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  1. Article ; Online: Safety, pharmacokinetics, and pharmacodynamics of SHR7280, an oral gonadotropin-releasing hormone receptor antagonist, in healthy men

    Xin Li / Feifei Sun / Xiaolei Zhang / Pingping Lin / Kai Shen / Yu Shen / Lingyu Ma / Yu Cao / Chenjing Wang

    BMC Medicine, Vol 21, Iss 1, Pp 1-

    a randomized, double-blind, placebo-controlled phase 1 study

    2023  Volume 10

    Abstract: Abstract Background Gonadotropin-releasing hormone (GnRH) antagonists are a promising therapeutic approach for treating hormone-dependent prostate cancer. Currently, the mainstream GnRH antagonists are polypeptide agents administered through subcutaneous ...

    Abstract Abstract Background Gonadotropin-releasing hormone (GnRH) antagonists are a promising therapeutic approach for treating hormone-dependent prostate cancer. Currently, the mainstream GnRH antagonists are polypeptide agents administered through subcutaneous injection. In this study, we evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SHR7280, an oral small molecule GnRH antagonist, in healthy men. Methods This phase 1 trial was a randomized, double-blind, placebo-controlled, and dose-ascending study. Eligible healthy men were randomized in a 4:1 ratio to receive either oral SHR7280 tablets or placebo twice daily (BID) for 14 consecutive days. The SHR7280 dose was initiated at 100 mg BID and then sequentially increased to 200, 350, 500, 600, 800, and 1000 mg BID. Safety, PK, and PD parameters were assessed. Results A total of 70 subjects were enrolled and received the assigned drug, including 56 with SHR7280 and 14 with placebo. SHR7280 was well-tolerated. The incidence of adverse events (AEs, 76.8% vs 85.7%) and treatment-related AEs (75.0% vs 85.7%), as well as the severity of AEs (moderate AEs, 1.8% vs 7.1%) were similar between the SHR7280 group and placebo group. SHR7280 was rapidly absorbed in a dose-dependent manner, with a median T max of each dose group ranging from 0.8 to 1.0 h on day 14 and a mean t 1/2 ranging from 2.8 to 3.4 h. The PD results demonstrated that SHR7280 exhibited a rapid and dose-proportional suppression of hormones, including LH, FSH, and testosterone, with maximum suppression achieved at doses of 800 and 1000 mg BID. Conclusions SHR7280 showed an acceptable safety profile, as well as favorable PK and PD profiles within a dose range of 100 to 1000 mg BID. This study proposes a rationale for further investigation of SHR7280 as a potential androgen deprivation therapy. Trial registration Clinical trials.gov NCT04554043; registered September 18, 2020.
    Keywords Gonadotropin-releasing hormone antagonists ; SHR7280 ; Trial in healthy men ; Safety ; Pharmacokinetics ; Pharmacodynamics ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Developing Nitrogen Isotopic Source Profiles of Atmospheric Ammonia for Source Apportionment of Ammonia in Urban Beijing

    Chenjing Wang / Xiujuan Li / Tianle Zhang / Aohan Tang / Min Cui / Xuejun Liu / Xin Ma / Yangyang Zhang / Xiaomeng Liu / Mei Zheng

    Frontiers in Environmental Science, Vol

    2022  Volume 10

    Abstract: Atmospheric ammonia (NH3) is the key precursor in secondary particle formation, which is identified as the most abundant components of haze in Beijing in most cases. It is critical to understand the characteristics of NH3 from various emission sources ... ...

    Abstract Atmospheric ammonia (NH3) is the key precursor in secondary particle formation, which is identified as the most abundant components of haze in Beijing in most cases. It is critical to understand the characteristics of NH3 from various emission sources and quantify each source contribution to NH3 in ambient atmosphere. Stable nitrogen (N) isotope composition (δ15N) is an effective tool to study NH3 source. However, this tool cannot be effectively applied in Beijing due to the lack of comprehensive N nitrogen isotope source profiles. Reliable source profiles are the basis of source apportionment of NH3 using the isotope mixing model. In this study, multiple NH3 source samples were collected at sites, representing six major NH3 source types in Beijing from 2017 to 2018 in four seasons. The δ15N values of 212 NH3 source samples were determined to build a local source profiles database of δ15N. NH3 from traffic source presents significantly higher δ15N values (−14.0 ± 5.4‰), distinguished from other sources. The δ15N values of other sources besides traffic were more depleted and did not clear differences (solid waste, sewage, human feces, fertilizer, and livestock for −33.6 ± 4.5‰, −34.1 ± 4.8‰, −32.2 ± 3.8‰, −35.0 ± 3.9‰, and −34.9 ± 4.4‰, respectively). These sources were classified into non-traffic source in this study. From March 2018 to March 2019, ambient NH3 samples were collected at an urban site in Beijing. With the newly developed source profiles in this study, the contribution of traffic and non-traffic sources to ambient NH3 in an urban site in Beijing was calculated using 15N isotope mass balance equations. Traffic and non-traffic sources contributed 8% and 92% to ambient NH3 in urban Beijing, respectively. The highest seasonal average contribution of traffic to ambient NH3 was found in winter (22%). Our results reveal the importance of traffic source and provide evidence for the need to control NH3 emission from traffic in urban Beijing in winter.
    Keywords ammonia ; nitrogen isotope ; source profile ; source apportionment ; Beijing ; Environmental sciences ; GE1-350
    Subject code 380
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The relationship between HPV prevalence and DNA damage in cervical cancer population in Gansu province, China.

    Zhong Guo / Tianyuan Zhu / Yunsong Zhou / Tianbin Si / Qiang Wang / Hongmei Qu / Chenjing Wang / Jin Zhao

    Intervirology (2022)

    2022  

    Abstract: Objectives: To assess the possible reason of high incidence and mortality of cervical cancer in Longnan, China. Materials and Methods: 147 and 124 invasive squamous cell carcinoma (SCC) samples from Longnan and different cities and districts of Gansu ... ...

    Abstract Objectives: To assess the possible reason of high incidence and mortality of cervical cancer in Longnan, China. Materials and Methods: 147 and 124 invasive squamous cell carcinoma (SCC) samples from Longnan and different cities and districts of Gansu province were collected in the present study. All the samples were obtained from patients who underwent biopsies with colposcopy or advanced operations and were evaluated by experienced pathologists. HPV genotypes were examined with a validated HPV subtypes kit. The prevalence of HPV infection in SCC patients of China was analyzed by evidence-based medicine in published literature. The markers of DNA damage response (DDR) - ATMpSer1981, H2AXp Ser139 (γH2AX), Chk2pThr68 and P53 - were analyzed by immunohistochemistry. Results: HPV positivity, high risk and multiple HPV positivity and HPV 58 infection were significantly higher in Longnan. Our results the prevalence of HPV infection in SCC patients of Longnan are consistent with the HPV prevalence in China. ATM, γH2AX and P53 expression in total and HPV+ samples were also higher in Longnan. Conclusions: HPV related DDR activation may be one reason for high incidence and mortality of Longnan cervical cancer.
    Keywords Specialties of internal medicine ; RC581-951
    Subject code 610 ; 616
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Karger Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A novel solvent-free co-grinding preparation improves curcumin bioavailability in healthy volunteers

    Chenjing Wang / Xin Jiang / Xiaolei Zhang / Yi Xu / Li Li / Xin Li / Shanglong Wang / Ping Shi / Xiaomeng Gao / Zimin Liu / W. Dennis Clark / Yu Cao

    Heliyon, Vol 9, Iss 1, Pp e12829- (2023)

    A single-center crossover study

    2023  

    Abstract: Curcumin, from the rhizome of turmeric (Curcuma longa L.), has a wide variety of biological activities. Unfortunately, its poor water-solubility greatly limits its bioavailability. The purpose of this study was to evaluate CUMINUP60®, a novel preparation ...

    Abstract Curcumin, from the rhizome of turmeric (Curcuma longa L.), has a wide variety of biological activities. Unfortunately, its poor water-solubility greatly limits its bioavailability. The purpose of this study was to evaluate CUMINUP60®, a novel preparation utilizing a solvent-free, co-grinding method designed to improve curcumin’s bioavailability. We performed a single-center crossover experiment to compare the new product with standard 95% curcumin in the blood plasma of twelve healthy adults (10 males, 2 females). Total bioavailability of curcumin and its sulfate and glucuronide conjugates from the test product, measured by their areas under the curve over 12 h (AUC0-T), showed a combined increase of 178-fold over standard curcumin and its conjugates from the reference product. The new product represents a significant improvement for providing greater bioavailability of curcumin, as compared with several other branded preparations. It therefore has broad applications for preparing curcumin as a more effective health ingredient in functional foods, beverages, and nutraceuticals.
    Keywords Curcumin ; Oral bioavailability ; Pharmacokinetics ; CUMINUP60® ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: LECT 2 Antagonizes FOXM1 Signaling via Inhibiting MET to Retard PDAC Progression

    Xin Li / Pingping Lin / Ye Tao / Xin Jiang / Ting Li / Yunshan Wang / Chenjing Wang / Yu Cao

    Frontiers in Cell and Developmental Biology, Vol

    2021  Volume 9

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with minimally effective treatments, highlighting the importance of developing novel biomarkers and therapeutic targets. Here, we disclosed the mechanisms that leukocyte cell- ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with minimally effective treatments, highlighting the importance of developing novel biomarkers and therapeutic targets. Here, we disclosed the mechanisms that leukocyte cell-derived chemotaxin-2 (LECT2) modulates PDAC development using in vitro and in vivo models. LECT2 is downregulated in metastatic PDACs compared with the primary tumor, and its expression is correlated with multiple clinical pathologic features and prognosis. The absence promotes multiple malignant behaviors, including cell proliferation, epithelial-mesenchymal transition, migration, and invasion. In vivo studies showed that LECT2 overexpression inhibits tumor growth and lung metastasis. Mechanistically, LECT2 inhibits FOXM1 signaling by targeting HGF/MET to retard PDAC progression, revealing LECT2 as a promising biomarker and therapeutic target for PDAC in the future.
    Keywords PDAC ; LECT2 ; HGF/MET ; FOXM1 signaling ; tumor growth ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19)

    Qian Dong / Hongmei Qiao / Huiyi Jiang / Lixiao Liu / Yanling Ge / Fang-Jiao Zong / Yanan Li / Bingzi Dong / Sujuan Hu / Dongmei Meng / Rong Jin / Xiangshi Wang / Hailing Chang / Xiaolong Xu / Chenjing Wang / Yu Cao / Han-Ting Zhang / Qingquan Liu

    Frontiers in Pharmacology, Vol

    A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers

    2023  Volume 14

    Abstract: Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine ... ...

    Abstract Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear.Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed.Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the ...
    Keywords traditional Chinese medicine ; Jin-Zhen oral liquid ; pediatric COVID-19 ; randomized controlled clinical trial ; multiple clinical centers ; Therapeutics. Pharmacology ; RM1-950
    Subject code 610
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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