Publications by authors named "Wen-Jing Yu"

21 Publications

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[Study on patterns and characteristics of in vivo tissue distribution of anti-inflammatory extract of Tetrastigma hemsleyanum aerial part in healthy and inflammatory pathological model rats].

Zhongguo Zhong Yao Za Zhi 2021 Mar;46(5):1224-1249

Department of Pharmacy,Fujian University of Traditional Chinese Medicine Fuzhou 350122,China.

The concentrations of seven anti-inflammatory components in blood and tissues were determined by UPLC-MS/MS after oral administration of Tetrastigma hemsleyanum aerial part(THAA) in healthy and inflammatory pathological model rats. The determination was carried out by using positive and negative ion switching technique, and multiple reaction monitoring(MRM) mode. The tissue distributions of the seven components in different physiological states were compared, and the patterns and characteristics of the effective components of THAA were studied. The results revealed that the seven effective components have large drug-time-curve areas(AUC) in heart, brain, small intestine, and stomach in both normal rats and inflammatory pathological model rats. This suggests that the anti-inflammatory effective component groups in THAA extract can all penetrate the blood-brain barrier, and have a large distribution area in gastrointestinal tract. It is inferred that gastrointestinal reabsorption may be one of the causes of the bimodal distribution of the drug-time curve of the drug blood distribution graph. As compared to normal rats, the effective component groups in THAA extract have higher drug-time curve area(AUC) in heart, brain, small intestine, stomach, liver, spleen, lung, kidney, and muscle of inflammatory pathological model rats. Among them, the effective component groups have the largest distribution area in heart, brain, small intestine, and stomach. This suggests that the binding force of organ tissues and drugs in the body may change under pathological conditions. It is speculated that the heart, brain, small intestine, and stomach may be the target tissues of THAA to produce anti-inflammatory effect. The retention times of THAA effective component groups in various organ tissues of rats in different physiological states are all relatively short, and do not have much difference. This suggests that no effective component accumulates in body, and that the pathological state of inflammation does not affect the onset times of the effective component groups. This experiment elucidates the patterns and characteristics of the in vivo target-effecting tissue distribution of THAA anti-inflammatory extract, and provides an experimental basis for clinical treatment.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200707.204DOI Listing
March 2021

Haploidentical hematopoietic stem cell transplantation for patients with myeloid sarcoma: a single center retrospective study.

Ann Hematol 2021 Mar 8;100(3):799-808. Epub 2021 Jan 8.

Peking University People's Hospital, Peking University Institute of Hematolo, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantationgy, National Clinical Research Center for Hematologic Disease, No.11, Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential strategy for myeloid sarcoma (MS). The previous reports focused mainly on matched sibling donor (MSD) or matched unrelated donor (MUD) transplantation. There are no reports on haploidentical HSCT (haplo-HSCT) in MS. We retrospectively reviewed 14 MS patients who underwent haplo-HSCT. All patients achieved complete donor engraftment. The median time for neutrophil engraftment and platelet engraftment were 10 (12-21) days and 18 (8-31) days. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) and 3-year cumulative incidence of chronic GVHD were 37.7% (95%CI, 23.2-52.1%) and 35.7% (95%CI, 22.2-49.2%). Cytomegalovirus (CMV) reactivation was documented in 86% patients, and only one patient developed CMV pneumonia. Treatment-related mortality occurred in one (7%) patient. The 1- and 3-year cumulative incidence of relapse was 21.4% (95%CI, 11.8-31.1%) and 35.7% (95%CI, 22.4-49.0%). The probability of overall survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 64.3% (95%CI, 43.5-95.0%), respectively. The probability of disease-free survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 57.1% (95%CI, 36.3-89.9%), respectively. In conclusion, haplo-HSCT is a feasible method for patients with MS who have no MSD or MUD.
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http://dx.doi.org/10.1007/s00277-020-04383-xDOI Listing
March 2021

Tracing consumption patterns of stimulants, opioids, and ketamine in China by wastewater-based epidemiology.

Environ Sci Pollut Res Int 2021 Apr 4;28(13):16754-16766. Epub 2021 Jan 4.

College of Environmental Science and Engineering, Dalian Maritime University, No. 1 Linghai Road, Dalian, China.

Illicit drug use has long been a key issue of international concern, and the true situation is unknown to the relevant authorities. To develop a profile of comprehensive consumption patterns of illicit drugs in China, data from 34 wastewater treatment plants in 25 cities were collected to analyze four classes of drugs, including amphetamine-type stimulants, opioids, ketamine, and cocaine. They were identified and quantified in samples using methods based on gas chromatography coupled to mass spectrometry. According to the wastewater-based epidemiology (WBE) approach, an analysis of the consumption pattern was performed regarding per inhabitant consumption based on the revised metabolic rate. The consumption quantity of illicit drug and precursor was divided into four categories based on statistical difference analyses: methamphetamine and ephedrine (precursor) were the predominant drugs in the first category, followed by ketamine and heroin in the second category, methcathinone and 3,4-methylenedioxymethamphetamine (MDMA) in the third category, and cocaine and methadone in the fourth category. There were distinctive spatial patterns: heroin and cocaine consumption was higher in Southern China than in Northern China, heroin consumption was higher in Western China than in Eastern China, and the consumption of each drug differed across seven regions of China, especially with ephedrine and methcathinone consumption higher in North China; heroin consumption higher in Southwest, Central, and Northwest China; and ketamine and MDMA consumption higher in East, South, and Central China. Compared with findings in previous studies, there were temporal patterns, in which ketamine consumption presented a downward trend but heroin remained stable. Based on correlation analyses, there were the polydrug abuse patterns between heroin and cocaine, methcathinone and ketamine, and cocaine and MDMA. In general, this study based on WBE provides a comprehensive evaluation of drug consumption in China.
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http://dx.doi.org/10.1007/s11356-020-12035-wDOI Listing
April 2021

MicroRNA-214 contributes to Ang II-induced cardiac hypertrophy by targeting SIRT3 to provoke mitochondrial malfunction.

Acta Pharmacol Sin 2021 Sep 27;42(9):1422-1436. Epub 2020 Nov 27.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou, 510006, China.

Reduction of expression and activity of sirtuin 3 (SIRT3) contributes to the pathogenesis of cardiomyopathy via inducing mitochondrial injury and energy metabolism disorder. However, development of effective ways and agents to modulate SIRT3 remains a big challenge. In this study we explored the upstream suppressor of SIRT3 in angiotensin II (Ang II)-induced cardiac hypertrophy in mice. We first found that SIRT3 deficiency exacerbated Ang II-induced cardiac hypertrophy, and resulted in the development of spontaneous heart failure. Since miRNAs play crucial roles in the pathogenesis of cardiac hypertrophy, we performed miRNA sequencing on myocardium tissues from Ang II-infused Sirt3 and wild type mice, and identified microRNA-214 (miR-214) was significantly up-regulated in Ang II-infused mice. Similar results were also obtained in Ang II-treated neonatal mouse cardiomyocytes (NMCMs). Using dual-luciferase reporter assay we demonstrated that SIRT3 was a direct target of miR-214. Overexpression of miR-214 in vitro and in vivo decreased the expression of SIRT3, which resulted in extensive mitochondrial damages, thereby facilitating the onset of hypertrophy. In contrast, knockdown of miR-214 counteracted Ang II-induced detrimental effects via restoring SIRT3, and ameliorated mitochondrial morphology and respiratory activity. Collectively, these results demonstrate that miR-214 participates in Ang II-induced cardiac hypertrophy by directly suppressing SIRT3, and subsequently leading to mitochondrial malfunction, suggesting the potential of miR-214 as a promising intervention target for antihypertrophic therapy.
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http://dx.doi.org/10.1038/s41401-020-00563-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379271PMC
September 2021

Bioaccumulation of perfluoroalkyl substances in greenhouse vegetables with long-term groundwater irrigation near fluorochemical plants in Fuxin, China.

Environ Res 2020 09 7;188:109751. Epub 2020 Jun 7.

Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, China.

The levels of perfluoroalkyl substances (PFASs) have been growing progressively in the groundwater beneath a fluorochemical industrial park (FIP) in Fuxin of China recently, however, little information is available about whether long-term irrigation with local groundwater could have a potential effect on the bioaccumulation of PFASs in greenhouse vegetables near the FIP. In the present study, groundwater, soil, and vegetable samples were collected from Fuxin with five sampling campaigns during a period of 40 days, and ten target analytes of PFASs in all the samples were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAS contaminants, perfluorooctanoic acid (PFOA) and perfluorobutane sulfonate (PFBS) in groundwater samples were determined with the maximum levels of 2.47 and 32.4 μg L, respectively. Furthermore, perfluorobutanoic acid (PFBA), PFOA, and PFBS were the major PFASs in greenhouse samples of soil (up to 6.1, 6.8, and 46 ng g dry weight (dw)), tomato (up to 87, 1.7, and 13 ng g dw), and cucumber (up to 63, 2.6, and 15 ng g dw), which were significantly correlated with those in groundwater samples, indicating PFAS contaminations could be introduced into soil and vegetables in the greenhouse through long-term groundwater irrigation. In addition, all the levels of three main PFAS analytes in soil and vegetables presented an overall increasing trend over the period of vegetable growth. The bioaccumulation efficiencies for PFAS contaminants from soil to vegetables were negatively associated with the carbon chain length in PFASs. According to the reference dose (RfD) for PFBA, PFOA, and PFBS from the Minnesota Department of Health (MDH), daily intakes of those three analytes by rural residents in Fuxin were lower than the respective RfD via consumption of greenhouse tomatoes and cucumbers so far. However, long-term surveillance would be focused on greenhouse vegetables near the Fuxin FIP to prevent potential health risks of local residents from increasing PFAS contaminations.
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http://dx.doi.org/10.1016/j.envres.2020.109751DOI Listing
September 2020

Removal of perfluoroalkanesulfonic acids (PFSAs) from synthetic and natural groundwater by electrocoagulation.

Chemosphere 2020 Jun 22;248:125951. Epub 2020 Jan 22.

School of Science, Shenyang University of Technology, Shenyang, 110870, China.

Severe contaminations of perfluoroalkanesulfonic acids (PFSAs) existed in the natural groundwater beneath a fluorochemical industrial park (FIP) in Fuxin of China. In the present study, systematic researches were performed to determine the best conditions of efficient treatment for 1 mg L of PFSAs in the synthetic groundwater samples with the periodically reverse electrocoagulation (PREC) using the Al-Zn electrodes. Based upon the orthogonal experiments, the removal efficiencies of perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) could reach 87.4%, 95.6%, and 100%, respectively, within the initial 10 min, under the optimal conditions of voltage at 12.0 V, pH at 7.0, and stirring speed at 400 rpm. In addition, the optimized PREC technique was further applied to remove the PFSA contaminations from the natural groundwater samples of the Fuxin FIP, subsequently generating the removal efficiencies of three target PFSA analytes in the range between 59.0% and 100% at 60 min. Moreover, the SEM-EDS analyses showed the hydroxide flocs formed during the process of PREC treatment had clear characteristics of floc aggregates, with the major constituents of O, Al, C, N, Zn, and F elements. As a result, long-chain PFHxS and PFOS tended to be eliminated completely from the natural groundwater by their absorptions on the Al-Zn hydroxide flocs, potentially because of their higher hydrophobicity compared with short-chain PFBS.
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http://dx.doi.org/10.1016/j.chemosphere.2020.125951DOI Listing
June 2020

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients.

J Hematol Oncol 2019 09 3;12(1):88. Epub 2019 Sep 3.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No.11, Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Background: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen.

Methods: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives.

Results: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001).

Conclusions: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.
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http://dx.doi.org/10.1186/s13045-019-0781-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724335PMC
September 2019

Ca signalling plays a role in celastrol-mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats.

Br J Pharmacol 2019 08 4;176(16):2922-2944. Epub 2019 Jul 4.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.

Background And Purpose: Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats.

Experimental Approach: We used computational docking, Ca dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca -mediated autophagy were analysed by histological, immunohistochemical and flow cytometric techniques. Anti-arthritic effects of celastrol, autophagy induction, and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes, using siRNA methods to study calmodulin, calpains, and calcineurin.

Key Results: Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via Ca /calmodulin-dependent kinase kinase-β-AMP-activated protein kinase-mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory- and autoimmunity-associated genes down-regulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca in celastrol-regulated gene expression.

Conclusion And Implications: Celastrol triggered Ca signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium-dependent/-binding proteins facilitating the exploitation of anti-arthritic drugs based on manipulation of Ca signalling.
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http://dx.doi.org/10.1111/bph.14718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637043PMC
August 2019

Perfluoroalkyl substances in groundwater and home-produced vegetables and eggs around a fluorochemical industrial park in China.

Ecotoxicol Environ Saf 2019 Apr 31;171:199-205. Epub 2018 Dec 31.

Department of Preventive Medicine, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.

High-level contaminations of perfluoroalkyl substances (PFASs) were determined in both surface water and groundwater around a fluorochemical industrial park (FIP) in Fuxin, China, over the past few years. Yet little is known about whether groundwater PFAS contaminations in Fuxin could be introduced into home-produced vegetables and eggs in local residences via the application of groundwater for the irrigation or feeding purposes. In the present study, ten PFAS analytes were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to investigate the extent of PFAS contaminations in the groundwater, soil, and home-produced vegetable and egg samples derived from Fuxin. As the predominant PFAS contaminants, perfluorobutane sulfonate (PFBS) and perfluorooctanoic acid (PFOA) were observed in groundwater beneath the Fuxin FIP with the maximum concentrations of 21.2 and 2.51 µg/L, respectively, which were 24-fold and 5-fold higher individually compared to those reported previously. Both of them were also higher than the updated health advisories for PFBS and PFOA in drinking water issued by the Minnesota Department of Health and the US Environmental Protection Agency. In addition, short-chain PFASs involving perfluorobutanoic acid (PFBA) and PFBS were found to be the major contaminants in both home-produced vegetables and eggs from the residential gardens around the FIP. Statistically significant relationships were determined between the levels of PFBA, PFOA, and PFBS in local groundwater and those observed in home-produced vegetables (p = 0.003, p = 0.025, and p < 0.001), suggesting potential entry of those PFAS contaminants into home-produced vegetables via irrigation with groundwater beneath the FIP.
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http://dx.doi.org/10.1016/j.ecoenv.2018.12.086DOI Listing
April 2019

Occurrence and Severity of Donor Lymphocyte Infusion-Associated Chronic Graft-versus-Host Disease Influence the Clinical Outcomes in Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2019 05 25;25(5):912-920. Epub 2018 Nov 25.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. Electronic address:

The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI)-associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (n = 104). The 5-year cumulative incidence of complete remission after Chemo-DLI was 81.0% (95% CI, 73.3% to 88.7%) and 84.6% (95% CI, 74.5% to 94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD group at 40.9% (95% CI, 29.3% to 52.5%) and non-cGVHD group at 29.2% (95% CI 23.1% to 35.3%). The cumulative incidence of nonrelapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2% to 70.2%) and 34.6% (95% CI, 15.3% to 78.2%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI, 2.4% to 34.1%) and non-cGVHD group at 8.3% (95% CI 3.3% to 21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9% to 82.7%) and 43.1% (95% CI, 22.1% to 84.0%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI 1.8% to 47.1%) and non-cGVHD group at 14.9% (95% CI, 7.3% to 30.2%). Our observations highlight the close relationship between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.024DOI Listing
May 2019

Comparison of illegal drug use pattern in Taiwan and Korea from 2006 to 2014.

Subst Abuse Treat Prev Policy 2016 Sep 23;11(1):34. Epub 2016 Sep 23.

School of Pharmacy and Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung City, 80708, Taiwan.

Background: Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence-based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea.

Methods: Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared.

Results: The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011.

Conclusion: While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan.
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http://dx.doi.org/10.1186/s13011-016-0078-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034652PMC
September 2016

pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin.

Int J Mol Sci 2016 Mar 30;17(4):364. Epub 2016 Mar 30.

School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China.

The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid-glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA-GA/HA-His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via ¹H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA-GA/HA-His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA-GA/HA-His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA-GA/HA-His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.
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http://dx.doi.org/10.3390/ijms17040364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848880PMC
March 2016

Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.

Biomed Res Int 2015 10;2015:968786. Epub 2015 Nov 10.

Centre for Clinical & Health Research Services, School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, Herts AL10 9AB, UK ; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.
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http://dx.doi.org/10.1155/2015/968786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657101PMC
September 2016

The immune factors involved in the pathogenesis, diagnosis, and treatment of Sjogren's syndrome.

Clin Dev Immunol 2013 9;2013:160491. Epub 2013 Jul 9.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Sjogren's syndrome (SS) is a systemic, autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Even though the mechanism of its pathology and progression has been researched ever since its discovery, the roles of different parts of immune system remain inconclusive. There is no straightforward and simple theory for the pathogenesis and diagnosis of Sjogren's syndrome because of the multiple kinds and functions of autoantibodies, changing proportion of different T-lymphocyte subsets with the progression of disease, unsuspected abilities of B lymphocytes discovered recently, crosstalk between cytokines connecting the factors mentioned previously, and genetic predisposition that contributes to the initiation of this disease. On the other hand, the number of significant reports and open-label studies of B-cell depletion therapy showing clinical efficacy in sjogren's syndrome has continued to accumulate, which provides a promising future for the patients. In a word, further elucidation of the role of different components of the immune system will open avenues for better diagnosis and treatment of SS, whose current management is still mainly supportive.
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http://dx.doi.org/10.1155/2013/160491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722847PMC
February 2014

[Influence of electroacupuncture stimulation of "tianshu" (ST 25), "quchi" (LI 11) and "shangjuxu" (ST 37) and their pairs on gastric motility in the rat].

Zhen Ci Yan Jiu 2013 Feb;38(1):40-7

Key Laboratory of Integrated Acupuncture and Drugs Constructed by Chinese Ministry of Education and Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing 210029, China.

Objective: To observe the effect of electroacupuncture (EA) stimulation of different acupoints or acupoint pairs on gastric motility so as to explore their modulation regularities under different conditions.

Methods: SD rats were randomly divided into normal control, starvation (food-deprivation for 24 h), atropine (antagonist for M-receptor), acetylcholine (Ach, agonist for M-receptor), propranolol (antagonist for beta-receptor) and clenbuterol (agonist for beta 2-receptor) and paired-acupoint groups (30 rats/group). The intragastric pressure was measured via a pressure transducer connected to a balloon inserted in the stomach cavity. EA (2 Hz /15 Hz, 2 mA) was applied to the left "Tianshu" (ST 25),"Quchi" (LI 11) and "Shangjuxu" (ST 37) which were formed in pairs: ST 25-LI 11, ST 25-ST 37 and LI 11-ST 37 for 2 min following intravenous injection of atropine (0.1%, 0.8 mL/kg, 40 microL x min(-1) x kg(-1)), 0.1% acetylcholine (20 microL x min(-1) x kg(-1)), 0. 2% clenbuterol (80 microL x min(-1) x kg(-1)) and 0.4% propranolol (1 mL/kg,40 microL x min(-1) x kg(-1)) under food-deprivation conditions.

Results: After intravenous injection of atropine and clenbuterol, the intragastric pressure were decreased significantly (P < 0.05), while after administration of Ach and propranolol, the intragastric pressure increased markedly (P < 0.05). Under normal and starvation conditions, and after intravenous administration of M-receptor antagonist (atropine) and agonist (Ach), beta-receptor antagonist (propranolol) and agonist (clenbuterol), EA stimulation of ST 25 produced an apparently inhibitory effects on gastric motility (80.00%, 86.67%, 76.67%, 86.67%, 73.33% and 86.67%, respectively) and intragatric pressure (P < 0.05) with the tendency being starvation > normal, acetylcholine > atropine and clenbuterol > propranolol. Whereas EA stimulation of LI 11 and ST 37 mainly produced an excitatory effect on gastric motility (60.00%, 56.67%, 93.33%, 40.00%, 53.33% and 50.00%, respectively for LI 11; 66.67%, 60.00%, 80.00%, 53.33%, 46.67% and 73.33%, respectively for ST 37). Following EA stimulation of the paired-acupoint groups, ST 25-ST 37 induced a predominately inhibitory effect on gastric motility (50.00%) and intragastric pressure, while LI 11-ST 37 stimulation had a principally excitatory effect on gastric motility (53.33%), and ST 25-LI 11 showed no apparent effect (50.00%).

Conclusion: EA stimulation of ST 25 area at the abdomen produces a predominant inhibitory effect on gastric motility, while EA of LI 11 and ST 37 on the upper and lower limbs induces an excitatory effect on gastric movement, when applied in pairs, EA of ST 25-ST 37 suppresses the gastric activity, and LI 11-ST 37 promotes the gastric activity, suggesting a specificity of the effect of different acupoint stimulation.
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February 2013

[Peripheral blood leukocyte double strand RNA-dependent protein kinase gene expression in patients with systemic lupus erythematosus].

Zhonghua Nei Ke Za Zhi 2012 Nov;51(11):855-8

Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.

Objective: To investigate the expression of the double-stranded RNA-dependent protein kinase (PKR) gene in the peripheral blood leukocyte of patients with systemic lupus erythematosus (SLE), and to evaluate the relationship between the gene expression and the disease activity.

Methods: The clinical data of 100 SLE patients, 40 non-SLE patients with rheumatic diseases, and 40 normal controls were collected. Total RNA was extracted from the peripheral blood and then reverse transcribed into cDNA. Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as 2(-ΔCt) value) of PKR in the three groups.

Results: (1) The 2(-ΔCt) value of PKR expression level in the SLE patients was (14.69 ± 7.62), which was significantly higher than those in the non-SLE patients (5.09 ± 4.73, P = 0.012)and normal controls(4.79 ± 3.49, P = 0.005). (2) The 2(-ΔCt) value of PKR expression level in the SLE patients with severe activity was (22.57 ± 2.61), which was significantly higher than those in the SLE patients with mild activity and no activity (12.94 ± 2.41, P = 0.000; 8.85 ± 2.17, P = 0.000). (3) The 2(-ΔCt) value of PKR expression level in the SLE patients with lupus nephritis was significantly higher than that in the SLE patients without lupus nephritis (16.85 ± 7.32 vs 8.35 ± 2.04, P = 0.034). (4) The 2(-ΔCt) value of PKR was correlated with the systemic lupus erythematosus index (SLEDAI) scores (r = 0.32, P = 0.000), WBC (r = 0.46, P = 0.000), Hb (r = -0.22, P = 0.035), the quantitation of urine protein in 24 hours (r = 0.21, P = 0.000), HDL-C (r = 0.21, P = 0.022), and anti-RNP antibody (r(s) = -0.21, P = 0.025).

Conclusions: The expression of PKR in the SLE patients is up-regulated, especially in those with severe activity. The expression level of PKR gene is associated with SLE disease activity.
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November 2012

Major food safety episodes in Taiwan: implications for the necessity of international collaboration on safety assessment and management.

Kaohsiung J Med Sci 2012 Jul 7;28(7 Suppl):S10-6. Epub 2012 Jul 7.

School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

The major food safety episodes that occurred in Taiwan during the past decade are briefly reviewed in this paper. Among the nine major episodes surveyed, with the exception of a U.S. beef (associated with Creutzfeldt-Jakob disease)-related incident, all the others were associated with chemical toxicants. The general public, which has a layperson attitude of zero tolerance toward food safety, may panic over these food-safety-associated incidents. However, the health effects and impacts of most incidents, with the exception of the melamine incident, were essentially not fully evaluated. The mass media play an important role in determining whether a food safety concern becomes a major incident. A well-coordinated and harmonized system for domestic and international collaboration to set up standards and regulations is critical, as observed in the incidents of pork with ractopamine, Chinese hairy crab with nitrofuran antibiotics, and U.S. wheat with malathion. In the future, it can be anticipated that food safety issues will draw more attention from the general public. For unknown new toxicants or illicit adulteration of food, the establishment of a more proactive safety assessment system to monitor potential threats and provide real-time information exchange is imperative.
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http://dx.doi.org/10.1016/j.kjms.2012.05.004DOI Listing
July 2012

Bis[4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole-κN,N]bis-(benzene-1,2-dicarb-oxy-lic acid-κO)copper(II) bis-(2-carb-oxy-benzoate).

Acta Crystallogr Sect E Struct Rep Online 2012 Feb 11;68(Pt 2):m129-30. Epub 2012 Jan 11.

College of Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Tianjin Normal University, Tianjin 300387, People's Republic of China.

In the complex cation of the title salt, [Cu(C(12)H(10)N(6))(2)(C(8)H(6)O(4))(2)](C(8)H(5)O(4))(2), the Cu(II) atom, lying on an inversion center, exhibits a distorted octa-hedral geometry defined by four N atoms from two 4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole ligands in the equatorial plane and two axial O atoms from two benzene-1,2-dicarb-oxy-lic acid ligands. In the crystal, the complex cations and the monodeprotonated 2-carb-oxy-benzoate anions are connected by O-H⋯O and N-H⋯O hydrogen bonds, forming a tape along [100]. Adjacent tapes are further linked into a three-dimensional arrangement via π-π stacking inter-actions between the triazole and benzene rings and between the pyridine and benzene rings [centroid-centroid distances = 3.6734 (14)/3.9430 (16) and 3.8221 (14) Å]. Intra-molecular N-H⋯N and O-H⋯O hydrogen bonds are also observed.
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http://dx.doi.org/10.1107/S1600536812000128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274868PMC
February 2012

Essentiality of HIV testing and education for effective HIV control in the national pilot harm reduction program: the Taiwan experience.

Kaohsiung J Med Sci 2012 Feb 14;28(2):79-85. Epub 2012 Jan 14.

School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

In 2005, a national pilot harm reduction program (PHRP), which mainly included a methadone maintenance treatment program (MMTP) and a needle/syringe exchange program (NSP), was implemented in Taiwan. We conducted this study to evaluate the effectiveness of harm reduction measures on HIV control among injecting drug users (IDUs) between PHRP and nonPHRP. The data on HIV, collected from incumbent Taiwanese authorities, were analyzed for their associations, risk and protective factors with PHRP measures. While the monthly HIV incidences did not show significant differences before and after PHRP in the four areas with PHRP (Taipei City, Taipei County, Taoyuan County and Tainan County), a significant increase in the HIV incidence was found in the 21 areas without PHRP. Hence, the implementation of the PHRP did result in a significant difference in the monthly HIV incidence between areas with and without the PHRP. Mandatory HIV testing was significantly associated with the HIV incidence according to the generalized estimation equations (GEE) model. With adjustments of time period and area with PHRP, and urban area, protective factors associated with HIV incidence were: educational materials, condoms, dilution water, and alcohol sponges/swabs. MMTP contributed to a higher HIV incidence, probably due to the concurrent HIV testing upon admission. Since HIV testing was not required in the NSP, the HIV testing-dependent MMTP may explain the association of the PHRP intervention and an increased HIV incidence. In summary, HIV testing and education were essential for effective HIV control upon implementing the PHRP.
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http://dx.doi.org/10.1016/j.kjms.2011.10.006DOI Listing
February 2012

[ZNF185 gene cloning and the localization in mouse testis].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2010 Oct;26(10):973-5

Department of Cell Biology, Weifang Medical University, Weifang 261053, China.

Aim: we Clone the ZNF185 gene and detect the position of ZNF185 in the mouse testis.

Methods: extracted from mouse testis RNA, by RT-PCR, and then the obtained fragment was cloned and identified; extracted from mouse liver, testis and ovary proteins were Western blot analysis; preparation of frozen sections of mouse testes, immunofluorescence techniques analysis.

Results: (1) ZNF185 gene cloning was correct. (2) Western blot showed that the most abundant in the testes ZNF185. (3) Immunofluorescence showed, ZNF185 located in Leydig cells and sperm, Leydig cells in the weak, and in round spermatids and mature sperm were highly expressed.

Conclusion: the gene cloning of ZNF185 was successful and initially proved the position of ZNF185 in the mouse testis.
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October 2010

Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels.

Neurosci Lett 2007 Jan 15;412(2):108-13. Epub 2006 Dec 15.

Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also exerts modulatory effects on many ligand-gated ion channels and voltage-gated Ca(2+) and K(+) channels. It has been reported previously that tacrine and some other AChE inhibitors suppressed I(K(A)) in central and peripheral neurons. The present study aimed to explore whether bis(7)-tacrine could modulate the function of native delayed rectifier potassium channels in DRG neurons and K(V)1.2 encoded potassium channels expressed in oocytes. We found that both delayed rectifier potassium currents (I(K(DR))) in rat DRG neurons and the currents recorded from oocytes expressing K(V)1.2 (I(K(K(V)1.2))) were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. The IC(50) values for bis(7)-tacrine and tacrine inhibition of I(K(KD)) in DRG neurons were 0.72+/-0.05 and 58.3+/-3.7 microM, respectively; while the two agents inhibited I(K(K(V)1.2)) in oocytes with an IC(50) of 0.24+/-0.06 and 102.1+/-21.5 microM, respectively. The possible mechanism for bis(7)-tacrine inhibition of I(K(A)) and I(K(K(V)1.2)) was identified as the suppression of their activation, inactivation.
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http://dx.doi.org/10.1016/j.neulet.2006.10.047DOI Listing
January 2007
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