ABSTRACT
As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified
ABSTRACT
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
ABSTRACT
Objective To assess the academic level of randomized controlled trial abstracts in papers on budesonid adjuvant therapy for children pneumonia and analyze its influencing factors. Methods The randomized controlled tri-al abstracts in papers on budesonid adjuvant therapy for children pneumonia were assessed according to the CON-SORT 2010 Statement and were statistically analyzed using the RevMan 5 . 3 . Results The items with a low reporting rate of the randomized controlled trial abstracts in the 282 papers included in this paper were "title judged as ran-dom","communication author","randomized","blind method","randomized grouping cases","fund-suppor-ted". Hierarchical analysis showed that the number of words in abstracts played an important role in affecting the reported items. Conclusion The academic level of randomized controlled trial abstracts in papers on budesonid adju-vant therapy for children pneumonia is significantly different from that of the abstracts in clinical papers according to the CONSORT 2010 Statement. Researchers should thus use the CONSORT 2010 Statement-defined items in writing their papers in order to improve the academic level and readability of their abstracts.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical manifestations, pathological characteristics, and treatments of urothelial-type mucinous adenocarcinoma of the prostate (UMAP).</p><p><b>METHODS</b>We reported a case of UMAP, reviewed relevant literature, and analyzed the clinicopaothological features, diagnosis, treatment, and prognosis of the disease.</p><p><b>RESULTS</b>The patient was a 60-year-old male and underwent transurethral resection of the prostate for dysuria. Postoperative pathology indicated mucinous adenocarcinoma and sigmoidoscopy revealed no primary colon cancer. Immunohistochemical staining showed the negative expressions of PSA and P504s and positive expressions of CK7, CK34 β E12, CK20, and CDX2. Thus UMAP was confirmed and treated by intensity-modulated radiotherapy. Then the patient was followed up for 30 months, which showed desirable therapeutic result, with neither local progression nor distant metastasis.</p><p><b>CONCLUSION</b>UMAP has a bad prognosis and its diagnosis depends on pathological and immunohistocchemical examinations. It responds well to radical prostatectomy but is not sensitive to endocrine therapy. Radiotherapy can be considered for those who are not fit to receive radical prostatectomy.</p>