生物化学教学中采用案例教学法之案例设计与分析

案例教学法是被普遍采用的一种教学方式,将其应用于生物化学教学中,并用图解的形式给出案例的归纳与分析,使抽象难懂、错综复杂、生涩冷僻的教学内容变得直观明了。加深了学生对教学内容的理解,增强了课堂教学的趣味性与学生学习的主动性,同时提高了学生分析问题和解决问题的能力。     

Left ventricular wall stress compendium

Left ventricular (LV) wall stress has intrigued scientists and cardiologists since the time of Lame and Laplace in 1800s. The left ventricle is an intriguing organ structure, whose intrinsic design enables it to fill and contract. The development of wall stress is intriguing to cardiologists and biomedical engineers. The role of left ventricle wall stress in cardiac perfusion and pumping as well as in cardiac pathophysiology is a relatively unexplored phenomenon. But even for us to assess this role, we first need accurate determination of in vivo wall stress. However, at this point, 150 years after Lame estimated left ventricle wall stress using the elasticity theory, we are still in the exploratory stage of (i) developing left ventricle models that properly represent left ventricle anatomy and physiology and (ii) obtaining data on left ventricle dynamics. In this paper, we are responding to the need for a comprehensive survey of left ventricle wall stress models, their mechanics, stress computation and results. We have provided herein a compendium of major type of wall stress models: thin-wall models based on the Laplace law, thick-wall shell models, elasticity theory model, thick-wall large deformation models and finite element models. We have compared the mean stress values of these models as well as the variation of stress across the wall. All of the thin-wall and thick-wall shell models are based on idealised ellipsoidal and spherical geometries. However, the elasticity model's shape can vary through the cycle, to simulate the more ellipsoidal shape of the left ventricle in the systolic phase. The finite element models have more representative geometries, but are generally based on animal data, which limits their medical relevance. This paper can enable readers to obtain a comprehensive perspective of left ventricle wall stress models, of how to employ them to determine wall stresses, and be cognizant of the assumptions involved in the use of specific models.     

Expression of Nemo-Like Kinase (NLK) in the Brain in a Rat Experimental Subarachnoid Hemorrhage Model

This study aimed to investigate the expression of the Nemo-like kinase (NLK) in the brain after experimental subarachnoid hemorrhage (SAH) in rats. A total of 90 rats were randomly divided into six groups: control group, day 1, day 3, day 5, day 7, and day 14. Day 1, day 3, day 5, day 7, and day 14 groups were all SAH groups in which the rats were killed on days 1, 3, 5, 7, and 14, respectively. In SAH groups, autologous arterial blood was injected into cisterna magna once on day 0. Cross-sectional area of basilar artery was measured by H&E staining. Immunostaining and immunoblotting experiments were performed to detect the expression of NLK protein. Real-time polymerase chain reaction was used to analyze the presence and quantity of NLK mRNA. The level of oxidative stress in the artery was also measured. The basilar arteries exhibited vasospasm after SAH and became the most severe on day 3. The expressions of NLK protein and mRNA were decreased remarkably in SAH groups compared with the control group. The down-regulated expression of NLK was detected after SAH and the low ebb was on day 3, which was oppositely the peak time of oxidative stress. The expression of NLK was present mainly in the neurons in the brain and smooth muscle cells in the basilar artery. NLK is decreasingly expressed in an opposite time-course to the development of cerebral vasospasm (CVS) and SAH-induced brain injury in this rat experimental model of SAH and these findings might have important implications during the administration of specific NLK agonist to prevent or reduce CVS or neuronal apoptosis caused by SAH.     

MFG-E8 and HMGB1 Are Involved in the Mechanism Underlying Alcohol-Induced Impairment of Macrophage Efferocytosis

Efferocytosis is a unique phagocytic process for macrophages to remove apoptotic cells in inflammatory loci. This event is maintained by milk fat globule-EGF factor 8 (MFG-E8), but attenuated by high mobility group box 1 (HMGB1). Alcohol abuse causes injury and inflammation in multiple tissues. It alters efferocytosis, but precise molecular mechanisms for this effect remain largely unknown. Here, we showed that acute exposure of macrophages to alcohol (25 mmol/L) inhibited MFG-E8 gene expression and impaired efferocytosis. The effect was mimicked by hydrogen peroxide. Moreover, N-acetylcysteine (NAC), a potent antioxidant, blocked acute alcohol effect on inhibition of macrophage MFG-E8 gene expression and efferocytosis. In addition, recombinant MFG-E8 rescued the activity of alcohol-treated macrophages in efferocytosis. Together, the data suggest that acute alcohol exposure impairs macrophage efferocytosis via inhibition of MFG-E8 gene expression through a reactive oxygen species dependent mechanism. Alcohol has been found to suppress or exacerbate immune cell activities depending on the length of alcohol exposure. Thus, we further examined the role of chronic alcohol exposure on macrophage efferocytosis. Interestingly, treatment of macrophages with alcohol for seven days in vitro enhanced MFG-E8 gene expression and efferocytosis. However, chronic feeding of mice with alcohol caused increase in HMGB1 levels in serum. Furthermore, HMGB1 diminished efferocytosis by macrophages that were treated chronically with alcohol, suggesting that HMGB1 might attenuate the direct effect of chronic alcohol on macrophage efferocytosis in vivo. Therefore, we speculated that the balance between MFG-E8 and HMGB1 levels determines pathophysiological effects of chronic alcohol exposure on macrophage efferocytosis in vivo.     

Dissection of DNA Damage Responses Using Multiconditional Genetic Interaction Maps

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Highlights? A resource of genetic modules and networks induced by distinct types of DNA damage ? Networks distinguish DNA damage response pathways with high statistical power ? Rtt109, a histone acetyltransferase, affects the mutagenic bypass of DNA lesions ? The neddylation machinery and Irc21 affect cell-cycle control and genome stability     

Inhibition by N′-nitrosonornicotine of the catalytic activity of glutamate dehydrogenase in α-ketoglutarate amination

The effect of N′-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the α-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with K_i, estimated as 199?μmol?l^?1 at 25°C and pH 8.0.     

Emission and Control Characteristics for Incineration of Sedum Plumbizincicola Biomass in a Laboratory-Scale Entrained Flow Tube Furnace

Experiments were conducted to investigate and control pollutant emission from incineration of Sedum plumbizincicola plants on a laboratory scale using an entrained flow tube furnace. Without control technologies, the flue gas contained 0.101 mg Nm^?3 of Cd, 46.4 mg Nm^?3 of Zn, 553 mg Nm^?3 of NOx, 131 pg Nm^?3 of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/Fs) and 35.4 mg Nm^?3 of polycyclic aromatic hydrocarbons (PAHs). In pollutants control experiments. Al₂O₃, CaO, and kaolin were compared as adsorbents and activated carbon was used as an end-of-pipe method for the capture of pollutants. Kaolin, the most effective of the three adsorbents, removed 91.2% of the Cd in flue gas. While 97.6% of the Cd and 99.6% of the PAHs were removed by activated carbon. Incineration may therefore be regarded as a viable option for the safe disposal of the biomass of the zinc and cadmium hyperaccumulator species S. plumbizincicola.     

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.     

Identification and Validation of Urinary Metabolite Biomarkers for Major Depressive Disorder

Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy–based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers—malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine—was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.Major depressive disorder (MDD)¹ is a debilitating mental disorder affecting up to 15% of the general population and accounting for 12.3% of the global burden of disease (1, 2). Currently, the diagnosis of MDD still relies on the subjective identification of symptom clusters rather than empirical laboratory tests. The current diagnostic modality results in a considerable error rate (3), as the clinical presentation of MDD is highly heterogeneous and the current symptom-based method is not capable of adequately characterizing this heterogeneity (4). An approach that can be used to circumvent these limitations is to identify disease biomarkers to support objective diagnostic laboratory tests for MDD.Metabonomics, which can measure the small molecules in given biosamples such as plasma and urine without bias (5), has been extensively used to characterize the metabolic changes of diseases and thus facilitate the identification of novel disease-specific signatures as putative biomarkers (6–10). Nuclear magnetic resonance (NMR) spectroscopy–based metabonomic approaches characterized by sensitive, high-throughput molecular screening have been employed previously in identifying novel biomarkers for a variety of neuropsychiatric disorders, including stroke, bipolar disorder, and schizophrenia (11–13).Specifically with regard to MDD, several animal studies have already characterized the metabolic changes in the blood and urine (14–19). These studies provide valuable clues as to the pathophysiological mechanism of MDD. However, no study has been designed with the aim of diagnosing this disease. Recently, using an NMR-based metabonomic approach, this research group identified a unique plasma metabolic signature that enables the discrimination of MDD from healthy controls with both high sensitivity and specificity (20). These findings motivated further study on urinary diagnostic metabolite biomarkers for MDD, which would be more valuable from a clinical applicability standpoint, as urine can be more non-invasively collected. Moreover, previous studies have also demonstrated the feasibility of identifying diagnostic metabolite biomarkers of psychiatric disorders in the urine. For example, using an NMR-based metabonomics approach, Yap et al. (21) identified a unique urinary metabolite signature that clearly discriminated autism patients from healthy controls. As systemic metabolic disturbances have been observed in the urine of a depressed animal model, it is likely that diagnostic metabolite markers for MDD can be detected in human urine.Therefore, in this study, NMR spectroscopy combined with multivariate pattern recognition techniques were used to profile 82 first-episode drug-naïve MDD subjects and 82 healthy controls (the training set) in order to identify potential metabolite biomarkers for MDD. Furthermore, 44 unselected MDD subjects and 52 healthy controls (the test set) were employed to independently validate the diagnostic performance of these urinary metabolite biomarkers.