Publications by authors named "Yanyan Jiang"

182 Publications

A triple combination strategy of UHPLC-MS, hypolipidemic activity and transcriptome sequencing to unveil the hypolipidemic mechanism of Nelumbo nucifera alkaloids.

J Ethnopharmacol 2021 Sep 10:114608. Epub 2021 Sep 10.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China. Electronic address:

Ethnopharmacological Relevance: Nelumbo nucifera (N. nucifera), a kind of edible Chinese herbal, has been studied in treating hyperlipidemia. However, the hypolipidemic mechanism of N. nucifera remains unknown. Aims of this review: We aimed to screen the effective constituent of N. nucifera alkaloids and elucidated the potential mechanism for treating hyperlipidemia. A triple combination strategy of UHPLC-MS, hypolipidemic activity and transcriptome sequencing was built to unveil the hypolipidemic mechanism of Nelumbo nucifera alkaloid.

Materials And Methods: We comprehensively investigated the characterization of N. nucifera alkaloids by using UHPLC-LTQ-Orbitrap MS. And the hypolipidemic activity of candidate active ingredients were evaluated on sodium oleate-induced HepG2 cell. Finally, O-nornuciferine and N. nucifera alkaloid extraction were analyzed by RNA sequence (RNA-seq) to decipher the underlying hypolipidemic mechanism and were verified by qRT-PCR.

Results: 35 compounds were identified from N. nucifera alkaloid extraction by UHPLC-LTQ-Orbitrap MS. Among them, O-nornuciferine and N. nucifera alkaloid extraction which showed significant hypolipidemic activity were analyzed by transcriptome sequencing. After the intervention of O-nornuciferine and N. nucifera alkaloid extraction, 1 and 158 differentially expressed genes (DEGs) were identified, severally. The enrichment analysis indicated that the hypolipidemic effect was adjusted by the expression of numerous key DEGs involved in bile secretion, glycerolipid and sphingolipid metabolism, PPAR signaling pathway.

Conclusions: O-nornuciferine and N. nucifera alkaloids had exibited significant effects in hyperlipidemia. The candidate genes were LDLR, LPL and ANGPTL4, etc. It was most likely that they adjusted lipid metabolism by modulating expression levels of various key factors which were involved in bile secretion, glycerolipid metabolism, sphingolipid metabolism and PPAR signaling pathway, and so on. This study clarified the hypolipidemic mechanism of the alkaloids in N. nucifera, and laid a foundation for the subsequent development of clinical application and better quality of N. nucifera.
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http://dx.doi.org/10.1016/j.jep.2021.114608DOI Listing
September 2021

Molecular Recognition of the Self-Assembly Mechanism of Glycosyl Amino Acetate-Based Hydrogels.

ACS Omega 2021 Aug 13;6(33):21801-21808. Epub 2021 Aug 13.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China.

The self-assembly of supramolecular hydrogels has attracted the attention of many researchers, and it also has a broad application prospect in biomedical fields. However, there are few studies on the intrinsic mechanism of molecular self-assembly of hydrogels. In this paper, the self-assembly process of glycolipid-based hydrogels is studied by combining quantum chemistry calculation and molecular dynamics simulation. Using quantum chemistry calculation, the stable stacking mode of gelator dimers was explored. Then, by varying the water content in the gelation system, three different morphologies of hydrogels after self-assembly were observed on the nanoscale. When the water content is low, the molecular chains were entangled with each other to form a three-dimensional network structure. When the water content is moderate, the system had obvious stratification, forming the typical structure of "gel-water-gel". The gelators can only form small micelle-like agglomerations when the water content is too high. According to the analysis of the interaction between gelators and that between gelators and water molecules, combined with the study of the radial distribution function and hydrogen bonding, it is determined that the hydrogen bonds formed between gel molecules are the main driving force of the gelation process. Our work is of guiding significance for further exploration of the formation mechanism of a hydrogel and developing its application in other fields.
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http://dx.doi.org/10.1021/acsomega.1c03510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388079PMC
August 2021

First report of causing wilt on in China.

Plant Dis 2021 Aug 18. Epub 2021 Aug 18.

Northeast Agricultural University, plant protection, Agricultural College, Northeast Agricultural University, Harbin Heilongjiang 150030, P.R.China, Harbin , China, 150030;

(Thunb.) D. Don is used in many fields, including landscape, medicine, and forest interplanting. In July 2019, shoot blight was observed on at three nurseries in Harbin, China. Approximately 15% of plants had symptoms of the disease, which included rapid, synchronized death of leaves on individual branches. Eventually the whole plant wilted. Leaves and stems turned dark blue to brown. Ten infected vascular tissue samples from 10 individual plants were surface-disinfested in 0.5% NaOCl for 5 min, rinsed 3 times in sterile distilled water, and cultured on potato dextrose agar (PDA) amended with 50 µg/ml streptomycin at 26°C. Six similar fungal isolates from ten samples were isolated and subcultured. Single-conidium isolates were generated with methods reported previously (Leslie and Summerell 2006). Colonies on PDA consisted of densely floccose aerial hyphae with light yellow and pinkish pigments. Microconidia were oval to obovoid or allantoid, 3.8 to 11.8 μm in length and 2.8 to 4.6 μm in width, mostly non-septate on carnation leaf agar (CLA). Macroconidia were naviculate-to-fusiform slender, 24.9 to 57.2 μm in length and 2.8 to 4.5 μm in width with 3- to 5- septate, with a beaked apical cell and a foot-shaped basal cell. According to these morphological characteristics, all isolates were identified as spp. (Aoki et al. 2001 ). Genomic DNA was extracted from a representative isolate LHS1. The internal transcribed spacer regions (), translation elongation factor 1-alpha gene () and β-tubulin () gene were amplified using the primers ITS1 and ITS4 (Yin et al. 2012),EF1-728F/EF1-986R (Carbone and Kohn 1999) and T1/Bt2b (Glass and Donaldson 1995), respectively. DNA sequences of LHS1 were deposited in GenBank (accession nos. MT914496 for , MT920920 for and MT920921 for , respectively). MegaBLAST analysis of the , , and sequences indicated 100%, 97.7% and 100% similarity with  isolate CBS 450.97 (accession no. MH862659.1 for , MT010992.1 for , and MT011040.1 for , respectively). To determine pathogenicity, plants were grown in 10-cm pots containing a commercial potting mix (five plants/pot). At the 10 to 12 leaf stage, 10 healthy plants (2 pots) were inoculated by spraying 5 ml of a conidial suspension (4×10 spores/ml) onto every plant. Ten plants treated with sterile distilled water served as a control. The test was repeated twice. All plants were placed in a humidity chamber (>95% RH, 26℃) for 48 h after inoculation and then transferred to a greenhouse at 22/28°C (night/day). All inoculated wilted with leaves and stems turning dark blue to brown 15 days after inoculation. No symptoms were observed on the control plants. The fungus was re-isolated and confirmed to be according to morphological characteristics and molecular identification. To our knowledge, this is the first report of on in world. The disease caused a large number of plants to wilt and die, seriously impacting the ability of the horticulture industry to produce . Although this pathogen causes leaf and shoot blight symptoms, it is not clear if the pathogen is also a vascular wilt disease. The occurrence of the new disease caused by highlights the importance of developing management strategies to protect .
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http://dx.doi.org/10.1094/PDIS-07-21-1490-PDNDOI Listing
August 2021

Prevalence and genetic characteristics of Blastocystis hominis and Cystoisospora belli in HIV/AIDS patients in Guangxi Zhuang Autonomous Region, China.

Sci Rep 2021 Aug 5;11(1):15904. Epub 2021 Aug 5.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology, National Health Commission of People's Republic of China, WHO Collaborating Centre for Tropical Diseases, Shanghai, 200025, China.

Blastocystis hominis and Cystoisospora belli are considered to be common opportunistic intestinal protozoa in HIV/AIDS patients. In order to investigate the prevalence and genetic characteristics of B. hominis and C. belli in HIV/AIDS patients, a total of 285 faecal samples were individually collected from HIV/AIDS patients in Guangxi, China. B. hominis and C. belli were investigated by amplifying the barcode region of the SSU rRNA gene and the internal transcribed spacer 1 (ITS-1) region of the rRNA gene, respectively. Chi-square test or Fisher's exact test were conducted to assess the risk factors related to B. hominis and C. belli infection. The prevalence of B. hominis and C. belli was 6.0% (17/285) and 1.1% (3/285) respectively. Four genotypes of B. hominis were detected, with ST3 (n = 8) and ST1 (n = 6) being predominant, followed by ST6 (n = 2) and ST7 (n = 1). Females had a statistically higher prevalence of B. hominis (11.6%) than males (4.2%). The statistical analysis also showed that the prevalence of B. hominis was significantly associated with age group and educational level. Our study provides convincing evidence for the genetic diversity of B. hominis, which indicates its potential zoonotic transmission and is the first report on the molecular characteristics of C. belli in HIV/AIDS patients in China.
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http://dx.doi.org/10.1038/s41598-021-94962-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342556PMC
August 2021

Modeling of Wetting Transition of Liquid Metals on Organic Liquid Surfaces.

Langmuir 2021 Aug 28;37(31):9429-9438. Epub 2021 Jul 28.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, China.

Wettability of liquid metal gallium is of vital significance in the field of modern industries, such as direct writing printing and microfluidics. A liquid interface is a recently developed and promising approach to regulate wettability but has not been well applied in liquid metals yet. This study focuses on the wetting performance of gallium droplets on organic liquid films. The results show that the organic liquid film could change the wetting state of the gallium droplet. Based on the solid substrate roughness and surface tension of the organic liquid, we could estimate whether the gallium droplet is in a slippery Wenzel or a Cassie state. Subsequently, we apply the thermodynamic stable model on different organic liquid films by spreading parameters to predict a priori whether an arbitrary combination of solid roughness and organic liquid is suitable for designing lubricant-infused surfaces (LIS) used in gallium droplets. More interestingly, we found that the "cloaking" could delay surface oxide formation, which will benefit the manipulation of liquid metal droplets. This paper would provide a better understanding of wettability of liquid metal on an organic liquid surface.
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http://dx.doi.org/10.1021/acs.langmuir.1c01092DOI Listing
August 2021

Macrophage-biomimetic anti-inflammatory liposomes for homing and treating of aortic dissection.

J Control Release 2021 Sep 21;337:224-235. Epub 2021 Jul 21.

Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address:

Aortic dissection (AD) is a life-threatening disease featured by the dissection of intimal layer and the formation of a blood-filled false lumen within the aortic wall. Recent studies revealed that the formation and progression of AD lesions is closely related to vascular inflammation and macrophage infiltration. However, the potential efficacy of anti-inflammatory therapy on the prevention and treatment of AD has not been extensively investigated. Herein, we proposed a biomimetic anti-inflammatory liposome (PM/TN-CCLP) co-loaded with curcumin and celecoxib (CC), modified with cell-penetrating TAT-NBD fusion peptide (TN), and further camouflaged by isolated macrophage plasma membrane (PM), as a potential nanotherapy for AD. In vitro results showed that PM/TN-CCLP exhibited low cytotoxicity and elevated cellular uptake by inflammatory macrophages, and prominently inhibited the transendothelial migration, inflammatory responses and ROS generation of macrophages. Moreover, the PM/TN-CCLP treatment significantly prevented the HO-induced smooth muscle cell apoptosis. In vivo experiments were performed on the acute and chronic AD mouse models, respectively. The results verified the elevated accumulation of PM-camouflaged liposome at the aorta lesions. Further, the anti-inflammatory liposomes, especially PM/TN-CCLP, could reduce the rupture rate of dissection, prevent the loss of elastic fibers, and reduce MMP-9 expression as well as macrophage infiltration in the aortic lesions. Notably, as compared with free drugs and TN-CCLP, the PM/TN-CCLP treatment displayed the longest survival period along with the minimal aortic injury on both acute and chronic AD mice. Taken together, the present study suggested that the macrophage-biomimetic anti-inflammatory nanotherapy would be a promising strategy for the prevention and therapy of aortic dissection.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.032DOI Listing
September 2021

PEG/Sodium Tripolyphosphate-Modified Chitosan/Activated Carbon Membrane for Rhodamine B Removal.

ACS Omega 2021 Jun 11;6(24):15885-15891. Epub 2021 Jun 11.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan 250061, People's Republic of China.

Textile dyes from wastewater effluent are highly toxic to both living species and aqueous environments. An environmentally friendly method to remove hazardous dyes from wastewater in the textile industry has been a challenge. Chitosan (CS) and activated carbon (AC) are widely used as adsorbents for dye removal. However, the poor porosity and unsatisfactory stability of CS and the unfriendly cost of AC limited their applications to be used alone as a single adsorbent. Here, we report a novel method to prepare a CS/AC membrane using PEG as a porogen and sodium tripolyphosphate (TPP) as a cross-linking agent. The adsorption efficiency and reusability of the PEG/TPP-modified CS/AC membrane to remove RhB were investigated based on dynamic and static adsorption models. The results reveal that the adsorption performance of CS/AC membranes was significantly improved after the PEG/TPP modification based on the abundance macroporous structure. The modified CS/AC membrane with a 30% AC doping ratio exhibited an excellent adsorption efficiency of 91.29 and 73.91% in the dynamic and static adsorption processes, respectively. These results provide new insights into designing membranes to remove dyes from wastewater efficiently.
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http://dx.doi.org/10.1021/acsomega.1c01444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223414PMC
June 2021

DNAPK Inhibition Preferentially Compromises the Repair of Radiation-induced DNA Double-strand Breaks in Chronically Hypoxic Tumor Cells in Xenograft Models.

Mol Cancer Ther 2021 Sep 22;20(9):1663-1671. Epub 2021 Jun 22.

CRUK & MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.

Radiation-induced DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). Recently, it has been found that chronic tumor hypoxia compromises HR repair of DNA DSBs but activates the NHEJ protein DNAPK. We therefore hypothesized that inhibition of DNAPK can preferentially potentiate the sensitivity of chronically hypoxic cancer cells to radiation through contextual synthetic lethality In this study, we investigated the impact of DNAPK inhibition by a novel selective DNAPK inhibitor, NU5455, on the repair of radiation-induced DNA DSBs in chronically hypoxic and nonhypoxic cells across a range of xenograft models. We found that NU5455 inhibited DSB repair following radiation in both chronically hypoxic and nonhypoxic tumor cells. Most importantly, the inhibitory effect was more pronounced in chronically hypoxic tumor cells than in nonhypoxic tumor cells. This is the first study to indicate that DNAPK inhibition may preferentially sensitize chronically hypoxic tumor cells to radiotherapy, suggesting a broader therapeutic window for transient DNAPK inhibition combined with radiotherapy.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611623PMC
September 2021

Carbon-Based MOF Derivatives: Emerging Efficient Electromagnetic Wave Absorption Agents.

Nanomicro Lett 2021 Jun 6;13(1):135. Epub 2021 Jun 6.

School of Materials Science and Engineering, Shandong University, Jinan, 250061, People's Republic of China.

To tackle the aggravating electromagnetic wave (EMW) pollution issues, high-efficiency EMW absorption materials are urgently explored. Metal-organic framework (MOF) derivatives have been intensively investigated for EMW absorption due to the distinctive components and structures, which is expected to satisfy diverse application requirements. The extensive developments on MOF derivatives demonstrate its significantly important role in this research area. Particularly, MOF derivatives deliver huge performance superiorities in light weight, broad bandwidth, and robust loss capacity, which are attributed to the outstanding impedance matching, multiple attenuation mechanisms, and destructive interference effect. Herein, we summarized the relevant theories and evaluation methods, and categorized the state-of-the-art research progresses on MOF derivatives in EMW absorption field. In spite of lots of challenges to face, MOF derivatives have illuminated infinite potentials for further development as EMW absorption materials.
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http://dx.doi.org/10.1007/s40820-021-00658-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180543PMC
June 2021

Investigation of giardiasis in captive animals in zoological gardens with strain typing of assemblages in China.

Parasitology 2021 Sep 8;148(11):1360-1365. Epub 2021 Jun 8.

Department of Parasitology, Zunyi Medical University, Zunyi563000, China.

Giardia duodenalis is a common zoonotic intestinal pathogen. It has been increasingly reported in humans and animals; however, genotyping information for G. duodenalis in captive animals is still limited. This study was conducted to assess the prevalence and multilocus genotyping of G. duodenalis in captive animals in zoological gardens in Shanghai, China. A total of 678 fresh fecal samples were randomly collected from captive animals including non-human primates (NHPs) (n = 190), herbivores (n = 190), carnivores (n = 151), birds (n = 138) and reptiles (n = 9) in a zoo and were examined for the presence of G. duodenalis using nested polymerase chain reaction (nested PCR). All G. duodenalis positive samples were assayed with PCR followed by sequencing at β-giardin (bg), glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) genes. In this study, 42 specimens (6.2%) were tested G. duodenalis-positive of the 678 fecal samples examined based on a single locus. A total of 30 (4.4%), 30 (4.4%) and 22 (3.2%) specimens were successfully amplified and sequenced at gdh, tpi and bg loci, respectively. Assemblages A and B were identified with assemblage B dominating in NHPs. Sequence analysis demonstrated that one, two and five new isolates were identified at bg, gdh and tpi loci. DNA sequences and new assemblage-subtypes of zoonotic G. duodenalis assemblages A and B were identified in the current study. Our data indicate the occurrence and molecular diversity of G. duodenalis and the potential zoonotic transmission in captive animals in China.
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http://dx.doi.org/10.1017/S0031182021000913DOI Listing
September 2021

The differential diagnostic value of a battery of oculomotor evaluation in Parkinson's Disease and Multiple System Atrophy.

Brain Behav 2021 07 30;11(7):e02184. Epub 2021 May 30.

Department of Neurology, Peking University First Hospital, Beijing, China.

Introduction: Clinical diagnosis of Parkinsonism is still challenging, and the diagnostic biomarkers of Multiple System Atrophy (MSA) are scarce. This study aimed to investigate the diagnostic value of the combined eye movement tests in patients with Parkinson's disease (PD) and those with MSA.

Methods: We enrolled 96 PD patients, 33 MSA patients (18 with MSA-P and 15 with MSA-C), and 40 healthy controls who had their horizontal ocular movements measured. The multiple-step pattern of memory-guided saccade (MGS), the hypometria/hypermetria of the reflexive saccade, the abnormal saccade in smooth pursuit movement (SPM), gaze-evoked nystagmus, and square-wave jerks in gaze-holding test were qualitatively analyzed. The reflexive saccadic parameters and gain of SPM were also quantitatively analyzed.

Results: The MGS test showed that patients with either diagnosis had a significantly higher incidence of multiple-step pattern compared with controls (68.6%, 65.2%, and versus. 2.5%, p < .05, in PD, MSA, versus. controls, respectively). The reflexive saccade test showed that MSA patients showing a prominent higher incidence of the abnormal saccade (63.6%, both hypometria and hypermetria) than that of PD patients and controls (33.3%, 7.5%, respectively, hypometria) (p < .05). The SPM test showed PD patients had mildly decreased gain among whom 28.1% presenting "saccade intrusions"; and that MSA patients had the significant decreased gain with 51.5% presenting "catch-up saccades"(p < .05). Only MSA patients showed gaze-evoked nystagmus (24.2%), square-wave jerks (6.1%) in gaze-holding test (p < .05).

Conclusions: A panel of eye movements tests may help to differentiate PD from MSA. The combined presence of hypometria and hypermetria in saccadic eye movement, the impaired gain of smooth pursuit movement with "catch-up saccades," gaze-evoked nystagmus, square-wave jerks in gaze-holding test, and multiple-step pattern in MGS may provide clues to the diagnosis of MSA.
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http://dx.doi.org/10.1002/brb3.2184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323034PMC
July 2021

Risk Factors for Infection in Residents of Binyang, Guangxi: A Cross-Sectional and Logistic Analysis Study.

Front Public Health 2021 5;9:588325. Epub 2021 May 5.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China.

Clonorchiasis is a serious food-borne parasitic disease caused by infection. , a major fish-borne trematode, is a known causative agent of cholangiocarcinoma. The risk factors for infection include individual eating behaviors and environmental factors. In this study, we evaluated the infection rate and the associated risk factors among residents in Binyang County, Guangxi, China. In 2016 and 2017, five villages from Binyang, Guangxi were selected by multistage cluster random sampling for a cross-sectional study. A modified Kato-Katz thick smear method was used to examine eggs in fecal samples in triplicate (three smears for each sample). Both uni-variate and multi-variate logistic regression analyses were carried out to identify the risk factors for infection. A total of 1,977 fecal samples were collected from villagers in the investigated areas. The overall infection rates of in Binyang County was 20.49% (405/1,977). The mean age of participants was 39.42 ± 23.48 (range: 3-89 years old), and the highest infection rate (33.72%) was seen in the age group of 40-49 years old, followed by those aged 50-59 (31.83%). Multi-variate logistic regression analysis showed that higher infection rates were significantly associated with males ( = 6.51, = 4.67-9.08), Zhuang ( = 2.41, = 1.62-3.59), ages ( = 33.51, = 10.13-110.86), frequency of raw fresh fish consumption ( = 14.56, = 9.80-21.63), and close contact with cats and dogs ( = 1.53, = 1.02-2.30). Occupations and education levels showed no significant association with infection ( > 0.05). High levels of infection were observed among residents in Binyang County, Guangxi. Intervention strategies should be strengthened among the investigated population at high risk, such as males, Zhuang and older individuals, especially those who frequently eat raw fresh fish. In addition, the individuals contacting with cats and/or dogs were observed to have significantly higher infection rate of than those having no contact with cats and dogs. The association between contacting with cats and/or dogs and infection needs to be explored and confirmed in the future study by more epidemiological investigations of human infection from different areas.
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http://dx.doi.org/10.3389/fpubh.2021.588325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131673PMC
May 2021

Progress in the research of nanomaterial-based exosome bioanalysis and exosome-based nanomaterials tumor therapy.

Biomaterials 2021 07 5;274:120873. Epub 2021 May 5.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan, China. Electronic address:

Exosomes and their internal components have been proven to play critical roles in cell-cell interactions and intrinsic cellular regulations, showing promising prospects in both biomedical and clinical fields. Although conventional methods have so far been utilized to great effect, accurate bioanalysis remains a major challenge. In recent years, the fast-paced development of nanomaterials with unique physiochemical properties has led to a boom in the potential bioapplications of such materials. In particular, the application of nanomaterials in exosome bioanalysis provides a great opportunity to overcome the current challenges and limitations of conventional methods. A timely review of the research progress in this field is thus of great significance to the continued development of new methods. This review outlines the properties and potential uses of exosomes, and discusses the conventional methods currently used for their analysis. We then focus on exploring the current state of the art regarding the use of nanomaterials for the isolation, detection and even the subsequent profiling of exosomes. The main methods are based on principles including fluorescence, surface-enhanced Raman spectroscopy, colorimetry, electrochemistry, and surface plasmon resonance. Additionally, research on exosome-based nanomaterials tumor therapy is also promising from a clinical perspective, so the research progress in this branch is also summarized. Finally, we look at ways in which the field might develop in the future.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120873DOI Listing
July 2021

Editorial: Advanced Silica Nanomaterials for Drug Delivery.

Front Chem 2021 20;9:677647. Epub 2021 Apr 20.

School of Chemistry, Xi'an Jiaotong University, Xi'an, China.

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http://dx.doi.org/10.3389/fchem.2021.677647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093819PMC
April 2021

Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3β-mPTP Pathway In Vitro.

Molecules 2021 Mar 8;26(5). Epub 2021 Mar 8.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Cardiotoxicity is one of the main side effects of doxorubicin (Dox) treatment. Dox could induce oxidative stress, leading to an opening of the mitochondrial permeability transition pore (mPTP) and apoptosis in cardiomyocytes. Previous studies have shown that Cryptotanshinone (Cts) has potential cardioprotective effects, but its role in Dox-induced cardiotoxicity (DIC) remains unknown. A Dox-stimulated H9C2 cell model was established. The effects of Cts on cell viability, reactive oxygen species (ROS), superoxide ion accumulation, apoptosis and mitochondrial membrane potential (MMP) were evaluated. Expressions of proteins in Akt-GSK-3β pathway were detected by Western blot. An Akt inhibitor was applied to investigate the effects of Cts on the Akt-GSK-3β pathway. The effects of Cts on the binding of p-GSK-3β to ANT and the formation of the ANT-CypD complex were explored by immunoprecipitation assay. The results showed that Cts could increase cell viability, reduce ROS levels, inhibit apoptosis and protect mitochondrial membrane integrity. Cts increased phosphorylated levels of Akt and GSK-3β. After cells were co-treated with an Akt inhibitor, the effects of Cts were abolished. An immunoprecipitation assay showed that Cts significantly increased GSK-3β-ANT interaction and attenuated Dox-induced formation of the ANT-CypD complex, thereby inhibiting opening of the mPTP. In conclusion, Cts could ameliorate oxidative stress and apoptosis via the Akt-GSK-3β-mPTP pathway.
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http://dx.doi.org/10.3390/molecules26051460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962658PMC
March 2021

Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model.

Br J Cancer 2021 May 19;124(11):1809-1819. Epub 2021 Mar 19.

CRUK & MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.

Background: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model.

Methods: To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology.

Results: Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity.

Conclusions: The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.
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http://dx.doi.org/10.1038/s41416-021-01296-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144220PMC
May 2021

Transferable Multilevel Attention Neural Network for Accurate Prediction of Quantum Chemistry Properties via Multitask Learning.

J Chem Inf Model 2021 03 25;61(3):1066-1082. Epub 2021 Feb 25.

Key Laboratory of Mesoscopic Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.

The development of efficient models for predicting specific properties through machine learning is of great importance for the innovation of chemistry and material science. However, predicting global electronic structure properties like Frontier molecular orbital highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels and their HOMO-LUMO gaps from the small-sized molecule data to larger molecules remains a challenge. Here, we develop a multilevel attention neural network, named DeepMoleNet, to enable chemical interpretable insights being fused into multitask learning through (1) weighting contributions from various atoms and (2) taking the atom-centered symmetry functions (ACSFs) as the teacher descriptor. The efficient prediction of 12 properties including dipole moment, HOMO, and Gibbs free energy within chemical accuracy is achieved by using multiple benchmarks, both at the equilibrium and nonequilibrium geometries, including up to 110,000 records of data in QM9, 400,000 records in MD17, and 280,000 records in ANI-1ccx for random split evaluation. The good transferability for predicting larger molecules outside the training set is demonstrated in both equilibrium QM9 and Alchemy data sets at the density functional theory (DFT) level. Additional tests on nonequilibrium molecular conformations from DFT-based MD17 data set and ANI-1ccx data set with coupled cluster accuracy as well as the public test sets of singlet fission molecules, biomolecules, long oligomers, and protein with up to 140 atoms show reasonable predictions for thermodynamics and electronic structure properties. The proposed multilevel attention neural network is applicable to high-throughput screening of numerous chemical species in both equilibrium and nonequilibrium molecular spaces to accelerate rational designs of drug-like molecules, material candidates, and chemical reactions.
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http://dx.doi.org/10.1021/acs.jcim.0c01224DOI Listing
March 2021

Screening of hypolipidemic active components in Jiang-Zhi-Ning and its preliminary mechanism research based on "active contribution value" study.

J Ethnopharmacol 2021 May 14;272:113926. Epub 2021 Feb 14.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China. Electronic address:

Ethnopharmacological Relevance: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect.

Aim Of The Study: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula.

Materials And Methods: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MS) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN.

Results: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside.

Conclusions: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.
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http://dx.doi.org/10.1016/j.jep.2021.113926DOI Listing
May 2021

Correlation between depression and quality of life in patients with Parkinson's disease.

Clin Neurol Neurosurg 2021 Mar 29;202:106523. Epub 2021 Jan 29.

Neurology Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, PR China. Electronic address:

Objective: To understand the distribution of Parkinson's disease questionnaire-39 (PDQ-39) scores in Parkinson's disease (PD) patients with or without depression, and to analyze the factors that influence the quality of life of PD patients.

Materials And Methods: 300 PD patients were enrolled. Patients' general information and the results of assessments including UPDRS, H-Y, HAMD, HAMA, ADL and PDQ-39 were collected. They were divided into depression group and non-depression group according to HAMD score. The relationship between PD-related depression and quality of life and the factors that influence the quality of life of PD patients were analyzed based on PDQ-39 score.

Results: 111 patients with depression (37.0 %) and 189 patients without depression (63.0 %) were enrolled. The scores of PDQ-39 summary index (PDQ-39 SI) in the depression group were significantly higher than those in the non-depression group in all domains (P < 0.05). Patients in the depression group had a longer disease duration (6.89 ± 4.70 vs. 5.52 ± 4.12, P < 0.038), a higher UPDRS-III score (30.1 ± 13.55 vs. 25.2 ± 11.73, P < 0.001), and a higher H-Y stage level (2.41 ± 0.853 vs. 2.13 ± 0.707, P < 0.001), compared with patients in the non-depression group. All factors including age, disease duration, UPDRS-III, H-Y stage, HAMD score and HAMA score, may independently affected PDQ-39SI in PD patients, among which HAMD had the greatest effect. HAMD and HAMA were correlated with PDQ-39 in its all eight domains.

Conclusion: PD patients with psychological problems such as anxiety and depression may lead to a significant decline in the quality of life of patients in all domains.
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http://dx.doi.org/10.1016/j.clineuro.2021.106523DOI Listing
March 2021

Mitochondrial morphology and MAVS-IFN1 signaling pathway in muscles of anti-MDA5 dermatomyositis.

Ann Clin Transl Neurol 2021 03 12;8(3):677-686. Epub 2021 Feb 12.

Department of Neurology, Peking University First Hospital, Beijing, 100034, China.

Objective: This study aimed to investigate mitochondrial changes and the mitochondrial antiviral-signaling protein (MAVS)-type I interferon (IFN1) signaling pathway in the muscles of anti-melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients.

Methods: Eleven anti-MDA5 DM and ten antibody-negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups. The expression of MDA5, MAVS, interferon (IFN) regulatory factor 7, and IFN-stimulated gene 15, which are components of the MAVS-IFN1 signaling pathway, was measured in muscle specimen. The correlation between MAVS expression in muscles and disease phenotypes and muscle pathology were analyzed.

Results: Anti-MDA5 DM showed a significantly lower incidence of the characteristic DM pathology (P < 0.05) than antibody-negative DM, including perifascicular fiber atrophy, inflammation, and vasculopathy. Mitochondrial abnormalities in anti-MDA5 patients revealed a high incidence of (8/11,72.7%) and different pattern from that in antibody-negative DM. MDA5, MAVS, IFN regulatory factor 7, and IFN stimulated gene 15 expression levels in the muscles of anti-MDA5 DM patients were higher than those of the controls (P < 0.05) but lower than those of antibody-negative DM patients (P < 0.05). The MAVS levels negatively correlated with manual muscle test 8 scores (r = 0.701, P = 0.016).

Conclusions: Compared to antibody-negative DM, we presented a different distribution of the mitochondrial pathology and less severe morphology in anti-MDA5 DM. We also revealed the enhanced but less intensive MAVS-IFN1 signaling pathway activity in muscles of anti-MDA5 DM. Such disparity suggested the potentially different mechanism of muscle injury in two DM groups.
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http://dx.doi.org/10.1002/acn3.51311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951095PMC
March 2021

Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Response.

Cancer Res 2021 04 8;81(7):1667-1680. Epub 2021 Feb 8.

Target Discovery Institute, University of Oxford, Nuffield Department of Medicine, Oxford, United Kingdom.

Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic mutational status to modify cancer risk, progression, and response to therapy. Focusing on a cancer risk SNP (rs78378222) with a well-documented ability to directly influence p53 activity as well as integration of germline datasets relating to cancer susceptibility with tumor data capturing somatically-acquired genetic variation provided supportive evidence for this hypothesis. Integration of germline and somatic genetic data enabled identification of a novel entry point for therapeutic manipulation of p53 activities. A cluster of cancer risk SNPs resulted in increased expression of prosurvival p53 target gene and attenuation of p53-mediated responses to genotoxic therapies, which were reversed by pharmacologic inhibition of the prosurvival c-KIT signal. Together, our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel combinatorial therapies. SIGNIFICANCE: These results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and present novel therapeutic targets.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0177DOI Listing
April 2021

Shining light on transition metal sulfides: New choices as highly efficient antibacterial agents.

Nano Res 2021 Jan 21:1-23. Epub 2021 Jan 21.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials Ministry of Education, Shandong University, Jinan, 250061 China.

Globally, millions of people die of microbial infection-related diseases every year. The more terrible situation is that due to the overuse of antibiotics, especially in developing countries, people are struggling to fight with the bacteria variation. The emergence of super-bacteria will be an intractable environmental and health hazard in the future unless novel bactericidal weapons are mounted. Consequently, it is critical to develop viable antibacterial approaches to sustain the prosperous development of human society. Recent researches indicate that transition metal sulfides (TMSs) represent prominent bactericidal application potential owing to the meritorious antibacterial performance, acceptable biocompatibility, high solar energy utilization efficiency, and excellent photo-to-thermal conversion characteristics, and thus, a comprehensive review on the recent advances in this area would be beneficial for the future development. In this review article, we start with the antibacterial mechanisms of TMSs to provide a preliminary understanding. Thereafter, the state-of-the-art research progresses on the strategies for TMSs materials engineering so as to promote their antibacterial properties are systematically surveyed and summarized, followed by a summary of the practical application scenarios of TMSs-based antibacterial platforms. Finally, based on the thorough survey and analysis, we emphasize the challenges and future development trends in this area.
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http://dx.doi.org/10.1007/s12274-021-3293-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818700PMC
January 2021

Alteration of the fecal microbiota in Chinese patients with Schistosoma japonicum infection.

Parasite 2021 8;28. Epub 2021 Jan 8.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 200025 Shanghai, PR China - Chinese Center for Tropical Diseases Research, 200025 Shanghai, PR China - World Health Organization Collaborating Centre for Tropical Diseases, 200025 Shanghai, PR China - Key Laboratory of Parasite and Vector Biology, National Health Commission of the People's Republic of China, 200025 Shanghai, PR China.

Schistosoma japonicum infection causes pathological injury to the host. Multiple studies have shown that intestinal helminth infection causes dysbiosis for the gut microbial community and impacts host immunology. However, the effect of acute S. japonicum infection on the gut microbiome structure (abundance and diversity) is still unclear. We collected fecal samples from healthy and infected patients from a single hospital in Hunan Province, China. The bacterial community was analyzed using 16S ribosomal RNA gene sequencing of the V4 hypervariable region using the HiSeq platform. Compared with healthy subjects, infected patients exhibited an increase in relative abundance of the TM7 phylum. At the genus level, there were seven differentially abundant genera between groups. The most significant finding was a Bacteroides enterotype in patients with acute schistosomiasis. These results suggest that S. japonicum infection has a significant effect on microbiome composition characterized by a higher abundance of the TM7 phylum and development of a Bacteroides enterotype.
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http://dx.doi.org/10.1051/parasite/2020074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792497PMC
February 2021

Identification of Uncommon (a Novel Subtype XVcA2G1c) and as Well as Common Assemblages A and B in Humans in Myanmar.

Front Cell Infect Microbiol 2020 25;10:614053. Epub 2020 Nov 25.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Key Laboratory of Parasite and Vector Biology, MOH, Shanghai, China.

and are two important zoonotic intestinal protozoa responsible for diarrheal diseases in humans and animals worldwide. Feces from infected hosts, water and food contaminated by oocysts and cysts as well as predictors such as poverty have been involved in their transmission. Myanmar is one of the world's most impoverished countries. To date, there are few epidemiological studies of and in humans. To understand the prevalence and genetic characterization of spp. and in humans in Myanmar, a molecular epidemiological investigation of the two protozoa was conducted in four villages of Shan State. 172 fecal specimens were collected from Wa people (one each) and identified for the presence of spp. and by sequence analysis of their respective small subunit ribosomal RNA genes. 1.74% of investigated people were infected with spp.- (n = 2) and (n = 1) while 11.05% infected with -assemblages A (n = 6) and B (n = 13). By sequence analysis of 60-kDa glycoprotein gene, the isolate belonged to a novel subtype XVcA2G1c. DNA preparations positive for were further subtyped. Five of them were amplified and sequenced successfully: different assemblage B sequences (n = 2) at the triosephosphate isomerase (tpi) locus; sub-assemblage AII sequence (n = 1) and identical assemblage B sequences (n = 2) at the β-giardin (bg) locus. This is the first molecular epidemiological study of spp. and in humans in Myanmar at both genotype and subtype levels. Due to unclear transmission patterns and dynamics of spp. and , future research effort should focus on molecular epidemiological investigations of the two parasites in humans and animals living in close contact in the investigated areas, even in whole Myanmar. These data will aid in making efficient control strategies to intervene with and prevent occurrence of both diseases.
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http://dx.doi.org/10.3389/fcimb.2020.614053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724083PMC
June 2021

Quantitative analysis and mathematic modeling of the global outbreak of COVID-19.

J Infect Dev Ctries 2020 Oct 31;14(10):1106-1110. Epub 2020 Oct 31.

Jingling High School Hexi Campus, Nanjing, China.

The coronavirus pandemic is the biggest in the past 100 years, affected over 200 countries and killed over 300 thousand people. To better understand the epidemics in different areas, the progress percentage was generated in this study by dividing everyday total confirmed case number by the up-to-date total case number, so data obtained from different countries and territories can be put together and compared directly regardless of the large difference in the magnitude of numbers. The global outbreak data were analyzed and categorized into 4 groups based on different epidemic curve stages. The grouping pattern suggests that the geographical position may not play a critical role in the progress of COVID-19 epidemic. In this report, we also used a mathematic model to predict the progress of COVID-19 outbreak in UK, USA and Canada in Group 3, providing valuable information for assessing the risk in these countries and the timing of reopening business.
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http://dx.doi.org/10.3855/jidc.13150DOI Listing
October 2020

Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss.

Sci Rep 2020 11 2;10(1):18801. Epub 2020 Nov 2.

Department of Pharmacology, UC Davis School of Medicine, 2419B Tupper Hall, One Shields Ave, Davis, CA, 95616, USA.

Myocardial infarction (MI) can result in sympathetic nerve loss in the infarct region. However, the contribution of hypo-innervation to electrophysiological remodeling, independent from MI-induced ischemia and fibrosis, has not been comprehensively investigated. We present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing a targeted-toxin (dopamine beta-hydroxylase antibody conjugated to saporin, DBH-Sap), and measure resulting electrophysiological and Ca handling dynamics. Five days post-surgery, sympathetic nerve density was reduced in the anterior left ventricular epicardium of DBH-Sap hearts compared to control. In Langendorff-perfused hearts, there were no differences in mean action potential duration (APD) between groups; however, isoproterenol (ISO) significantly shortened APD in DBH-Sap but not control hearts, resulting in a significant increase in APD dispersion in the DBH-Sap group. ISO also produced spontaneous diastolic Ca elevation in DBH-Sap but not control hearts. In innervated hearts, sympathetic nerve stimulation (SNS) increased heart rate to a lesser degree in DBH-Sap hearts compared to control. Additionally, SNS produced APD prolongation in the apex of control but not DBH-Sap hearts. These results suggest that hypo-innervated hearts have regional super-sensitivity to circulating adrenergic stimulation (ISO), while having blunted responses to SNS, providing important insight into the mechanisms of arrhythmogenesis following sympathetic nerve loss.
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http://dx.doi.org/10.1038/s41598-020-75903-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608682PMC
November 2020

Autophagy as a novel insight into mechanism of Danqi pill against post-acute myocardial infarction heart failure.

J Ethnopharmacol 2021 Feb 5;266:113404. Epub 2020 Oct 5.

College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Ethnopharmacological Relevance: Danqi Pill, composed of the root of Salvia miltiorrhiza Bunge and the root of Panax notoginseng, is effective in the clinical treatment of myocardial ischemia in coronary heart diseases. A number of studies have shown that autophagy plays an essential role in cardiac function and energy metabolism, and disordered autophagy is associated with the progression of heart failure. However, the effect and mechanism of Danqi pill on autophagy have not been reported yet.

Aim Of The Study: This study aims to elucidate whether Danqi pill restores autophagy to protect against HF and its potential mechanism.

Materials And Methods: Left anterior descending ligation was established to induce an HF rat model, HO-stimulated H9C2 cells model was conducted to clarify the effects and potential mechanism of Danqi pill. In vivo, Danqi pill (1.5 g/kg) were orally administered for four weeks and Fenofibrate (10 mg/kg) was selected as a positive group. In vitro, Danqi pill (10-200 μg/mL) was pre-cultured for 24 h and co-cultured with HO stimulation for 4 h. Importantly, transmission electron microscopy and fluorescence GPF-mRFP-LC3 reporter system were combined to monitor autophagy flux. Furtherly, we utilized Compound C, a specific AMPK inhibitor, to validate whether the autophagy was mediated by AMPK-TSC2-mTOR pathway.

Results: Danqi pill significantly improved cardiac function and myocardial injury in HF rats. Intriguingly, Danqi pill potently regulated autophagy mainly by promoting the formation of autophagosomes in vivo. Further results demonstrated that expressions of p-AMPK (P < 0.001) and p-TSC2 (P < 0.001) in cardiac tissue were upregulated by Danqi pill, accompanied with downregulation of p-mTOR (P < 0.01) and p-ULK1(P < 0.01). In parallel with the vivo experiment, in vitro study indicated that Danqi pill dramatically restored autophagy flux and regulated expressions of critical autophagy-related molecules. Finally, utilization of Compound C abrogated the effects of Danqi pill on autophagy flux and the expressions of p-TSC2 (P < 0.05), p-mTOR (P < 0.01) and p-ULK1 (P < 0.05).

Conclusion: Danqi pill could improve cardiac function and protect against cardiomyocytes injury by restoring autophagy via regulating the AMPK-TSC2-mTOR signaling pathway.
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http://dx.doi.org/10.1016/j.jep.2020.113404DOI Listing
February 2021

Efficiency of Different Treatment Regimens Combining Anti-tumor and Anti-inflammatory Liposomes for Metastatic Breast Cancer.

AAPS PharmSciTech 2020 Sep 10;21(7):259. Epub 2020 Sep 10.

Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.

Nanomedicines such as liposomes have been widely exploited in the treatment of tumors, and are also involved in combination therapies to enhance anti-tumor efficacy and reduce side effects. However, few studies have systematically discussed the significance and optimized regimens for nanomedicine-based combination therapy. In this study, we used anti-inflammatory and anti-tumor liposomes for co-administration, and compared three regimens: intermittent, metronomic, or sequential administration (IA, MA, and SA). The anti-inflammatory liposome HA/TN-CCLP was constructed in our previous research, which co-loaded curcumin (CUR) and celecoxib (CXB), modified with TAT-NBD peptide (TN) and finally coated with hyaluronic acid (HA), thereby inhibiting NF-κB and STAT3 pathways in the treatment of metastatic breast cancer. Furthermore, doxorubicin liposomes with and without TN modification (namely TN-DOXLP and DOXLP) were constructed and administrated with HA/TN-CCLP. The anti-tumor and anti-metastasis efficacy of different regimens was investigated. Results showed that in vitro cytotoxicity of DOXLP and TN-DOXLP was significantly enhanced when combined with HA/TN-CCLP. In vivo experiments also revealed the superiority of three combination therapies in inhibiting tumor growth, prolonging the survival of tumor-bearing mice, inducing apoptosis, and reducing lung metastases. In particular, the combination therapy could reduce MDSCs (Gr-1/CD11b) and CSCs (CD44/CD24) infiltration, which are two important factors in tumor metastasis and recurrence. Among three regimens, sequential administration (SA) showed the best therapeutic outcome and was especially effective for the inhibition of CSCs. In general, the results demonstrated that combination therapy, particularly the sequential administration of anti-inflammatory and anti-tumor liposome, was superior to monotherapy in inhibiting the development and metastasis of inflammation-related tumors.
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http://dx.doi.org/10.1208/s12249-020-01792-zDOI Listing
September 2020

Prevalence and Characterization of Species and Genotypes in Four Farmed Deer Species in the Northeast of China.

Front Vet Sci 2020 10;7:430. Epub 2020 Aug 10.

Chinese Center for Disease Control and Prevention, National Institute of Parasitic Diseases, Shanghai, China.

Cryptosporidiosis is a major public health problem in humans and animals. Information on the prevalence and molecular diversity of in farmed deer in northeastern China is limited. In this study, the prevalence of these parasites was investigated in four farmed deer species, including 125 reindeer, 109 red deer, 86 sika deer, and 18 Siberian roe deer by nested PCR amplification of the partial small subunit of ribosomal RNA (SSU rRNA) gene. isolates were subtyped using nested PCR and sequence analysis of the 60-kDa glycoprotein () gene. The overall prevalence of was 7.1%, with 15.1% for sika deer, 4.0% for reindeer, 4.6% for red deer, and 5.6% for roe deer. ( = 4), ( = 2), and deer genotype ( = 18) were identified. All four isolates belonged to the XIIa subtype ( = 4). This study confirms that deer genotype is widely occurring in deer in the investigated areas. Presence of zoonotic XIIa subtype indicates that farmed deer represent potential source of zoonotic cryptosporidia and might pose a threat to human health.
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http://dx.doi.org/10.3389/fvets.2020.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438801PMC
August 2020

Development of arsenic trioxide sustained-release pellets for reducing toxicity and improving compliance.

Drug Dev Ind Pharm 2020 Nov 16;46(11):1809-1818. Epub 2020 Sep 16.

Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, China.

Arsenic trioxide (ATO) is first-line drug for acute promyelocytic leukemia. Clinically, the continuously slow intravenous infusion is adopted to maintain effective blood concentration and reduce toxic effects, but it causes poor patient' compliance for a considerable infusion period. To overcome these disadvantages, we developed an oral ATO sustained-release preparation which was constructed via the ATO core pellets prepared by extrusion spheronization and followed by a coating membrane by fluid-bed technology. The prepared coated pellets displayed a round surface and uniform particle size. All release profiles of ATO pellets in different pH media and rotation speeds had no statistical difference. Importantly, the coated pellets can release completely in 12 h without obvious burst release. There was no distinct change in appearance and release behaviors in stability experiments. pharmacokinetics was studied by one-time intragastric administration of rats. Compared with free drug, the AUC of the ATO coated pellets was 2.3-fold higher, indicating the oral bioavailability was significantly increased. decreased by about a half and extended about 15 h. In particularly, the ATO level at 96 h only decreased about 20% of , suggesting that the ATO sustained-release preparation could not only decrease the peak concentration, but also maintain a relatively constant blood concentration for a long period. Further, the absorption could be well predicted by release experiments. Therefore, the ATO sustained-release preparation formulated by the mature preparation technology, possessing satisfactory stability and improving bioavailability, had great application potentials for industrialization.
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http://dx.doi.org/10.1080/03639045.2020.1821050DOI Listing
November 2020
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