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Metabonomic study of the biochemical profiles of heterozygous myostatin knockout swine

Jianxiang XU,Dengke PAN,Jie ZHAO,Jianwu WANG,Xiaohong HE,Yuehui MA,Ning LI

《农业科学与工程前沿（英文）》 2015年 第2卷 第1期   页码 90-99 doi: 10.15302/J-FASE-2015045

摘要： Myostatin is a transforming growth factor-β family member that normally acts to limit skeletal muscle growth. Myostatin gene ( ) knockout (KO) mice show possible effects for the prevention or treatment of metabolic disorders such as obesity and type 2 diabetes. We applied chromatography and mass spectrometry based metabonomics to assess system-wide metabolic response of heterozygous KO ( ) swine. Most of the metabolic data for swine were similar to the data for wild type (WT) control swine. There were, however, metabolic changes related to fatty acid metabolism, glucose utilization, lipid metabolism, as well as BCAA catabolism caused by monoallelic depletion.The statistical analyses suggested that: (1) most metabolic changes were not significant in swine compared to WT swine; (2) only a few metabolic properties were significantly different between KO and WT swine, especially for lipid metabolism. Significantly, these minor changes were most evident in female KO swine and suggested differences in gender sensitivity to myostatin.

关键词： myostatin     transforming growth factor-β family     skeletal muscle     metabolic disorders     chromatography     mass spectrometry     metabonomics    

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Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders of

Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang

《医学前沿（英文）》 2020年 第14卷 第4期   页码 498-505 doi: 10.1007/s11684-020-0791-8

摘要： Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. “Chaining” inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.

关键词： disorders of sex development (DSD)     intelligent diagnosis     dynamic uncertain causality graph    

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Therapeutic effects of thalidomide in hematologic disorders: a review

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 290-300 doi: 10.1007/s11684-013-0277-z

摘要：

The extensive autoimmune, anti-inflammatory, and anticancer applications of thalidomide have inspired a growing number of studies and clinical trials. As an inexpensive agent with relatively low toxicity, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases. We review its therapeutic effects in hematology, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graft-versus-host disease. Most studies have shown satisfactory results, although several have reported the opposite. Aside from optimal outcomes, the toxicities and adverse effects of thalidomide should also be examined. The current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur, although more studies should be devoted to this aspect. With appropriate safeguards, thalidomide may benefit patients suffering from a broad variety of disorders, particularly refractory and resistant diseases.

关键词： thalidomide     multiple myeloma     lymphoma    

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New insights into different surfactants’ impacts on sludge fermentation: Focusing on the particular metabolic

《环境科学与工程前沿（英文）》 2022年 第16卷 第8期 doi: 10.1007/s11783-022-1527-6

摘要：

• The promoting effects for VFA generation follow the order of APG>SDBS>HTAB.

关键词： Waste activated sludge (WAS)     Volatile fatty acids (VFA)     Surfactant types     Functional microorganisms     Metabolic activity upregulation    

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Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

《医学前沿（英文）》 2019年 第13卷 第2期   页码 138-151 doi: 10.1007/s11684-018-0627-y

摘要： As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

关键词： mesenchymal stem cell     clinical transition     immune disorders    

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function

《医学前沿（英文）》 doi: 10.1007/s11684-023-1006-x

摘要： Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141p.Trp90*/p.Trp90* mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder     autosomal recessive intellectual disability     consanguinity     spastic paraplegia     hearing loss     TMEM141    

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Metabolic hypertension: concept and practice

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 201-206 doi: 10.1007/s11684-013-0264-4

摘要：

Hypertension is a serious public health problem worldwide. More than 60% of the risk factors for hypertension are associated with metabolic disturbances. Metabolic abnormalities increase the risk for hypertension and cause high blood pressure. Improving metabolic disturbances is beneficial for hypertension treatment. Due to the importance of metabolic abnormalities in the pathogenesis of hypertension, we propose a concept of metabolic hypertension. In this review, we discuss and review the clinical types, pathogenesis, risk evaluation and management of metabolic hypertension. Elucidation of the mechanism of metabolic hypertension should facilitate the design of novel pharmacotherapeutics and dedicated antihypertensive manipulations.

关键词： hypertension     cardiometabolic risk factors     metabolic abnormalities    

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation     obesity     cytokine     energy expenditure     insulin resistance    

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electron transfer and its application in dictating routes of biochemical processes associated with metabolic

《医学前沿（英文）》 2021年 第15卷 第5期   页码 679-692 doi: 10.1007/s11684-021-0866-1

摘要： Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.

关键词： metabolic reprogramming     potential of electron transfer     cell proliferation     aerobic glycolysis     cancer metabolism    

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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    

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Metformin and metabolic diseases: a focus on hepatic aspects

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 173-186 doi: 10.1007/s11684-015-0384-0

摘要：

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

关键词： metformin     diabetes     hepatic steatosis     inflammatory response     insulin resistance    

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denitrification system with short-term pyridine exposure: Process capability, inhibition kinetics and metabolic

《环境科学与工程前沿（英文）》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1433-3

摘要：

• Short-term effect of the pyridine exposure on the SAD process was investigated.

关键词： Anammox     Inhibition     Metabolic pathway     Microbial community     Pyridine     SAD    

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Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners: A metabolic

《环境科学与工程前沿（英文）》 2022年 第16卷 第9期 doi: 10.1007/s11783-022-1548-1

摘要：

• Water-dispersible nano-pollutions exhibit type-specific toxic effects on E. coli.

关键词： Nano-toxicity     Nano-plastics     Quantum dots     Microbial metabolite     Metabolic dysregulation    

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Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

《医学前沿（英文）》 2019年 第13卷 第4期   页码 471-481 doi: 10.1007/s11684-019-0686-8

摘要： Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus . Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics     tacrolimus     glucose disorders     microbiome    

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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    

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标题 作者 时间 类型 操作

Metabonomic study of the biochemical profiles of heterozygous myostatin knockout swine

Jianxiang XU,Dengke PAN,Jie ZHAO,Jianwu WANG,Xiaohong HE,Yuehui MA,Ning LI

期刊论文

Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders of

Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang

期刊论文

Therapeutic effects of thalidomide in hematologic disorders: a review

null

期刊论文

New insights into different surfactants’ impacts on sludge fermentation: Focusing on the particular metabolic

期刊论文

Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

期刊论文

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function

期刊论文

Metabolic hypertension: concept and practice

null

期刊论文

Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

期刊论文

electron transfer and its application in dictating routes of biochemical processes associated with metabolic

期刊论文

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

null

期刊论文

Metformin and metabolic diseases: a focus on hepatic aspects

null

期刊论文

denitrification system with short-term pyridine exposure: Process capability, inhibition kinetics and metabolic

期刊论文

Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners: A metabolic

期刊论文

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

期刊论文

The FGF metabolic axis

Xiaokun Li

期刊论文