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Complex system in medicine

Angela Mazzeo, Enrico Jardim Clemente Santos
The biology of stem cells is one of the most dynamic and promising fields of the biological sciences, since it is the basis for the development of organisms. Its biological complexity demands efforts from several lines of research aimed mainly at its therapeutic use. Nanotechnology has been emerging as a new field of study, which shows great potential in the treatment of various diseases. This new area of health has been called "Nanomedicine" or "Bionanotechnology", which can be applied in Medicine by transport and drug delivery systems, robotic tools to be used in diagnostic and surgical processes, nanobiomaterials, gene therapies, nanobiomedical devices, among others...
November 29, 2018: Einstein
Marcos Renato de Assis, Valdair Pinto
Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars...
December 2018: Therapeutic Advances in Musculoskeletal Disease
Yulin Tian, Qing Lin
Photo-cross-linkers are invaluable tools for identifying drug targets and off-targets as well as probing the binding sites in medicinal chemistry and chemical biology. In this review, we summarize recent development of the ligand-based and genetically encoded photo-cross-linkers and their use in biological system. In particular, we highlight our discovery of 2-aryl-5-carboxytetrazole (ACT) as a novel class of photo-cross-linkers and their successful applications in drug target identification as well as identifying transient protein-protein interaction complexes in mammalian cells...
November 30, 2018: Chimia
Yinghong Xiao, Ming Zhang, Yunting Fan, Qicheng Zhang, Yuli Wang, Wenwen Yuan, Ninglin Zhou, Jianfei Che
A novel drug carrier is constructed by compositing hydrophilic hydroxypropyl-β-cyclodextrins (HP-β-CD) and carboxylated graphene nanomaterial (GO-COOH). Fourier transform infrared spectroscopy confirms that the two materials are successfully combined via chemical bonds. Further, a crosslinking agent of glutaraldehyde is applied to fabricate composite GO-COO-HP-β-CD nanospheres, as demonstrated by an atomic force microscope. Dexamethasone (DEX) is selected as the model drug, and the drug loading efficiency and water solubility of the nanospheres greatly increased...
November 28, 2018: Colloids and Surfaces. B, Biointerfaces
Bryn Lander, Ellen Balka
RATIONALE, AIMS, AND OBJECTIVES: Local health administrators implemented chronic obstructive pulmonary disease and heart failure admission order sets to increase guideline adherence. We explored the impact of these order sets on workflows and guideline adherence in the internal medicine specialty in two Canadian teaching hospitals. METHODS: A mixed methods study combined shadowing care providers (250 h), meeting observation and interviews (11 h), and patient medical chart audits for heart failure (n = 120) and chronic obstructive pulmonary disease (n = 120) patients...
December 3, 2018: Journal of Evaluation in Clinical Practice
Ashley A Reinke, Shih-Hon Li, Mark Warnock, Maxim E Shaydakov, Naga Sandhya Guntaka, Enming J Su, Jose A Diaz, Cory D Emal, Daniel A Lawrence
Plasminogen activator inhibitor type-1 (PAI-1) is a serine protease inhibitor (serpin) implicated in numerous pathological processes, including coronary heart disease, arterial and venous thrombosis, and chronic fibrotic diseases. These associations have made PAI-1 an attractive pharmaceutical target. However, the complexity of the serpin inhibitory mechanism, the inherent metastability of serpins, and the high-affinity association of PAI-1 with vitronectin in vivo has made it difficult to identify pharmacologically effective small-molecule inhibitors...
December 3, 2018: Journal of Biological Chemistry
Albert van den Berg, Christine L Mummery, Robert Passier, Andries D van der Meer
Organs-on-chips are microfluidic systems with controlled, dynamic microenvironments in which cultured cells exhibit functions that emulate organ-level physiology. They can in principle be 'personalised' to reflect individual physiology, for example by including blood samples, primary human tissue, and cells derived from induced pluripotent stem cell-derived cells, as well as by tuning key physico-chemical parameters of the cell culture microenvironment based on personal health data. The personalised nature of such systems, combined with physiologically relevant read-outs, provides new opportunities for person-specific assessment of drug efficacy and safety, as well as personalised strategies for disease prevention and treatment; together, this is known as 'precision medicine'...
December 3, 2018: Lab on a Chip
Kaitlyn Sadtler, Matthew T Wolf, Sudipto Ganguly, Christopher A Moad, Liam Chung, Shoumyo Majumdar, Franck Housseau, Drew M Pardoll, Jennifer H Elisseeff
The immune system plays a critical role in wound healing and the response to biomaterials. Biomaterials-directed regenerative immunology is an immunoengineering strategy that targets the immune system to promote tissue repair. Biomaterial scaffolds employed in regenerative medicine can be broadly classified as biological (such as those derived from the tissue extracellular matrix) or synthetic. Here, we show in depth the divergent myeloid response to biological versus synthetic biomaterial scaffolds. While neutrophil depletion and changes in physical properties such as shape and mechanics can modulate the pro-inflammatory myeloid immune response to synthetic materials to a degree, the overall general divergent myeloid responses persist...
November 9, 2018: Biomaterials
S Yu Lukin, Yu P Soldatov, M V Stogov
Experimental and clinical studies have shown that a skeletal trauma causes a whole complex of pathophysiological disorders, both local and systemic. The main factors determining the severity of the trauma, as well as the nature of the course of the post-traumatic period, are the degree of hypoxia (acidosis), hypercoagulation and immune disorders. To influence these pathophysiological disorders in the patients presenting the with skeletal traumas, various approaches have been proposed, including the use of antihypoxants and antioxidants, the methods and means for the stimulation and support of the immune system, medications to regulate hemostasis...
2018: Voprosy Kurortologii, Fizioterapii, i Lechebnoĭ Fizicheskoĭ Kultury
Jake R Conway, Eric Kofman, Shirley S Mo, Haitham Elmarakeby, Eliezer Van Allen
Immune checkpoint blockade (ICB) therapies, which potentiate the body's natural immune response against tumor cells, have shown immense promise in the treatment of various cancers. Currently, tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are the primary biomarkers evaluated for clinical management of cancer patients across histologies. However, the wide range of responses has demonstrated that the specific molecular and genetic characteristics of each patient's tumor and immune system must be considered to maximize treatment efficacy...
November 29, 2018: Genome Medicine
Ruoting Yang, Daniel Watson, Joshua Williams, Raina Kumar, Ross Campbell, Uma Mudunuri, Rasha Hammamieh, Marti Jett
BACKGROUND: Network medicine aims to map molecular perturbations of any given diseases onto complex networks with functional interdependencies that underlie a pathological phenotype. Furthermore, investigating the time dimension of disease progression from a network perspective is key to gaining key insights to the disease process and to identify diagnostic or therapeutic targets. Existing platforms are ineffective to modularize the large complex systems into subgroups and consolidate heterogeneous data to web-based interactive animation...
November 29, 2018: BMC Bioinformatics
(no author information available yet)
Reports an error in "Latent factor structure of DSM-5 posttraumatic stress disorder: Evaluation of method variance and construct validity of novel symptom clusters" by Daniel J. Lee, Michelle J. Bovin, Frank W. Weathers, Patrick A. Palmieri, Paula P. Schnurr, Denise M. Sloan, Terence M. Keane and Brian P. Marx ( Psychological Assessment , Advanced Online Publication, Aug 16, 2018, np). In the article, the affiliations of multiple authors were incorrectly listed in the author byline and author note...
November 29, 2018: Psychological Assessment
Nina N Ferenc, Michael Levin
Transformative applications in regenerative medicine await increased control of processes implementing repair and remodeling of complex living structures. Recent work reveals ion channel drugs as a powerful toolkit for modulating endogenous bioelectric circuits that control growth and form in vivo and in vitro. It is therefore especially important to develop assays in model systems that will enable the testing of these "morphoceuticals"-compounds with predictable effects on anatomical structure. The regenerative planaria are an ideal model system for this purpose...
November 28, 2018: Macromolecular Bioscience
Gang Xie, Zhihua Cui, Kai Peng, Xiehai Zhou, Quan Xia, Dujuan Xu
BACKGROUND: Clinical research has paid increasing attention to quality of life (QoL) in recent years, but the assessment of QoL is difficult, hampered by the subjectivity, complexity, and adherence of patients and physicians. According to previous studies, QoL in cancer patients is related to performance status (PS) and influenced by chemotherapy-related toxicity. Aidi injection, a traditional Chinese medicine injection, is used as an adjuvant drug to enhance effectiveness of chemotherapy...
November 27, 2018: Integrative Cancer Therapies
Fred J DiMenna, Avigdor D Arad
Type 2 diabetes and obesity epidemics are in effect in the United States and the two pathologies are linked. In accordance with the growing appreciation that 'exercise is medicine,' it is intuitive to suggest that exercise can play an important role in the prevention and/or treatment of these conditions. However, if exercise is to truly be considered as a viable alternative to conventional healthcare prevention/treatment strategies involving pharmaceuticals, it must be prescribed with similar scrutiny. Indeed, it seems reasonable to posit that the recent initiative calling for 'precision medicine' in the US standard healthcare system should also be applied in the exercise setting...
2018: BMC Sports Science, Medicine and Rehabilitation
Ryan G Anderson, Brianna M Jett, Andrew McNally
Heteroaryl thioethers, comprised of pyridines and diazines, are an important class of compounds with relevance to medicinal chemistry. Metal-catalyzed cross-couplings and SN Ar are traditionally used to form C-S bonds in these systems but are limited by available halogenated precursors. An alternative approach is presented where pyridines and diazines are transformed into heterocyclic phosphonium salts and then C-S bonds are formed by adding thiolate nucleophiles. The process is 4-selective for pyridines, simple to execute and can be used to make derivatives of complex pharmaceuticals...
June 21, 2018: Tetrahedron
Yue Ma, Li Xie, Bo Yang, Weidong Tian
The tooth and its supporting tissues are organized with complex three-dimensional (3D) architecture, including the dental pulp with a blood supply and nerve tissues, complex multilayer periodontium, and highly aligned periodontal ligament (PDL). Mimicking such 3D complexity and the multicellular interactions naturally existing in dental structures represents great challenges in dental regeneration. Attempts to construct the complex system of the tooth and tooth-supporting apparatus (i.e., the periodontal ligament, alveolar bone and cementum) have made certain progress owing to 3D printing biotechnology...
November 26, 2018: Biotechnology and Bioengineering
Leilei Wen, Lu Liu, Ke Xue, Yong Cui
Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disease characterized by loss of tolerance to self-antigens, complement activation, dysregulated type 1 IFN responses, and immune-mediated tissue damage. The clinical features of SLE are pleomorphic, affecting virtually any organ system, such as skin, joints, central nervous system, or kidneys. Currently, the etiology and pathogenesis of SLE are not fully understood. Generally, it is considered that genetic factors, immune abnormalities, sex hormones, and environmental factors are associated with SLE, and mainly caused by genetic and environmental interactions, typical for a complex disease with multiple susceptibility genes...
December 2018: Journal of Investigative Dermatology. Symposium Proceedings
Daniel Bojar, Tobias Fuhrer, Martin Fussenegger
Capitalizing on the ability of mammalian cells to conduct complex post-translational modifications, most protein therapeutics are currently produced in cell culture systems. Addition of a signal peptide to the product protein enables its accumulation in the cell culture supernatant, but separation of the product from endogenously secreted proteins remains costly and labor-intensive. We considered that global downregulation of translation of non-product proteins would be an efficient strategy to minimize downstream processing requirements...
November 20, 2018: Metabolic Engineering
Lorenzo Alibardi
Some hypotheses on the evolution of regeneration in amphibians and reptiles are presented. Amphibian regeneration is derived from metamorphosis present in sarcopterygian fish and amphibians of the Devonian-Carboniferous. The genetic ability to rebuild organs during metamorphosis was maintained in form of "regeneration" in urodele and anuran tadpoles. Amphibian regeneration may be a consequence of the transition from an aquatic to a terrestrial environment through the evolution of a developmental program for the tadpole stage and replacements of adult organs controlled by the endocrine and immune system...
November 23, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
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