A numerical study on nonlinear DPL model for analyzing heat transfer in tissue during thermal therapy

In the present paper, therapeutic treatment of infected tumorous cells has been studied through mathematical modeling and simulation of heat transfer in tissues by using a nonlinear dual-phase lag bioheat transfer model with Dirichlet boundary condition. The components of volumetric heat source in this model such as blood perfusion and metabolism are assumed experimentally validated temperature-dependent function, which gives more accurate temperature distribution in tissues through this model. We have used the finite difference and RK (4, 5) techniques of numerical methods to solve the proposed problem and obtained the exact solution in a particular case. After comparison, we got a good agreement between them. We have used dimensionless quantities throughout this paper. The effect of relaxation and thermalization time with respect to dimensionless temperature distribution has been analyzed in the treatment process.     

谷氨酰胺代谢在原发性肝癌发生发展及治疗中的研究进展

肝癌是我国高发并且危害性极大的恶性肿瘤，其具有高死亡率并起病隐匿等特点。目前，肝癌治疗主要是以靶向药物，手术和放化疗为主，容易出现复发率高、耐药性强等现象。本文以谷氨酰胺代谢为切入点，对目前研究较多的肝癌相关的谷氨酰胺代谢酶及相关基因分别予以综述，以期为肝癌的发病机制及药物治疗提供开放性新思路。     

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet,but Not without Exercise Training

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Leucokinin and Associated Neuropeptides Regulate Multiple Aspects of Physiology and Behavior in Drosophila

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. LKs act on G-protein-coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep–metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (abdominal LK neurons, ABLKs) of the abdominal neuromeres co-express LK and a diuretic hormone (DH44), and together, these regulate water and ion homeostasis and associated stress as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs (anterior LK neurons), in the brain express LK in larvae, but inconsistently so in adults. These ALKs co-express three other neuropeptides and regulate water and ion homeostasis, feeding, and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT₂-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT₁ and MT₂ binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation.     

Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.