Publications by authors named "Jiaqi Yu"

45 Publications

Electrophysiological Properties of Substantia Gelatinosa Neurons in the Preparation of a Slice of Middle-Aged Rat Spinal Cord.

Front Aging Neurosci 2021 10;13:640265. Epub 2021 Mar 10.

Hubei Key Laboratory of Embryonic Stem Cell Research, Department of Anesthesiology, Institute of Anesthesiology & Pain (IAP), Taihe Hospital, Hubei University of Medicine, Shiyan, China.

A patch-clamp recording in slices generated from the brain or the spinal cord has facilitated the exploration of neuronal circuits and the molecular mechanisms underlying neurological disorders. However, the rodents that are used to generate the spinal cord slices in previous studies involving a patch-clamp recording have been limited to those in the juvenile or adolescent stage. Here, we applied an N-methyl-D-glucamine HCl (NMDG-HCl) solution that enabled the patch-clamp recordings to be performed on the superficial dorsal horn neurons in the slices derived from middle-aged rats. The success rate of stable recordings from substantia gelatinosa (SG) neurons was 34.6% (90/260). When stimulated with long current pulses, 43.3% (39/90) of the neurons presented a tonic-firing pattern, which was considered to represent γ-aminobutyric acid-ergic (GABAergic) signals. Presumptive glutamatergic neurons presented 38.9% (35/90) delayed and 8.3% (7/90) single-spike patterns. The intrinsic membrane properties of both the neuron types were similar but delayed (glutamatergic) neurons appeared to be more excitable as indicated by the decreased latency and rheobase values of the action potential compared with those of tonic (GABAergic) neurons. Furthermore, the glutamatergic neurons were integrated, which receive more excitatory synaptic transmission. We demonstrated that the NMDG-HCl cutting solution could be used to prepare the spinal cord slices of middle-aged rodents for the patch-clamp recording. In combination with other techniques, this preparation method might permit the further study of the functions of the spinal cord in the pathological processes that occur in aging-associated diseases.
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http://dx.doi.org/10.3389/fnagi.2021.640265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987937PMC
March 2021

Traditional Chinese medicines differentially modulate the gut microbiota based on their nature (Yao-Xing).

Phytomedicine 2021 Feb 10;85:153496. Epub 2021 Feb 10.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address:

Background: Property theory is a unique principle guiding traditional Chinese medicine (TCM) that classifies various TCMs into four natures (hot, warm, cool, and cold) to reflect their medical actions on the human body. Despite successful application for thousands of years, characterizing the nature of medical TCMs by modern physiological indicators remains a challenge.

Purpose: In this study, we investigated the potential relationship between the nature of TCMs and their modulation of the gut microbiota.

Study Design: We selected twelve TCMs with hot, warm, cool, or cold natures that possess antidiarrheal effects. Their aqueous extracts were orally administered to C57BL/6 mice at a clinical dose for 4 weeks. The gut microbiota was measured by 16S rRNA-based metagenomics, and the correlation between microbial composition/function and TCM nature was analyzed.

Results: Antidiarrheal TCMs with different natures showed distinct impacts on the gut microbiota. Hot-natured TCMs had no influence on the gut microbiota, warm-natured TCMs had a moderate influence, cool-natured TCMs had a strong influence, and cold-natured TCMs substantially changed the structure of the gut microbial community. The abundance of Anaerotruncus, Tyzzerella and Ruminiclostridium steadily increased, while that of Ruminococcaceae_UCG-010, Parasutterella and Bifidobacterium continuously decreased as the herbal nature turned from cold to hot. Microbiome functional prediction for Cluster of Orthologous Groups (COG) of proteins and Kyoto Encyclopedia of Genes and Genomes (KEGG) categories showed that colder TCMs imposed a stronger influence on microbial functional repertoires. Specifically, the abundance of ABC transporters, key bacterial proteins involved in nutrient absorption and drug resistance, was gradually decreased by colder TCMs.

Conclusion: Our results demonstrated that the nature of TCMs could be reflected by their modulation of gut microbes. Cold TCMs may exert their antidiarrheal effects, at least partially, by modulating the gut microbiota, while hot TCMs may alleviate dysentery in other ways.
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http://dx.doi.org/10.1016/j.phymed.2021.153496DOI Listing
February 2021

Downregulation of CISD2 Has Prognostic Value in Non-Small Cell Lung Cancer and Inhibits the Tumorigenesis by Inducing Mitochondrial Dysfunction.

Front Oncol 2020 1;10:595524. Epub 2021 Feb 1.

Department of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

CISD2, a NEET protein that coordinates 2Fe-2S clusters through its CDGSH domain, is critical for normal development and iron homeostasis. CISD2 plays an important role in Fe-S cluster transfer and promotes cancer proliferation. However, its specific role in the development of non-small cell lung cancer (NSCLC) remains unclear. Bioinformatics of pan-cancer analysis from The Cancer Genome Atlas show that CISD2 has an aberrant expression in most types of human cancers. Moreover, CISD2 expression is associated with a higher hazard ratio and exhibits significantly poorer overall survival in lung adenocarcinoma (LUAD), uveal melanoma, head and neck squamous cell carcinoma, brain lower grade glioma, kidney chromophobe, and liver hepatocellular carcinoma. Further investigation revealed that CISD2 is highly expressed in LUAD and LUSC, which is associated with clinical pathological stages. In addition, survival data collected from GSE31210 and GSE13213, two datasets from the NCBI Gene Expression Omnibus, also confirmed that high CISD2 expression is associated with unfavorable survival in patients with LUAD. A cell-based assay indicated that the knockdown of CISD2 inhibited proliferation, invasion, and migration in A549 cells. Additionally, CISD2 knockdown accelerated the accumulation of cellular and mitochondrial reactive oxygen species, destroying the mitochondrial morphology and function. Moreover, CISD2 inhibition activated the iron starvation response, thus, accelerating iron accumulation in A549 cells. Pretreatment with DFO, the iron chelator, blocked mitochondrial dysfunction in CISD2-knockdown cells. Collectively, the present study provides novel insights into the regulatory role of CISD2 in NSCLC and presents a potential target to improve antitumor activity based on oxidative stress.
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http://dx.doi.org/10.3389/fonc.2020.595524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882736PMC
February 2021

Changes in Clinical and Histological Characteristics of Nasal Polyps in Northern China over the Past 2-3 Decades.

Int Arch Allergy Immunol 2021 Feb 17:1-10. Epub 2021 Feb 17.

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Introduction: Recent studies have shown that inflammatory patterns of nasal polyps from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) in East Asia have changed over time. However, to date there is a marked lack of similar data for CRSwNP in Northern China. This study thus aimed to assess the changes in the clinical and histological characteristics of CRSwNP patients from Northern China over the past 2-3 decades.

Methods: This was a retrospective study, which examined data from 2 groups of 150 CRSwNP patients each, who had undergone endoscopic sinus surgery in Beijing Tongren Hospital from 1993 to 1995 (group A) and from 2015 to 2019 (group B). All relevant data for demographic, clinical, and histological parameters were collected for each patient from the 2 groups and compared for overall changes between the 2 groups.

Results: The comorbidity of CRSwNP and asthma increased over time and the cellular phenotype of CRSwNPchanged significantly; in particular, the proportion of eosinophil-dominant CRSwNP increased, lymphocyte-dominant and plasma-dominant CRSwNP decreased significantly, and the proportions of neutrophil-dominant and mixed CRSwNP were not altered. The rate of polyp recurrence increased in CRSwNP but did not in eosinophilic CRSwNP. Smoking and age did not significantly impact the inflammatory patterns of CRSwNP.

Conclusions: The inflammatory patterns of CRSwNP patients have changed and comorbidity of asthma significantly increased in CRSwNP patients in Northern China over the past 2-3 decades.
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http://dx.doi.org/10.1159/000513312DOI Listing
February 2021

Duet FeC and FeN Sites for HO Generation and Activation toward Enhanced Electro-Fenton Performance in Wastewater Treatment.

Environ Sci Technol 2021 01 8;55(2):1260-1269. Epub 2021 Jan 8.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia 5005, Australia.

Heterogeneous electro-Fenton (HEF) reaction has been considered as a promising process for real effluent treatments. However, the design of effective catalysts for simultaneous HO generation and activation to achieve bifunctional catalysis for O toward •OH production remains a challenge. Herein, a core-shell structural Fe-based catalyst (FeNC@C), with FeC and FeN nanoparticles encapsulated by porous graphitic layers, was synthesized and employed in a HEF system. The FeNC@C catalyst presented a significant performance in degradation of various chlorophenols at various conditions with an extremely low level of leached iron. Electron spin resonance and radical scavenging revealed that •OH was the key reactive species and Fe would play a role at neutral conditions. Experimental and density function theory calculation revealed the dominated role of FeC in HO generation and the positive effect of FeN sites on HO activation to form •OH. Meanwhile, FeNC@C was proved to be less pH dependence, high stability, and well-recycled materials for practical application in wastewater purification.
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http://dx.doi.org/10.1021/acs.est.0c06825DOI Listing
January 2021

Pinpointing miRNA and genes enrichment over trait-relevant tissue network in Genome-Wide Association Studies.

BMC Med Genomics 2020 12 28;13(Suppl 11):191. Epub 2020 Dec 28.

Department of Biology, Eastern Michigan University, Ypsilanti, MI, 48197, USA.

Background: Understanding gene regulation is important but difficult. Elucidating tissue-specific gene regulation mechanism is even more challenging and requires gene co-expression network assembled from protein-protein interaction, transcription factor and gene binding, and post-transcriptional regulation (e.g., miRNA targeting) information. The miRNA binding affinity could therefore be changed by SNP(s) located at the 3' untranslated regions (3'UTR) of the target messenger RNA (mRNA) which miRNA(s) interacts with. Genome-wide association study (GWAS) has reported significant numbers of loci hosting SNPs associated with many traits. The goal of this study is to pinpoint GWAS functional variants located in 3'UTRs and elucidate if the genes harboring these variants along with their targeting miRNAs are associated with genetic traits relevant to certain tissues.

Methods: By applying MIGWAS, CoCoNet, ANNOVAR, and DAVID bioinformatics software and utilizing the gene expression database (e.g. GTEx data) to study GWAS summary statistics for 43 traits from 28 GWAS studies, we have identified a list of miRNAs and targeted genes harboring 3'UTR variants, which could contribute to trait-relevant tissue over miRNA-target gene network.

Results: Our result demonstrated that strong association between traits and tissues exists, and in particular, the Primary Biliary Cirrhosis (PBC) trait has the most significant p-value for all 180 tissues among all 43 traits used for this study. We reported SNPs located in 3'UTR regions of genes (SFMBT2, ZC3HAV1, and UGT3A1) targeted by miRNAs for PBC trait and its tissue association network. After employing Gene Ontology (GO) analysis for PBC trait, we have also identified a very important miRNA targeted gene over miRNA-target gene network, PFKL, which encodes the liver subunit of an enzyme.

Conclusions: The non-coding variants identified from GWAS studies are casually assumed to be not critical to translated protein product. However, 3' untranslated regions (3'UTRs) of genes harbor variants can often change the binding affinity of targeting miRNAs playing important roles in protein translation degree. Our study has shown that GWAS variants could play important roles on miRNA-target gene networks by contributing the association between traits and tissues. Our analysis expands our knowledge on trait-relevant tissue network and paves way for future human disease studies.
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http://dx.doi.org/10.1186/s12920-020-00830-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771066PMC
December 2020

Sorafenib induces mitochondrial dysfunction and exhibits synergistic effect with cysteine depletion by promoting HCC cells ferroptosis.

Biochem Biophys Res Commun 2021 01 6;534:877-884. Epub 2020 Nov 6.

Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. The prognosis of HCC remains poor. Currently, sorafenib is the first-line drug for advanced HCC. Although sorafenib's mechanism of action involving several established cancer-related protein kinase targets is well-characterized, the underlying molecular mechanism is still unclear. Here, we found that sorafenib inhibited viability, proliferation, and migration of HCC cells in a dose-dependent manner. Sorafenib treatment of HCC cells destroyed mitochondrial morphology, accompanied by decreased activity of oxidative phosphorylation, collapse of mitochondrial membrane potential, and reduced synthesis of ATP, with consequent cell death due to ferroptosis. Pharmacological utilization of glutathione (GSH) rescued the sorafenib-induced ferroptosis, eliminated the accumulation of cellular mitochondrial reactive oxygen species (ROS), and lipid peroxide. GSH depletion through cysteine deprivation or cysteinase inhibition exacerbated sorafenib-induced ferroptotic cell death and lipid peroxides generation, and enhanced oxidative stress and mitochondrial ROS accumulation. Collectively, these findings indicate that depletion of cysteine acts synergistically with sorafenib and renders HCC cells vulnerable to ferroptosis, presenting the potential value of new therapeutic combinations for advanced HCC.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.083DOI Listing
January 2021

A dry powder inhalable formulation of salvianolic acids for the treatment of pulmonary fibrosis: safety, lung deposition, and pharmacokinetic study.

Drug Deliv Transl Res 2020 Oct 3. Epub 2020 Oct 3.

Department of Chinese Medicinal Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Yang Guang South Street, Fangshan District, Beijing, 102488, China.

Salvianolic acids (SAL), the main bioactive component extracted from Salvia miltiorrhiza, is a natural product with a reported anti-pulmonary fibrosis (PF) effect. SAL is commonly administrated orally; however, it has a low oral bioavailability (less than 5%). The objective of this work was to develop a new dry powder inhalable formulation intended to facilitate the access of SAL to the target place. We prepared the new SAL powder formulation containing L-arginine and 2% of lecithin using the ball milling technique. L-arginine was used to regulate the strong acidity of the SAL solution, and lecithin was added to disperse the powder and improve the flowability. The resulting powder had a content in salvianolic acid B (SALB, the main active principle of SAL) of 66.67%, a particle size of less than 5 μm and a good flowability. In vivo fluorescence imaging showed that the powder could be successfully aerosolized and delivered to the lung. The acute lung irritation study proved that the presence of L-arginine improved the biocompatibility of the powder. Finally, according to the pharmacokinetic study, the new SAL powder formulation was found to significantly increase drug concentration in the lung and the bioavailability. In conclusion, the new dry powder inhalable formulation of SAL developed in this study could be a strategy to enhance the performance of SAL at the lung level. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-020-00857-7DOI Listing
October 2020

Role of CFD based in silico modelling in establishing an in vitro-in vivo correlation of aerosol deposition in the respiratory tract.

Adv Drug Deliv Rev 2021 03 22;170:369-385. Epub 2020 Sep 22.

School of Materials Science and Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address:

Effective evaluation and prediction of aerosol transport deposition in the human respiratory tracts are critical to aerosol drug delivery and evaluation of inhalation products. Establishment of an in vitro-in vivo correlation (IVIVC) requires the understanding of flow and aerosol behaviour and underlying mechanisms at the microscopic scale. The achievement of the aim can be facilitated via computational fluid dynamics (CFD) based in silico modelling which treats the aerosol delivery as a two-phase flow. CFD modelling research, in particular coupling with discrete phase model (DPM) and discrete element method (DEM) approaches, has been rapidly developed in the past two decades. This paper reviews the recent development in this area. The paper covers the following aspects: geometric models of the respiratory tract, CFD turbulence models for gas phase and its coupling with DPM/DEM for aerosols, and CFD investigation of the effects of key factors associated with geometric variations, flow and powder characteristics. The review showed that in silico study based on CFD models can effectively evaluate and predict aerosol deposition pattern in human respiratory tracts. The review concludes with recommendations on future research to improve in silico prediction to achieve better IVIVC.
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http://dx.doi.org/10.1016/j.addr.2020.09.007DOI Listing
March 2021

The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.

Biomed Pharmacother 2020 Nov 28;131:110667. Epub 2020 Aug 28.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address:

The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.
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http://dx.doi.org/10.1016/j.biopha.2020.110667DOI Listing
November 2020

Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system.

BMC Cancer 2020 Jul 29;20(1):705. Epub 2020 Jul 29.

Department of pathology, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, 130041, Jilin, China.

Background: This study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system.

Methods: In total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically.

Results: STAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis.

Conclusions: Our findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.
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http://dx.doi.org/10.1186/s12885-020-07200-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391600PMC
July 2020

Research on Prediction Model for Durability of Straw Bale Walls in Warm (Humid) Continental Climate-A Case Study in Northeast China.

Materials (Basel) 2020 Jul 6;13(13). Epub 2020 Jul 6.

School of Architecture, Harbin Institute of Technology, Harbin 150001, China.

This research analyses straw degradation inside straw bale walls in the region and develops the prediction of degradation inside straw bale walls. The results show that the straw inside straw bale walls have no serious concerns of degradation in the high hygrothermal environment in the region with only moderate concerns of degradation in the area 2-3 cm deep behind the lime render. The onsite investigations indicate that the degradation isopleth model can only predict straw conditions behind the rendering layer, whereas the isothermal model fits the complete situation inside straw bale walls. This research develops the models for predicting straw degradation levels inside a straw bale building in a warm (humid) continental climate. The impact of this research will help the growth of low carbon energy efficient straw bale construction with confidence pertaining to its long-term durability characteristics both in the region and regions sharing similar climatic features globally.
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http://dx.doi.org/10.3390/ma13133007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372436PMC
July 2020

Purification and characterization of angiotensin-I-converting enzyme inhibitory peptides isolated from whey proteins of milk fermented with Lactobacillus plantarum QS670.

J Dairy Sci 2020 Jun 27;103(6):4919-4928. Epub 2020 Mar 27.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China. Electronic address:

An angiotensin-converting enzyme inhibitory (ACEI) peptide with a median inhibitory concentration (IC) of 1.26 mg/mL was purified from whey proteins resulting from a fermentation using Lactobacillus plantarum QS670. The peptide was subsequently derived from an α-casein, κ-casein, β-lactoglobulin, or serum albumin fraction. Analysis via liquid chromatography tandem mass spectrometry indicated that it had an amino acid sequence of Gly-Ala (GA). The GA dipeptide was also synthesized using an Fmoc solid-phase method. The GA dipeptide exhibited an IC of 1.22 mg/mL and was shown to be stable across both temperature (20 to 60°C) and pH (2 to 12). Digestive enzymes including pepsin, trypsin, and chymotrypsin had negligible effects on activity. The whey exerted hypotensive effects when fed to spontaneously hypertensive rats (SHR), which exhibited a blood pressure drop of 2.33 kPa. A 4-wk gavage treatment resulted in greater decreases of 7.46 kPa. Results of this study indicate that milk fermented using Lb. plantarum QS306 has potential to be used as a functional food to help prevent or reduce hypertension-associated diseases.
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http://dx.doi.org/10.3168/jds.2019-17594DOI Listing
June 2020

A UPLC-Q-TOF-MS-based metabolomics approach for the evaluation of fermented mare's milk to koumiss.

Food Chem 2020 Aug 16;320:126619. Epub 2020 Mar 16.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China. Electronic address:

The fermentation of mare's milk into koumiss produces many beneficial functional compounds depending on the metabolism of the initial microbial flora. In this study, metabolites found in mare's milk and resulting koumiss were identified. Major metabolic pathways in the fermentation were also identified using an UPLC-Q-TOF-MS-based metabolomics method. In total, 354 metabolites were identified: 61 were up-regulated and 105 were down-regulated. Metabolic pathway analyses revealed that c-5-branched dibasic acid metabolism, valine, leucine and isoleucine degradation, arginine and proline metabolism, valine, leucine and isoleucine biosynthesis, vascular smooth muscle contraction, aminoacyl-tRNA biosynthesis and ß-alanine metabolism showed significant increases. A hierarchical cluster analysis of metabolites indicated a clear grouping pattern in which the relative concentrations of p-pyruvate, 20-HETE, 4-aminobutanoate, uracil, acetoacetate, and γ-linolenic acid differed significantly between milk and koumiss. This study provides reference values for metabolic isolates and bioactive compounds purification in mare's milk and koumiss.
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http://dx.doi.org/10.1016/j.foodchem.2020.126619DOI Listing
August 2020

MicroRNAs expressed by human cytomegalovirus.

Virol J 2020 03 12;17(1):34. Epub 2020 Mar 12.

Department of Medical Microbiology, Weifang Medical University, Weifang, 261053, China.

Background: MicroRNAs (miRNAs) are small non-coding RNAs about 22 nucleotides in length, which play an important role in gene regulation of both eukaryotes and viruses. They can promote RNA cleavage and repress translation via base-pairing with complementary sequences within mRNA molecules.

Main Body: Human cytomegalovirus (HCMV) encodes a large number of miRNAs that regulate transcriptions of both host cells and themselves to favor viral infection and inhibit the host's immune response. To date, ~ 26 mature HCMV miRNAs have been identified. Nevertheless, their roles in viral infection are ambiguous, and the mechanisms have not been fully revealed. Therefore, we discuss the methods used in HCMV miRNA research and summarize the important roles of HCMV miRNAs and their potential mechanisms in infection.

Conclusions: To study the miRNAs encoded by viruses and their roles in viral replication, expression, and infection will not only contribute to the planning of effective antiviral therapies, but also provide new molecular targets for the development of antiviral drugs.
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http://dx.doi.org/10.1186/s12985-020-1296-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069213PMC
March 2020

Using a Material Library to Understand the Impacts of Raw Material Properties on Ribbon Quality in Roll Compaction.

Pharmaceutics 2019 Dec 7;11(12). Epub 2019 Dec 7.

Department of Chinese Medicine Information Science, Beijing University of Chinese Medicine, Beijing 100029, China.

The purpose of this study is to use a material library to investigate the effect of raw material properties on ribbon tensile strength (TS) and solid fraction (SF) in the roll compaction (RC) process. A total of 81 pharmaceutical materials, including 53 excipients and 28 natural product powders (NPPs), were characterized by 22 material descriptors and were compacted under five different hydraulic pressures. The transversal and longitudinal splitting behaviors of the ribbons were summarized. The TS-porosity and TS-pressure relationships were used to explain the roll compaction behavior of powdered materials. Through defining the target ribbon quality (i.e., 0.6 ≤ SF ≤ 0.8 and TS ≥ 1 MPa), the roll compaction behavior classification system (RCBCS) was built and 81 materials were classified into three categories. A total of 24 excipients and five NPPs were classified as Category I materials, which fulfilled the target ribbon quality and had less occurrence of transversal splitting. Moreover, the multivariate relationships between raw material descriptors, the hydraulic pressure and ribbon quality attributes were obtained by PLS regression. Four density-related material descriptors and the cohesion index were identified as critical material attributes (CMAs). The multi-objective design space summarizing the feasible material properties and operational region for the RC process were visualized. The RCBCS presented in this paper enables a formulator to perform the initial risk assessment of any new materials, and the data modeling method helps to predict the impact of formulation ingredients on strength and porosity of compacts.
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http://dx.doi.org/10.3390/pharmaceutics11120662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956229PMC
December 2019

A compression behavior classification system of pharmaceutical powders for accelerating direct compression tablet formulation design.

Int J Pharm 2019 Dec 21;572:118742. Epub 2019 Oct 21.

Department of Chinese Medicine Information Science, Beijing University of Chinese Medicine, Beijing 100029, PR China; Beijing Key Laboratory of Chinese Medicine Manufacturing Process Control and Quality Evaluation, Beijing 100029, PR China. Electronic address:

In this paper, a compression behavior classification system (CBCS) for direct compression (DC) pharmaceutical powders is presented. Seven descriptors from a series of compression models for powder compressibility, compactibility and tabletability analysis were included in the CBCS. A new tabletability index d was proposed to differentiate three categories of tensile strength (TS) vs. pressure relationships, and its physical meaning was explained thoroughly. 130 materials containing diverse pharmaceutical excipients and natural product powders (NPPs) were fully characterized and were compiled into an in-house developed material library, in which 70 materials with potential DC applications were used to justify the effectiveness of the CBCS. Principle component analysis (PCA) was used to uncover the latent structure of compression variables. Moreover, partial least squares (PLS) regression models are established in prediction of both tablet TS and solid fraction (SF) based on the raw materials' physical characteristics, the compression behavior indices and the compression force. The obtained scores and loadings are used to group the materials and the compression variables, respectively. Different categories of tabletability for DC powders were clearly clustered along two orthogonal directions pointing to the index d and the compression force. Finally, a multi-objective design space was identified under the latent variable space, summarizing the operationally possible region for both material properties and compression pressure required in DC tablet formulation design.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118742DOI Listing
December 2019

Novel manganese(II)-based metal-organic gels: synthesis, characterization and application to chemiluminescent sensing of hydrogen peroxide and glucose.

Mikrochim Acta 2019 10 15;186(11):696. Epub 2019 Oct 15.

Anhui Key Laboratory of Chemo/Biosensing, College of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241000, People's Republic of China.

A metal-organic gel (MOG) was synthesized that is composed of manganese(II) as the central ion and 1,10-phenanthroline-2,9-dicarboxylic acid as the ligand. The resulting MOG exhibits excellent activity for catalyzing the chemiluminescence (CL) of the luminol/hydrogen peroxide system. The CL system was characterized by CL spectra, UV-vis absorption spectra and by studying potential interferences by common radical scavengers. The CL reaction was exploited in a new scheme for the determination of hydrogen peroxide. CL intensity increases linearly in the 0.4 μM ~ 3 mM hydrogen peroxide concentration range, and the limit of detection (LOD) is 0.12 μM. The method was extended to an enzymatic assay for glucose by using glucose oxidase and by measurement of the enzymatically formed hydrogen peroxide. The assay works in the 0.2 μM ~ 3 mM glucose concentration range, and the LOD is 0.08 μM. Graphical abstract Schematic representation of the synthesized Mn-containing MOGs catalyzing luminol-hydrogen peroxide chemiluminescent reaction, which can be used to establish a new CL method for the detection of hydrogen peroxide and glucose.
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http://dx.doi.org/10.1007/s00604-019-3808-8DOI Listing
October 2019

Rectal adenocarcinoma coexisting with incidentally found microscopic gastrointestinal stromal tumor: A case report.

Medicine (Baltimore) 2019 Aug;98(31):e16644

Department of the General Surgery.

Rationale: Adenocarcinoma coexists with adjacent microscopic gastrointestinal stromal tumor (micro-GIST) is rare, especially in the rectum, where the gastrointestinal stromal tumors (GISTs) have the lower incidence rate. It is easy to ignore the concurrent micro-GIST due to the untypical symptoms.

Patient Concerns: A 77-year-old male patient suffered from lower abdominal pain for 20 days and presented with per rectal bleeding for 10 days. He had the medical history of hypertension and diabetes for more than 25 years.

Diagnoses: Endoscopy revealed that the patient had rectum adenocarcinoma and multiple rectum polyps. Besides, the gastrointestinal stromal tumor was diagnosed by the pathologist.

Interventions: The patient underwent surgery of laparoscopic rectum resection and prophylactic ileostomy and took 6 courses of Capecitabine tablets orally.

Outcomes: One year after surgery, the patient had no local relapse by the CT scan. However, not long after the CT examination, he died of cardiovascular disease.

Lessons: Although micro-GIST may be noninvasive and asymptomatic, it may have the potential for transforming to malignancies. More attention should be paid to the patients diagnosed with gastrointestinal malignancy coexisting with micro-GIST.
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http://dx.doi.org/10.1097/MD.0000000000016644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708707PMC
August 2019

Four-week administration of nicotinemoderately impacts blood metabolic profile and gut microbiota in a diet-dependent manner.

Biomed Pharmacother 2019 Jul 14;115:108945. Epub 2019 May 14.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100094, China. Electronic address:

As the primary active component in tobacco, nicotine affects many aspects of human metabolism. Diet and gut microbiota are key factors that profoundly influence human lipid and glucose metabolism. However, the diet-based differential impacts of nicotine on blood lipid and glucose levels as well as on the gut microbiota are still largely unknown. Here we show that 4-week oral administration of nicotine (2 mg/kg) resulted in bodyweight and fat decrease in both normal-chow (NCD)- and high-fat diet (HFD)-fed mice. But nicotine showed little influence on the plasma levels of lipids, glucose and inflammatory cytokines in NCD-fed mice but moderately deteriorated these parameters in HFD-fed ones. 16S sequencing showed that nicotine perturbed bacterial diversity and community composition of gut microbiota more pronouncedly in HFD mice. At genus level, nicotine dramatically increased Ruminococcaceae UCG-009 in HFD condition but not in NCD feeding. Interestingly, co-treatment with antibiotics (ampicillin + norfloxacin) substantially abolished the lipid-enhancing effect of nicotine in HFD-fed mice, suggesting an important role of gut microbes in the lipid-modulatory effect of nicotine. Together, our results indicate that the harmful effects of nicotine on metabolism and systemic inflammation are diet-dependent. Chronic exposure to nicotine may alter the gut microbiota especially in HFD-fed animals.
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http://dx.doi.org/10.1016/j.biopha.2019.108945DOI Listing
July 2019

Light-emitting-diode-pumped active Q-switched Nd:YLF laser.

Opt Lett 2019 Apr;44(8):1956-1959

An active Q-switching light-emitting diode (LED)-pumped laser is demonstrated by Nd:YLF crystal with acousto-optic modulation for the first time. The spectrum-band pump characteristic is grasped to describe the essential difference between an LED pump and single-absorption-peak matching of laser-diode pump or no matching of lamp pump. An effective absorption spectrum concept is proposed to characterize the absorption features of the gain material with LED-band pumping. According to this new theory, a flat-top beam profile is designed for pumping Nd:YLF crystal with only a 14  W/cm peak power, resulting in 165 μJ output energy at 1047 nm. More importantly, by using the acousto-optic Q-switching technique, this LED-pumped Nd:YLF laser has successfully realized a TEM mode output with a pulse energy of 10.6 μJ and a pulse width of 452 ns.
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http://dx.doi.org/10.1364/OL.44.001956DOI Listing
April 2019

The pandanus tectorius fruit extract (PTF) modulates the gut microbiota and exerts anti-hyperlipidaemic effects.

Phytomedicine 2019 May 18;58:152863. Epub 2019 Feb 18.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address:

Background: The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota.

Purpose: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects.

Methods: Male C57BL/6 J mice were induced with hyperlipidaemia by consuming a high-fat diet (HFD) for 4 weeks. Then, the mice were orally administered PTF, antibiotics (ampicillin+ norfloxacin), PTF+antibiotics or vehicle for another 6 weeks. Body weights and 24-h food intake were assessed weekly. At the end of the experiment, fresh stools were collected for 16S RNA pyrosequencing, and blood and liver and fat tissue were collected for pharmacological analysis.

Results: PTF was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia and significantly changed the structure of the gut microbiota. However, the anti-hyperlipidaemic effect of PTF was not influenced by the co-treatment with antibiotics (ampicillin+norfloxacin). A microbiological analysis of the gut microbiotas revealed that PTF selectively enhanced the relative abundance of Lactobacillus and decreased the relative abundance of Bacteroides and Alistipes. A correlation analysis between biochemical indexes and individual taxon showed that Lactobacillus was negatively associated with serum lipids and glucose while Bacteroides and Alistipes were positively associated with serum lipids and glucose. The modulatory effect of PTF on Lactobacillus, Bacteroides and Alistipes was not disturbed by the administration of antibiotics.

Conclusion: These results demonstrated that the polyphenol-rich PTF as a unique gut microbiota modulating agent and highlighted the richness of Lactobacillus and the decreased abundance of Bacteroides and Alistipes as an effective indicator of the therapeutic effect of medicinal foods on hyperlipidaemia.
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http://dx.doi.org/10.1016/j.phymed.2019.152863DOI Listing
May 2019

Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase (AMPK)-dependent pathway.

Acta Pharm Sin B 2019 Jan 17;9(1):135-143. Epub 2018 Oct 17.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue (WAT) contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin (Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in WAT and 3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase (AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.
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http://dx.doi.org/10.1016/j.apsb.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361849PMC
January 2019

Asperlin Stimulates Energy Expenditure and Modulates Gut Microbiota in HFD-Fed Mice.

Mar Drugs 2019 Jan 9;17(1). Epub 2019 Jan 9.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Asperlin is a marine-derived, natural product with antifungal, anti-inflammatory and anti-atherosclerotic activities. In the present study, we showed that asperlin effectively prevented the development of obesity in high-fat diet (HFD)-fed mice. Oral administration of asperlin for 12 weeks significantly suppressed HFD-induced body weight gain and fat deposition without inhibiting food intake. Hyperlipidemia and liver steatosis were also substantially ameliorated. A respiratory metabolism monitor showed that asperlin efficiently increased energy expenditure and enhanced thermogenic gene expression in adipose tissue. Accordingly, asperlin-treated mice showed higher body temperature and were more tolerant of cold stress. Meanwhile, asperlin also increased the diversity and shifted the structure of gut microbiota. Oral administration of asperlin markedly increased the relative abundance of Bacteroidetes, leading to a higher Bacteroidetes-to-Fimicutes ratio. The HFD-induced abnormalities at both phylum and genus levels were all remarkably recovered by asperlin. These results demonstrated that asperlin is effective in preventing HFD-induced obesity and modulating gut microbiota. Its anti-obesity properties may be attributed to its effect on promoting energy expenditure.
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http://dx.doi.org/10.3390/md17010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356881PMC
January 2019

Codelivery of Adriamycin and P-gp Inhibitor Quercetin Using PEGylated Liposomes to Overcome Cancer Drug Resistance.

J Pharm Sci 2019 05 2;108(5):1788-1799. Epub 2019 Jan 2.

School of Chinese Material Medical, Beijing University of Chinese Medicine, Chaoyang District, Beijing 100102, PR China.

Transmembrane protein P-gp's overexpression at the drug-resistant cell membrane is the most important characteristic of multidrug resistance (MDR). Quercetin (QUE) can effectively suppress the function of P-gp to reverse MDR. This study uses QUE as the P-gp inhibitor andfilm-ultrasound technique with ammonium sulfate transmembrane gradient method to prepare long-circulating liposomes simultaneously encapsulating QUE and Adriamycin (doxorubicin) (AMD/DOX). The optimal conditions for the preparation of AMD_QUE_long-circulating liposomes (SLs) are as follows: hydrogenated soybean phospholipids (HSPC):cholesterol:DSPE-PEG 2000 = 73.07:24.36:2.57 mol/mol, QUE:HSPC = 1:20 mol/mol, AMD:HSPC = 1:7.9 w/w (NHSO 0.15 mol/L, drug loaded (AMD) at 55°C for 25 min). The average encapsulation efficiency of AMD and QUE was 97.49% and 95.50%, respectively. The average particle size is 85 nm (n = 3), and the average zeta potential is -14.9 mV. First, the pharmacokinetic study proved that codelivery liposomes enveloping QUE and AMD (AMD_QUE_SL) can obviously increase the blood concentration of AMD (C: 140.50 ± 32.37 μg/mL) and extend the half-life period of AMD in plasma (t:14.02 ± 1.54 h). Second, AMD_QUE_SL can obviously enhance the cell toxicity to AMD-resistant cell strains (HL-6/ADR and MCF-7/ADR), and the reverse effects on the resistance of HL-6/ADR and MCF-7/ADR is increased to 4.81-fold and 3.21-fold, respectively. Third, according to the in vivo pharmacodynamic study, the relative tumor volume and relative tumor growth of the AMD_QUE_SL group were the lowest. The inhibition rate of tumor growth of this group was the highest. It can be concluded that AMD_QUE_SL can effectively reverse MDR, lower cardiac toxicity of AMD in clinical treatment, and improve the clinical treatment effect of AMD.
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http://dx.doi.org/10.1016/j.xphs.2018.12.016DOI Listing
May 2019

Butylene fipronil induces apoptosis in PC12 murine nervous cells via activation of p16-CDK4/6-cyclin D1 and mitochondrial apoptotic pathway.

J Biochem Mol Toxicol 2019 Mar 31;33(3):e22264. Epub 2018 Dec 31.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Butylene fipronil (BFPN) is a phenylpyrazole insecticide, acting at the γ-aminobutyric acid (GABA) receptor. Here, we show that BFPN inducedcytotoxicity in PC12 murinenervous cells, which lacks GABA receptor. Treatment with BFPN for 48 hours significantly enhanced G0/G1 arrest and induced apoptosis. BFPN decreased the expression of cyclin-dependent kinase (CDK4 and CDK6) and increased P16 and cyclin D1. Simultaneously, Bcl-2 protein was declined while Bax and cytochrome c were significantly enhanced in BFPN-treated groups. The apoptotic enzymes caspase-8, -9, and -3 were also activated by BFPN. Furthermore, treatment with BFPN significantly stimulated reactive oxygen species (ROS) generation, and pretreatment with antioxidant diphenyleneiodonium, substantially reduced cell death. Overall, these results suggest that BFPN is effective to induce G0/G1-phase arrest and apoptosis in PC12 murine nervous cell. Stimulating ROS generation and activation of P16-CDK4/6-cyclin D1 and mitochondrial apoptotic pathway may participate in the cytotoxicity of BFPN.
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http://dx.doi.org/10.1002/jbt.22264DOI Listing
March 2019

Identifying the Multielectron Effect on Chemical Bond Rearrangement of CHCl Molecules in Strong Laser Fields.

J Phys Chem A 2018 Nov 19;122(43):8427-8432. Epub 2018 Oct 19.

Institute of Atomic and Molecular Physics, Jilin Provincial Key Laboratory of Applied Atomic and Molecular Spectroscopy , Jilin University , Changchun 130012 , P. R. China.

Strong field double ionization that triggers the chemical bond rearrangement of CHCl is investigated by impulsive control of the alignment of molecules. The alignment and laser intensity dependent H and H yields in linearly polarized femtosecond laser have been measured, and the obtained data show that the maximum signal of H appears at the laser polarization parallel to the C-Cl axis of molecules and H species are more likely to eject at the laser polarization parallel to the C-Cl axis at low laser intensity while the H signal peaks at laser polarization perpendicular to the C-Cl axis at high laser intensity. The measurements indicate that electrons from HOMO - 1 and HOMO - 2 orbitals have been ionized for the generation of bond rearrangement at different laser intensity. Our results demonstrate the importance of multielectron effects and also provide an effective control method in the process of chemical bond rearrangement of the molecules in strong laser fields.
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http://dx.doi.org/10.1021/acs.jpca.8b06415DOI Listing
November 2018

The aqueous extract of Phellinus igniarius (SH) ameliorates dextran sodium sulfate-induced colitis in C57BL/6 mice.

PLoS One 2018 5;13(10):e0205007. Epub 2018 Oct 5.

Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou, China.

Phellinus igniarius, which is called Sanghuang in Chinese, is a fungal herb widely used in Traditional Chinese Medicine to treat stomachache, inflammation and tumors. Recent studies have demonstrated the antitumor, anti-diabetic, anti-inflammatory and immunity-modulating activities of P. igniarius. In the present study, we investigated that ameliorating effect of the aqueous extract of P. igniarius fruiting body (SH) on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice. Treatment with SH (250 and 400 mg/kg) for 8 weeks effectively alleviated the pathological indicators of colitis such as bodyweight reduction, disease activity index score, shortening of colon length and abnormal colon histology. The plasma levels of lipopolysaccharide (LPS) and inflammatory factors such as interleukin-6 (IL-6), IL-1β and tumor necrosis factor (TNF)-α were all significantly reduced. Supplementation of SH (10 mg/L) also inhibited LPS-elicited IL-1β production by RAW264.7 macrophages. Real-time PCR and western blot showed that treatment with SH significantly inhibited the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and decreased the expression of IL-6/IL-1β-maturation genes such as apoptosis-associated speck-like protein (ASC3) and caspase-1 in the colon of DSS-induced colitis mice. These results suggest that SH is adequate for the treatment of colitis. Inhibiting the expression and release of inflammatory factors may participate in the colitis-ameliorating effect of SH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205007PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173430PMC
March 2019

Preparation and Quality Evaluation of Salvianolic Acids and Tanshinones Dry Powder Inhalation.

J Pharm Sci 2018 09 6;107(9):2451-2456. Epub 2018 Jun 6.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, People Republic of China. Electronic address:

Salvianolic acids and tanshinones both exhibit efficacy in treating idiopathic pulmonary fibrosis (IPF), but their formulation limits their clinical use. This study aimed to prepare the salvianolic acids and tanshinones dry powder for inhalation (SPI) to achieve pulmonary delivery for the treatment of IPF. The variable quantities of salvianolic acids and tanshinones composite powder were optimized using the central composite design-response surface method. Different carriers with various drug-carrier ratios were optimized to prepare SPI. The final optimized formulation of SPI was as follows: InhaLac 230 was selected as the carrier with drug:carrier = 1:6, and the milled lactose InhaLac 400 was added at 5%. The developed SPI characterized with an angle of repose 52.46 ± 1.04°, Carr's index of 34.00 ± 0.50% and showed high lung deposition in vitro, indicating the potential of pulmonary delivery for the treatment of IPF.
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http://dx.doi.org/10.1016/j.xphs.2018.05.018DOI Listing
September 2018

Acoustically enhanced microfluidic mixer to synthesize highly uniform nanodrugs without the addition of stabilizers.

Int J Nanomedicine 2018 8;13:1353-1359. Epub 2018 Mar 8.

Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, VIC.

Background: This article presents an acoustically enhanced microfluidic mixer to generate highly uniform and ultra-fine nanoparticles, offering significant advantages over conventional liquid antisolvent techniques.

Methods: The method employed a 3D microfluidic geometry whereby two different phases - solvent and antisolvent - were introduced at either side of a 1 μm thick resonating membrane, which contained a through-hole. The vibration of the membrane rapidly and efficiently mixed the two phases, at the location of the hole, leading to the formation of nanoparticles.

Results: The versatility of the device was demonstrated by synthesizing budesonide (a common asthma drug) with a mean diameter of 135.7 nm and a polydispersity index of 0.044.

Conclusion: The method offers a 40-fold reduction in the size of synthesized particles combined with a substantial improvement in uniformity, achieved without the need of stabilizers.
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http://dx.doi.org/10.2147/IJN.S153805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849384PMC
May 2018