Publications by authors named "Yanqing Song"

38 Publications

Changes of Lipopolysaccharide-Induced Acute Kidney and Liver Injuries in Rats Based on Metabolomics Analysis.

J Inflamm Res 2021 6;14:1807-1825. Epub 2021 May 6.

Department of Pharmacy, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China.

Background: The bacterial endotoxin lipopolysaccharide (LPS) was the classic inducer to establish many inflammatory disease models, especially multiple organ injury. Evidences indicated that the mechanism that causes inflammation response is not just related to cytokine release. The main aim of this study was to better elucidate the possible links between metabolic changes and the pathogenesis of LPS-induced acute liver and kidney in order to understand the mechanisms and screening therapeutic targets for developing early diagnostic strategies and treatments.

Methods: An experimental rat model was established by intraperitoneal injection of 10 mg/kg LPS. An untargeted metabolomics analysis of the serum in the LPS and control groups was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). LPS-induced pathological damage in the lungs, liver, kidneys, and colon was observed, along with changes in biochemical indexes, indicating that there was a severe inflammatory response in many organs after administration of LPS for 8 h. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed distinct separation in the serum metabolite profiles between the LPS and control groups, indicating significant changes in endogenous metabolites.

Results: The untargeted metabolomics analysis showed that there were 127 significantly different serum metabolites and 53 altered pathways after LPS administration, including pathways related to the metabolism of D-glutamine and D-glutamate, taurine and hypotaurine, beta-alanine, glutathione, and butanoate, which are involved in the inflammatory response, oxidative stress, and amino acid metabolism.

Conclusion: The study suggested that LPS-induced acute liver and kidney injury mainly involves inflammatory response, oxidative stress, and protein synthesis, finally causing multi-organ damage. Correcting the disturbances to the metabolites and metabolic pathways may help to prevent and/or treat LPS-induced acute liver and kidney damage.
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http://dx.doi.org/10.2147/JIR.S306789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110281PMC
May 2021

A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant .

Front Cell Infect Microbiol 2021 25;11:660431. Epub 2021 Mar 25.

School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Science Center for Synthetic Biology, Tianjin University, Tianjin, China.

Multidrug-resistant (MDR) strains can cause severe infections in intensive care units, and are rapidly developing resistance to the last-resort of existing antibiotics, posing a major global threat to health care system. Berberine hydrochloride (BBH), a kind of isoquinoline alkaloids extracted from Berberis and other plants, has been widely used as an antibacterial medicine for its reliable therapeutic efficiency. The synergistic effects of BBH with antibiotics against MDR were determined. BBH alone had weak antimicrobial activity (e.g., MIC≥256 mg/L) against MDR . However, it dramatically increased the susceptibility of MDR strains against antibiotics with FICI values <0.5, even reversed their resistance to antibiotics (e.g., tigecycline, sulbactam, meropenem and ciprofloxacin). study has suggested BBH with sulbactam had stronger antimicrobial efficiency than monotherapy in a neutropenic murine thigh infection model. The antibiotic-sensitizing mechanism of action of BBH was evaluated as well. BBH boosted gene expression and bound to the AdeB transporter protein, resulting in low uptake of BBH, which may contribute to less extrusion of antibiotics by the AdeABC pump. Knockout of the gene increased uptake of BBH and diminished the antibiotic sensitization and synergistic effects between antibiotics and BBH in MDR strains. Together, BBH effectively re-sensitizes this MDR pathogen to a range of antibiotics that have become barely effective due to antibiotic resistance, which indicates BBH may be a promising therapeutic adjuvant candidate to combat MDR .
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http://dx.doi.org/10.3389/fcimb.2021.660431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027359PMC
March 2021

Post-operative procalcitonin and C-reactive protein predict pancreatic fistula after laparoscopic pancreatoduodenectomy.

BMC Surg 2021 Mar 30;21(1):171. Epub 2021 Mar 30.

Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jilin University, No. 1 Xinmin Road, Changchun, 130021, Jilin, China.

Background: Clinically relevant pancreatic fistula (CRPF) is a serious complication following laparoscopic pancreaticoduodenectomy (LPD). This study aimed to determine if C-reactive protein (CRP) and procalcitonin (PCT) serum levels could be used as early biomarkers to predict CRPF after LPD.

Methods: In this retrospective study, we collected peri-operative data of patients who underwent LPD between January 2019 and November 2019. We compared serum levels of white blood cells (WBC), CRP, and PCT on post-operative days (POD) 1, 2, 3, 5, and 7 between the CRPF and non-CRPF groups and analyzed the predictive risk factors for CRPF.

Results: Among the 186 patients included in this study, 18 patients (9.7%) developed CRPF, including 15 and 3 patients with grade B and C fistulas, respectively. The mean WBC, CRP, and PCT levels were higher on most PODs in the CRPF group compared to the non-CRPF group. Receiver operating characteristic (ROC) analysis indicated that CRP levels on POD 2, 5, and 7 can predict CRPF development after LPD, with the area under the curve (AUC) value reaching the highest level on POD 2 (AUC 0.794). PCT levels on POD 2, 3, 5, and 7 were highly predictive of CRPF after LPD. The highest AUC value was achieved on POD 3 [PCT > 2.10 ng/ml (AUC 0.951; sensitivity 88.2%, specificity 92.9%, P < 0.001)].

Conclusions: Both CRP and PCT levels can be used to predict CRPF development after LPD, with PCT having a higher predictive value.
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http://dx.doi.org/10.1186/s12893-021-01177-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008693PMC
March 2021

Deploying Spatial Data for Coastal Community Resilience: A Review from the Managerial Perspective.

Int J Environ Res Public Health 2021 01 19;18(2). Epub 2021 Jan 19.

School of Public Affairs, Chongqing University, Chongqing 400044, China.

The use of spatial data for coastal community resilience applications has diversified as a consequence of the increasing availability of data, and extensive development in data processing. However, the true value of spatial data is not fully exploited as a result of lacking scientific managerial models that incorporate spatial data into decision-making. This article synthesizes the cross-disciplinary literature review on deploying spatial data for coastal community resilience from the managerial perspective. It systematically reviews research addressing the topic of deploying spatial data for coastal resilience operations from the earliest available to 1999. The review uses 142 studies to address three research questions: (1) What kind of data can be obtained for coastal resilience situational awareness? (2) What outcomes have spatial data attributed to coastal resilience applications? and (3) What are the missing pieces (gaps) in connecting the spatial data with coastal resilience applications? In addressing these research questions, the authors review articles based on three dimensions including the availability of spatial data, the availability of applications, and limitations. Based on the findings of the analysis, the authors conclude that the managerial perspective of deploying spatial data in coastal hazards are understudies, and outline problem formulation, mission prioritization, and information salience as an agenda for future research.
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http://dx.doi.org/10.3390/ijerph18020830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835848PMC
January 2021

Water/pH dual responsive in situ calcium supplement collaborates simvastatin for osteoblast promotion mediated osteoporosis therapy via oral medication.

J Control Release 2021 Jan 3;329:121-135. Epub 2020 Dec 3.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. Electronic address:

Calcium supplement is the most commonly adopted treatment for osteoporosis but usually requires high dose and frequency. The modality of calcium supplement is therefore overlooked by current nanomedicine-based osteoporosis therapies without proper oral formulations. Herein, we proposed a tetracycline (Tc) modified and monostearin (MS) coated amorphous calcium carbonate (ACC) platform (TMA) as oral bone targeted and osteoporosis microenvironment (water/pH) responsive carrier for in situ calcium supplement. Moreover, current osteoporosis therapies also fall short of finding suitable molecular target and effective therapeutic regimen to further increase the therapeutic efficacy over available treatment means. As a result, the simvastatin (Sim) was loaded into TMA to construct drug delivery system (TMA/Sim) capable of synergistically activating the bone morphogenetic proteins (BMPs)-Smad pathway to provide a novel therapeutic regimen for osteoblast promotion mediated osteoporosis therapy. Our results revealed that optimized TMA showed high accessibility and oral availability with targeted drug delivery to bone tissue. Most importantly, benefit from the effective in situ calcium supplement and targeted Sim delivery, this therapeutic regime (TMA/Sim) achieved better synergetic effects than conventional combination strategies with promising osteoporosis reversion performance under low calcium dosage (1/10 of commercial calcium carbonate tablet) and significantly attenuated side effects.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.059DOI Listing
January 2021

Altered metabolic profiles and biomarkers associated with astragaloside IV-mediated protection against cisplatin-induced acute kidney injury in rats: An HPLC-TOF/MS-based untargeted metabolomics study.

Biochem Pharmacol 2021 01 24;183:114299. Epub 2020 Oct 24.

Department of Pharmacy, The First Hospital of Jilin University, Changchun 130021, China. Electronic address:

Cisplatin (CDDP)-induced acute kidney injury (AKI) limits the therapeutic use of CDDP, which urgently needs to be addressed. Our previous study demonstrated that astragaloside IV (AS IV), an active compound of the traditional Chinese herb Astragalus membranaceus, alleviated CDDP-induced AKI. To explore the mechanism, we performed a metabolomics study to explore the altered metabolic pathways and screen for sensitive biomarkers. Twenty-four rats were randomly divided into three groups, which were treated with vehicle solutions (Control), intraperitoneally injected CDDP, and intraperitoneally injected CDDP plus oral AS IV, respectively. Metabolic profiles of serum, urine, and kidney samples were analyzed by high-performance liquid chromatography-time of flight mass spectrometry. There were 38 key metabolites in the urine samples, 20 in the serum samples, and 16 in the kidney samples that were significantly altered due to AS IV-mediated protection against CDDP-induced AKI relative to CDDP-only treatment. CDDP + AS IV co-treatment significantly altered two pathways in the blood (biosynthesis of unsaturated fatty acids and alanine, aspartate, and glutamate metabolism), five pathways in the urine (phenylalanine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; arginine and proline metabolism; and histidine metabolism), and five pathways in the kidneys (glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; and D-glutamine and D-glutamate metabolism). The metabolic pathways were mainly associated with improvements in inflammatory responses, oxidative stress, and energy metabolism. Adrenic acid in serum and L-histidine and L-methionine in urine were identified as sensitive biomarkers. This study provides new insights to understand the mechanism of AS IV-mediated protection against CDDP-induced AKI and has identified three candidate biomarkers to evaluate preventative treatment and assess therapeutic effectiveness.
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http://dx.doi.org/10.1016/j.bcp.2020.114299DOI Listing
January 2021

Randomized clinical trial: efficacy and tolerability of two different split dose of low-volume polyethylene glycol electrolytes for bowel preparation before colonoscopy in hospitalized children.

Pediatr Res 2020 Oct 26. Epub 2020 Oct 26.

Department of Pediatric Gastroenterology Unit, The First Hospital of Jilin University, Changchun, Jilin, China.

Background: Eighty milliliter per kilogram of polyethylene glycol (PEG) for bowel preparation (BP) has been recommended, but the amount of liquid orally without nasogastric intubation is difficult to achieve. This study is to compare the efficacy and tolerability of two different low-volume PEG electrolyte solutions for BP in children.

Methods: The randomized, double-blind, controlled trial enrolled 150 children aged 6-18 years undergoing colonoscopy in our center. Patients were randomly assigned to receive 60 ml/kg (PEG-ELS 60) or 40 ml/kg (PEG-ELS 40) of PEG electrolytes (PEG-ELS) 4000. The Boston Bowel Preparation Scale was used for bowel cleansing evaluation. Primary end point was overall colon cleansing. Tolerability was also evaluated.

Results: PEG-ELS 40 and PEG-ELS 60 had similar efficacy in bowel cleansing for both whole colon and various colonic segments. The proportions of patients experiencing any adverse symptoms, or those who were willing to have BP repeated if necessary were similar in both groups. More patients considered the BP solution easy to take and be satisfied with the preparation in PEG-ELS 40 than PEG-ELS 60.

Conclusions: Low volume of PEG-ELS for BP has good efficacy in bowel cleansing. PEG-ELS with 40 ml/kg volume was not inferior to that of 60 ml/kg.

Impact: PEG-ELS 40 and PEG-ELS 60 had similar efficacy in bowel cleansing for whole and various colonic segments. The proportions of patients experiencing any adverse symptoms, or those who were willing to have BP repeated if necessary were similar in both groups. More patients considered BP solution easy to take and be satisfied with the preparation in PEG-ELS 40 than PEG-ELS 60. This study showed that low-volume PEG-ELS monotherapy was effective in bowel cleansing and explored a possibly feasible BP method for pediatrics in China that PEG-ELS 40 was comparable to PEG-ELS 60 regimen.
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http://dx.doi.org/10.1038/s41390-020-01216-5DOI Listing
October 2020

Calcium Supplement by Tetracycline guided amorphous Calcium Carbonate potentiates Osteoblast promotion for Synergetic Osteoporosis Therapy.

Theranostics 2020 9;10(19):8591-8605. Epub 2020 Jul 9.

College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.

The calcium supplement is a clinically approved approach for osteoporosis therapy but usually requires a large dosage without targetability and with poor outcome. This modality is not fully explored in current osteoporosis therapy due to the lack of proper calcium supplement carrier. In this study, we constructed a tetracycline (Tc) modified and simvastatin (Sim) loaded phospholipid-amorphous calcium carbonate (ACC) hybrid nanoparticle (Tc/ACC/Sim). The resulted Tc/ACC/Sim was able to enhance its accumulation at the osteoporosis site. Most importantly, the combination of calcium supplement and Sim offered synergetic osteoblast promotion therapy of osteoporosis with advanced performance than non-targeted system or mono therapy. This platform provides an alternative approach to stimulate bone formation by synergetic promotion of osteoblast differentiation using calcium supplement and Sim.
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http://dx.doi.org/10.7150/thno.45142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392017PMC
May 2021

Quercetin attenuates NLRP3 inflammasome activation and apoptosis to protect INH-induced liver injury via regulating SIRT1 pathway.

Int Immunopharmacol 2020 Aug 31;85:106634. Epub 2020 May 31.

Department of Pharmacy, the First Hospital of Jilin University, Changchun 130021, China. Electronic address:

Severe hepatotoxicity greatly limits the clinical application of the first-line anti-tuberculosis drug isoniazid(INH). Quercetin(Que) has multiple pharmacological properties, and is regarded as a potential protective agent against a variety of organ injuries. However, the exact effect of quercetin on INH-induced hepatotoxicity and the underlying mechanisms are not yet completely understood. In this study, liver injury models were established in rats and L02 cells toreveal the protective effect of Que on INH-induced hepatotoxicity and the relevant mechanism. The in vivo results indicated that Que pretreatment reduced the level of ALT/AST, improved the liver histopathological changes and substantially mitigated apoptosis in rats. In vitro, it evidently relieved INH-induced cell viability loss and apoptosis in L02 cells. Furthermore, thestudiesonmechanisms elucidated that Que remarkably elevated the expression of SIRT1 and suppressed NLRP3 inflammasome activation. Meanwhile, Que significantly inhibited the level of tumor suppressor P53, Bax, cleaved-cas3 expressionl and increased Bcl-2 expression to reduce apoptosis in vivo and in vitro. However, SIRT1 inhibitor EX527 reversed the suppression of Que on NLRP3 inflammasome activation and the protection of Que on rat liver injury and cell apoptosis. In short, our findings showed that Que exhibited protective effects against INH-induced liver damage via inhibiting the activation of NLRP3 inflammasome and apoptosis in a SIRT-dependent manner.
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http://dx.doi.org/10.1016/j.intimp.2020.106634DOI Listing
August 2020

Skin irritation potential of cosmetic preservatives: An exposure-relevant study.

J Cosmet Dermatol 2021 Jan 3;20(1):195-203. Epub 2020 Jun 3.

Department of Cosmetics, School of Science, Beijing Technology and Business University, Beijing, China.

Background: Preservatives represent one of the main causes of skin irritation and contact allergies.

Aims: To comprehensively evaluate the skin irritation potential of phenoxyethanol, methylparaben, propylparaben, imidazolidinyl urea, and DMDM hydantoin under regulatory acceptable concentrations.

Methods: A patch test and repeated open application test (ROAT) were applied to evaluate skin irritation in vivo. In vitro alternative methods consisting of the keratinocyte cytotoxicity assay, red blood cell (RBC) test, and hen's egg test-chorioallantoic membrane (HET-CAM) were performed to elucidate the mechanism of preservative-induced irritation responses.

Results: The patch test showed that all test substances showed a weak erythema response. Propylparaben had the highest occlusive irritancy potential in the patch test, owing to damage to the cell membrane. The two formaldehyde releasers showed noticeable skin irritation potential in the ROAT through their cytotoxicity to keratinocytes, while a visible response was observed after applying phenoxyethanol and the two parabens. No filtration was noticed in the in vivo tests, which might be attributed to the failure of subcutaneous vessel alteration by the preservatives.

Conclusions: Commonly used cosmetic preservatives have minor skin irritation potential with mild erythema reaction under practical use, especially formaldehyde releasers and propylparaben.
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http://dx.doi.org/10.1111/jocd.13502DOI Listing
January 2021

Omeprazole attenuates cisplatin-induced kidney injury through suppression of the TLR4/NF-κB/NLRP3 signaling pathway.

Toxicology 2020 07 11;440:152487. Epub 2020 May 11.

Department of Pharmacy, the First Hospital of Jilin University, Changchun, Jilin, 130021, PR China. Electronic address:

Renal toxicity is the primary factor that limits clinical use of cisplatin (CP). A previous study showed that omeprazole (OME) protected against CP-induced toxicity in human renal tubular HK-2 cells and rat kidneys. However, the protective mechanisms of OME have not been characterized. We evaluated the ability of OME to inhibit CP-induced inflammation, and characterized the pathways responsible for this effect. Rats were randomly divided into five groups (n = 10/group). The OME groups were intraperitoneally injected with 1.8 or 3.6 mg OME /kg body weight once daily for 5 days. One hour after final administration of vehicle or OME, all rats (except those in control group and OME alone group) were intraperitoneally injected with 15 mg/kg CP. Twenty-four hours after CP injection, the surgery was applied. The time points and dosing of OME and CP were calculated based on previous studies and the therapeutic dose for patients. Omeprazole attenuated CP-induced apoptosis and damage in vivo and in vitro, as evidenced by increased cell viability and prevention of structural damage. Omeprazole ameliorated CP-induced renal injury through inhibition of NF-κB activation and IκBα degradation, and down-regulation of toll-like receptor 4 (TLR4) and Nod-like receptor protein 3 (NLRP3). Lipopolysaccharide, a TLR4 agonist, was used to verify this mechanism. The results indicated that OME inhibited CP-induced expression of inflammatory proteins, and this effect was blunted by co-treatment with LPS in HK-2 cells. These findings suggested that the protective effects of OME against CP-induced kidney damage may occur through inhibition of the TLR4/NF-κB/NLRP3 signaling pathway. This study provided evidence that OME may be a promising agent to inhibit CP-induced nephrotoxicity.
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http://dx.doi.org/10.1016/j.tox.2020.152487DOI Listing
July 2020

Astragaloside IV enhances cisplatin chemosensitivity in hepatocellular carcinoma by suppressing MRP2.

Eur J Pharm Sci 2020 May 4;148:105325. Epub 2020 Apr 4.

Department of Technical center, Changchun customs district, Changchun 130062, China. Electronic address:

Decreased chemosensitivity among tumor cells is often an obstacle in cisplatin (Cis) chemotherapy. Overexpression of multidrug resistance-associated protein 2 (MRP2) is a key mechanism underlying decreased Cis chemosensitivity and resistance. Astragaloside IV (AS IV) is an important component derived from the well-known traditional Chinese herb Astragalus membranaceus. The aim of this study was to explore the role of AS IV in enhancing the antitumor effect of Cis by suppressing MRP2 expression in HepG2 cells and H22 tumor-bearing mice. After co-treatment of HepG2 cells with Cis and AS IV, we assessed the effects on cell proliferation and apoptosis. Tumor growth and apoptosis assessment were performed to assess chemosensitivity in H22 tumor-bearing mice. We used western blotting, immunofluorescence assays, and immunohistochemistry assays to detect MRP2 expression in HepG2 cells, H22 tumor tissues and mouse kidney tissues. AS IV enhanced Cis chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth in vitro and in vivo. MRP2 overexpression in tumor cells was induced by Cis, which contributes to decreased chemosensitivity and Cis resistance. Co-administration of AS IV suppressed MRP2 expression in tumor tissues, which might be an important mechanism for enhancing Cis chemosensitivity in hepatocellular carcinoma. Moreover, AS IV alleviated Cis-induced kidney injury in mice without changing MRP2 expression. In total, AS IV enhanced the antitumor effect of Cis against hepatocellular carcinoma by suppressing MRP2 expression in tumor cells. The results provide a new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.
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http://dx.doi.org/10.1016/j.ejps.2020.105325DOI Listing
May 2020

2-Deoxy-Rh2: A novel ginsenoside derivative, as dual-targeting anti-cancer agent via regulating apoptosis and glycolysis.

Biomed Pharmacother 2020 Apr 25;124:109891. Epub 2020 Jan 25.

Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, 130021, PR China. Electronic address:

20(S)-Rh2 is a ginsenoside isolated from Panax ginseng, which exhibits anti-cancer activities on various human cancer cells. A novel 20(S)-Rh2 derivative, 2-Deoxy-Rh2 was synthesized and hybridized with protopanaxadiol and 2-deoxy-glucose in an attempt to enhance the anticancer activity. Through screening the antitumor effect against various cell lines by MTT assay, 2-Deoxy-Rh2 especially resulted in a concentration-dependent and time-dependent inhibition of viability in MCF-7 human breast cancer cells. Multiple methods were used to explore the cellular and molecular mechanisms of 2-Deoxy-Rh2 as a potent anti-cancer agent. In MCF-7 cells, 2-Deoxy-Rh2 triggered apoptosis, stimulated ROS production and disrupted normal mitochondrial membrane potential. Meantime, 2-Deoxy-Rh2 eff ;ectively suppressed the glucose uptake capabilities and intracellular ATP production. The cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were significantly decreased in response to 2-Deoxy-Rh2, which were carried out to assess the overall glycolytic flux and mitochondrial respiration. Docking studies and molecular dynamics simulations were performed to verify the binding mode of 2-DG and 2-Deoxy-Rh2 with hexokinase II, with results showing that 2-Deoxy-Rh2 could easily fit into the similar active site of 2-DG, finally binding to hexokinase II to suppress glycolysis. Taken together, the results suggest that 2-Deoxy-Rh2 exhibited remarkable anticancer activity based on regulating mitochondrial apoptosis pathway, dampening glycolysis and inhibiting mitochondrial respiration, which support development of 2-Deoxy-Rh2 as a potential agent for cancer therapy.
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http://dx.doi.org/10.1016/j.biopha.2020.109891DOI Listing
April 2020

Identification of key metabolites during cisplatin-induced acute kidney injury using an HPLC-TOF/MS-based non-targeted urine and kidney metabolomics approach in rats.

Toxicology 2020 02 8;431:152366. Epub 2020 Jan 8.

AB Sciex Analytical Instrument Trading Co., Ltd, Beijing 100015, PR China.

Kidney injury is a major adverse effect of cisplatin use. Metabolomics has been used to characterize physiological or pathological conditions through identification of metabolites and characterization of the metabolic pathway. Metabolomics profiling could allow for identification of nephrotoxic mechanisms of cisplatin and identification of biomarkers of cisplatin-induced injury. In this study, we performed metabolomics analysis to characterize key changes in metabolite levels during cisplatin-induced acute kidney injury (AKI) in rats, and screened for sensitive biomarkers for early diagnosis using HPLC-TOF/MS. Rats were intraperitoneally injected with 7.5 mg/kg or 15 mg/kg of cisplatin, or normal saline, and 12 h urine and kidney samples were collected after 72 h. Serum biochemical parameters and kidney histological evaluations showed dose-dependent AKI in response to cisplatin. Metabolomics analysis showed that 37 and 35 endogenous metabolite levels changed in rat urine and kidneys, respectively. Seven key metabolic pathways were disrupted, including the tricarboxylic acid cycle (TCA cycle), phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, d-glutamine and d-glutamate metabolism, and nicotinate and nicotinamide metabolism. These pathways are involved in energy generation, and amino acid and lipid metabolism, and disruption of these pathways could contribute to oxidative stress injury, inflammation, and cell membrane damage. Furthermore, 11 sensitive metabolites in urine were screened as potential biomarkers of AKI. To validate these biomarkers, we quantified 4 off these biomarkers, and confirmed that levels of these metabolites were altered in urine of rats treated with CDDP.
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http://dx.doi.org/10.1016/j.tox.2020.152366DOI Listing
February 2020

Calycosin ameliorates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and inflammation via the sirtuin 1-NOD-like receptor protein 3 pathway.

Phytother Res 2020 Mar 20;34(3):649-659. Epub 2019 Dec 20.

Department of Pharmacy, The First Hospital of Jilin University, Changchun, China.

The limitation of doxorubicin (DOX), which is widely used for the treatment of solid tumors and hematologic malignancies, is a vital problem in clinical application. The most serious of limit factors is cardiotoxicity. Calycosin (CA), an isoflavonoid that is the major active component in Radix astragali, has been reported in many bioactivities including antitumor, anti-inflammatory, and cardioprotection. The aim of the study was to investigate the effects and mechanisms of CA on DOX-induced cardiotoxicity in vitro and in vivo. CA increased H9c2 cell viability and reduced apoptosis induced by DOX via Bcl-2, Bax, and the PI3K-Akt signaling pathway. Moreover, CA prevented DOX-induced oxidative stress in cells by decreasing the generation of reactive oxygen species. Similarly, oxidative stress was inhibited by CA through the increased activities of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase and decreased the levels of aspartate aminotransferase, lactate dehydrogenase, and malondialdehyde in vivo. Furthermore, the levels of sirtuin 1 (Sirt1)-NOD-like receptor protein 3 (NLRP3) and related proteins were ameliorated by CA in cells and in mice hearts. When H9c2 cells were treated by Ex527 (Sirt1 inhibitor), the effect of CA on expressions of NLRP3 and thioredoxin-interacting protein was suppressed. In conclusion, the results suggested that CA might be a cotreatment with DOX to ameliorate cardiotoxicity by Sirt1-NLRP3 pathway.
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http://dx.doi.org/10.1002/ptr.6557DOI Listing
March 2020

Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway.

J Biochem Mol Toxicol 2019 Sep 23;33(9):e22369. Epub 2019 Jul 23.

Department of Pharmacy, the First Hospital of Jilin University, Changchun, China.

Isoniazid (INH) is one of the most commonly used antituberculosis drugs, but its clinical applications have been limited by severe hepatic toxicity. Quercetin (Que), a natural flavonoid, has been proved to have many medicinal properties. This study aimed to clarify the possible protective effects of Que against INH-induced hepatotoxicity using HepG2 cells. Our results indicated that Que significantly increased cell viability, superoxide dismutase, and GSH levels, while decreased alanine aminotransferase/aspartate aminotransferase levels. Besides, Que significantly abrogated INH-induced cell apoptosis by upregulating the expression levels of Bcl-2 and decreasing the levels of Bax, cleaved caspase-3, and cleaved caspase-9. Furthermore, Que obviously reversed the inhibition of INH on Sirtuin 1 (SIRT1) expression and extracellular signal-regulated kinase (ERK) phosphorylation. Next, the SIRT1 inhibitor EX527 blocked the enhancement of Que upon ERK phosphorylation. Notably, EX527 partially abolished the beneficial effects of Que. In brief, our results provided the first evidence that Que protected against INH-induced HepG2 cells by regulating the SIRT1/ERK pathway.
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http://dx.doi.org/10.1002/jbt.22369DOI Listing
September 2019

Dissecting horizontal and vertical gene transfer of antibiotic resistance plasmid in bacterial community using microfluidics.

Environ Int 2019 10 18;131:105007. Epub 2019 Jul 18.

Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK. Electronic address:

The spread of antibiotic resistance genes (ARGs) has become an emerging threat to the global health. Although horizontal gene transfer (HGT) is regarded as one of the major pathways, more evidence has shown the significant involvement of vertical gene transfer (VGT). However, traditional cultivation-based methods cannot distinguish HGT and VGT, resulting in often contradictory conclusions. Here, single-cell microfluidics with time-lapse imaging has been successfully employed to dissect the contribution of plasmid-mediated HGT and VGT to ARG transmission in an environmental community. Using Escherichia coli with an ARG-coded plasmid pKJK5 with trimethoprim resistance as the donor, we quantified the effects of three representative antibiotics (trimethoprim, tetracycline and amoxicillin) on the ARG transfer process in an activated sludge bacterial community. It was found that HGT was influenced by the inhibitory mechanism of an antibiotic and its targets (donor, recipient alone or together), whereas VGT contributes significantly to the formation of transconjugants and consequently ARG spreading. Trimethoprim is highly resisted by the donor and transconjugants, and its presence significantly increased both the HGT and VGT rates. Although tetracycline and amoxicillin both inhibit the donor, they showed different effects on HGT rate as a result of different inhibitory mechanisms. Furthermore, we show the kinetics of HGT in a community can be described using an epidemic infection model, which in combination with quantitative measure of HGT and VGT on chip provides a promising tool to study and predict the dynamics of ARG spread in real-world communities.
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http://dx.doi.org/10.1016/j.envint.2019.105007DOI Listing
October 2019

Retrospective study of budesonide in children with eosinophilic gastroenteritis.

Pediatr Res 2019 10 29;86(4):505-509. Epub 2019 May 29.

The First Hospital of Jilin University, 130021, Changchun, China.

Background: The effectiveness of budesonide (BUD), a locally active steroid, on eosinophilic gastroenteritis (EGE) is not well understood. This study is to retrospectively evaluate the efficacy of BUD in children with EGE.

Methods: Forty-four children, diagnosed with EGE, were enrolled from 2013 to 2017 in our center. According to patients' preference, all the patients were treated with dietary elimination (DE) and montelukast therapy, or combined with prednisone (PRED)/BUD. Patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Twenty-four patients (7 PRED, 7 BUD, 10 DE) received therapy for ≥8 weeks, followed by repeat endoscopy and biopsies. Histological response was defined as <20 eos/hpf (eosinophils per high-power field).

Results: Significant number of patients in DE+PRED (6/7, 85.7%) and DE+BUD (6/7, 85.7%) groups achieved histological response than in the DE group (3/10.30%) (p = 0.024). Mean post-treatment peak eos/hpf in the DE+PRED group was 16.57 ± 6.85 vs. 10.00 ± 5.07 in the DE+BUD group vs. 36.60 ± 24.57 in the DE group (p = 0.009). Change of eos/hpf from pre- to post-treatment was -49.86 ± 45.02 vs. -34.29 ± 23.44 in the BUD group vs. -0.3 ± 23.95 in the DE group (p = 0.011). There were no significant differences between DE+PRED and DE+BUD groups (p = 0.470, p = 0.363, respectively).

Conclusion: BUD is effective in the treatment of EGE and has similar effectiveness with PRED.
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http://dx.doi.org/10.1038/s41390-019-0444-2DOI Listing
October 2019

Salvianolic Acid B Attenuates Apoptosis of HUVEC Cells Treated with High Glucose or High Fat via Sirt1 Activation.

Evid Based Complement Alternat Med 2019 21;2019:9846325. Epub 2019 Apr 21.

Department of Pharmacy, The First Hospital of Jilin University, Changchun 130021, China.

High glucose and high fat are important inducements for the development and progression of diabetic cardiopathy. Salvianolic acid B (SAB), which is the most abundant and bioactive compound in Danshen, attenuates oxidative stress-related disorders, such as cardiovascular diseases, cerebral ischemia, and diabetes. However, the effect of SAB on diabetic cardiopathy is not clear. The aim of study was to investigate the effect and the underlying molecular mechanisms of SAB on diabetic cardiopathy in vitro model. The human umbilical vein endothelial (HUVEC) cells were treated with high glucose (HG, 30 mM) or high fat (palmitic acid, PA, 0.75 mM) in the presence or absence of SAB (100, 200, and 400 mg/L) and incubated for 24 h. We found that HG or PA induced apoptosis of HUVEC cells, while treatment with SAB inhibited the apoptosis. We also found that SAB reversed HG- or PA-induced oxidative stress, apoptosis cell cytokines production, and expression of thioredoxin-interacting protein (TXNIP). Moreover, SAB increased HG- or PA-induced expression of Sirtuin 1 (Sirt1), a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase. Exposure of HUVEC cells to Ex527 (Sirt1 inhibitor) suppressed the effect of SAB on acetyl-p53 and procaspase-3 expressions. In conclusion, the results suggested that SAB could attenuate HUVEC cells damage treated with HG or PA via Sirt1 and might be a potential therapy agent for the diabetic cardiopathy treatment.
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http://dx.doi.org/10.1155/2019/9846325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500650PMC
April 2019

Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats.

J Toxicol Sci 2019 ;44(3):167-175

Department of Pharmacy, the First Hospital of Jilin University, China.

The aim of this study was to explore the role of the NOD-like receptor family, pyrin domain containing (NLRP3) inflammasome and autophagy in Astragaloside IV (AS IV)-mediated protection against cisplatin-induced liver and kidney injury in rats. Rats were intraperitoneally administered cisplatin at a dose of 15 mg/kg and orally administered AS IV for 7 days. Histopathological and biochemical analysis were used to assess liver and kidney function. The levels and localization of NLRP3 and autophagy-associated protein were determined by Western blot and immunohistochemistry. Intraperitoneal administration of cisplatin induced acute liver and kidney injury, and activated the NLRP3 inflammasome. Oral administration of AS IV for 7 days protected against the cisplatin-induced injury, and inhibited the expression of NLRP3, as well as the production of pro-inflammatory cytokines. Moreover, cisplatin modulated the conversion of LC3 II and the expression of p62, thereby inhibiting autophagy and the activation of NLRP3. AS IV effectively protected against cisplatin-induced injury by inducing autophagy and limiting the expression of NLRP3. Autophagy-mediated NLRP3 inhibition might play a crucial role in AS IV-mediated protection against cisplatin-induced toxicity. These results provide evidence of a novel therapeutic that may be used to alleviate the toxic effects of platinum-based chemotherapy.
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http://dx.doi.org/10.2131/jts.44.167DOI Listing
March 2019

Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials.

Can J Gastroenterol Hepatol 2019 10;2019:3192351. Epub 2019 Jan 10.

Department of Pharmacy, The First Hospital of Jilin University, Changchun 130021, China.

Background: Prophylactic therapy with silymarin to prevent the development of antituberculosis drug-induced liver injury (anti-TB DILI) has been under debate. We aimed to evaluate the effect of silymarin in the prevention of anti-TB DILI.

Methods: We searched MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to 30th November 2018. Randomized controlled trials (RCTs) that compared silymarin and placebo to prevent anti-TB DILI were included. All statistical analyses were conducted using STATA 12.0 software. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CIs) were used to evaluate the effect of silymarin. The quality of included studies was assessed according to Cochrane handbook. Funnel plots and Egger's tests were carried out to evaluate publication bias. Sensitivity analysis was conducted to assess the influence of each study.

Results: A total of 1198 patients from five RCTs (585 with silymarin and 613 with placebo groups) were included. Overall, silymarin significantly reduced the occurrence of anti-TB DILI at week 4 [RR: 0.33, 95% CI (0.15, 0.75)]. In addition, silymarin exerted protective effect on liver function in patients undergoing anti-TB drugs [SMD = - 0.15, 95% CI (-0.24, -0.07), P < 0.001 (ALT); SMD =-0.14, 95% CI (-0.23, -0.06), P = 0.001(AST); SMD =-0.12, 95% CI (-0.20, -0.03), P = 0.008 (ALP)]. Silymarin led to similar AEs in placebo groups [OR: 1.09, 95% CI (0.86, 1.39), P = 0.47].

Conclusion: Prophylactic therapy of silymarin is contributed to a noticeably reduced risk of development of anti-TB DILI four weeks after the initiation. In addition, silymarin significantly improved the liver function in patients who are receiving anti-TB drugs.
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http://dx.doi.org/10.1155/2019/3192351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348824PMC
June 2019

Mapping the face of young population in China: Influence of anatomical sites and gender on biophysical properties of facial skin.

Skin Res Technol 2019 May 10;25(3):325-332. Epub 2019 Jan 10.

Department of Cosmetics, School of Science, Beijing Technology and Business University, Beijing, China.

Background: Facial skin exhibits unique biophysical properties, which are influenced by anatomical regions and genders. The aim of this study was to comprehensively assess the regional and gender differences in facial skin biophysical parameters among Chinese population.

Materials And Methods: The 12 skin biophysical parameters at four distinct facial skin sites (forehead, cheek, canthus and chin) were measured in a normal population (n = 212) with 42 males and 141 females aged 18-29 years living in Beijing. These parameters consisted of skin hydration, transepidermal water loss, sebum content, erythema/melanin indices, L*a*b* color, skin gloss and elasticity, all quantifying with non-invasive instruments.

Results: The results demonstrated that the characteristics of the facial skin were significantly different between the regions and genders. The forehead had weaker skin barrier function but secreted the most sebum content, while the cheek was the driest and brightest region on the face. The canthus was the most hydrated area and the chin displayed higher sebum secretion, darker skin color and less elastic. The females showed more hydrated, less oil, lighter and more elastic facial skin compared with males.

Conclusion: This study indicates that the young Chinese facial skin significantly varies with face anatomical regions and differs between genders.
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http://dx.doi.org/10.1111/srt.12652DOI Listing
May 2019

Omeprazole protects against cisplatin-induced nephrotoxicity by alleviating oxidative stress, inflammation, and transporter-mediated cisplatin accumulation in rats and HK-2 cells.

Chem Biol Interact 2019 Jan 16;297:130-140. Epub 2018 Nov 16.

Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, 130021, PR China. Electronic address:

The present study assessed the therapeutic potential of omeprazole (OME), the most commonly prescribed proton pump inhibitor (PPI) used to treat gastroesophageal hyperacidity, against cisplatin (CP)-induced toxicity in human renal tubular HK-2 cells and rat kidneys. Herein, we observed that exposure of HK-2 cells to OME reversed the injury caused by CP, including enhancing cell viability and alleviating intracellular reactive oxygen species (ROS) generation and membrane damage. Concomitantly, acute exposure of male SD rats to CP induced histopathological changes, which were prevented by co-administration with OME. Inflammation and oxidative stress were inhibited by OME during CP-induced renal injury by increasing the activity of superoxide dismutase, and reducing the levels of malondialdehyde, both in vivo and in vitro. The expression levels of major inflammatory response markers were significantly decreased in HK-2 cells and rat kidneys in response to OME. OME reduced CP cellular uptake through organic cation transporters 2 (OCT2) and the prompt efflux of CP by P-glycoprotein (P-gp), thereby reducing the accumulation of CP in kidney tissue and increasing its serum levels. These data demonstrate that CP-induced kidney damage is positively correlated with its cellular accumulation. Concurrently, OME showed renoprotective effect against CP-induced toxicity in HK-2 cells and rat kidneys, by suppressing oxidative stress and mediating NF-κB-dependent inflammation, apoptosis, and transporter function. As OME is commonly used in combination with CP during chemotherapy treatment, this study highlights the clinical significance of OME in alleviating CP-induced nephrotoxicity.
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http://dx.doi.org/10.1016/j.cbi.2018.11.008DOI Listing
January 2019

Salvianolic acid inhibits the effects of high glucose on vascular endothelial dysfunction by modulating the Sirt1-eNOS pathway.

J Biochem Mol Toxicol 2019 Feb 15;33(2):e22245. Epub 2018 Nov 15.

Depatment of Pharmacy, The First Hospital of Jilin University, Changchun, China.

Salvianolic acid (SA) is known for improving blood circulation, scavenging hydroxyl radicals, and preventing platelet aggregation. The research explored whether SA can protect against cardiovascular disease induced by high glucose conditions. Our results indicate that SA significantly increases cells viability and nitric oxide levels while decreasing reactive oxygen species generation. SA upregulated the expression levels of Bcl-2 and decreased the levels of Bax, cleaved caspase-3, and cleaved caspase-9. Furthermore, the expression levels of Sirtuin 1 (Sirt1) and p-endothelial nitric oxide synthase (eNOS) were markedly increased in response to SA treatment. Moreover, exposure of human umbilical vein endothelial cells to Ex527 resulted in reducing expression of p-eNOS. However, the beneficial effects of SA were abolished partially when Ex527 was added. These findings suggest that SA can be used as a potential therapeutic to protect against high glucose-induced endothelial injury by modulating Sirt1-eNOS pathway.
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http://dx.doi.org/10.1002/jbt.22245DOI Listing
February 2019

Autophagy inhibition-enhanced assembly of the NLRP3 inflammasome is associated with cisplatin-induced acute injury to the liver and kidneys in rats.

J Biochem Mol Toxicol 2018 Oct 6:e22208. Epub 2018 Oct 6.

Department of Pharmacy, The First Hospital of Jilin University, Changchun, China.

The nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has a key role in the inflammatory response. We found that cisplatin (7.5, 15 mg/kg, IV) could induce acute injury to the liver and kidneys of rats. Western blot and immunohistochemical analyses showed that expression of NLRP3, caspase-1 and interleukin-1β was upregulated significantly in a dose-dependent manner after cisplatin exposure. Autophagy could inhibit NLRP3 expression and assembly of the NLRP3 inflammasome. Expression of light chain 3 II/I and p62 suggested that autophagy was inhibited during injury to the liver and kidneys. These data suggested that cisplatin might activate NLRP3 by inhibiting autophagy in the liver and kidneys of rats.
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http://dx.doi.org/10.1002/jbt.22228DOI Listing
October 2018

Dysregulation of BSEP and MRP2 May Play an Important Role in Isoniazid-Induced Liver Injury via the SIRT1/FXR Pathway in Rats and HepG2 Cells.

Biol Pharm Bull 2018 ;41(8):1211-1218

Department of Pharmacy, The First Hospital of Jilin University.

To explore the role of the abnormal expression of the bile salt export pump (BSEP) and multidrug resistance protein 2 (MRP2) in isoniazid (INH)-induced liver injury, we assessed the liver injury induced by INH in rats and HepG2 cells in vitro. The regulatory pathways via Sirtuin 1 (SIRT1) and farnesoid X receptor (FXR) were also determined. Rat liver injury was assessed by histopathological and biochemical analysis and HepG2 cytotoxicity was assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The levels of protein were determined by Western blot. The results indicated that INH could induce hepatotoxicity in vivo and in vitro in a dose dependent manner. The liver index and serum biochemical analysis, especially the levels of total bile acids (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL), were significantly increased in rats. The INH hepatotoxicity was severe in the high dose group, and occurred alongside the down-regulation of BSEP and MRP2 in vivo and in vitro, leading to the accumulation of toxic substrates in the hepatocytes. The SIRT1/FXR pathway was identified as being important for the down-regulation of transporters. In summary, our study indicated that the down-regulation of BSEP and MRP2 represents one mechanism of INH-induced liver injury and the down-regulation of SIRT1/FXR may be a key regulator. This will inform the development of novel therapies and enable the prevention of INH-induced liver injury.
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http://dx.doi.org/10.1248/bpb.b18-00028DOI Listing
October 2018

delays the excretion of doxorubicin and aggravates doxorubicin-induced cardiotoxicity and nephrotoxicity by inhibiting the expression of P-glycoprotein in mice liver and kidney.

Xenobiotica 2019 Sep 15;49(9):1116-1125. Epub 2019 May 15.

a Department of Pharmacy , the First Hospital of Jilin University , Changchun , PR China.

We aimed to investigate the drug-drug interaction (DDI) between doxorubicin (DOX) and (DB) solution in mice, and to explore the effect of P-glycoprotein (P-gp) on this type of DDI. The toxicity of DOX in the liver, kidneys, and heart was assessed with alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea nitrogen (BUN), creatine kinase MB (CK-MB), creatine kinase (CK) and histopathology. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentrations of DOX in the serum, liver, kidneys and heart. Immunohistochemistry and western blots were used to determine the expression levels of P-gp in these tissues. Our results demonstrated that, after co-administration of DOX and DB, survival was significantly decreased compared with either administration of DOX or DB alone, or water. Co-administration of DOX and DB induced elevated levels of toxicity in the heart and kidneys, but not the liver, compared with DOX alone. We conclude that concurrent treatment with DOX and DB results in increased levels of toxicity due to the accumulation of DOX in the body. Delayed excretion of DOX is associated with inhibition of P-gp in liver and kidneys.
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http://dx.doi.org/10.1080/00498254.2018.1498560DOI Listing
September 2019

Effect of Laser Irradiation on Cell Function and Its Implications in Raman Spectroscopy.

Appl Environ Microbiol 2018 04 2;84(8). Epub 2018 Apr 2.

School of Engineering, University of Glasgow, Glasgow, United Kingdom

Lasers are instrumental in advanced bioimaging and Raman spectroscopy. However, they are also well known for their destructive effects on living organisms, leading to concerns about the adverse effects of laser technologies. To implement Raman spectroscopy for cell analysis and manipulation, such as Raman-activated cell sorting, it is crucial to identify nondestructive conditions for living cells. Here, we evaluated quantitatively the effect of 532-nm laser irradiation on bacterial cell fate and growth at the single-cell level. Using a purpose-built microfluidic platform, we were able to quantify the growth characteristics, i.e., specific growth rates and lag times of individual cells, as well as the survival rate of a population in conjunction with Raman spectroscopy. Representative Gram-negative and Gram-positive species show similar trends in response to a laser irradiation dose. Laser irradiation could compromise the physiological function of cells, and the degree of destruction is both dose and strain dependent, ranging from reduced cell growth to a complete loss of cell metabolic activity and finally to physical disintegration. Gram-positive bacterial cells are more susceptible than Gram-negative bacterial strains to irradiation-induced damage. By directly correlating Raman acquisition with single-cell growth characteristics, we provide evidence of nondestructive characteristics of Raman spectroscopy on individual bacterial cells. However, while strong Raman signals can be obtained without causing cell death, the variety of responses from different strains and from individual cells justifies careful evaluation of Raman acquisition conditions if cell viability is critical. In Raman spectroscopy, the use of powerful monochromatic light in laser-based systems facilitates the detection of inherently weak signals. This allows environmentally and clinically relevant microorganisms to be measured at the single-cell level. The significance of being able to perform Raman measurement is that, unlike label-based fluorescence techniques, it provides a "fingerprint" that is specific to the identity and state of any (unlabeled) sample. Thus, it has emerged as a powerful method for studying living cells under physiological and environmental conditions. However, the laser's high power also has the potential to kill bacteria, which leads to concerns. The research presented here is a quantitative evaluation that provides a generic platform and methodology to evaluate the effects of laser irradiation on individual bacterial cells. Furthermore, it illustrates this by determining the conditions required to nondestructively measure the spectra of representative bacteria from several different groups.
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http://dx.doi.org/10.1128/AEM.02508-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881070PMC
April 2018

Prescription Optimization and Oral Bioavailability Study of Salvianolic Acid Extracts W/O/W Multiple Emulsion.

Biol Pharm Bull 2017 Dec 23;40(12):2081-2087. Epub 2017 Sep 23.

Changchun University of Chinese Medicine.

The purpose of this study is to develop a new method of preparing salvianolic acid extracts (SAE) water-in-oil-in-water (W/O/W) multiple emulsion (ME). SAE injection is used in the treatment of brain infarct and promotion of blood circulation in China. However, the injection is not convenient, and the oral preparation has poor bioavailability. Hence, a new preparation that is convenient and stable with good biological availability is required. SAE ME was prepared by two-step emulsification method. Combined with single-factor investigation and orthogonal test, the embedding rate and centrifugal retention rate were taken as the comprehensive indexes to optimize the formulation of SAE ME. The ME size was tested by laser particle size analyzer. The pharmacokinetic studies were conducted in Sprague-Dawley rats with HPLC-MS/MS method. The blood coagulation and hemorheology tests were conducted to assess the effect of preparation in rats. The best preparation technique for SAE ME is by the use of trospium chloride; SAE represent 12% of water in the phase, lipophilic emulsifier hydrophilic lipophilic balance value=4.3, lipophilic emulsifier is 20% of the oil phase. The median diameter of particle is (0.608±0.05) µm and the C of ME is 3-fold higher compared to C of free drug. The oral biavailability of ME is 26.71-fold higher than that of free drug with good effect on blood circulation. SAE ME is stable hence, improves the biological availability and slows down drug release.
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http://dx.doi.org/10.1248/bpb.b17-00162DOI Listing
December 2017

Single-Cell Microfluidics to Study the Effects of Genome Deletion on Bacterial Growth Behavior.

ACS Synth Biol 2017 12 5;6(12):2219-2227. Epub 2017 Sep 5.

College of Science and Engineering, Division of Biomedical Engineering, School of Engineering, University of Glasgow , Glasgow G12 8QQ, U.K.

By directly monitoring single cell growth in a microfluidic platform, we interrogated genome-deletion effects in Escherichia coli strains. We compared the growth dynamics of a wild type strain with a clean genome strain, and their derived mutants at the single-cell level. A decreased average growth rate and extended average lag time were found for the clean genome strain, compared to those of the wild type strain. Direct correlation between the growth rate and lag time of individual cells showed that the clean genome population was more heterogeneous. Cell culturability (the ratio of growing cells to the sum of growing and nongrowing cells) of the clean genome population was also lower. Interestingly, after the random mutations induced by a glucose starvation treatment, for the clean genome population mutants that had survived the competition of chemostat culture, each parameter markedly improved (i.e., the average growth rate and cell culturability increased, and the lag time and heterogeneity decreased). However, this effect was not seen in the wild type strain; the wild type mutants cultured in a chemostat retained a high diversity of growth phenotypes. These results suggest that quasi-essential genes that were deleted in the clean genome might be required to retain a diversity of growth characteristics at the individual cell level under environmental stress. These observations highlight that single-cell microfluidics can reveal subtle individual cellular responses, enabling in-depth understanding of the population.
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http://dx.doi.org/10.1021/acssynbio.7b00177DOI Listing
December 2017