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Microbes & Immunity Big data and DNN-based DTI model in CHP

Concurrently, candidate drugs are predicted to dock with prednisone are commonly used to treat hypersensitivity
selected biomarkers. Potent drugs often carry high-risk pneumonitis. They can quickly relieve lung inflammation
damage, so considerations of toxicity, allergenicity, and the symptoms, but long-term use can lead to osteoporosis,
balance between efficacy and adverse reactions are crucial. hypertension, diabetes, peptic ulcers, and increased
To ensure the stability and safety of clinical drug trials, the risk of infection. Clinical evidence indicates that some
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drug’s stability and safety must be considered in the design patients may develop a dependency on corticosteroids,
of clinical guidelines, such as regulatory capacity, toxicity, making it difficult to discontinue the medication. In this
sensitivity, and specificity. To measure the regulatory study, we utilize database mining, CHP whole-genome
capacity of candidate molecular drugs, available regulatory microarray data, and systems biology methods to identify
capacity data were downloaded from the L1000 Level 5 core GWGEN and establish core signaling pathways of
dataset, which includes data on 1453 genes treated in 156 CHP and downstream cellular dysfunctions, as shown in
different cell lines with 21,043 compounds. Regulatory Figure 4. This was done to investigate the pathogenetic
capacity data, with positive values indicating upregulation mechanism and identify significant biomarkers as drug
and negative values indicating downregulation, were used targets, predicting potential molecular drugs to treat
to identify molecular drugs suitable for cell downregulation. CHP. Using the prediction of the DNN-based DTI model,
Based on this criterion, we searched for molecular drugs we aim to find new multi-molecular drugs to treat CHP.
in appropriate cell lines that could reverse the expression Considering sensitivity, toxicity, and regulatory capacity
of biomarkers leading to pulmonary cell fibrosis, restoring as drug specifications, we combine deep learning and
their normal expression. In addition, lower drug toxicity systems biology methods to find suitable molecular drugs
helps reduce side effects, as indicated by the median lethal for the treatment of CHP. Finally, the molecular drugs
dose (LD ), typically sourced from DrugBank. The lower azathioprine, masitinib, and primaquine were chosen and
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the LD value, the higher the toxicity. Furthermore, higher formulated into a multi-molecular drug treatment for
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drug sensitivity (lower half maximal effective concentration CHP, as shown in Table 2.
[EC ] values) allows for reduced drug dosages. Drug
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sensitivity data were obtained from the PRISM dataset, Azathioprine is an immunosuppressant that reduces
which includes information on 4,518 drugs tested in 578 inflammation by inhibiting immune system activity
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human cell lines. EC measures drug potency, with lower and helps control disease progression. In the CHP
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+
EC values indicating greater efficacy at lower doses. By microenvironment, the overactivation of CD4 T cells in
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selecting the correct drug, abnormal expressions in diseases the Th17 signaling pathway leads to abnormal anti-Th1
can be well-reversed. Predicting candidate drugs through and Th2 cell signaling, exacerbating the immune response
the DNN-based DTI model, we identified several potential and creating a vicious cycle of uncontrolled cell apoptosis
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drugs for these biomarkers. The DNN-based DTI model, and proliferation. According to the European Respiratory
based on identified biomarkers, provided predictions for Society, azathioprine shows some efficacy in improving
some candidate drugs along with their regulatory capacity, lung function, particularly in enhancing the diffusing
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toxicity, and sensitivity information, as shown in Table 1. capacity for carbon monoxide. While its improvement
Based on the three-drug design criteria (appropriate in forced vital capacity is not significant, azathioprine is
regulatory capacity, high sensitivity, and low toxicity), valuable in reducing the long-term side effects of steroid
potential drugs such as azathioprine, masitinib, and use, showing significant clinical value. Azathioprine
mycophenolate-mofetil were screened and combined into a inhibits the JAK signaling pathway, reducing inflammation
multi-molecular drug for treating CHP, as shown in Table 2. and inhibiting TGF-β, thereby reducing B-cell activation
and inflammation. It’s anti-IL-6 or anti-TNF-α antibodies
4. Discussion target specific inflammatory mediators for precise
inflammation treatment.
In the stage of recurrence, the most straightforward method
to treat CHP is to avoid prolonged exposure to allergens. Masitinib can reduce inflammation by inhibiting the
This primarily includes organic dust, microorganisms, activation of mast cells and eosinophils, thereby reducing
animal proteins, and certain chemicals. However, some the release of inflammatory mediators. In addition, by
1
allergens are almost unavoidable in general households, inhibiting multiple tyrosine kinase receptors, masitinib
such as indoor mold and pet dander. In addition, due can affect various cell signaling pathways, providing a more
to occupational reasons, some patients cannot avoid comprehensive anti-inflammatory effect. It downregulates
environments rich in allergens, such as beryllium and CCL20, CDC23, and CXCL1, thereby inhibiting tumor
other metal dust. Therefore, medication is necessary to cell growth and immune cell activation. By blocking these
alleviate allergic symptoms. At present, corticosteroids like cells’ activity, masitinib can reduce inflammation and

Volume 2 Issue 2 (2025) 100 doi: 10.36922/mi.4620