In the light of the rapid development of science and technology, the lingering question is – what does academia lack? The answer may be “effective integration”. Scientific problems are complicated and often interdisciplinary, which implies that in-depth collaboration among experts in various fields is vital. Interdisciplinary research is the essence of social development, innovation and gaining a broader perspective in problem solving. The mission of interdisciplinary integration is to break down barriers, reorient insights, and to produce significant breakthroughs in academic research.
{"title":"The Significance of Interdisciplinary Integration in Academic Research and Application","authors":"P. Saw, Shanping Jiang","doi":"10.15212/bioi-2020-0005","DOIUrl":"https://doi.org/10.15212/bioi-2020-0005","url":null,"abstract":"In the light of the rapid development of science and technology, the lingering question is – what does academia lack? The answer may be “effective integration”. Scientific problems are complicated and often interdisciplinary, which implies that in-depth collaboration among experts in various fields is vital. Interdisciplinary research is the essence of social development, innovation and gaining a broader perspective in problem solving. The mission of interdisciplinary integration is to break down barriers, reorient insights, and to produce significant breakthroughs in academic research.","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126642619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuhao Chen, Meng Du, Jinsui Yu, L. Rao, Xiaoyuan Chen, Zhiyi Chen
Abstract Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application. It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy. It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.
{"title":"Nanobiohybrids: A Synergistic Integration of Bacteria and Nanomaterials in Cancer Therapy","authors":"Yuhao Chen, Meng Du, Jinsui Yu, L. Rao, Xiaoyuan Chen, Zhiyi Chen","doi":"10.15212/bioi-2020-0008","DOIUrl":"https://doi.org/10.15212/bioi-2020-0008","url":null,"abstract":"Abstract Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In\u0000 view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application.\u0000 It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate\u0000 as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an\u0000 abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized\u0000 the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy.\u0000 It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122731891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dinghong Yang, Xiaoyun Xiao, Haohu Wang, Huan Wu, W. Qin, Xiaofeng Guan, Q. Jiang, B. Luo
Background: Benign or malignant breast lesions with typical ultrasonic characteristics could be easily and correctly diagnosed with two-dimensional ultrasound (2D US). However, diagnosis of atypical lesions remains a challenge. Most atypical lesions have different ultrasonographic features with probe direction variation. Thus, the interpretation of ultrasonographic features based on static images empirically collected by sonographers might be inaccurate. We aimed to investigate the section discrepancy and diagnostic performance of breast lesions in 2D US by dynamic videos versus static images.Methods: Static images and dynamic videos based on two perpendicular planes of 468 breast lesions were collected and evaluated. The Breast Imaging and Reporting Data System (BI-RADS®) US lexicon was used. Category 3 was used as the cut-off point, and section discrepancy was defined as two perpendicular planes showing different BI-RADS categories (3 versus 4A, 4B, 4C, and 5).Results: This retrospective study included 315 benign and 153 malignant lesions. There were 53 and 50 lesions with section discrepancy during static and dynamic observations, respectively. The proportion of benign lesions with section discrepancy was significantly higher than that of malignant lesions (P < 0.05) either in dynamic or static observation, and the contingency coefficient was 0.2 between section discrepancy and histopathology. Duct changes were more clearly depicted in dynamic videos than in static images (P < 0.05) both in malignant and benign lesions. Calcification and architectural distortion were more sensitively detected by dynamic videos than with static images (P < 0.05) in malignant lesions. The interpretation of “margin” significantly differed in benign lesions between static images and dynamic videos (P < 0.05). The areas under the curve of static image-horizontal, static image-sagittal, dynamic video-horizontal, and dynamic video-sagittal were 0.807, 0.820, 0.837, and 0.846, respectively. The specificities of dynamic videos were higher than those of static images (P < 0.05).Conclusion: Breast lesions have section discrepancy in 2D US. Observations based on dynamic videos could more accurately reflect lesion features and increase the specificity of US in the differentiation of atypical breast lesions.
{"title":"Section Discrepancy and Diagnostic Performance of Breast Lesions in Two-dimensional Ultrasound by Dynamic Videos versus Static Images","authors":"Dinghong Yang, Xiaoyun Xiao, Haohu Wang, Huan Wu, W. Qin, Xiaofeng Guan, Q. Jiang, B. Luo","doi":"10.15212/bioi-2021-0021","DOIUrl":"https://doi.org/10.15212/bioi-2021-0021","url":null,"abstract":"\u0000 Background: Benign or malignant breast lesions with typical ultrasonic characteristics could be easily and correctly diagnosed with two-dimensional ultrasound (2D US). However, diagnosis of atypical lesions remains a challenge. Most atypical lesions have different ultrasonographic features with probe direction variation. Thus, the interpretation of ultrasonographic features based on static images empirically collected by sonographers might be inaccurate. We aimed to investigate the section discrepancy and diagnostic performance of breast lesions in 2D US by dynamic videos versus static images.Methods: Static images and dynamic videos based on two perpendicular planes of 468 breast lesions were collected and evaluated. The Breast Imaging and Reporting Data System (BI-RADS®) US lexicon was used. Category 3 was used as the cut-off point, and section discrepancy was defined as two perpendicular planes showing different BI-RADS categories (3 versus 4A, 4B, 4C, and 5).Results: This retrospective study included 315 benign and 153 malignant lesions. There were 53 and 50 lesions with section discrepancy during static and dynamic observations, respectively. The proportion of benign lesions with section discrepancy was significantly higher than that of malignant lesions (P < 0.05) either in dynamic or static observation, and the contingency coefficient was 0.2 between section discrepancy and histopathology. Duct changes were more clearly depicted in dynamic videos than in static images (P < 0.05) both in malignant and benign lesions. Calcification and architectural distortion were more sensitively detected by dynamic videos than with static images (P < 0.05) in malignant lesions. The interpretation of “margin” significantly differed in benign lesions between static images and dynamic videos (P < 0.05). The areas under the curve of static image-horizontal, static image-sagittal, dynamic video-horizontal, and dynamic video-sagittal were 0.807, 0.820, 0.837, and 0.846, respectively. The specificities of dynamic videos were higher than those of static images (P < 0.05).Conclusion: Breast lesions have section discrepancy in 2D US. Observations based on dynamic videos could more accurately reflect lesion features and increase the specificity of US in the differentiation of atypical breast lesions.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"237 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122518239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nanotechnology is associated with the development of particles in the nano-size range that can be used in a wide range of applications in the medical field. It has gained more importance in the pharmaceutical research field particularly in drug delivery, as it results in enhanced therapeutic drug performance, improved drug solubility, targeted drug delivery to the specific sites, minimized side effects, and prolonged drug retention time in the targeted site. To date, the application of nanotechnology continues to offer several benefits in the treatment of various chronic diseases and results in remarkable improvements in treatment outcomes. The use of nano-based delivery systems such as liposomes, micelles, and nanoparticles in pulmonary drug delivery have shown to be a promising strategy in achieving drug deposition and maintained controlled drug release in the lungs. They have been widely used to minimize the risks of drug toxicity in vivo. In this review, recent advances in the application of nano- and micro-based delivery systems in pulmonary drug delivery for the treatment of various pulmonary diseases, such as lung cancer, asthma, and chronic obstructive pulmonary disease, are highlighted. Limitations in the application of these drug delivery systems and some key strategies in improving their formulation properties to overcome challenges encountered in drug delivery are also discussed.
{"title":"Progress in the Application of Nano- and Micro-based Drug Delivery Systems in Pulmonary Drug Delivery","authors":"Rejoice Thubelihle Ndebele, Qing Yao, Yannan Shi, Yuan-Yuan Zhai, Helin Xu, Cui-tao Lu, Ying-zheng Zhao","doi":"10.15212/bioi-2021-0028","DOIUrl":"https://doi.org/10.15212/bioi-2021-0028","url":null,"abstract":"\u0000 Nanotechnology is associated with the development of particles in the nano-size range that can be used in a wide range of applications in the medical field. It has gained more importance in the pharmaceutical research field particularly in drug delivery, as it results in enhanced therapeutic drug performance, improved drug solubility, targeted drug delivery to the specific sites, minimized side effects, and prolonged drug retention time in the targeted site. To date, the application of nanotechnology continues to offer several benefits in the treatment of various chronic diseases and results in remarkable improvements in treatment outcomes. The use of nano-based delivery systems such as liposomes, micelles, and nanoparticles in pulmonary drug delivery have shown to be a promising strategy in achieving drug deposition and maintained controlled drug release in the lungs. They have been widely used to minimize the risks of drug toxicity in vivo. In this review, recent advances in the application of nano- and micro-based delivery systems in pulmonary drug delivery for the treatment of various pulmonary diseases, such as lung cancer, asthma, and chronic obstructive pulmonary disease, are highlighted. Limitations in the application of these drug delivery systems and some key strategies in improving their formulation properties to overcome challenges encountered in drug delivery are also discussed.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129599319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingdun Xie, Zhenhua Qi, Xiaoling Luo, Fang Yan, W. Xing, W. Zeng, Dongtai Chen, Qiang Li
Background: N6-Methyladenosine (m6A) RNA methylation of eukaryotic mRNA is involved in the progression of various tumors. We aimed to investigate m6A-related genes and m6A regulators in hepatocellular carcinoma (HCC) and their association with prognosis in HCC.Methods: We downloaded liver cancer sample data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database. A total of 21 m6A regulators and 1258 m6A-related genes were then analyzed by consensus clustering, Spearman’s correlation, GO, KEGG, LASSO Cox regression, and univariate Cox regression analyses. Finally, we constructed a risk prognostic model.Results: We obtained 192 candidate m6A-related genes and 3 m6A regulators, including YTHDF1, YTHDF2, and YTHDC1. The expression of these genes and regulators differed significantly in different stages of HCC. Based on Cox regression analysis, 19 of 98 m6A-related prognostic genes were obtained to construct a risk score model. The 1- and 3-year area under the curves (AUCs) among HCC patients were greater than 0.7. Finally, based on analysis of mutation differences between high- and low-risk score groups, we determined that TP53 had the highest mutation frequency in the high-risk HCC patient group, whereas titin (TTN) had the highest mutation frequency in the low-risk HCC patient group.Conclusion: This study comprehensively analyzed m6A regulators and m6A-related genes through an integrated bioinformatic analysis, including expression, clustering, protein–protein interaction, and prognosis, thus providing novel insights into the roles of m6A regulators and m6A-related genes in HCC.
{"title":"Integration Analysis of m6A Regulators and m6A-Related Genes in Hepatocellular Carcinoma","authors":"Jingdun Xie, Zhenhua Qi, Xiaoling Luo, Fang Yan, W. Xing, W. Zeng, Dongtai Chen, Qiang Li","doi":"10.15212/BIOI-2021-0002","DOIUrl":"https://doi.org/10.15212/BIOI-2021-0002","url":null,"abstract":"\u0000 Background: N6-Methyladenosine (m6A) RNA methylation of eukaryotic mRNA is involved in the progression of various tumors. We aimed to investigate m6A-related genes and m6A regulators in hepatocellular carcinoma (HCC) and their association with prognosis in HCC.Methods: We downloaded liver cancer sample data from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database. A total of 21 m6A regulators and 1258 m6A-related genes were then analyzed by consensus clustering, Spearman’s correlation, GO, KEGG, LASSO Cox regression, and univariate Cox regression analyses. Finally, we constructed a risk prognostic model.Results: We obtained 192 candidate m6A-related genes and 3 m6A regulators, including YTHDF1, YTHDF2, and YTHDC1. The expression of these genes and regulators differed significantly in different stages of HCC. Based on Cox regression analysis, 19 of 98 m6A-related prognostic genes were obtained to construct a risk score model. The 1- and 3-year area under the curves (AUCs) among HCC patients were greater than 0.7. Finally, based on analysis of mutation differences between high- and low-risk score groups, we determined that TP53 had the highest mutation frequency in the high-risk HCC patient group, whereas titin (TTN) had the highest mutation frequency in the low-risk HCC patient group.Conclusion: This study comprehensively analyzed m6A regulators and m6A-related genes through an integrated bioinformatic analysis, including expression, clustering, protein–protein interaction, and prognosis, thus providing novel insights into the roles of m6A regulators and m6A-related genes in HCC.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128766850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial note: A Review on Toxicity and Challenges in Transferability of Surface-functionalized Metallic Nanoparticles from Animal Models to Humans","authors":"","doi":"10.15212/bioi-2022-1001","DOIUrl":"https://doi.org/10.15212/bioi-2022-1001","url":null,"abstract":"<jats:p>\u0000 \u0000 </jats:p>","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"101 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131684095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Lin, Zhixiao Han, Yanni Fu, Xiaoqiu Zhu, Jin Li, Hui Xu, Jing Wen, Fei Wang, M. Guo
In arthroscopic shoulder surgery, general anesthesia (GA) is the common method of anesthesia. Recently, the combined usage of interscalene brachial plexus block with general anesthesia (ISB/GA) was reported to have a lower incidence of adverse side effects than GA alone. However, to date, no study has compared stress and inflammatory responses between these two methods. Since stress and inflammatory responses are critical on intraoperative management and postoperative recovery, we integrated the laboratory and clinical methods and compared the stress and inflammatory factors, such as epinephrine, norepinephrine, glucose, lactate, inflammatory factors tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6), as well as the clinical outcomes to determine whether ISB/GA provides an advantage on stress and inflammatory inhibition. Data showed that ISB/GA resulted in significantly lower epinephrine, norepinephrine, and glucose levels perioperatively. Six hours after operation, the TNF-a and IL-6 levels were also significantly lower in the ISB/GA group. ISB/GA patients had lower blood pressure, a more stable heart rate, lower visual analog scale score, and less opioid consumption during and after surgery. Our results indicate that ISB/GA is a better choice for arthroscopic shoulder surgery, owing to less stress and inflammatory responses during and after operation, which provides better clinical outcomes. Therefore, we recommend ISB/GA as a preferred anesthesia method for arthroscopic shoulder surgery.
{"title":"Combination of Interscalene Brachial Plexus Block with General Anesthesia Attenuates Stress and Inflammatory Response in Arthroscopic Shoulder Surgery","authors":"D. Lin, Zhixiao Han, Yanni Fu, Xiaoqiu Zhu, Jin Li, Hui Xu, Jing Wen, Fei Wang, M. Guo","doi":"10.15212/bioi-2021-0013","DOIUrl":"https://doi.org/10.15212/bioi-2021-0013","url":null,"abstract":"\u0000 In arthroscopic shoulder surgery, general anesthesia (GA) is the common method of anesthesia. Recently, the combined usage of interscalene brachial plexus block with general anesthesia (ISB/GA) was reported to have a lower incidence of adverse side effects than GA alone. However, to date, no study has compared stress and inflammatory responses between these two methods. Since stress and inflammatory responses are critical on intraoperative management and postoperative recovery, we integrated the laboratory and clinical methods and compared the stress and inflammatory factors, such as epinephrine, norepinephrine, glucose, lactate, inflammatory factors tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6), as well as the clinical outcomes to determine whether ISB/GA provides an advantage on stress and inflammatory inhibition. Data showed that ISB/GA resulted in significantly lower epinephrine, norepinephrine, and glucose levels perioperatively. Six hours after operation, the TNF-a and IL-6 levels were also significantly lower in the ISB/GA group. ISB/GA patients had lower blood pressure, a more stable heart rate, lower visual analog scale score, and less opioid consumption during and after surgery. Our results indicate that ISB/GA is a better choice for arthroscopic shoulder surgery, owing to less stress and inflammatory responses during and after operation, which provides better clinical outcomes. Therefore, we recommend ISB/GA as a preferred anesthesia method for arthroscopic shoulder surgery.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115681822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suiwen Ye, W. Zhuang, Yunni Lin, Xiuping Lai, Junyi Chen, Jing Wang, Guoping Zhong, H. Yao, Junyan Wu
Background: As the structure of the human diet changes, the prevalence of hyperuricemia is increasing each year. Hyperuricemia and its comorbidities, such as gout, severely affect quality of life. Moreover, hyperuricemia causes renal impairment and is associated with chronic kidney disease. Topiroxostat, a selective xanthine oxidoreductase inhibitor, has been approved to treat hyperuricemia or gout in Japan. Topiroxostat has shown good tolerance and efficacy in the Japanese population. However, its pharmacokinetic (PK) characteristics, efficacy, and safety in the Chinese population remains unknown.Objective: This trial evaluated the PK profile, safety, efficacy, and food effects of Topiroxostat in healthy Chinese participants.Methods: The major endpoint was determination of the PK profile of Topiroxostat. Topiroxostat concentrations were detected with LC-MS/MS. PK parameters were calculated in Phoenix WinNonlin 8.1. Minor endpoints were safety and efficacy assessments. Assessment of adverse events and safety was performed by clinicians. Plasma uric acid concentration (ΔECmax and ΔAUEC) was determined as the pharmacodynamic index. This study consisted of three arms: single ascending dose (20, 40, and 80 mg, N = 10), multiple dose (80 mg BID, 7 days, N = 10), and food effects (40 mg single dose, fasting-fed cross-over design, N = 10).Results: In the single-ascending-dose arm, Topiroxostat showed rapid absorption and excretion, with Tmax <1.6 h and T1/2 2.49–3.72 h. Additionally, Topiroxostat showed a wide distribution, on the basis of moderate Vz/F (242.8–336.36 L). The main PK parameters Cmax, AUC0-t, and AUC0-C showed a linear relationship with dose (R2 = 0.5146, 0.8416, 0.8386, respectively). In the multiple-dose arm, no significant differences were observed in Cmin on days 3–6 (P = 0.265). No serious adverse events were observed. Regarding efficacy, plasma uric acid levels were controlled to low levels during multiple-dose administration. In the food-effects arm, the fed group showed a lower Cmax than the fasting group (316.00 ± 135.81 vs. 478.40 ± 175.42 ng/mL, P = 0.033) but demonstrated better efficacy (ΔECmax, P < 0.001; ΔAUEC, P < 0.001).Conclusions: Topiroxostat showed rapid absorption and a broad distribution in healthy Chinese adults. Additionally, it showed good safety and tolerance in the Chinese population. Moreover, the pharmacodynamic profile indicated that post cibum administration increased the efficacy of Topiroxostat.
背景:随着人类饮食结构的改变，高尿酸血症的患病率逐年上升。高尿酸血症及其合并症，如痛风，严重影响生活质量。此外，高尿酸血症引起肾脏损害，并与慢性肾脏疾病有关。Topiroxostat是一种选择性黄嘌呤氧化还原酶抑制剂，在日本已被批准用于治疗高尿酸血症或痛风。托吡司他在日本人群中表现出良好的耐受性和疗效。然而，其在中国人群中的药代动力学(PK)特性、疗效和安全性尚不清楚。目的:本试验评估托吡司他在中国健康受试者中的PK谱、安全性、有效性和食用效应。方法:以托吡司他的PK谱测定为主要终点。采用LC-MS/MS法检测托吡司他浓度。在Phoenix WinNonlin 8.1软件中计算PK参数。次要终点是安全性和有效性评估。临床医生对不良事件和安全性进行了评估。测定血浆尿酸浓度(ΔECmax和ΔAUEC)作为药效学指标。本研究分为三组:单次递增剂量(20、40和80 mg, N = 10)、多次递增剂量(80 mg BID, 7天，N = 10)和食物效应(40 mg单次递增剂量，禁食交叉设计，N = 10)。结果:托吡司他在单剂量上升组吸收排泄迅速，Tmax <1.6 h, T1/2为2.49 ~ 3.72 h，分布广泛，Vz/F适中(242.8 ~ 336.36 L)，主要PK参数Cmax、AUC0-t、AUC0-C与剂量呈线性关系(R2分别为0.5146、0.8416、0.8386)。在多剂量组，3-6天Cmin无显著差异(P = 0.265)。未观察到严重不良事件。关于疗效，在多次给药期间血浆尿酸水平被控制在较低水平。在食物效应组中，喂食组的Cmax低于禁食组(316.00±135.81∶478.40±175.42 ng/mL, P = 0.033)，但效果更好(ΔECmax, P < 0.001;Δauec, p < 0.001)。结论:托吡司他在中国健康成人体内吸收迅速，分布广泛。此外，它在中国人群中显示出良好的安全性和耐受性。此外，药效学分析表明，西布仑给药后增加了托吡司他的疗效。
{"title":"A Phase I, Randomized, Single-Ascending-Dose, Multiple-Dose, and Food-Effect Trial of the Safety, Efficacy, and Pharmacokinetics of Topiroxostat in Healthy Chinese Participants","authors":"Suiwen Ye, W. Zhuang, Yunni Lin, Xiuping Lai, Junyi Chen, Jing Wang, Guoping Zhong, H. Yao, Junyan Wu","doi":"10.15212/bioi-2022-0006","DOIUrl":"https://doi.org/10.15212/bioi-2022-0006","url":null,"abstract":"\u0000 Background: As the structure of the human diet changes, the prevalence of hyperuricemia is increasing each year. Hyperuricemia and its comorbidities, such as gout, severely affect quality of life. Moreover, hyperuricemia causes renal impairment and is associated with chronic kidney disease. Topiroxostat, a selective xanthine oxidoreductase inhibitor, has been approved to treat hyperuricemia or gout in Japan. Topiroxostat has shown good tolerance and efficacy in the Japanese population. However, its pharmacokinetic (PK) characteristics, efficacy, and safety in the Chinese population remains unknown.Objective: This trial evaluated the PK profile, safety, efficacy, and food effects of Topiroxostat in healthy Chinese participants.Methods: The major endpoint was determination of the PK profile of Topiroxostat. Topiroxostat concentrations were detected with LC-MS/MS. PK parameters were calculated in Phoenix WinNonlin 8.1. Minor endpoints were safety and efficacy assessments. Assessment of adverse events and safety was performed by clinicians. Plasma uric acid concentration (ΔECmax and ΔAUEC) was determined as the pharmacodynamic index. This study consisted of three arms: single ascending dose (20, 40, and 80 mg, N = 10), multiple dose (80 mg BID, 7 days, N = 10), and food effects (40 mg single dose, fasting-fed cross-over design, N = 10).Results: In the single-ascending-dose arm, Topiroxostat showed rapid absorption and excretion, with Tmax <1.6 h and T1/2 2.49–3.72 h. Additionally, Topiroxostat showed a wide distribution, on the basis of moderate Vz/F (242.8–336.36 L). The main PK parameters Cmax, AUC0-t, and AUC0-C showed a linear relationship with dose (R2 = 0.5146, 0.8416, 0.8386, respectively). In the multiple-dose arm, no significant differences were observed in Cmin on days 3–6 (P = 0.265). No serious adverse events were observed. Regarding efficacy, plasma uric acid levels were controlled to low levels during multiple-dose administration. In the food-effects arm, the fed group showed a lower Cmax than the fasting group (316.00 ± 135.81 vs. 478.40 ± 175.42 ng/mL, P = 0.033) but demonstrated better efficacy (ΔECmax, P < 0.001; ΔAUEC, P < 0.001).Conclusions: Topiroxostat showed rapid absorption and a broad distribution in healthy Chinese adults. Additionally, it showed good safety and tolerance in the Chinese population. Moreover, the pharmacodynamic profile indicated that post cibum administration increased the efficacy of Topiroxostat.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124533220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. M. Thomas, Sandra Lisa Gumpil, S. F. Simat, V. Subbiah
Human amnion is a favorable potential source of mesenchymal stem cells (MSC) for future cell-therapy-based clinical applications, because of the painless collection procedure and easy accessibility of the placenta. Human amnion mesenchymal stem cells (hAMCs) have multilineage differentiation ability and high proliferation ability, are non-tumorigenic and have a relatively low risk of rejection after transplantation. Given the beneficial properties of hAMCs, herein, we review the isolation methods and characteristics of hAMCs. Furthermore, we summarize current hAMC applications and preservation methods.
{"title":"Isolation, Characteristics, Differentiation and Exploitation of Human Amnion Mesenchymal Stem Cells","authors":"F. M. Thomas, Sandra Lisa Gumpil, S. F. Simat, V. Subbiah","doi":"10.15212/bioi-2022-0017","DOIUrl":"https://doi.org/10.15212/bioi-2022-0017","url":null,"abstract":"\u0000 Human amnion is a favorable potential source of mesenchymal stem cells (MSC) for future cell-therapy-based clinical applications, because of the painless collection procedure and easy accessibility of the placenta. Human amnion mesenchymal stem cells (hAMCs) have multilineage differentiation ability and high proliferation ability, are non-tumorigenic and have a relatively low risk of rejection after transplantation. Given the beneficial properties of hAMCs, herein, we review the isolation methods and characteristics of hAMCs. Furthermore, we summarize current hAMC applications and preservation methods.\u0000","PeriodicalId":431549,"journal":{"name":"BIO Integration","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116986013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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