The use of artificial intelligence in the treatment of rare diseases: A scoping review.

With the increasing application of artificial intelligence (AI) in medicine and healthcare, AI technologies have the potential to improve the diagnosis, treatment, and prognosis of rare diseases. Presently, existing research predominantly focuses on the areas of diagnosis and prognosis, with relatively fewer studies dedicated to the domain of treatment. The purpose of this review is to systematically analyze the existing literature on the application of AI in the treatment of rare diseases. We searched three databases for related studies, and established criteria for the selection of retrieved articles. From the 407 unique articles identified across the three databases, 13 articles from 8 countries were selected, which investigated 10 different rare diseases. The most frequently studied rare disease group was rare neurologic diseases (n = 5/13, 38.46%). Among the four identified therapeutic domains, 7 articles (53.85%) focused on drug research, with 5 specifically focused on drug discovery (drug repurposing, the discovery of drug targets and small-molecule inhibitors), 1 on pre-clinical studies (drug interactions), and 1 on clinical studies (information strength assessment of clinical parameters). Across the selected 13 articles, we identified total 32 different algorithms, with random forest (RF) being the most commonly used (n = 4/32, 12.50%). The predominant purpose of AI in the treatment of rare diseases in these articles was to enhance the performance of analytical tasks (53.33%). The most common data source was database data (35.29%), with 5 of these studies being in the field of drug research, utilizing classic databases such as RCSB, PDB and NCBI. Additionally, 47.37% of the articles highlighted the existing challenge of data scarcity or small sample sizes.

[Retracted] Downregulation of microRNA­195 promotes angiogenesis induced by cerebral infarction via targeting VEGFA.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data shown in Fig. 3C were strikingly similar to data appearing in different form in another article by different authors at a diferent research institute. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 5434­5440, 2017; DOI: 10.3892/mmr.2017.7230].

MicroRNA­29a contributes to intracranial aneurysm by regulating the mitochondrial apoptotic pathway.

Intracranial aneurysm (IA) is an abnormal expansion in the intracranial arteries that weakens the arterial wall by consistently pushing the vascular wall outwards, which leads to a higher risk of aneurysm rupture. A number of reports have demonstrated that apoptosis is associated with the growth and rupture of IA. MicroRNAs (miRNAs/miRs) perform vital roles in the regulation of the mitochondrial apoptotic pathway and signaling proteins. Increasing evidence has already revealed the role of miR­29a in injury, including liver injury, cardiovascular injury and ischaemia­reperfusion injury. However, the role of miR­29a in IA remains unclear at present. The present study investigated the role of miR­29a in IA pathogenesis and the underlying mechanisms. By using reverse transcription­quantitative polymerase chain reaction and western blot analysis, the present study demonstrated that genes, including caspase­3, ­8 and ­9, and proteins, including cytochrome c and myeloid cell leukemia 1 (Mcl­1), involved in mitochondrial apoptosis pathways were upregulated in IA groups compared with controls. In addition, microarray analysis demonstrated that miR­29a, one of the most altered miRs in IA mice, was overexpressed in IA mice compared with controls. In vitro experiments revealed that miR­29a downregulation attenuated human brain vascular smooth muscle cell (HBVSMC) apoptosis, while miR­29a overexpression increased the apoptosis of HBVSMCs. Furthermore, luciferase reporter analysis revealed that Mcl­1 is a direct target gene of miR­29a. An in vivo IA model confirmed that miR­29a overexpression may promote apoptosis through mitochondrial pathways. It was therefore concluded that miR­29a may contribute to the progression of IA by regulating mitochondrial apoptotic pathways. Thus, miR­29a is a potential therapeutic target for IA.

Downregulation of microRNA-195 promotes angiogenesis induced by cerebral infarction via targeting VEGFA.

Angiogenesis, the formation of new blood vessels from preexisting endothelium, is a process that involves a series of interassociated and mutually interactive pathophysiological processes. It is accepted that microRNAs (miRNAs) regulate endothelial cell behavior, including their involvement in angiogenesis. However, it remains unclear whether miRNAs are involved in the regulation of angiogenesis following cerebral ischemia. Therefore, the present study aimed to investigate the role of miRNAs in angiogenesis and the underlying mechanism following cerebral ischemia. Expression profiles of miRNAs in rat brain samples following middle cerebral artery occlusion (MCAO) were investigated using a miRNA microarray. The expression of candidate miRNA, miR­195 was further validated using reverse transcription­quantitative polymerase chain reaction. Then, the effects of miR­195 on cell migration and tube formation of human umbilical vein vascular endothelial cells (HUVECs) were investigated following miR­195 silencing, and overexpression. The specific target genes of miR­195 were predicted using microRNA prediction bioinformatics software (http://www.microrna.org/microrna/home.do), and then confirmed using a dual­luciferase reporter assay and rescue experiment. It was demonstrated that miR­195 was significantly downregulated in the brains of rats following MCAO and in hypoxia­induced HUVECs. Furthermore, it was revealed that miR­195 overexpression inhibited the invasion ability and tube formation of HUVECs in vitro, while miR­195 silencing enhanced these functions. In addition, vascular endothelial growth factor A (VEGFA) was identified as a direct target of miR­195 and was negatively correlated with miR­195 expression. In addition, the rescue experiment revealed that overexpression of VEGFA reversed the inhibitory effects of miR­195 overexpression on the invasion ability and tube formation of HUVECs. The present study has provided a novel insight into the promoting roles of miR­195 downregulation on angiogenesis following cerebral infarction and suggests that the miR­195/VEGFA signaling pathway is a putative therapeutic target in cerebral ischemia.