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The FGF metabolic axis

Xiaokun Li

《医学前沿(英文)》 2019年 第13卷 第5期   页码 511-530 doi: 10.1007/s11684-019-0711-y

摘要: Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.

关键词: FGF19     FGF21     FGF23     FGFR     metabolism     endocrine     Klotho    

FGF23 associated bone diseases

null

《医学前沿(英文)》 2013年 第7卷 第1期   页码 65-80 doi: 10.1007/s11684-013-0254-6

摘要:

Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

关键词: fibroblast growth factor 23     FGF receptor     phosphate metabolism     Klotho     bone disease    

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

《医学前沿(英文)》 2022年 第16卷 第6期   页码 896-908 doi: 10.1007/s11684-022-0944-z

摘要: Fibroblast growth factor 13 (FGF13) is aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in the development of acute myeloid leukemia (AML) and emphasize its associations with bone marrow niches. Results showed that FGF13 was lowly expressed in patients with AML and that its elevated expression was related to prolonged overall survival (OS). Univariate and multivariate Cox regression analyses identified FGF13 as an independent prognostic factor. A prognostic nomogram integrating FGF13 and clinicopathologic variables was constructed to predict 1-, 3-, and 5-year OS. Gene mutation and functional analyses indicated that FGF13 was not associated with AML driver mutations but was related to bone marrow niches. As for immunity, FGF13 was remarkably associated with T cell count, immune checkpoint genes, and cytokines. In addition, FGF13 overexpression substantially inhibited the growth and significantly induced the early apoptosis of AML cells. The xenograft study indicated that FGF13 overexpression prolonged the survival of recipient mice. Overall, FGF13 could serve as an independent prognostic factor for AML, and it was closely related to the bone marrow microenvironment.

关键词: acute myeloid leukemia     FGF13     prognosis     immune-related genes     bone marrow niches    

Influence of retinoic acid on TBX1 expression in myocardial cells induced by Shh and Fgf8

Miao LIU, Xiaoyan WU, Jiawei XU, Runming JIN

《医学前沿(英文)》 2009年 第3卷 第1期   页码 61-66 doi: 10.1007/s11684-009-0007-8

摘要: The aim of this study was to explore the regulatory mechanism of retinoic acid (RA) on the TBX1 gene expression in myocardial cells. Ventricular cardiocytes were isolated from neonatal rats and cultured, and then treated with different concentrations of retinoic acid. The expression of Shh and Fgf8 at mRNA and protein levels in neonatal rat myocardial cells were measured by using RT-PCR and Western blot technique, respectively. There was basal expression of Shh and Fgf8 in the control group. When treated with 3×10 mol/L RA, we observed that the expression of Shh mRNA and protein in neonatal rat myocardial cells were up-regulated by 1.51 ( <0.05) and 1.10 times ( <0.05), respectively. In comparison with the control group, under the concentration of 5×10 mol/L RA, they were up-regulated by 2.21 ( <0.05) and 2.38 times ( <0.05) individually. Meanwhile, we could detect that the expression of Fgf8 mRNA and protein were up-regulated by 2.50 times ( <0.05) and 80% ( <0.05) separately compared with the control group after stimulation of 3×10 mol/L RA, and they were up-regulated by 3.48 ( <0.05) and 2.04 times ( <0.05) individually after stimulation of 5×10 mol/L RA. The results indicated that RA could induce the expression of Shh and Fgf8 in neonatal rat myocardial cells. At the same time, it has shown that Shh and Fgf8 were involved in the regulation process of RA on TBX1 expression.

关键词: retinoic acid     Tbx1 protein     Shh protein     Fgf8 protein    

Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

《医学前沿(英文)》 2013年 第7卷 第1期   页码 25-30 doi: 10.1007/s11684-013-0244-8

摘要:

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

关键词: FGF21     metabolism     pharmacology     physiology     clinical relevance    

A review of the safety and efficacy of current COVID-19 vaccines

《医学前沿(英文)》 2022年 第16卷 第1期   页码 39-55 doi: 10.1007/s11684-021-0893-y

摘要: Vaccination is the most effective and feasible way to contain the coronavirus disease 2019 (COVID-19) pandemic. The rapid development of effective COVID-19 vaccines is an extraordinary achievement. This study reviewed the efficacy/effectiveness, immunogenicity, and safety profile of the 12 most progressed COVID-19 vaccines and discussed the challenges and prospects of the vaccine-based approaches in a global crisis. Overall, most of the current vaccines have shown safety and efficacy/effectiveness during actual clinical trials or in the real-world studies, indicating a development of pandemic control. However, many challenges are faced by pandemic control in terms of maximizing the effect of vaccines, such as rapid vaccine coverage, strategies to address variants with immune escape capability, and surveillance of vaccine safety in the medium- and long-terms.

关键词: COVID-19     SARS-CoV-2     vaccine     safety     efficacy     effectiveness     immunogenicity    

Innovation-driven trend shaping COVID-19 vaccine development in China

《医学前沿(英文)》 doi: 10.1007/s11684-023-1034-6

摘要: Confronted with the coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

关键词: SARS-CoV-2     COVID-19 vaccine     vaccine development    

SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic

《医学前沿(英文)》 2022年 第16卷 第2期   页码 185-195 doi: 10.1007/s11684-021-0913-y

摘要: The record speed at which Chinese scientists identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shared its genomic sequence with the world, has greatly facilitated the development of coronavirus disease (COVID-19) diagnostics, drugs, and vaccines. It is unprecedented in pandemic control history to develop a dozen successful vaccines in the first year and to immunize over half of the global population in the second year, due to the efforts of the scientific community, biopharmaceutical industry, and regulatory agencies worldwide. The challenges are both great and multidimensional due to the rapid emergence of virus variants and waning of vaccine immunity. Vaccination strategies need to adapt to these challenges to keep population immunity above the herd immunity threshold, by increasing vaccine coverage, especially for older adults and young people, and providing timely booster doses with homologous or heterologous vaccine boosts. Further research should be undertaken to develop more effective vaccines against SARS-CoV-2 variants and to understand the best prime-boost vaccine combinations and immunization strategies to provide sufficient and sustainable immune protection against COVID-19.

关键词: COVID-19     pandemics     SARS-CoV-2     vaccination    

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

《医学前沿(英文)》 doi: 10.1007/s11684-023-1010-1

摘要: Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

关键词: exosomes induce activation     impair function CD19     exosomal CD19 antigen    

Traditional Chinese medicine for combating COVID-19

Kaixian Chen, Hongzhuan Chen

《医学前沿(英文)》 2020年 第14卷 第5期   页码 529-532 doi: 10.1007/s11684-020-0802-9

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19

《医学前沿(英文)》 doi: 10.1007/s11684-023-1040-8

摘要: Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients’ symptoms, promote organ function recovery, boost the quality of patients’ life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.

关键词: traditional Chinese medicine     COVID-19     SARS-CoV-2     clinical evidence-based study     mechanism     integrated traditional Chinese and Western medicine    

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

《医学前沿(英文)》 2022年 第16卷 第1期   页码 139-149 doi: 10.1007/s11684-021-0835-8

摘要: The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

关键词: B-cell acute lymphoblastic leukemia     bispecific antibody     trispecific antibody     CD19     CD20    

COVID-19: why not learn from the past?

《医学前沿(英文)》 2021年 第15卷 第5期   页码 776-781 doi: 10.1007/s11684-021-0883-0

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center

《医学前沿(英文)》 2022年 第16卷 第1期   页码 111-125 doi: 10.1007/s11684-021-0854-5

摘要: The coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (≥245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528–29.523; P <0.001) and coagulation-related biomarker D-dimer (≥0.5 μg/mL, HR= 4.321, 95% CI= 1.443–12.939; P = 0.009) and decreased albumin (<35 g/L, HR= 0.131, 95% CI= 0.048–0.361; P <0.001) and albumin/globulin ratio (<1.5, HR= 0.123, 95% CI= 0.017–0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

关键词: COVID-19     chronic hepatitis B     liver injury     coagulation dysfunction    

Repercussions of COVID-19 pandemic on solid waste generation and management strategies

《环境科学与工程前沿(英文)》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1407-5

摘要:

• Implication of COVID-19 on medical waste and MSW generation is studied.

关键词: COVID-19     Medical waste     Personal protective equipment     Municipal solid waste     Waste management    

标题 作者 时间 类型 操作

The FGF metabolic axis

Xiaokun Li

期刊论文

FGF23 associated bone diseases

null

期刊论文

FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches

期刊论文

Influence of retinoic acid on TBX1 expression in myocardial cells induced by Shh and Fgf8

Miao LIU, Xiaoyan WU, Jiawei XU, Runming JIN

期刊论文

Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

期刊论文

A review of the safety and efficacy of current COVID-19 vaccines

期刊论文

Innovation-driven trend shaping COVID-19 vaccine development in China

期刊论文

SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic

期刊论文

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

期刊论文

Traditional Chinese medicine for combating COVID-19

Kaixian Chen, Hongzhuan Chen

期刊论文

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19

期刊论文

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

期刊论文

COVID-19: why not learn from the past?

期刊论文

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center

期刊论文

Repercussions of COVID-19 pandemic on solid waste generation and management strategies

期刊论文