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共33条结果
  • 1.

    【2hr】Connexin-43 Enhances the Redesigned Cytosine Deaminase Activity for Suicide Gene Therapy in Human Breast Cancer Cells

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    机译 连接蛋白43增强了人乳腺癌细胞自杀基因治疗的重新设计的胞嘧啶脱氨酶活性。
    摘要：Background:Escherichia coli cytosine deaminase (CD) converts 5-fluorocytosine (5-FC), a prodrug, into 5-fluorouracil (5-FU), a chemotherapeutic drug. However, the poor binding affinity of CD towards 5-FC as compared to the natural substrate cytosine, limits its application towards a successful suicide gene therapy. Although F186W mutant was developed to enhance the effect of wild-type CD, still scope for its improvement remains to further minimize the dose-dependent cytotoxicity of the drugs. Hence, in this study, we employ the anti-tumour attribute of the gap junction forming protein connexin-43 (Cx43) in conjunction with CD or F186W mutant.
  • 2.

    【2hr】The Role of Insulin-Like Growth Factors and Insulin-Like GrowthFactor–Binding Proteins in the Nervous System

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    机译 胰岛素样生长因子和胰岛素样生长的作用神经系统中的因子结合蛋白
    摘要：The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.
  • 3.

    【2hr】A High Creatine Kinase Concentration Might Be a Sign of McArdle Disease in Patient With Type 1 Diabetes

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    机译 肌酸激酶浓度高可能是1型糖尿病患者McArdle病的征兆
    摘要：Type 1 diabetes (the pancreas producing little or no insulin) is usually diagnosed in children and young adults and was previously known as juvenile diabetes. McArdle disease is a common metabolic defect caused by an inherited deficit of myophosphorylase. These 2 diseases might have some clinical heterogeneity. Here, we discuss a McArdle disease case where insulin-dependent diabetes overshadows its early diagnosis. In this case, an insulin-dependent 22-year-old female patient with diabetes mellitus had been on diabetes treatment for 15 years. Although her blood glucose was regulated, her anamnesis showed that muscle weakness, fatigue, cramps or myalgia never healed. Based on her anamnesis, the patient was asked to take a nonischemic forearm exercise test, which revealed significant elevation in levels of creatine kinase (5968-7906 U/L), but no increase was found in lactate concentration, but a slight increase in ammonia concentration (not statistically significant) at the end of the test made us consider McArdle disease. A genetic test was done to confirm this possibility. A homozygous c.2128_2130delTTC/p.Phe710del mutation was detected in the examination of exons of the PYGM gene, which confirmed the diagnosis of McArdle disease in our patient. According to the data, this is a rare case of McArdle disease with type 1 diabetes. During treatment for diabetes, if the above-mentioned symptoms are present in a patient, and especially if the patient’s creatine kinase concentration is high, muscle diseases should be suspected. Therefore, we suggest that this case report will provide new insight to clinicians on metabolic defects in this disease and increase the patient comfort. In such cases, an early diagnosis should reduce health costs.
  • 4.

    【2hr】Aerococcus urinae and Globicatellasanguinis Persist in Polymicrobial Urethral Catheter BiofilmsExamined in Longitudinal Profiles at the Proteomic Level

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    机译 小球菌和球菌sanguinis坚持使用微生物尿道导管生物膜在蛋白质组学水平上检查纵向概况
    摘要：Aerococcus urinae (Au) and Globicatella sanguinis (Gs) are gram-positive bacteria belonging to the family Aerococcaceae and colonize the human immunocompromised and catheterized urinary tract. We identified both pathogens in polymicrobial urethral catheter biofilms (CBs) with a combination of 16S rDNA sequencing, proteomic analyses, and microbial cultures. Longitudinal sampling of biofilms from serially replaced catheters revealed that each species persisted in the urinary tract of a patient in cohabitation with 1 or more gram-negative uropathogens. The Gs and Au proteomes revealed active glycolytic, heterolactic fermentation, and peptide catabolic energy metabolism pathways in an anaerobic milieu. A few phosphotransferase system (PTS)–based sugar uptake and oligopeptide ABC transport systems were highly expressed, indicating adaptations to the supply of nutrients in urine and from exfoliating squamous epithelial and urothelial cells. Differences in the Au vs Gs metabolisms pertained to citrate lyase and utilization and storage of glycogen (evident only in Gs proteomes) and to the enzyme Xfp that degradesd-xylulose-5′-phosphate and the biosynthetic pathways for 2 proteincofactors, pyridoxal 6′-phosphate and 4′-phosphopantothenate (expressed only inAu proteomes). A predicted ZnuA-like transition metal ionuptake system was identified for Gs while Auexpressed 2 LPXTG-anchored surface proteins, one of which had a predicted pilinD adhesion motif. While these proteins may contribute to fitness and virulencein the human host, it cannot be ruled out that Au andGs fill a niche in polymicrobial biofilms without being thedirect cause of injury in urothelial tissues.
  • 5.

    【2hr】Cellular States and Secondary Chemical Bonding: A Biochemical View of Major Human Diseases

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    机译 细胞状态和次级化学键合：人类主要疾病的生化视图。
    摘要：Nasopharyngeal carcinoma is prevalent in hot and humid areas such as south coastal China and Southeast Asia, but not in the non-coastal southern Chinese Yunnan Province. Secondary chemical bonding may underlie such phenomena. Cancer may be caused by strong acids such as HCl, whereas insoluble and rigid salts such as calcium oxalate are the potential causative factors of heart disease and the Alzheimer disease. The weak organic acids produced by plants counteract strong acids and dissolve insoluble salts, therefore boasting dual roles in disease prevention and treatments. The aforementioned perspective sheds light on the underlying mechanism of human disorders and opens new avenues in the interventions of numerous diseases.
  • 6.

    【2hr】The Roles of N6-Methyladenosine in HumanDiseases

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    机译 N6-甲基腺苷在人类中的作用疾病
    摘要：N 6-Methyladenosine methylations and demethylations are associated with a number of human diseases. A chemical and biochemical perspective can complement the biological view of the epigenetic mechanism. The orbital of imino nitrogen and nitrogen-hydrogen orbital displays p-π conjugation and σ-σ hyperconjugation. The electron delocalization attenuates secondary chemical bonding, resulting in low affinities on the imino nitrogen atom to cations. Reduced proton accumulation via N 6-methyladenosine correlates to lower cellular proton levels which may reflect cell physiology and pathogenesis. The lower affinity of the imino nitrogen to divalent cations in the methylated form versus the nonmethylated form may lead to reduced formation of insoluble and rigid calcium oxalate, which was proposed to be the cause of many diseases. The chemical and biochemical attributes of N 6-methyladenosine crosstalk with biological pathways upregulating and/or downregulating gene expressions to give rise to various physiological and biochemical outcomes at the cellular levels and the organismal levels.
  • 7.

    【2hr】Aerobic Respiration: Criticism of the Proton-centric Explanation Involving Rotary Adenosine Triphosphate Synthesis, Chemiosmosis Principle, Proton Pumps and Electron Transport Chain

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    机译 有氧呼吸：质子中心解释涉及旋转三磷酸腺苷合成，化学渗透原理，质子泵和电子传输链的批评。
    摘要：The acclaimed explanation for mitochondrial oxidative phosphorylation (mOxPhos, or cellular respiration) is a deterministic proton-centric scheme involving four components: Rotary adenosine triphosphate (ATP)-synthesis, Chemiosmosis principle, Proton pumps, and Electron transport chain (abbreviated as RCPE hypothesis). Within this write-up, the RCPE scheme is critically analyzed with respect to mitochondrial architecture, proteins’ distribution, structure-function correlations and their interactive dynamics, overall reaction chemistry, kinetics, thermodynamics, evolutionary logic, and so on. It is found that the RCPE proposal fails to explain key physiological aspects of mOxPhos in several specific issues and also in holistic perspectives. Therefore, it is imperative to look for new explanations for mOxPhos.
  • 8.

    【2hr】The Role of the Growth Hormone/Insulin-Like Growth Factor System in Visceral Adiposity

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    机译 生长激素/胰岛素样生长因子系统在内脏脂肪中的作用
    • 作者：Moira S Lewitt
    • 刊名：Biochemistry Insights
    • 2017年第期
    摘要：There is substantial evidence that the growth hormone (GH)/insulin-like growth factor (IGF) system is involved in the pathophysiology of obesity. Both GH and IGF-I have direct effects on adipocyte proliferation and differentiation, and this system is involved in the cross-talk between adipose tissue, liver, and pituitary. Transgenic animal models have been of importance in identifying mechanisms underlying these interactions. It emerges that this system has key roles in visceral adiposity, and there is a rationale for targeting this system in the treatment of visceral obesity associated with GH deficiency, metabolic syndrome, and lipodystrophies. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.
  • 9.

    【2hr】DNA Microarray Analysis of Estrogen Responsive Genes in Ishikawa Cells by Glabridin

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    机译 石蜡细胞中石川细胞中雌激素反应基因的DNA微阵列分析
    摘要：Based on a previous study, glabridin displayed a dose-dependent increase in estrogenic activity and cell proliferative activity in Ishikawa cells. However, when treated in combination with 17β-E2, synergistic estrogenic effect was observed but without the same synergistic increase in cell proliferative effect. This study aimed to identify the estrogen and nonestrogen-regulated activities induced by glabridin and in combination with 17β-E2 in comparison with 17β-E2. The results showed that 10 µM glabridin and the combination treatment of 100 nM glabridin with 1 nM 17β-E2 regulated both the genomic and nongenomic estrogen pathways to possibly provide benefits of estrogens in cardiovascular, circulatory, and vasculature systems. Meanwhile, the combination of 100 nM glabridin with 1 nM 17β-E2 seems to be more suitable to be used as an estrogen replacement. Finally, the results of this study have added on to the present knowledge of glabridin’s function as a phytoestrogen and suggested new ideas for the usage of glabridin.
  • 10.

    【2hr】Prophylactic Iron Supplementation in Pregnancy: A Controversial Issue

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    机译 妊娠期预防性补充铁剂：一个有争议的问题
    摘要：In our world today, iron deficiency (ID) is the most frequent nutritional deficiency and it is being considered as an epidemic public health crisis. Women of reproductive age and infants are at particular risk of ID, especially in underdeveloped countries. During pregnancy, iron deficiency anemia is a specific risk factor associated with negative maternal and perinatal outcomes. Many countries have iron supplementation (IS) programs—as recommended by the World Health Organization—during pregnancy; however, IS clinical benefits and risks are unclear. This review aims to discuss the threats and benefits of routine IS on maternal and infant outcomes.
  • 11.

    【2hr】Structure and Function of Caltrin (Calcium Transport Inhibitor) Proteins

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    机译 钙调蛋白（钙转运抑制剂）蛋白的结构和功能
    摘要：Caltrin (calcium transport inhibitor) is a family of small and basic proteins of the mammalian seminal plasma which bind to sperm cells during ejaculation and inhibit the extracellular Ca2+ uptake, preventing the premature acrosomal exocytosis and hyperactivation when sperm cells ascend through the female reproductive tract. The binding of caltrin proteins to specific areas of the sperm surface suggests the existence of caltrin receptors, or precise protein-phospholipid arrangements in the sperm membrane, distributed in the regions where Ca2+ influx may take place. However, the molecular mechanisms of recognition and interaction between caltrin and spermatozoa have not been elucidated. Therefore, the aim of this article is to describe in depth the known structural features and functional properties of caltrin proteins, to find out how they may possibly interact with the sperm membranes to control the intracellular signaling that trigger physiological events required for fertilization.
  • 12.

    【2hr】Enzyme Immobilization on Nanoporous Gold: A Review

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    机译 纳米多孔金的酶固定化研究进展
    • 作者：Keith J Stine
    • 刊名：Biochemistry Insights
    • 2017年第期
    摘要：Nanoporous gold (referred to as np-Au or NPG) has emerged over the past 10 years as a new support for enzyme immobilization. The material has appealing features of ease of preparation, tunability of pore size, high surface to volume ratio, and compatibility with multiple strategies for enzyme immobilization. The np-Au material is especially of interest for immobilization of redox enzymes for biosensor and biofuel cell applications given the ability to construct electrodes of high surface area and stability. Adjustment of the pore size of np-Au can yield enhancements in enzyme thermal stability. Glucose oxidase immobilization on np-Au has been a focus for development of glucose sensors. Immobilization of laccase and related enzymes has demonstrated the utility of np-Au for construction of biofuel cells. Np-Au has been used to immobilize other redox enzymes, enzyme conjugates for use in bioassays, and enzymes of interest for industrial processes.
  • 13.

    【2hr】Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in Diabetes and Its Complications

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    机译 蛋白修饰作为糖尿病及其合并症高血糖糖毒性的表现。
    摘要：Diabetes and its complications are hyperglycemic toxicity diseases. Many metabolic pathways in this array of diseases become aberrant, which is accompanied with a variety of posttranslational protein modifications that in turn reflect diabetic glucotoxicity. In this review, we summarize some of the most widely studied protein modifications in diabetes and its complications. These modifications include glycation, carbonylation, nitration, cysteine S-nitrosylation, acetylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and succination. All these posttranslational modifications can be significantly attributed to oxidative stress and/or carbon stress induced by diabetic redox imbalance that is driven by activation of pathways, such as the polyol pathway and the ADP-ribosylation pathway. Exploring the nature of these modifications should facilitate our understanding of the pathological mechanisms of diabetes and its associated complications.
  • 14.

    【2hr】Serum, Saliva, and Urine Irisin with and Without Acute Appendicitis and Abdominal Pain

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    机译 伴或不伴急性阑尾炎和腹部疼痛的血清，唾液和尿液鸢尾素
    摘要：A 112-amino-acid protein irisin (IRI) is widely expressed in many organs, but we currently do not know whether appendix tissue and blood cells express it. If appendix tissue and neutrophil cells express IRI, measuring its concentration in biological fluids might be helpful in the diagnosis of acute appendicitis (AA), since neutrophil cells are the currently gold-standard laboratory parameters for the diagnosis of AA. Therefore, the purpose of this study was to investigate the suitability of enzyme-linked immunosorbent assay-based measurements of the proposed myokine IRI for the discrimination of patients with AA from those with acute abdominal pain (AP) and healthy controls. Moreover, immunoreactivity to IRI was investigated in appendix tissues and blood cells. Samples were collected on admission (T1), 24 hours (T2), and 72 hours (T3) postoperatively from patients with suspected AA and from patients with AP corresponding to T1–T3, whereas control subject blood was once corresponding to T1. IRI was measured in serum, saliva, and urine by using enzyme-linked immunosorbent assay, whereas in appendix tissue and blood cells, IRI was detected by immunohistohcemistry. Appendix tissue and blood cells (except for erythrocytes) are new sources of IRI. Basal saliva, urine, and serum levels were higher in children with AA compared with postoperative levels (T2) that start to decline after surgery. This is in line with the finding that IRI levels are higher in children with AA when compared with those with AP or control subject levels, most likely due to a large infiltration of neutrophil cells in AA that release its IRI into body fluids. Measurement of IRI in children with AA parallels the increase or decrease in the neutrophil count. This new finding shows that the measurement of IRI and neutrophil count can together improve the diagnosis of AA, and it can distinguish it from AP. IRI can be a candidate marker for the diagnosis of AA and offers an additional parameter to neutrophil count. The promising receiving operating curve results indicate the following sensitivities and specificities, respectively, for IRI: serum 90% and 55%, saliva 90% and 60%, and urine 90% and 50%. Serum neutrophil count gave a sensitivity of 90% and a specificity of 90%. This promising result now needs to be confirmed in a larger group of patients.
  • 15.

    【2hr】Effects of Sterculia setigera Del. Stem Bark Extract on Hematological and Biochemical Parameters of Wistar Rats

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    机译 三角菊干茎皮提取物对Wistar大鼠血液学和生化指标的影响
    摘要：Africa is rich in a wide range of flora that are exploited as herbal medicines and remedies. Several diseases such as diabetes, diarrhea, dysentery and jaundice have been successfully managed using herbal medicines. Herbal decoctions or concoctions have been used as pain killers, antibiotics, and hematinics. This study evaluated the hematopoietic and biochemical properties of the stem bark of Sterculia setigera Del. in Wistar rats. Results showed that S. setigera decoction has copiously high tannin and cardiac glycoside levels. Ingestion of the decoction by rats over a 16-day period significantly (P < 0.05) increased the body weights of rats by 22.4% in the S. setigera-treated group. Hematological profiles showed raised levels of red blood cells, hemoglobin, packed cell volume, mean corpuscular volume, mean cell hemoglobin, mean cell hemoglobin concentration, and platelets, while biochemical parameters showed lower levels of alanine aminotransferase and aspartate aminotransferase, and slight increase in albumin and TP levels. We posit that the results justify the use of the stem bark of S. setigera as a hematinic by traditional medical practitioners and show its relative safety. Further experiments are needed to evaluate its safety.
  • 16.

    【2hr】Production, Purification, and Identification of Cholest-4-en-3-one Produced by Cholesterol Oxidase from Rhodococcus sp. in Aqueous/Organic Biphasic System

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    机译 红球菌属胆固醇氧化酶产生的Cholest-4-en-3-one的生产，纯化和鉴定。在水/有机双相系统中
    摘要：Cholest-4-en-3-one has positive uses against obesity, liver disease, and keratinization. It can be applied in the synthesis of steroid drugs as well. Most related studies are focused on preparation of cholest-4-en-3-one by using whole cells as catalysts, but production of high-quality cholest-4-en-3-one directly from cholesterol oxidase (COD) using an aqueous/organic two-phase system has been rarely explored. This study set up an enzymatic reaction system to produce cholest-4-en-3-one. We developed and optimized the enzymatic reaction system using COD from COX5-6 (a strain of Rhodococcus) instead of whole-cell biocatalyst. This not only simplifies and accelerates the production but also benefits the subsequent separation and purification process. Through extraction, washing, evaporation, column chromatography, and recrystallization, we got cholest-4-en-3-one with purity of 99.78%, which was identified by nuclear magnetic resonance, mass spectroscopy, and infrared spectroscopy. In addition, this optimized process of cholest-4-en-3-one production and purification can be easily scaled up for industrial production, which can largely decrease the cost and guarantee the purity of the product.
  • 17.

    【2hr】La3+ Alters the Response Properties of Neurons in the Mouse Primary Somatosensory Cortex to Low-Temperature Noxious Stimulation of the Dental Pulp

    包量

    机译 La3 +改变小鼠初级体感皮层中神经元对牙髓的低温有害刺激的响应特性
    • 作者：Yanjiao Jin
    • 刊名：Biochemistry Insights
    • 2015年第Suppl 1期
    摘要：Although dental pain is a serious health issue with high incidence among the human population, its cellular and molecular mechanisms are still unclear. Transient receptor potential (TRP) channels are assumed to be involved in the generation of dental pain. However, most of the studies were conducted with molecular biological or histological methods. In vivo functional studies on the role of TRP channels in the mechanisms of dental pain are lacking. This study uses in vivo cellular electrophysiological and neuropharmacological method to directly disclose the effect of LaCl3, a broad spectrum TRP channel blocker, on the response properties of neurons in the mouse primary somatosensory cortex to low-temperature noxious stimulation of the dental pulp. It was found that LaCl3 suppresses the high-firing-rate responses of all nociceptive neurons to noxious low-temperature stimulation and also inhibits the spontaneous activities in some nonnociceptive neurons. The effect of LaCl3 is reversible. Furthermore, this effect is persistent and stable unless LaCl3 is washed out. Washout of LaCl3 quickly revitalized the responsiveness of neurons to low-temperature noxious stimulation. This study adds direct evidence for the hypothesis that TRP channels are involved in the generation of dental pain and sensation. Blockade of TRP channels may provide a novel therapeutic treatment for dental pain.
  • 18.

    【2hr】LIGAND-RECEPTOR INTERACTIONS AND DRUG DESIGN

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    机译 配体-受体相互作用和药物设计
    摘要：
  • 19.

    【2hr】Carbamylated Erythropoietin: A Prospective Drug Candidate for Neuroprotection

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    机译 氨基甲酸酯化促红细胞生成素：神经保护的候选药物
    摘要：Carbamylated erythropoietin (cEpo), which is neuroprotective but lacks hematopoietic activity, has been attracting rising concerns. However, the cellular and molecular mechanisms involved in the process of neuroprotection of cEpo are not well known. Based on several recent reports, the neuroprotective effects of cEpo are illustrated, and signaling pathways involved in the different effects of erythropoietin and cEpo are discussed. These newly reported researches may shed new light on the development and application of cEpo, a prospective drug candidate for neuroprotection.
  • 20.

    【2hr】Correction to: “Carbamylated Erythropoietin: A Prospective Drug Candidate for Neuroprotection”

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    机译 更正为：“氨基甲酸酯化的促红细胞生成素：神经保护的潜在药物候选者”
    摘要：
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