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1.
Drug Discov Today ; 29(5): 103975, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580164

RESUMO

Discoidin domain receptor (DDR)-1 has a crucial role in regulating vital processes, including cell differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. Overexpression or activation of DDR1 in various pathological scenarios makes it a potential therapeutic target for the treatment of cancer, fibrosis, atherosclerosis, and neuropsychiatric, psychiatric, and neurodegenerative disorders. In this review, we summarize current therapeutic approaches targeting DDR1 from a medicinal chemistry perspective. Furthermore, we analyze factors other than issues of low selectivity and risk of resistance, contributing to the infrequent success of DDR1 inhibitors. The complex interplay between DDR1 and the extracellular matrix (ECM) necessitates additional validation, given that DDR1 might exhibit complex and synergistic interactions with other signaling molecules during ECM regulation. The mechanisms involved in DDR1 regulation in cancer and inflammation-related diseases also remain unknown.


Assuntos
Receptor com Domínio Discoidina 1 , Terapia de Alvo Molecular , Neoplasias , Humanos , Receptor com Domínio Discoidina 1/metabolismo , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Animais , Neoplasias/tratamento farmacológico , Matriz Extracelular/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Medicine (Baltimore) ; 101(7): e28843, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363179

RESUMO

BACKGROUND: Constipation is one of the common problems in stroke patients, which seriously affects the life quality of patients and even leads to the recurrence of cerebrovascular disease. The clinical trials of acupoint herbal patching (AHP) in the adjuvant treatment of constipation after stroke (CAS) is currently in progress. However, there is no systematic review or meta-analysis to evaluate the effects of AHP on CAS. METHODS: We will search articles in 8 electronic databases including the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Database, and the Chinese Scientific Journal Database for randomized controlled trials of CAS treated by AHP from their inception to November 1, 2021. The primary outcome measures will be clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements. The data meeting the inclusion criteria were analyzed by RevMan V.5.4 software. Two authors evaluated the study using the Cochrane collaborative risk bias tool. We will use a scoring method to assess the overall quality of evidence supporting the main results. RESULTS: This study will analyze the clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements after stroke. CONCLUSION: The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for CAS. INPLASY REGISTRATION NUMBER: INPLASY202210065.


Assuntos
Pontos de Acupuntura , Acidente Vascular Cerebral , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/etiologia , Humanos , Metanálise como Assunto , Acidente Vascular Cerebral/complicações , Revisões Sistemáticas como Assunto
3.
J Chem Phys ; 154(18): 184708, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34241022

RESUMO

Amine-templated metal oxides are a class of hybrid organic-inorganic compounds with great structural diversity; by varying the compositions, 0D, 1D, 2D, and 3D inorganic dimensionalities can be achieved. In this work, we created a dataset of 3725 amine-templated metal oxides (including some metalloid oxides), their composition, amine identity, and dimensionality, extracted from the Cambridge Structure Database (CSD), which spans 71 elements, 25 main group building units, and 349 amines. We characterize the diversity of this dataset over reactants and in time. Artificial neural network models trained on this dataset can predict the most and least probable outcome dimensionalities with 71% and 95% accuracies, respectively, using only information about reactant identities, without stoichiometric information. Surprisingly, the amine identity plays only a minor role in most cases, as omitting this information only reduces the accuracy by <2%. The generality of this model is demonstrated on a time held-out test set of 36 amine-templated lanthanide oxalates, vanadium tellurites, vanadium selenites, vanadates, molybdates, and molybdenum sulfates, whose syntheses and structural characterizations are reported here for the first time, and which contain two new element combinations and four amines that are not present in the CSD.

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