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Leptin signaling and leptin resistance

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 207-222 doi: 10.1007/s11684-013-0263-5

摘要：

Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

关键词： leptin signaling     leptin receptor     energy balance     leptin resistance     obesity    

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Construction and identification of lentiviral RNA interference vector of rat leptin receptor gene

Zhengjuan LIU, Jie BIAN, Yuchuan WANG, Yongli ZHAO, Dong YAN, Xiaoxia WANG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 57-60 doi: 10.1007/s11684-009-0003-z

摘要： Leptin resistance is a main mechanism of acquired childhood obesity, and the suppression of long form of leptin receptor (OBRb) gene expression in diet-induced obese rats indicates that the down-regulation of OBRb gene expression plays a pivotal role in the mechanism of leptin resistance. The aim of the present study was to construct the lentiviral RNA interference (RNAi) vector of rat OBRb gene and evaluate the effects of siRNA on silencing OBRb gene expression. The target sequence of siRNA-OBRb was designed, and the complementary DNA containing both sense and antisense oligonucleotides was synthesized. After phosphorylation and annealing, these double-stranded DNA was cloned to pRNA-lentivector-VGFP to construct pRNA-Lenti-OBRb-VGFP recombinants with U6-containing promoter, target sequence and Poly III terminator. Then, the products were confirmed by electrophoresis and sequencing analysis, and the effects of RNAi on reducing gene expression were further confirmed by real-time polymerase chain reaction in transfected rat glioma cells expressing OBRb. The target sequence of siRNA-OBRb was successfully cloned to pRNA-lentivector-VGFP, and the RNAi protocol specifically reduced the expression of OBRb mRNA by approximately 80% compared with controls in transfected rat glioma cells. The successful construction of rat lentivirus vectors expressing OBRb-specific shRNA may be useful for further investigation .

关键词： receptors     leptin     RNA interference     lentivirus vector    

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The change of serum leptin and its relationship with platelet membrane glycoprotein Ib in patients with

XIA Dasheng, SONG Yanqiu, LI Chao, ZHANG Feng, WEI Minxin

《医学前沿（英文）》 2007年 第1卷 第4期   页码 352-355 doi: 10.1007/s11684-007-0067-6

摘要： The aim of this paper was to investigate the change of serum leptin and its relationship with platelet membrane glycoprotein Ib (GP Ib) in patients with coronary heart disease (CHD). The enrolled included 50 patients with CHD (CHD group) and 30 patients without CHD (control group) who were diagnosed by coronary angiography. The positive percentage and the average fluorescence intensity of platelet membrane GP Ib were detected by full-blood flow cytometry. Serum leptin was detected by enzyme linked immunosorbent assay. The positive percentage and the average fluorescence intensity of platelet membrane GP Ib in the CHD group were significantly lower than those in the control group (<0.05). After correcting the differences of systolic blood pressure, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting glucose, PPBS, fasting insulin and quantitative insulin sensitive index, serum leptin level in the CHD group was significantly higher than that in the control group (<0.05). Single factor correlative analysis revealed that serum leptin in CHD patients was negatively correlated with the average fluorescence intensity of platelet membrane GP Ib (<0.05). Multifactorial stepwise regression analysis showed that serum leptin in CHD patients was independently negatively correlated with the average fluorescence intensity of platelet membrane GP Ib (<0.05). Logistic analysis demonstrated that serum leptin was independently correlated with the risk of CHD (<0.05). Hyperleptinemia was verified in CHD patients. The increase of serum leptin could affect blood platelet activation. Hyperleptinemia may play an important role in the pathogenesis of CHD.
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Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels

LIN Ji, YAN Guangtao, HAO Xiuhua, ZHANG Kai, GAO Xiaoning, LIAO Jie

《医学前沿（英文）》 2007年 第1卷 第1期   页码 87-92 doi: 10.1007/s11684-007-0017-3

摘要： The aim of this paper is to explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and to examine the roles of leptin and orexin-A in acute inflammatory responses. An intestinal I/R injury model of rats was made; the rats were grouped according to the time of after 60 min ischemia. Radioimmunoassay was employed to detect the levels of leptin in serum and adipose tissue and orexin-A levels in plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was used to detect mRNA expressions of adipose leptin and hypothalamus orexin-A. Compared with the levels before the injury, serum leptin in 60 min ischemia/30 min reperfusion (I60´R30´) group decreased and that of I60´R360´ group increased. Compared with sham-operation group (sham group) after injury, serum leptin level of I60´R360´ group increased, adipose leptin levels of I60´R30´ and I60´R90´ decreased, and adipose leptin in I60´R360´ group increased. After the injury, adipose leptin mRNA expressions of I60´R30´, I60´R240´ and I60´R360´ increased, whereas that of I60´R150´ group decreased as compared with the sham group. There was no significant difference in the protein levels of orexin-A, either between plasma and hypothalamus or between pre- and post-I/R injury. Compared with sham group, hypothalamus orexin-A mRNA expressions of I60´R30´ and I60´R90´ decreased gradually after the injury, with that of I60´R150´ group reaching the lowest, and those of I60´R240´ and I60´R360´ recovering gradually, although they were still significantly lower than that of sham group. Leptin and orexin-A respond to intestinal I/R injury in a time-dependent manner, with leptin responding more quickly than orexin-A does, and both of them may contribute to the metabolic disorders in acute inflammation.

关键词： significant difference     intestinal I/R     transcriptase-polymerase     metabolic     central secretory    

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Prevalence of antifolate drug resistance markers in in China

《医学前沿（英文）》 2022年 第16卷 第1期   页码 83-92 doi: 10.1007/s11684-021-0894-x

摘要： The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax and antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

关键词： drug resistance     antifolates     molecular markers     Plasmodium vivax     China    

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Metagenomic analysis on resistance genes in water and microplastics from a mariculture system

《环境科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 4-4 doi: 10.1007/s11783-021-1438-y

摘要：

Microplastics existing widely in different matrices have been regarded as a reservoir for emerging contaminants. Mariculture systems have been observed to host microplastics and antibiotic resistance genes (ARGs). However, more information on proliferation of ARGs and metal resistance genes (MRGs) in mariculture system at the presence of microplastics is needed.

关键词： Antibiotic resistance genes     Metal resistance genes     Metagenomic analysis     Microplastics     Mariculture    

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Glyco-functionalised quantum dots and their progress in cancer diagnosis and treatment

Jayshree Ashree, Qi Wang, Yimin Chao

《化学科学与工程前沿（英文）》 2020年 第14卷 第3期   页码 365-377 doi: 10.1007/s11705-019-1863-7

摘要： Despite all major breakthroughs in recent years of research, we are still unsuccessful to effectively diagnose and treat cancer that has express and metastasizes. Thus, the development of a novel approach for cancer detection and treatment is crucial. Recent progress in Glyconanotechnology has allowed the use of glycans and lectins as bio-functional molecules for many biological and biomedical applications. With the known advantages of quantum dots (QDs) and versatility of carbohydrates and lectins, Glyco-functionalised QD is a new prospect in constructing biomedical imaging platform for cancer behaviour study as well as treatment. In this review, we aim to describe the current utilisation of Glyco-functionalised QDs as well as their future prospective to interpret and confront cancer.

关键词： carbohydrate     leptin     glyco-functionalised QD     bioimaging     cancer diagnosis and treatment    

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Taking advantage of drug resistance, a new approach in the war on cancer

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 490-495 doi: 10.1007/s11684-018-0647-7

摘要：

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer     drug resistance     genetic screens     senescence     targeted therapy    

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Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

《医学前沿（英文）》 2022年 第16卷 第5期   页码 701-713 doi: 10.1007/s11684-022-0951-0

摘要： A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.

关键词： acquired resistance     EGFR inhibitor     apoptosis     lung cancer    

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Transmission of antibiotic resistance genes in agroecosystems: an overview

Jizheng HE, Zhenzhen YAN, Qinglin CHEN

《农业科学与工程前沿（英文）》 2020年 第7卷 第3期   页码 329-332 doi: 10.15302/J-FASE-2020333

摘要：

The use of antibiotics in human medicine and animal husbandry has resulted in the continuous release of antibiotics into the environment, which imposes high selection pressure on bacteria to develop antibiotic resistance. The spread and aggregation of antibiotic resistance genes (ARGs) in multidrug-resistant pathogens is one of the most intractable clinical challenges. Numerous studies have been conducted to profile the patterns of ARGs in agricultural ecosystems, as this is closely related to human health and wellbeing. This paper provides an overview of the transmission of ARGs in agricultural ecosystems resulting from the application of animal manures and other organic amendments. The future need to control and mitigate the spread of antibiotic resistance in agricultural ecosystems is also discussed, particularly from a holistic perspective, and requires multiple sector efforts to translate fundamental knowledge into effective strategies.

关键词： agroecosystem     antibiotic resistance     public health     soil-plant system    

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swine manure with sulfamethoxazole and norfloxacin: Dynamics of microbial communities and evolution of resistance

《环境科学与工程前沿（英文）》 2021年 第15卷 第5期 doi: 10.1007/s11783-020-1342-x

摘要：

• SMX addition had negative effect on acetoclastic methanogens in mesophilic AD.

关键词： Pig manure     Antibiotics     Anaerobic digestion     Resistance genes     Microbial community    

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Degradation of extracellular genomic, plasmid DNA and specific antibiotic resistance genes by chlorination

Menglu Zhang, Sheng Chen, Xin Yu, Peter Vikesland, Amy Pruden

《环境科学与工程前沿（英文）》 2019年 第13卷 第3期 doi: 10.1007/s11783-019-1124-5

摘要：

Extracellular DNA structure damaged by chlorination was characterized.

Integrity of extracellular ARG genetic information after chlorination was determined.

Typical chlorine doses will likely effectively diminish extracellular DNA and ARGs.

Plasmid DNA/ARGs were less readily broken down than genomic DNA.

The Bioanalyzer methodology effectively documented damage incurred to DNA.

关键词： Antibiotic resistance     Antibiotic resistance genes (ARGs)     Extracellular DNA/ARGs     Chlorination    

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Insulin resistance and the metabolism of branched-chain amino acids

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 53-59 doi: 10.1007/s11684-013-0255-5

摘要：

Insulin resistance (IR) is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders. IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network. Branched-chain amino acids (BCAAs), namely valine, leucine and isoleucine, are among the nine essential amino acids, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency. Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight, it is only recently that BCAAs are found to be closely associated with IR. This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

关键词： branched-chain amino acids     leucine     isoleucine     valine     insulin resistance    

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Immunometabolism: a new dimension in immunotherapy resistance

《医学前沿（英文）》 2023年 第17卷 第4期   页码 585-616 doi: 10.1007/s11684-023-1012-z

摘要： Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

关键词： immune cell     immunometabolism     metabolic reprogramming     immunotherapy     resistance     tumor microenvironment     immune checkpoint inhibitor    

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Characteristics of two transferable aminoglycoside resistance plasmids in

Chengjun Pu, Xiaoyan Gong, Ying Sun

《环境科学与工程前沿（英文）》 2019年 第13卷 第3期 doi: 10.1007/s11783-019-1119-2

摘要：

pRKZ3 is a non-conjugative IncQ plasmid, while pKANJ7 is a conjugative IncX plasmid.

The optimal mating time of pKANJ7 varied under different conditions.

Both of the two transferable ARPs had little impact on the growth of their hosts.

A relatively high level of fitness cost was observed for pKANJ7.

The fitness cost of ARPs depended on their hosts.

关键词： Escherichia coli     Characteristics     Aminoglycoside resistance plasmids     Transfer     Persistence    

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标题 作者 时间 类型 操作

Leptin signaling and leptin resistance

null

期刊论文

Construction and identification of lentiviral RNA interference vector of rat leptin receptor gene

Zhengjuan LIU, Jie BIAN, Yuchuan WANG, Yongli ZHAO, Dong YAN, Xiaoxia WANG

期刊论文

The change of serum leptin and its relationship with platelet membrane glycoprotein Ib in patients with

XIA Dasheng, SONG Yanqiu, LI Chao, ZHANG Feng, WEI Minxin

期刊论文

Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels

LIN Ji, YAN Guangtao, HAO Xiuhua, ZHANG Kai, GAO Xiaoning, LIAO Jie

期刊论文

Prevalence of antifolate drug resistance markers in in China

期刊论文

Metagenomic analysis on resistance genes in water and microplastics from a mariculture system

期刊论文

Glyco-functionalised quantum dots and their progress in cancer diagnosis and treatment

Jayshree Ashree, Qi Wang, Yimin Chao

期刊论文

Taking advantage of drug resistance, a new approach in the war on cancer

null

期刊论文

Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

期刊论文

Transmission of antibiotic resistance genes in agroecosystems: an overview

Jizheng HE, Zhenzhen YAN, Qinglin CHEN

期刊论文

swine manure with sulfamethoxazole and norfloxacin: Dynamics of microbial communities and evolution of resistance

期刊论文

Degradation of extracellular genomic, plasmid DNA and specific antibiotic resistance genes by chlorination

Menglu Zhang, Sheng Chen, Xin Yu, Peter Vikesland, Amy Pruden

期刊论文

Insulin resistance and the metabolism of branched-chain amino acids

null

期刊论文

Immunometabolism: a new dimension in immunotherapy resistance

期刊论文

Characteristics of two transferable aminoglycoside resistance plasmids in

Chengjun Pu, Xiaoyan Gong, Ying Sun

期刊论文