Hereditary disease, especially monogenic disease is one of the major causes for malformation and disability of children. Most hereditary diseases have no effective therapy besides clinical symptomatic treatment. Biological techniques targeting casual genes or related signaling genes, such as transgenic, RNA interfere, genome editing, have been successfully applied in treating some hereditary diseases. However, most biological, treatments were carried out in animals, further confirmation of the effectiveness and safety of these therapies, and development of more therapeutic approaches based on mechanisms are needed before clinical trials.
Animals ; Biological Therapy ; Disease Models, Animal ; Genetic Diseases, Inborn ; therapy ; Genetic Therapy ; Humans

OBJECTIVETo review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies (DMD and BMD).

DATA SOURCESInformation included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological. Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected.

RESULTSThe key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects.

CONCLUSIONSFurther understanding of pathophysiological mechanisms at molecular levels and regenerative properties of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.

Animals ; Disease Models, Animal ; Dystrophin ; genetics ; physiology ; Genetic Therapy ; methods ; Humans ; Models, Biological ; Muscular Dystrophies ; genetics ; physiopathology ; therapy ; Mutation ; genetics ; Utrophin ; therapeutic use

Retinal model is an essential part in the retinal prosthesis. Based on the retinal physiology and the experimental data, the model is able to simulate the information processing in the retina, and can be used to investigate the relation between the input image and the neuron firing. We can categorize the models into circuit realization and algorithm realization. This article is a state-of-art review of different types of retinal models.
Algorithms ; Humans ; Models, Biological ; Models, Neurological ; Neural Networks (Computer) ; Prostheses and Implants ; Retina ; anatomy & histology ; physiology

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.
gamma-Aminobutyric Acid/metabolism ; Taurine/analogs & derivatives/therapeutic use ; Recurrence ; Receptors, Opioid, mu/genetics/metabolism ; Receptors, Opioid/antagonists & inhibitors ; Polymorphism, Genetic ; Neurons/metabolism ; Naltrexone/therapeutic use ; N-Methylaspartate/metabolism ; Models, Neurological ; Models, Biological ; Humans ; Glutamine/metabolism ; Disulfiram/therapeutic use ; Alcoholism/*drug therapy ; Alcohol Deterrents/*therapeutic use

Behcet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behcet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behcet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness.
Animals ; *Behcet Syndrome/epidemiology/immunology/therapy ; Biological Therapy/*trends ; Disease Models, Animal ; Humans ; Prevalence ; *World Health

This study aimed to identify the direct pharmacological targets of Jingfang Granules in treating infectious pneumonia via "target fishing" strategy. Moreover, the molecular mechanism of Jingfang Granules in treating infectious pneumonia was also investigated based on target-related pharmacological signaling pathways. First, the Jingfang Granules extract-bound magnetic nanoparticles were prepared, which were incubated with lipopolysaccharide(LPS)-induced mouse pneumonia tissue lysates. The captured proteins were analyzed by high-resolution mass spectrometry(HRMS), and the target groups with specific binding to the Jingfang Granules extract were screened out. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was used to identify the target protein-associated signaling pathways. On this basis, the LPS-induced mouse model of infectious pneumonia was established. The possible biological functions of target proteins were verified by hematoxylin-eosin(HE) staining and immunohistochemical assay. A total of 186 Jingfang Granules-specific binding proteins were identified from lung tissues. KEGG pathway enrichment analysis showed that the target protein-associated signaling pathways mainly included Salmonella infection, vascular and pulmonary epithelial adherens junction, ribosomal viral replication, viral endocytosis, and fatty acid degradation. The target functions of Jingfang Granules were related to pulmonary inflammation and immunity, pulmonary energy metabolism, pulmonary microcirculation, and viral infection. Based on the in vivo inflammation model, Jingfang Granules significantly improved the alveolar structure of the LPS-induced mouse model of infectious pneumonia and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6). Meanwhile, Jingfang Gra-nules significantly up-regulated the expressions of key proteins of mitochondrial function COX Ⅳ and ATP, microcirculation-related proteins CD31 and Occludin, and proteins associated with viral infection DDX21 and DDX3. These results suggest that Jingfang Gra-nules can inhibit lung inflammation, improve lung energy metabolism and pulmonary microcirculation, resist virus infection, thus playing a protective role in the lung. This study systematically explains the molecular mechanism of Jingfang Granules in the treatment of respiratory inflammation from the perspective of target-signaling pathway-pharmacological efficacy, thereby providing key information for clinical rational use of Jingfang Granules and expanding potential pharmacological application.
Animals ; Mice ; Lipopolysaccharides ; Pneumonia ; Inflammation ; Anti-Infective Agents ; Biological Assay ; Disease Models, Animal ; Interleukin-6

Data are presented which strongly indicate that the locus occupied by the mutant wz lies to the left of, or on the same locus of apricot (wa). The fact that wz shows a non-suppressor effect in combination with zeste as a typical phenomenon in mutants of sites 1, 2, and 3 of the white locus, also supports that wz is a mutant at or left of apricot (site 3). A "model" for the genetic fine structure of the mutants (wzm, wzl, and wz) is proposed and discussed to account for the mutability among those three mutants. Analysis of wz leads to the hypothesis that it is the result of an inversion (sites 3 and 4) at the white locus, by two mechanisms which are discussed briefly here.
Animals ; *Drosophila ; Female ; *Genes ; Male ; Models, Biological ; *Mutation ; *Recombination, Genetic

There are many differences between traditional Chinese medicine (TCM) and western medicine, and the use of TCM has its feature under the guide of TCM theory. Determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs is the base of TCM treatment, the main form of TCM apply is compatibility, formula corresponding differentiation of symptoms and signs is the key for TCM to get better effects, integrated adjustment is the TCM mode of action. All above determined the methods and standards to evaluate the pharmacodynamic effect of TCM cannot completely accord to Western medicine. Use modern technology and combine the feature of TCM to estabilish the method for effects evaluation and standard system of TCM, which is the key point to correctly appraise the effects of TCM. Stabilized quality control is the precondition of pharmacodynamic action appraisement, animal models combined disease and symptoms are the necessary tools for effect appraisement, integrated adjustment need mutiple index to appraise pharmacodynamic action, the method to avoid subjective error in TCM reseach is using mathematical model and parameter to scientificly analyse data, also the explaination of mechanism of action need standard clinical pharmacology experimental date.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; standards ; Humans ; Medicine, Chinese Traditional ; methods ; standards ; Models, Biological ; Quality Control ; Treatment Outcome

With the progresses of the research on "Digital Human", more and more information has been needed for the setting up of the three-dimensional digital models of human organs. In the present paper, based on the method of block mapping with a normal-style bump mapping method, we normalized the vector of the surface of the models, computed offset of the texture coordinates and added to them. The projection of the coordinates to the tangential space complemented the disturbance to the vector of models' surface. The method was proposed with bump texture mapping on the surface of the biological models of organs to improve the impression of the visualization of the organ models and to enhance the sense of reality of the models.
Humans ; Models, Anatomic ; Models, Biological

The physiomic approach is now widely used in the diagnosis of cardiovascular diseases. There are two possible methods for cardiovascular physiome: the traditional mathematical model and the machine learning (ML) algorithm. ML is used in almost every area of society for various tasks formerly performed by humans. Specifically, various ML techniques in cardiovascular medicine are being developed and improved at unprecedented speed. The benefits of using ML for various tasks is that the inner working mechanism of the system does not need to be known, which can prove convenient in situations where determining the inner workings of the system can be difficult. The computation speed is also often higher than that of the traditional mathematical models. The limitations with ML are that it inherently leads to an approximation, and special care must be taken in cases where a high accuracy is required. Traditional mathematical models are, however, constructed based on underlying laws either proven or assumed. The results from the mathematical models are accurate as long as the model is. Combining the advantages of both the mathematical models and ML would increase both the accuracy and efficiency of the simulation for many problems. In this review, examples of cardiovascular physiome where approaches of mathematical modeling and ML can be combined are introduced.
Cardiovascular Diseases ; Diagnosis ; Humans ; Jurisprudence ; Machine Learning ; Models, Theoretical ; Patient-Specific Modeling