Regenerative Medicine
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2019
·
IF 2.383
Yijia Li,Frances Verter,Bin Wang,Ning Gu
This report describes changes to cell therapy research and clinical practice in China as a result of guidelines from the central government finalized at the end of 2017. The tables list Chinese authorities and regulations on human cells for medical research over the years 1993–2018. Under the new regulations, cell therapy products (CTPs) are treated like drugs, in alignment with policy in the USA and European Union. At civil institutions in China, there are now two pathways for human clinical trials: research versus pharmaceutical development. At the end of 2018, trials of CTPs were only authorized at 114 approved hospitals. It is hoped that the new policies will help CTPs developed in China gain acceptance by health regulators in the west.
研究领域:
医学
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生物技术
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药理学
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DOI
PubMed
高影响因子
MethodsX
·
2024
·
IF 1.6
Júlia Oliveira Penteado,Laiz Coutelle Honscha,Caroline Lopes Feijo Fernandes,Paula Florencio Ramires,Ronan Adler Tavella,Fernanda Oliveira Reis,Mariane Pergher Soares,Lisiane Martins Volcão,Marina dos Santos,Ana Luiza Muccillo-Baisch,Flavio Manoel Rodrigues da Silva-Júnior
Randomized clinical trials are considered the gold standard for studies with dietary interventions, which is mainly due to the fact that they can establish causal relationships between food exposure and body composition measures or biomarkers. The aim of this study was to describe the details of a double-blind, randomized, clinical trial protocol to identify, characterize and evaluate the effects of human dietary exposure to pesticide residues in food. Specific aspects of planning (development of a research question, determination of objectives, selection of participants, randomization and blinding) and performance (recruitment of participants, measures to improve adherence, data collection, follow-up and evaluation of results) are addressed in this study. The study design proved effective in characterizing dietary patterns with foods originating from both conventional and organic agriculture. A total of 148 individuals were recruited for the study. The conventional group was represented by 47 % of the sample and the organic group was represented by 53 %. The practice of evidence-based nutrition has demanded that trials be well designed and systematically performed in the field of clinical nutrition. Therefore, this clinical trial emphasizes the importance of improving studies with toxicological nutrition that assess sources of exposure through food. • This double-blind, randomized clinical trial details the protocol for identifying, characterizing, and evaluating the effects of dietary exposure to pesticide residues. • The protocol demonstrates that well-designed and systematically conducted trials emphasize the importance of robust methodologies in evidence-based nutrition. • In the face of the global climate crisis, this clinical trial underscores the importance of enhancing studies in toxicological nutrition, particularly those evaluating sources of exposure through food, to better understand the dietary impacts on health.
研究领域:
营养学
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毒理学
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公共卫生
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DOI
PubMed
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2021
·Vol. 78
·期 4
·581
·
IF 3.105
Wang Yue,Wang Joanne W.,Wang Yanbin,Yang Bing,Yinghua Du Alicia,Kong Ziqing,Chen Minglong,Wang Jie
Proper medication compliance is critical for the integrity of clinical practice, directly related to the success of clinical trials to evaluate both pharmacological-based and device-based therapies. Here, we established a liquid chromatography–tandem mass spectrometry method to accurately detect 55 chemical entities in the human urine sample, which accounting for the most commonly used 172 antihypertensive drugs in China. The established method had good accuracy and intraday and interday precision for all analyses in both bench tests and validated in 21 hospitalized patients. We used this method to monitor and ensure drug compliance and exclude the inferring impacts of medication compliance as a key confounder for our pivotal trial of a catheter-based, renal mapping and selective renal denervation to treat hypertension. It is found that in the urine samples from 92 consecutive subjects, 85 subjects (92.4%) were consistent with their prescriptions after 28 days run-in periods, 90 (97.8%) and 85 (95.5%) patients completely complied with their medications during the 3-month and 6-month follow-up period, respectively. Thus, using the liquid chromatography–tandem mass spectrometry method with specificity, accuracy, and precision, we ensured drug compliance of patients, excluded the key confounder of drug interferences, and ensured the quality of our device-based clinical trial for treatment of hypertension.
研究领域:
医学
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药理学
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临床研究
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF NUTRITION
·
2023
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IF 3.6
Fan Du,Min Yan,Lili Duan,Guolong Xie,Xiuhua Yao,Wenjing Hu,Yu Liu,Min Meng,Jiepeng Chen,Di Shao
Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
研究领域:
药理学
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营养学
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临床研究
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Zhenmei Yang,Ying Liu,Kun Zhao,Weiqiang Jing,Lin Gao,Xianghui Dong,Yan Wang,Maosen Han,Chongdeng Shi,Chunwei Tang,Peng Sun,Rui Zhang,Zhipeng Fu,Jing Zhang,Danqing Zhu,Chen Chen,Xinyi Jiang
Hepatocellular carcinoma (HCC) is a prevalent and lethal disease, and tumor regression rarely occurs in advanced HCC patients due to limited effective therapies. Given the enrichment of macrophages in HCC and their role in tumor immunity, transforming them into chimeric antigen receptor macrophages (CAR-Ms) is thought to increase HCC cell-directed phagocytosis and tumoricidal immunity. To test this hypothesis, mRNA encoding CAR is encapsulated in a lipid nanoparticle (LNP) that targets liver macrophages. Notably, the LNPs adsorb specific plasma proteins that enable them to target HCC-associated macrophages. Moreover, mRNA encoding Siglec-G lacking ITIMs (Siglec-GΔITIMs) is codelivered to liver macrophages by LNP to relieve CD24-mediated CAR-Ms immune suppression. Mice treated with LNPs generating CAR-Ms as well as CD24-Siglec-G blockade significantly elevate the phagocytic function of liver macrophages, reduce tumor burden and increase survival time in an HCC mouse model. Arguably, our work suggests an efficacious and flexible strategy for the treatment of HCC and warrants further rigorous evaluation in clinical trials .
研究领域:
肿瘤学
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免疫治疗
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分子生物学
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纳米技术
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Maolin Li,Yuting Zhang,Xiuyuan Jiang,Jiao Jiang,Xina Gu,Hua Zhang
Transcription factors play crucial roles in governing gene expression and are implicated in various physiological and pathological processes. Here, we propose a novel electrochemiluminescence (ECL) biosensor for the sensitive and specific detection of the transcription factor NF-kB p50, utilizing CRISPR/Cas12a-assisted hyperbranched rolling circle amplification (HRCA) technology. The biosensor achieves a remarkable limit of detection (LOD) of 3.6 fM and demonstrates excellent specificity against interfering proteins. Optimization of experimental parameters further enhances the biosensor’s performance, ensuring its reliability and accuracy. In addition, validation in real biological samples confirms the feasibility of biosensor for practical applications, offering a promising tool for clinical trials and disease diagnosis.
研究领域:
生物技术
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分子生物学
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分析化学
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临床诊断
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Jie Tang,Yu Li,Xuefeng Hu,Wei Hua,Haoning Xu,Li Li,Fujian Xu
The systemic use of tranexamic acid (TA) as an oral drug could bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies, are suffering from low drug load rates, plus its synthesis complexity, time-consumption etc., adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) was developed. The encapsulation efficiency of TA@ZIF-8 reached nearly 25% through physical adsorption and chemical bonding of TA indicated by theoretical simulation and the improved TA penetration was elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments have demonstrated the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials have demonstrated the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration. This article is protected by copyright. All rights reserved
研究领域:
药学
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皮肤病学
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纳米技术
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药理学
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临床研究
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
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IF 10.633
Bin Liang,Dawei Jiang,Luqi Pan,Fang Xiong,Shuya Feng,Shenghao Wu,Haige Ye,Zhijie Yu,Changcan Shi,Shenmeng Gao
Selective BCL2 inhibitor ABT-199 has been approved to treat hematological malignancies including acute myeloid leukemia (AML). However, acquired drug resistance and severe side effects occur after extended treatment limiting the clinical usage of ABT-199. Here, we successfully encapsulated pure ABT-199 in amphiphilic mPEG- b -PTMC 169 block copolymer , forming mPEG-b-PTMC 169 @ABT-199 nanoparticles (abbreviated as PEG-ABT-199), which presented better aqueous dispersion and higher efficiency of loading and encapsulation than pure ABT-199. We then compared the anti-leukemic ability of pure ABT-199 and PEG-ABT-199 in vitro and in vivo . PEG-ABT-199 had a lower IC50 value compared with pure ABT-199 in MV4-11 and MOLM-13 cell lines. In addition, PEG-ABT-199 significantly induced apoptosis and decreased colony number than pure ABT-199. Most importantly, PEG-ABT-199 markedly reduced leukemic burden, inhibited the infiltration of leukemic blasts in the spleen, and extended the overall survival (OS) in MLL-AF9-transduced murine AML compared with free ABT-199. Meanwhile, the blank PEG169 NP was non-toxic to normal hematopoiesis in vitro and in vivo , suggesting that PEG169 NP is a safe carrier. Mechanistically, PEG-ABT-199 enhanced mitochondria-targeted delivery of ABT-199 to trigger the collapse of mitochondrial membrane potential (MMP), the release of cytochrome c (cyt-c), and mitochondria-based apoptosis. In conclusion, our results suggest that PEG-ABT-199 has more vital anti-leukemic ability than pure ABT-199. PEG-ABT-199 has potential application in clinical trials to alleviate side effects and improve anti-leukemia ability. Statement of significance ATB-199, an orally selective inhibitor for BCL2 protein, presents marked activity in relapsed or refractory AML, T-ALL, and CLL patients. However, ABT-199 resistance severely limits the further clinical usage because of off-target effects, non-specific toxicities, and low delivery of drugs. To reduce the side-effects and improve the solubility and bioavailability, ABT-199 was encapsulated into the amphiphilic mPEG- b -PTMC block copolymer by co-assembly method to obtain mPEG- b [email protected] nanoparticles (PEG-ABT-199). PEG-ABT-199 has several advantages compared with pure ABT-199. 1.PEG-ABT-199 presents better aqueous dispersion and higher efficiencies of loading and encapsulation than pure ABT-199. 2. PEG-ABT-199 substantially enhances the anti-leukemic ability in vitro and in vivo compared with pure ABT-199. 3. PEG-ABT-199 has little effects on normal cells. 4. PEG-ABT-199 can reduce treatment cost.
研究领域:
药理学
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肿瘤学
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纳米技术
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血液学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-8
·
IF 16.6
Lu Yahui,Chen Xing,Han Fang,Zhao Qian,Xie Tao,Wu Jingjun,Zhang Yuhua
3D printing can produce intuitive, precise, and personalized anatomical models, providing invaluable support for precision medicine, particularly in areas like surgical training and preoperative planning. However, conventional 3D printed models are often significantly more rigid than human organs and cannot undergo repetitive resection, which severely restricts their clinical value. Here we report the stereolithographic 3D printing of personalized liver models based on physically crosslinked self-healing elastomers with liver-like softness. Benefiting from the short printing time, the highly individualized models can be fabricated immediately following enhanced CT examination. Leveraging the high-efficiency self-healing performance, these models support repetitive resection for optimal trace through a trial-and-error approach. At the preliminary explorative clinical trial (NCT06006338), a total of 5 participants are included for preoperative planning. The primary outcomes indicate that the negative surgery margins are achieved and the unforeseen injuries of vital vascular structures are avoided. The 3D printing of liver models can enhance the safety of hepatic surgery, demonstrating promising application value in clinical practice.
研究领域:
生物医学工程
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外科技术
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材料科学
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医学影像
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产品关联
DOI
PubMed
高影响因子
Vaccines
·
2024
·Vol. 12
·期 6
·689
·
IF 5.2
Zhenwei Han,Shen Wang,Ting Mu,Ping Zhao,Lingli Song,Ying Zhang,Jin Zhao,Wen Yin,Yue Wu,Huan Wang,Bo Gong,Min Ji,Richard B. S. Roden,Yanping Yang,Michel Klein,Ke Wu
Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11–88) from five human alphapapillomavirus genotypes inE. coliunder cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standardin vitroandin vivotoxicology studies suggest a promising safety profile. These findings suggest LBTA’s promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).
研究领域:
病毒学
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免疫学
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公共卫生
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疫苗研发
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jianlin Lv,Yajun Xu,Ya Liu,Kazuo Sakurai,Haiyang Yu,Zhaohui Tang
ABSTRACT It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)- b -poly( D,L -lactide) (mPEG- b -PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG- b -PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9% tumor suppression rate and a 20% cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
·
2020
·Vol. 30
·期 9
·794-809
·
IF 20.507
Wu Jun,Song Dingyun,Li Zhongwen,Guo Baojie,Xiao Yani,Liu Wenjing,Liang Lingmin,Feng Chunjing,Gao Tingting,Chen Yanxia,Li Ying,Wang Zai,Wen Jianyan,Yang Shengnan,Liu Peipei,Wang Lei,Wang Yukai,Peng Liang,Stacey Glyn Nigel,Hu Zheng,Feng Guihai,Li Wei,Huo Yan,Jin Ronghua,Shyh-Chang Ng,Zhou Qi,Wang Liu,Hu Baoyang,Dai Huaping,Hao Jie
Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on lung disorders.
研究领域:
干细胞生物学
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肺病学
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再生医学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）