Publications by authors named "Ping Ling"

35 Publications

Targeting angiopoietin-like 3 (ANGPTL3) in atherosclerosis: from bench to bedside.

Diabetes Obes Metab 2021 May 28. Epub 2021 May 28.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Atherosclerotic cardiovascular disease (ASCVD) is the largest cause of morbidity and mortality worldwide. Lipid-lowering therapies are the current major cornerstone of ASCVD management. Statins, ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduce plasma low-density lipoprotein cholesterol (LDL-C) level in most individuals at risk of atherosclerosis. Still, some patients (such as those with homozygous familial hypercholesterolemia), who did not respond to standard therapies, and some patients who cannot take these agents remain at a high risk of ASCVD. Recent years have witnessed tremendous progress in understanding the mechanism and efficacy of lipid-lowering strategies. Apart from the recently approved PCSK9 and ATP citrate lyase (ACLY) inhibitors, angiopoietin-like 3 (ANGPTL3) is another potential target for the treatment of dyslipidemia and its clinical sequalae-atherosclerosis. ANGPTL3 is a pivotal modulator of plasma triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels achieved by inhibiting the activities of lipoprotein lipase (LPL) and endothelial lipase (EL). Familial combined hypolipidemia is derived from the ANGPTL3 loss-of-function (LOF) mutations, which leads to low levels of LDL-C, HDL-C, and TG and has a 34 percent decreased risk of ASCVD compared with non-carriers. To date, monoclonal antibodies (evinacumab) and antisense oligonucleotides against ANGPTL3 have been investigated in clinical trials for dyslipidemia therapy. Herein, we reviewed the biology and function of ANGPTL3, as well as the latest developments of ANGPTL3 targeted therapies. We also summarized evidence from basic research to clinical trials, with an aim to provide novel insights into biological functions of ANGPTL3 and related targeted therapies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14450DOI Listing
May 2021

miR-1184 regulates inflammatory responses and cell apoptosis by targeting TRADD in an LPS-induced cell model of sepsis.

Exp Ther Med 2021 Jun 15;21(6):630. Epub 2021 Apr 15.

Pediatric Intensive Care Unit, Guiyang Maternal and Child Health Care Hospital, Guiyang, Guizhou 550003, P.R. China.

MicroRNAs (miRs) have been reported to be potential clinical biomarkers for sepsis. miR-1184 is a multifunctional microRNA that exerts roles in the development of various diseases. However, the role of miR-1184 in children with sepsis remain unknown. In the present study, THP-1 cells were stimulated with 1 µg/ml lipopolysaccharide (LPS) for 24 h to establish an sepsis model. Reverse transcription-quantitative PCR was used to evaluate the expression of miR-1184 in clinical specimens, and of IL-6, TNF-α, IL-1β, miR-1184 and TNF receptor type 1-associated DEATH domain protein (TRADD) in cells with and without LPS treatment. Cell apoptosis was assessed using flow cytometry. Binding between miR-1184 and TRADD was predicted using bioinformatics software, and a luciferase reporter assay was performed to verify the interaction between miR-1184 and TRADD in LPS-induced THP-1 cells. In addition, western blot analysis was performed to detect TRADD and proteins associated with the NF-κB pathway. The results showed that miR-1184 was downregulated in the blood of children with sepsis and LPS-induced THP-1 cells. Overexpression of miR-1184 alleviated the LPS-induced production of inflammatory cytokines and cell apoptosis. Moreover, TRADD was verified to be a direct target of miR-1184. Upregulation of TRADD reversed the effects of miR-1184 on the LPS-induced inflammatory response and apoptosis of THP-1 cells. Furthermore, the NF-κB pathway was shown to be associated with the regulatory role of miR-1184 in sepsis. The present study provides evidence that miR-1184 exerts inhibitory effects on inflammatory responses and apoptosis in sepsis by targeting TRADD, which suggests that miR-1184 may be a novel potential target for the therapy of children with sepsis.
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http://dx.doi.org/10.3892/etm.2021.10062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082660PMC
June 2021

Current practice and perspectives of healthcare providers regarding preconception care for women with type 1 diabetes in China.

Diabetes Metab Res Rev 2021 May 13;37(4):e3454. Epub 2021 Apr 13.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Aims: We aimed to investigate the current practice and perspectives of healthcare providers (HCPs) regarding preconception care (PCC) for women with type 1 diabetes (T1D) in China.

Materials And Methods: A questionnaire based on in-depth interviews with HCPs involved in PCC was released online and advertised via doctor unions in China. The data were categorical variables and were analysed by multivariable logistic regression, Chi-square test, or Wilcoxon rank-sum test.

Results: From November 2016 to January 2017, 992 responses from 31 provinces of China were received (77.3% doctors and 22.7% nurses). Regarding the current status of PCC for T1D, 62.5% of HCPs treated ≤1 woman with T1D monthly on average. Only 16.5% thought they provided proper PCC, and 29.6% reported having sufficient knowledge. Regarding attitudes towards pregnancy with T1D, 92.2% were in favour of women with T1D getting pregnant after proper glycaemic control, and 94.7% perceived their worries regarding pregnancy. Regarding doctor-patient communication, 56.6% spent <10 min per visit, while 58.3% thought ≥20 min was required for adequate communication. HCPs emphasised the importance of multidisciplinary PCC, professional training, and social support. PCC practice was associated with hospital level (OR = 2.450, 95%CI: 1.580-3.799, p < 0.001), HCPs' experience of treating women with T1D (OR = 2.196, 95%CI: 1.516-3.180, p < 0.001), and their communication sufficiency (OR = 3.706, 95%CI: 2.550-5.387, p < 0.001).

Conclusions: The current PCC practice for T1D in China was suboptimal and it was associated with hospital level, HCPs' experience and communication. It is necessary to reinforce professional training and appeal for social resources to improve PCC.
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http://dx.doi.org/10.1002/dmrr.3454DOI Listing
May 2021

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

EClinicalMedicine 2021 Feb 13;32:100743. Epub 2021 Feb 13.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China.

Methods: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated.

Findings: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (-8.8 days, 95%CI -9.7, -7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (-2.35 days, 95%CI -3.65, -1.06) compared to interferon-beta-1b monotherapy.

Interpretation: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients.

Funding: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.
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http://dx.doi.org/10.1016/j.eclinm.2021.100743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881744PMC
February 2021

Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID-19: A continuous glucose monitoring-based observational study.

J Diabetes Investig 2021 Feb 4. Epub 2021 Feb 4.

Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Aims/introduction: The coronavirus disease 2019 (COVID-19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people's lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long-term effect. We aimed to investigate the impact of COVID-19 lockdown on glycemic control in children and adolescents with type 1 diabetes.

Materials And Methods: This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud-based platform before, during and after lockdown. Demographics and lifestyle change-related information were collected from the database or questionnaires. We compared these data before, during and after lockdown.

Results: A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9-10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25-9.53%) before lockdown to 2.91% (IQR 1.43-5.95%) during lockdown, but reversed to 4.95% (IQR 2.11-9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14-2.21%), 0.38% (IQR 0.05-1.35%) and 0.82% (IQR 0.22-1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently.

Conclusion: Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID-19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long-term effect.
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http://dx.doi.org/10.1111/jdi.13519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014845PMC
February 2021

Effects of sources of social support and resilience on the mental health of different age groups during the COVID-19 pandemic.

BMC Psychiatry 2021 01 7;21(1):16. Epub 2021 Jan 7.

Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100049, China.

Background: A pandemic is a very stressful event, especially for highly vulnerable people (e.g., older adults). The purpose of the current study was to investigate the main and interactive relationships of social support and resilience on individual mental health during the COVID-19 pandemic across three age groups: emerging adults, adults, and older adults.

Methods: A survey was conducted with 23,192 participants aged 18-85. Respondents completed a questionnaire, including items on the COVID-19-related support they perceived from different sources, the abbreviated version of the Connor-Davidson Resilience Scale, and the Mental Health Inventory.

Results: Latent profile analysis identified five profiles of social support, and the patterns of potential profiles were similar in all groups. However, category distribution in the five profiles was significantly different among the age groups. Furthermore, analysis using the BCH command showed significant differences in mental health among these profiles. Lastly, interactive analyses indicated resilience had a positive relationship with mental health, and social support served as a buffer against the negative impact of low resilience on mental health.

Conclusions: This study provides quantitative evidence for socioemotional selectivity theory (SST) and enables several practical implications for helping different age groups protecting mental health during pandemic.
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http://dx.doi.org/10.1186/s12888-020-03012-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789076PMC
January 2021

Elevated fasting blood glucose within the first week of hospitalization was associated with progression to severe illness of COVID-19 in patients with preexisting diabetes: A multicenter observational study.

J Diabetes 2021 Jan 30;13(1):89-93. Epub 2020 Oct 30.

Department of Endocrinology, the First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.

Highlights Fasting blood glucose < 10 mmol/L was proposed as a target of glycemic control during the first week of hospitalization in patients with preexisting diabetes. Poor HbA1c levels prior to coronavirus disease 2019 (COVID-19) might not be associated with severity among patients with preexisting diabetes. Mean blood glucose seemed not to be associated with poor prognosis of COVID-19.
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http://dx.doi.org/10.1111/1753-0407.13121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675481PMC
January 2021

Association between glutathione peroxidase-3 activity and carotid atherosclerosis in patients with type 2 diabetes mellitus.

Brain Behav 2020 10 29;10(10):e01773. Epub 2020 Aug 29.

Department of Neurology, Suzhou Ninth People's Hospital, Suzhou, China.

Background And Aims: Deficiency of glutathione peroxidase 3 (GPx3) has been recognized as an independent risk factor for cardiovascular events. However, little is known regarding the role of GPx3 in carotid atherosclerosis, which is ubiquitously observed in type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between GPx3 activity and carotid atherosclerosis among patients with T2DM.

Methods: From January 2018 to December 2018, 245 consecutive patients with T2DM were enrolled in this observational study. Assessment of serum GPx3 activity was performed after admission. We also used carotid ultrasound to measure the mean carotid intima-media thickness (CIMT) and to assess the presence of carotid plaque.

Results: Of the 245 patients, the median serum GPx3 activity was 22.5 U/ml (interquartile range, 12.4-35.9 U/ml). Carotid plaque was observed in 113 (46.1%) patients, and mean CIMT was 0.8 ± 0.1 mm. Univariate analysis showed that age, smoking, previous coronary heart disease, carotid plaque, and level of mean CIMT and hypersensitive C-reactive protein were significantly associated with decreasing tertile of GPx3. Furthermore, after adjusting for all potential confounders by multivariable logistic regression analysis, PGx3 activity was significantly and independently associated with the mean CIMT (β = -.406, p = .002) and carotid plaque (first tertile of GPx3, odds ratio, 1.870, 95% confidence intervals, 1.124-3.669, p = .024).

Conclusions: This study demonstrated that serum GPx3 activity was inversely associated with mean CIMT and carotid plaque, suggesting that lower GPx3 activity may be an independent predictor for carotid atherosclerosis in T2DM.
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http://dx.doi.org/10.1002/brb3.1773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559603PMC
October 2020

Nobiletin Inhibits Helicobacterium pylori Infection-Induced Gastric Carcinogenic Signaling by Blocking Inflammation, Apoptosis, and Mitogen-Activated Protein Kinase Events in Gastric Epithelial-1 Cells.

J Environ Pathol Toxicol Oncol 2020 ;39(1):77-88

Department of General Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China.

Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer. Consequently, meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans. Nobiletin, an important dietary polymethoxylated flavonoid in citrus fruits, possesses multidimensional pharmaceutical properties, including its ability to act as an anticancer, anti-inflammatory, antioxidative, cardiovascularly defensive, neuroprotective, and antimetabolic agent. Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial (GES)-1 cell line. Our results show that the culture system of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species (ROS), mediating DNA injury and augmenting nuclear fragmentations. Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/phosphatase and tensin homolog signaling have been implicated to affect cell endurance, inflammation, proliferation, and carcinogenic activity in gastric GES-1 cells. We find that nobiletin strongly impedes tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, PI3K, AKT, and mitogen-activated protein kinase molecules, including p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. We conclude that nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2020031272DOI Listing
June 2020

Association between population migration and epidemic control of Coronavirus disease 2019.

Sci China Life Sci 2020 Jun 14;63(6):936-939. Epub 2020 Apr 14.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.

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http://dx.doi.org/10.1007/s11427-020-1695-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163913PMC
June 2020

Clinical Characteristics of Fulminant Type 1 Diabetes Compared with Typical Type 1 Diabetes: One-Year Follow-Up Study from the Guangdong T1DM Translational Medicine Study.

J Diabetes Res 2020 19;2020:8726268. Epub 2020 Feb 19.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou 510630, China.

Background: Fulminant type l diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus (T1DM) with abrupt onset, but data on its progression was limited. This study was aimed at exploring the clinical features through one-year follow-up. . Patients with T1DM finishing at least one-year follow-up from June 2011 to July 2018 were enrolled from Guangdong Type 1 Diabetes Translational Medicine Study. Patients who fulfilled the respective criteria were categorized as an FT1DM group and a typical T1DM group (TT1DM). The 1 : 4 propensity score matching based on onset age, duration, and gender was performed between the FT1DM and TT1DM groups. Characteristics at the onset and after one-year follow-up were compared between the two groups.

Results: A total of 53 patients with FT1DM and 212 matched patients with TT1DM were included. At the onset, there was a shorter duration of symptomatic period before diagnosis observed in the FT1DM group than in the TT1DM group (2 [1, 7] vs. 30 [10, 60] days, < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis ( < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (.

Conclusion: Patients with FT1DM had more severe metabolic derangement and deficiency of insulin secretion than patients with TT1DM at the onset, but glycaemic and metabolic control was not worse than that in TT1DM.
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http://dx.doi.org/10.1155/2020/8726268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049830PMC
December 2020

Potency of the Sabin inactivated poliovirus vaccine (sIPV) after exposure to freezing temperatures in cold chains.

Hum Vaccin Immunother 2020 08 2;16(8):1866-1874. Epub 2020 Mar 2.

Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College , Kunming, Yunnan, China.

With more demand for Sabin inactivated poliovirus vaccines (sIPVs) to support the global polio eradication effort worldwide, data regarding the potency characteristics of sIPV after exposure to freezing temperatures are urgently required. In the present study, the sIPVs were stored at -20°C for 24 h, 1 week, and 2 weeks in the freezer or in a vaccine carrier for 1 or 3 freeze-thaw cycle to evaluate the effect mediated by freezing temperatures that may be encountered during routine storage and transfer. The potency was then determined by a D-antigen enzyme-linked immunosorbent assay, and the potency was evaluated in Wistar rats. In the study for freezer storage groups, the D-antigen contents for all three types decreased and were lower than the release specifications after storing at -20°C for 2 weeks. After storing at -20°C for 1 week, the D-antigen contents for types I and III in combined group of a total of 45 vials, and for type II in the specific lot groups containing 15 vials decreased, but were within the release specifications. Moreover, no significant change in potency was observed. For vaccine carrier transfer groups, the D-antigen contents did not decrease after 1 freeze-thaw cycle; in contrast, it decreased, but no significant potency loss was observed after 3 freeze-thaw cycles. These results suggest that it may be possible to retain sufficient sIPV potency after short periods of freezing or freeze-thawing during transport.
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http://dx.doi.org/10.1080/21645515.2019.1709352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482872PMC
August 2020

Current status of metformin in addition to insulin therapy in adult patients with type 1 diabetes mellitus: An analysis from the Guangdong Type 1 Diabetes Mellitus Translational Medicine Study.

J Diabetes 2020 Oct 25;12(10):754-760. Epub 2020 Feb 25.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Background: Limited data on the efficacy of the additional metformin therapy in patients with type 1 diabetes mellitus (T1DM) under real-life conditions have been available so far.

Methods: Patients aged ≥18 years with a duration of T1DM for at least 1 year were included in this multicenter observational study. Patients with insulin combined with metformin therapy (MET group) were compared with those with insulin therapy only (INS group).

Results: A total of 76 patients in the MET group were compared with 655 patients in the INS group. At baseline, patients with dyslipidemia were more prevalent in the MET group (17.6% vs 9.0%; P = .006), and they also had a higher body mass index (BMI) (21.7 ± 3.2 kg/m vs 20.4 ± 2.6 kg/m ; P < .001) than those in the INS group. But glycosylated hemoglobin (HbA1c) and daily insulin dose were not significantly different between the two groups. After 1-year follow-up, HbA1c decreased in both groups, while the daily insulin dose decreased in the MET group, but did not change in the INS group (-0.02 IU/kg [-0.16, 0.09] vs 0 IU/kg [-0.09, 0.09]; P = .029). The additional metformin therapy led to no change of BMI and weight in the MET group, while the body weight increased from 53.7 ± 8.6 kg to 55.0 ± 7.9 kg in the INS group (P < .001).

Conclusions: Metformin is initiated more in T1DM patients with dyslipidemia or higher BMI in current practice in China. The addition of metformin is effective in maintaining weight and reducing the insulin dosage without improving glycemic control in patients with T1DM.
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http://dx.doi.org/10.1111/1753-0407.13025DOI Listing
October 2020

Effects of high-fat diet-induced adipokines and cytokines on colorectal cancer development.

FEBS Open Bio 2019 12 18;9(12):2117-2125. Epub 2019 Nov 18.

Department of General Surgery I, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China.

Colorectal cancer (CRC) is the third most common tumor worldwide, and recent epidemiological studies have indicated that obesity contributes to the morbidity and mortality of CRC. Furthermore, obesity-related adipokines have been shown to be closely related to the incidence of CRC, but the underlying mechanisms are unclear. Here, we investigated the effects of high-fat diet-induced adipokines and cytokines on the development of CRC in vitro and in vivo. For the in vivo assays, we divided 2-week-old C57BL/6J-ApcMin/J male mice into three groups: normal-fat diet (ND), high-fat and high-sugar feed (HFHS), and high-fat and low-sugar feed (HFLS). After 1 week, all mice were injected with 20 mg·kg 1,2-dimethylhydrazine once weekly for 10 consecutive weeks. Body weight, liver weight, epididymal fat weight and blood glucose levels were greatly increased in HFHS and HFLS groups compared with the ND group, and the expression levels of some adipokines and cytokines were obviously higher in HFHS or HFLS mice compared with ND mice. For the in vitro assays, HCT116 CRC cells were treated with sera of ND, HFHS or HFLS groups, or serum-free media as a negative control. We observed that sera derived from HFHS or HFLS mice that contain excess adipokines and cytokines promoted the proliferation, migration and invasion of HCT116 cells compared with the ND sera-conditioned medium or serum-free medium group. Therefore, high-fat diet-induced adipokines and cytokines may promote the progression of CRC in vivo and in vitro.
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http://dx.doi.org/10.1002/2211-5463.12751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886304PMC
December 2019

Incidence, clinical characteristics, and outcome of interstitial pneumonia in patients with lymphoma.

Ann Hematol 2018 Jan 31;97(1):133-139. Epub 2017 Oct 31.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China.

Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P < 0.001). In a multivariate Cox regression analysis, B symptoms and a history of drug allergies were identified as risk factors for IP. In conclusion, IP is a life-threatening complication in lymphoma patients. Glucocorticoid therapy with continuous monitoring of chest radiographic changes may be a favourable strategy for treating IP. However, IP may recur, especially in patients re-treated with a similar chemotherapy regimen.
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http://dx.doi.org/10.1007/s00277-017-3157-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748403PMC
January 2018

Influence of static electric field on cognition in mice.

Bioengineered 2016 Jul;7(4):241-5

b State Grid Shanghai Municipal Electric Power Company , Shanghai , China.

With the rapid development of high voltage direct current transmission, the possibility of health effects associated with static electric field (SEF) has caused wide public concern. To examine the effects of long-lasting, full-body exposure to SEF on cognition, Institute of Cancer Research mice were exposed to SEF for 35 d. The intensities of SEF in experimental group I (EG-I), experimental group II (EG-II) and control group (CG) were 2.30∼15.40 kV/m, 9.20∼21.85 kV/m and 0 kV/m, respectively. The performance in learning and memory of mice were tested by Morris water maze (MWM) on days 2∼6, 16∼20 and 30∼34 during the exposure period. The concentrations of hippocampal amino acid neurotransmitters were evaluated on days 7, 21 and 35. Results showed that the latency in the MWM test had no significant difference among the EG-I, EG-II and CG (P > 0.05) during the exposure period. The percentage of time spent in the target quadrant was significantly decreased in the EG-II on day 34 during the exposure period (P < 0.05), whereas the percentage of time spent in the opposite quadrant increased markedly (P < 0.01). The glutamate and gamma-aminobutyric acid concentrations showed no significant differences among the EG-I, EG-II and CG (P > 0.05) during the exposure period. These results indicated that long-lasting, full-body exposure to SEF with certain intensity would not cause significant influence on learning ability, but it might associate with memory impairment of receptors. Meanwhile, this effect of memory impairment was dose-dependent and not causally linked to the glutamate and gamma-aminobutyric acid levels in the hippocampus.
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http://dx.doi.org/10.1080/21655979.2016.1197632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970585PMC
July 2016

Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma.

Leuk Lymphoma 2016 4;57(6):1355-62. Epub 2016 Jan 4.

a Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma , Peking University Cancer Hospital & Institute , Beijing , China ;

The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.
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http://dx.doi.org/10.3109/10428194.2015.1116121DOI Listing
January 2017

Improve the diagnosis of atrial hypertrophy with the local discriminative support vector machine.

Biomed Mater Eng 2015 ;26 Suppl 1:S1813-20

Department of Training, Air Force Logistics of P. L. A, Xuzhou 221000, China.

Computer-aided diagnosis (CAD) approaches succeed in detecting a number of diseases, however, they are not good at addressing atrial hypertrophy disease due to the lack of training data. Support Vector Machine (SVM) is very popular in few CAD solutions to atrial hypertrophy. Yet the performance of SVM is moderate in atrial hypertrophy detection compared to its success in other classification problems. In this paper we propose a novel CAD algorithm, Local Discriminative SVM (LDSVM), to overcome the above-mentioned difficulty. LDSVM consists of a global SVM that is trained on the training data, and a local kNN that is trained based on the information of SVM and query. When a query arrives, SVM gives the initial decision. If the initial decision is less confident, local kNN begins to modify the initial decision. LDSVM improves the accuracy of SVM through some contributions: the risk tube, the discriminant information derived from SVM hyperplane, the new metric and the self-tuning size of neighborhood. Empirical evidence on real medical datasets show high performance of LDSVM over the peers in addressing atrial hypertrophy problems.
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http://dx.doi.org/10.3233/BME-151483DOI Listing
July 2016

Moxibustion relieves visceral hyperalgesia via inhibition of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein (HSP) 70 expression in rat bone marrow cells.

Acupunct Med 2016 Apr 3;34(2):114-9. Epub 2015 Sep 3.

Basic Medical College of Nanchang University, Nanchang, China.

Objective: To investigate the effects of moxibustion on visceral hyperalgesia (VH) and bone marrow cell transient receptor potential vanilloid type 1 (TRPV1) and heat shock protein (HSP) 70 expression in a rat model of VH.

Methods: Mechanical colorectal distension was performed to induce VH in neonatal Sprague-Dawley rats. Eight-week-old VH rats were treated with moxibustion at acupuncture point BL25 or an ipsilateral non-acupuncture point. Abdominal withdrawal reflex (AWR) scoring and pain threshold pressure assessment were performed before and after moxibustion treatment for 7 consecutive days. The expression of TRPV1 and HSP70 in bone marrow cells was quantified by real-time quantitative PCR.

Results: The expression of TRPV1 and HSP70 in bone marrow cells was increased in rats with VH. Moxibustion at BL25 significantly decreased AWR scores and increased pain threshold pressure in rats with VH. Furthermore, moxibustion at BL25 significantly inhibited the VH-induced increase in the expression of TRPV1 and HSP70 in bone marrow cells.

Conclusions: The up-regulation of TRPV1 and HSP70 expression in bone marrow cells may be involved in visceral pain development and the analgesic effect of moxibustion on VH may be mediated through down-regulation of TRPV1 and HSP70 expression in bone marrow cells.
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http://dx.doi.org/10.1136/acupmed-2015-010788DOI Listing
April 2016

The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis.

Ann Rheum Dis 2014 Mar 14;73(3):600-8. Epub 2013 Oct 14.

Department of Immunology, Janssen Research & Development, , San Diego, California, USA.

Objective: The histamine H4 receptor (H4R) has been shown to drive inflammatory responses in models of asthma, colitis and dermatitis, and in these models it appears to affect both innate and adaptive immune responses. In this study, we used both H4R-deficient mice and a specific H4R antagonist, JNJ 28307474, to investigate the involvement of the H4R in mouse arthritis models.

Methods: H4R-deficient mice and wild-type mice administered the H4R antagonist were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The impact on Th17 cells was assessed by restimulation of inguinal lymphocytes in the disease or immunisation models and with in vitro stimulation of whole blood.

Results: Both H4R-deficient mice and mice treated with the H4R antagonist exhibited reduced arthritis disease severity in both CAIA and CIA models. This was evident from the reduction in disease score and in joint histology. In the CIA model, treatment with the H4R antagonist reduced the number of interleukin (IL)-17 positive cells in the lymph node and the total production of IL-17. Th17 cell development in vivo was reduced in H4R-deficient mice or in mice treated with an H4R antagonist. Finally, treatment of both mouse and human blood with an H4R antagonist reduced the production of IL-17 when cells were stimulated in vitro.

Conclusions: These results implicate the H4R in disease progression in arthritis and in the production of IL-17 from Th17 cells. This work supports future clinical exploration of H4R antagonists for the treatment of rheumatoid arthritis.
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http://dx.doi.org/10.1136/annrheumdis-2013-203832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151522PMC
March 2014

[Catheter directed thrombolysis for early left lower extremity deep venous thrombosis without vena cava filters protection].

Zhonghua Wai Ke Za Zhi 2012 Jan;50(1):15-8

General Surgical Department, Kunhua Affiliated Hospital of Kunming Medical College, the First People's Hospital of Yunnan Province, Kunming 650032, China.

Objective: To investigate the indications, safety and efficacy of catheter directed thrombolysis for early left lower extremity deep venous thrombosis (DVT) without vena cava filters protection.

Methods: Clinical data of 54 cases of early left lower extremity DVT received catheter directed thrombolysis without vena cava filters from July 2008 to June 2010 were retrospectively analyzed. The thrombosis was entire without free floating clots and no thrombosis in vena cava detected with ultrasound scan. Twenty-five patients were male and 29 were female with the average age of 52.8 years. Fifty-one of which were iliofemoral and popliteal, the other 3 were iliofemoral. The course were ≤ 7 d in 45 cases and these were 8 to 30 d in 9 cases. Urokinase of 300 000 U was infused through catheters per 2 h twice a day. Meanwhile 4000 U of low weight heparin was administered subcutaneously per 12 h, or heparin infusion at dosage of 18 U×kg(-1)×h(-1).

Results: The procedure technically succeeded in all patients. In total cases venous score decreased to 4.6 ± 2.1 post 6 to 10 d of thrombolysis from 10.8 ± 1.0 with thrombolysis rate of 58% ± 18% which was not significantly different between groups of ≤ 7 d and 8 to 30 d (t = 1.02, P = 0.34). On 14(th) day, 11 patients (20.4%) completely recovered, 35 cases (64.8%) experienced large improvement, 8 patients (14.8%) had mild improvement and nobody was failed, resulting in total efficacy of 100%. No patient developed clinical symptomatic pulmonary embolism. SpO2 did not alter markedly post thrombolysis [(91.0 ± 2.6)% vs. (90.8 ± 2.4)%, t = 2.03, P = 0.05]. No patients suffered from cerebral hemorrhage and haemoturia, and catheter induced inflammation occurred in 4 cases (7.41%). There was mild bleeding in puncture sites in 11 patients (20.4%) during the course. There were 36 patients (66.7%) had been followed up with the time of 6 to 21 months. In which 31 cases had no lower extremity edema or had mild edema after activities. Two patients developed serious edema after activities for deep venous insufficiency. Three cases combined with malignant tumor or renal failure recurred.

Conclusions: For early left extremity DVT which is entire without free floating clots and no thrombosis in vena cava, catheter directed thrombolysis without filter protection maybe administered with safety, efficiency and lower expense.
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January 2012

[Discussion of the characteristic indexs in using three-dimensional fluorescence method to identify different crude oils].

Guang Pu Xue Yu Guang Pu Fen Xi 2009 Dec;29(12):3335-8

Shenzhen Academy of Metrology and Quality Inspection, Shenzhen 518131, China.

The present paper investigates the influence of solvent purity on the test of three-dimensional fluorescence spectra, determines the process of its pre-purification, and studies the influence of the concentrations on the three-dimensional fluorescence characteristic indexes such as the characteristic peaks position, fluorescence intensity (F), and ratio (R) of fluorescence intensity when the phenomena of fluorescence quenching won't appear. The result shows that the concentration affects the value F and value R largely but its effect on the relative peak intensity (R(s)) is relatively small. Different crude oils has different value R(s). According to those characteristics, this paper presents that the value R(s) can be used as a new characteristic index for identification of crude oil. This conclusion was confirmed by testing many crude oils stably and reliably from different areas with their concentrations at 5 mg x L(-1). This method can be applied to identify most crude oils preliminary and further accurate analysis can be carried out together with other index.
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December 2009

Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner.

J Gen Virol 2010 Mar 11;91(Pt 3):591-8. Epub 2009 Nov 11.

Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 70101, PR China.

Acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) causes severe diseases in immunocompromised patients, so identification of new therapies is needed. Interferons (IFNs) are used to treat several other viral infections in the clinic, and IFN-beta and IFN-gamma are known to cooperatively reduce wild-type HSV-1 replication in the corneas of immunocompetent mice. Because IFN-gamma has been shown to exert an antiviral effect mostly through T cells, whether combined IFN treatment can still inhibit ACV-resistant HSV-1 replication, especially in immunocompromised hosts, is unknown. The present study evaluated the efficacy of combined IFN treatment on ACV-resistant HSV-1 mutants. In vitro results showed that IFN-beta acted synergistically with IFN-gamma to inhibit HSV-1 replication in both human and mouse cell lines. Some ACV-resistant mutants were actually hypersensitive to combined IFN treatment. In vivo results showed that topical treatment with a low dose of IFN-beta plus IFN-gamma (200 U each) on mouse corneas efficiently reduced the viral loads by up to 4, 4 and 3 logs, respectively, in the eyes, trigeminal ganglia and brainstems of wild-type and also immunocompromised nude mice infected or co-infected with ACV-resistant HSV-1 in a manner independent of T cells. A highly efficient reduction in HSV acute replication by combined IFN treatment led to a dramatic decrease in subsequent virus reactivation from neural tissues, trigeminal ganglia, brainstems and spinal cords of latently infected mice. Thus, a combination of IFN-beta and IFN-gamma could be a potential treatment for ACV-resistant HSV-1 in immunocompromised patients.
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http://dx.doi.org/10.1099/vir.0.016964-0DOI Listing
March 2010

[Treatment on post-operational complications of aortic endovascular grafting exclusion].

Zhonghua Wai Ke Za Zhi 2009 May;47(9):653-6

The First General Surgical Department, the First People's Hospital of Yunnan Province, Kunhua Affiliated Hospital of kunming Medical College, Kunming 650032, China.

Objective: To investigate the post-operative complications of aortic endovascular grafting exclusion (EVGE) and its reasons and treatments.

Methods: Clinical data of 82 cases received aortic endovascular grafting exclusion from January 2002 to October 2008 were retrospectively analyzed. Seventy-one cases were male and 11 cases were female with the age of 33 to 78 years and the average age of 49.2 years. There were 66 cases of thoracic aortic dissecting aneurysms and 16 cases of abdominal aortic aneurysm. The effect, post-operational complications and its treatment were investigated.

Results: There were 90.1% patients had been followed up with the time of 3 to 78 months with technical success of 90.3%, clinical success of 94.1%, peri-operational mortality of 2.4%, total mortality of 6.1% and mortality associated with EVGE of 2.4%. Twenty-one cases underwent complications including type I endoleak (13 cases), abdominal aortoduodenal fistula (1 case), narrow true lumen (2 cases), reverse Stanford A dissection (2 cases), post EVGE syndrome (12 cases), delayed healing of inguinal incision (5 cases), constipation (3 cases), cerebral infarction (1 case). No paraplegia, left subclavian artery ischemia, contrast media associated nephrosis, ischemic colitis, ischemic neurologic injury, and artery embolism occurred. Post operation 4 cases had the second intervention including 2 type I endoleak and 2 narrow true lumen.

Conclusions: The technique-related complications still hinder the long-term effect of EVGE. It needs to be further investigated on technique improvement and treatment standardization.
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May 2009

[The clinical investigation of early visual function in cataract patients after implantation with aspheric intraocular lens].

Yan Ke Xue Bao 2007 Mar;23(1):43-7

Ophthalmic Center, Foshan Second People's Hospital, Foshan 528000, China.

Purpose: To initially evaluate the early visual function after implantation with aspheric intraocular lens

Methods: Eighty-eight subjects (91 eyes) were divided randomly into three groups: AcrySof IQ (SN60WF) group, KS-3Ai group and AcrySof Natural (SN60AT) group. Best corrected visual acuity was observed 1 day, 1 week and 1 month postoperatively, while contrast sensitivity and subjective vision were observed 1 month later.

Results: Best corrected visual acuity was obviously better in KS-3Ai group than in the other groups 1 day postoperatively (P < 0.05), but no significant difference was found 1 week and 1 month later among the groups (P > 0.05). When the pupil diameter was in 2.5 to 4.0 mm and 5.0 to 6.0 mm, AcrySof IQ and KS-3Ai groups were better than the AcrySof Natural group in the low and middle spatial frequency (P < 0.05). However, there was no significant difference between AcrySof IQ and KS-3Ai groups (P > 0.05). VF/QOL questionnaire was obtained, showing that implantation with AcrySof IQ and KS-3Ai satisfied patients preferably.

Conclusions: Aspheric intraocular lens can greatly improve patients' contrast sensitivity and quality of vision.
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March 2007

Inhibitors of unactivated p38 MAP kinase.

Bioorg Med Chem Lett 2006 Dec 12;16(23):6102-6. Epub 2006 Sep 12.

Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202, Raritan, NJ 08869, USA.

Inhibition of the p38 map kinase pathway has been shown to be beneficial in the treatment of inflammatory diseases. The first class of potent p38 kinase inhibitors was the pyridinylimidazole compounds from SKB. Since then several pyridinylimidazole-based compounds have been shown to inhibit activated p38 kinase in vitro and in vivo. We have developed a novel series of pyridinylimidazole-based compounds, which potently inhibit the p38 pathway by binding to unactivated p38 kinase and only weakly inhibiting activated p38 kinase activity in vitro.
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http://dx.doi.org/10.1016/j.bmcl.2006.08.101DOI Listing
December 2006

Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists.

J Med Chem 2005 Dec;48(26):8289-98

Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA.

Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4 and 5-positions led to increased activity in a [(3)H]histamine radiolabeled ligand competitive binding assay. In vitro metabolism and initial pharmacokinetic studies were performed on selected compounds leading to the identification of indole 8 and benzimidazole 40 as potent H(4) antagonists with the potential for further development. In addition, both 8 and 40 demonstrated efficacy in in vitro mast cell and eosinophil chemotaxis assays.
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http://dx.doi.org/10.1021/jm0502081DOI Listing
December 2005

Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.

J Pharmacol Exp Ther 2005 Sep 9;314(3):1310-21. Epub 2005 Jun 9.

Leiden/Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, The Netherlands.

The histamine H(4) receptor (H(4)R) is involved in the chemotaxis of leukocytes and mast cells to sites of inflammation and is suggested to be a potential drug target for asthma and allergy. So far, selective H(4)R agonists have not been identified. In the present study, we therefore evaluated the human H(4)R (hH(4)R) for its interaction with various known histaminergic ligands. Almost all of the tested H(1)R and H(2)R antagonists, including several important therapeutics, displaced less than 30% of specific [(3)H]histamine binding to the hH(4)R at concentrations up to 10 microM. Most of the tested H(2)R agonists and imidazole-based H(3)R ligands show micromolar-to-nanomolar range hH(4)R affinity, and these ligands exert different intrinsic hH(4)R activities, ranging from full agonists to inverse agonists. Interestingly, we identified 4-methylhistamine as a high-affinity H(4)R ligand (K(i) = 50 nM) that has a >100-fold selectivity for the hH(4)R over the other histamine receptor subtypes. Moreover, 4-methylhistamine potently activated the hH(4)R (pEC(50) = 7.4 +/- 0.1; alpha = 1), and this response was competitively antagonized by the selective H(4)R antagonist JNJ 7777120 [1-[(5-chloro-1H-indol-2-yl)-carbonyl]-4-methylpiperazine] (pA(2) = 7.8). The identification of 4-methylhistamine as a potent H(4)R agonist is of major importance for future studies to unravel the physiological roles of the H(4)R.
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http://dx.doi.org/10.1124/jpet.105.087965DOI Listing
September 2005

Histamine H4 receptor antagonists: the new antihistamines?

Curr Opin Investig Drugs 2004 Nov;5(11):1174-83

Johnson & Johnson Pharmaceutical Research & Development LLC, 3210 Merryfield Row, San Diego, CA 92121, USA.

Antihistamines (histamine H1 receptor antagonists) are a mainstay treatment for atopic allergy, yet they are only partially effective in relieving the symptoms of the disease. They also have very limited value for the treatment of asthma, despite the well-characterized bronchoconstrictory effects of histamine. The recent discovery of a fourth histamine receptor (H4), and the realization that it is exclusively expressed on hematopoietic cell types that are most implicated in the development and symptomatology of allergy and asthma, suggests that pharmacological targeting of the H4 receptor, either alone or in combination with H1 receptor antagonists, may prove useful for treating both allergy and asthma. Here we review the known biology associated with the H4 receptor, as well the effects of a highly selective H1 receptor antagonist.
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November 2004