Preclinical models for Type 1 Diabetes Mellitus - A practical approach for research.
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ABSTRACT:
SUBMITTER: Peng X
PROVIDER: S-EPMC10583179 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Preclinical models for Type 1 Diabetes Mellitus - A practical approach for research.
Peng Xi X Rao Guocheng G Li Xinqiong X Tong Nanwei N Tian Yan Y Fu Xianghui X
International journal of medical sciences 20231002 12
Numerous preclinical models have been developed to advance biomedical research in type 1 diabetes mellitus (T1DM). They are essential for improving our knowledge of T1DM development and progression, allowing researchers to identify potential therapeutic targets and evaluate the effectiveness of new medications. A deeper comprehension of these models themselves is critical not only to determine the optimal strategies for their utilization but also to fully unlock their potential applications in b ...[more]
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| S-EPMC5480317 | biostudies-other
Project description:AimsTo reduce the burden of type 2 diabetes (T2DM), the disease decision model plays a vital role in supporting decision-making. Currently, there is no comprehensive summary and assessment of the existing decision models for T2DM. The objective of this review is to provide an overview of the characteristics and capabilities of published decision models for T2DM. We also discuss which models are suitable for different study demands.Materials and methodsFour databases (PubMed, Web of Science, Embase, and the Cochrane Library) were electronically searched for papers published from inception to August 2020. Search terms were: "Diabetes-Mellitus, Type 2", "cost-utility", "quality-of-life", and "decision model". Reference lists of the included studies were manually searched. Two reviewers independently screened the titles and abstracts following the inclusion and exclusion criteria. If there was insufficient information to include or exclude a study, then a full-text version was sought. The extracted information included basic information, study details, population characteristics, basic modeling methodologies, model structure, and data inputs for the included applications, model outcomes, model validation, and uncertainty.ResultsFourteen unique decision models for T2DM were identified. Markov chains and risk equations were utilized by four and three models, respectively. Three models utilized both. Except for the Archimedes model, all other models (n = 13) implemented an annual cycle length. The time horizon of most models was flexible. Fourteen models had differences in the division of health states. Ten models emphasized macrovascular and microvascular complications. Six models included adverse events. Majority of the models (n = 11) were patient-level simulation models. Eleven models simulated annual changes in risk factors (body mass index, glycemia, HbA1c, blood pressure (systolic and/or diastolic), and lipids (total cholesterol and/or high-density lipoprotein)). All models reported the main data sources used to develop health states of complications. Most models (n = 11) could deal with the uncertainty of models, which were described in varying levels of detail in the primary studies. Eleven studies reported that one or more validation checks were performed.ConclusionsThe existing decision models for T2DM are heterogeneous in terms of the level of detail in the classification of health states. Thus, more attention should be focused on balancing the desired level of complexity against the required level of transparency in the development of T2DM decision models.
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| S-EPMC10667983 | biostudies-literature
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Project description:Diabetes Mellitus Type 1 miRnome
| PRJEB51173 | ENA
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Project description:IntroductionDirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research.MethodsAs a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis.ResultsNon-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc-/- (NSG and NXG) and recombination-activating gene (RAG)2-/-γc-/- mouse strains yielded viable D. immitis larvae at 2-4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days.DiscussionFuture adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.
| S-EPMC10324412 | biostudies-literature