi.org/10.1002/cbdv.202100314DOI Listing
August 2021

Magnesium Deficiency Causes a Reversible, Metabolic, Diastolic Cardiomyopathy.

J Am Heart Assoc 2021 06 5;10(12):e020205. Epub 2021 Jun 5.

Division of Cardiology Department of Medicine The Lillehei Heart InstituteUniversity of Minnesota at Twin Cities Minneapolis MN.

Background Dietary Mg intake is associated with a decreased risk of developing heart failure, whereas low circulating Mg level is associated with increased cardiovascular mortality. We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods and Results C57BL/6J mice were fed with a low Mg (low-Mg, 15-30 mg/kg Mg) or a normal Mg (nl-Mg, 600 mg/kg Mg) diet for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with nl-Mg diet for another 6 weeks. Low-Mg diet significantly decreased mouse serum Mg (0.38±0.03 versus 1.14±0.03 mmol/L for nl-Mg; <0.0001) with a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited impaired cardiac relaxation (ratio between mitral peak early filling velocity E and longitudinal tissue velocity of the mitral anterior annulus e, 21.1±1.1 versus 15.4±0.4 for nl-Mg; =0.011). Cellular ATP was decreased significantly in low-Mg hearts. The changes were accompanied by mitochondrial dysfunction with mitochondrial reactive oxygen species overproduction and membrane depolarization. cMyBPC (cardiac myosin-binding protein C) was -glutathionylated in low-Mg mouse hearts. All these changes were normalized with Mg repletion. In vivo (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride treatment during low-Mg diet improved cardiac relaxation, increased ATP levels, and reduced -glutathionylated cMyBPC. Conclusions Mg deficiency caused a reversible diastolic cardiomyopathy associated with mitochondrial dysfunction and oxidative modification of cMyBPC. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure.
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http://dx.doi.org/10.1161/JAHA.120.020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477865PMC
June 2021
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