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.

Long non-coding RNAs (lncRNAs) are considered to be important regulators in breast cancer. In the present study, the potential mechanisms and functional roles of lncRNA PSMG3-antisense (AS)1 were investigated in vivo and in vitro. The relative expression levels of lncRNA PSMG3-AS1 and microRNA (miR)-143-3p were determined using reverse-transcription quantitative PCR. The protein expression levels of collagen type 1 alpha 1 (COL1A1) and proliferating cell nuclear antigen (PCNA) were obtained using western blot analysis. Bioinformatics analysis was used to identify the relationship between PSMG3-AS1, miR-143-3p and COL1A1. Colony forming and Cell Counting Kit-8 assays were used to detect cell proliferation. Transwell and wound-healing assays were used to determine cell migration. The results of the present study demonstrated that PSMG3-AS1 expression was increased in breast cancer tumor tissues and cell lines, and that of miR-143-3p was decreased. Knockdown of PSMG3-AS1 increased the level of miR-143-3p expression, which led to the mitigation of proliferation and migration capacity in breast carcinoma cells. Additionally, PSMG3-AS1 knockdown was demonstrated to reduce the mRNA and protein expression levels of COL1A1. miR-143-3p mimic transfection reduced proliferation and migration in MDA-MB-231 and MCF-7 cell lines. Furthermore, miR-143-3p inhibition significantly increased the proliferation and migration of breast cancer cells compared with the negative control group. The mRNA and protein expression levels of PCNA were reduced in the MCF-7 cell line when transfected with miR-143-3p mimics and si-PSMG3-AS1. However, PCNA expression was increased in cells transfected with a miR-143-3p inhibitor. In conclusion, the results of the present study identified a novel lncRNA PSMG3-AS1, which serves as a sponge for miR-143-3p in the pathogenesis of breast cancer. PSMG3-AS1 may be used as a potential therapeutic target gene in breast cancer treatment.

BackgroundGastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.ResultsAnalysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.ConclusionsThis study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.

As a key enzyme in de novo pyrimidine biosynthesis, the expression level of dihydroorotate dehydrogenase (DHODH) has been reported to be elevated in various types of malignant tumors and its tumor-promoting effect was considered to relate to its pyrimidine synthesis function. Here, we revealed one intriguing potential mechanism that DHODH modulated β-catenin signaling in esophageal squamous cell carcinoma (ESCC). We demonstrated that DHODH directly bound to the NH2 terminal of β-catenin, thereby, interrupting the interaction of GSK3β with β-catenin and leading to the abrogation of β-catenin degradation and accumulation of β-catenin in the nucleus, which in turn, resulted in the activation of β-catenin downstream genes, including CCND1, E2F3, Nanog, and OCT4. We further demonstrated that the regulation of β-catenin by DHODH was independent of DHODH catalyzing activity. Univariate and multivariate analyses suggested that DHODH expression might be an independent prognostic factor for ESCC patients. Collectively, our study highlights the pivotal role of DHODH mediated β-catenin signaling and indicates that DHODH may act as a multi-functional switcher from catalyzing pyrimidine metabolism to regulating tumor-related signaling pathways in ESCC.

No abstract

Breast cancer (BC) is the most common cause of death in women throughout the world. MicroRNAs (miRNAs, miR) have been identified as key regulators in carcinogenesis of several cancers, including BC. MicroRNA‐216a (miR‐216a) is downregulated in several cancers. Here, we evaluated the effects of miRNA‐216a on breast cancer cells and the underlying mechanisms. miR‐216a level was quantified by real‐time RT‐PCR. Cell viability was analyzed by MTT assay. Wound‐healing assay was performed for detection of cell migration. Apoptosis was detected by TUNEL and caspase‐3 activity assay. Moreover, the level of protein expression was determined by Western blot. We found that miR‐216a expression was remarkably decreased in both human BC tissues and MCF‐7 cells. miR‐216a overexpression dramatically suppressed the migration and promoted the apoptosis in cultured MCF‐7 cells. We validated PKCα (protein kinase C alpha, PRKCA) as a direct target of miR‐216a. Knockdown of PKCα induced apoptosis and inhibited migration in cultured MCF‐7 cells which were reversed by miR‐216a inhibitor. Moreover, the level of miR‐216a is negatively correlated with PKCα in cell lines. Our results collectively suggest that miR‐216a suppressed migration and promoted apoptosis in breast cancer cells by targeting PKCα. These findings indicate that manipulation of miR‐216a expression may represent a novel therapeutic strategy in the treatment of breast cancer.

Objectives. This systematic review aims to summarize the existing literature on Tai Chi randomized controlled trials (RCTs) and recommend Tai Chi exercise prescriptions for different diseases and populations. Methods. A systematic search for Tai Chi RCTs was conducted in five electronic databases (PubMed, Cochrane Library, EMBASE, EBSCO, and Web of Science) from their inception to December 2019. SPSS 20.0 software and Microsoft Excel 2019 were used to analyze the data, and the risk of bias tool in the RevMan 5.3.5 software was used to evaluate the methodological quality of RCTs. Results. A total of 139 articles were identified, including diseased populations (95, 68.3%) and healthy populations (44, 31.7%). The diseased populations included the following 10 disease types: musculoskeletal system or connective tissue diseases (34.7%), circulatory system diseases (23.2%), mental and behavioral disorders (12.6%), nervous system diseases (11.6%), respiratory system diseases (6.3%), endocrine, nutritional or metabolic diseases (5.3%), neoplasms (3.2%), injury, poisoning and certain other consequences of external causes (1.1%), genitourinary system diseases (1.1%), and diseases of the eye and adnexa (1.1%). Tai Chi exercise prescription was generally classified as moderate intensity. The most commonly applied Tai Chi style was Yang style (92, 66.2%), and the most frequently specified Tai Chi form was simplified 24-form Tai Chi (43, 30.9%). 12 weeks and 24 weeks, 2-3 times a week, and 60 min each time was the most commonly used cycle, frequency, and time of exercise in Tai Chi exercise prescriptions. Conclusions. We recommend the more commonly used Tai Chi exercise prescriptions for different diseases and populations based on clinical evidence of Tai Chi. Further clinical research on Tai Chi should be combined with principles of exercise prescription to conduct large-sample epidemiological studies and long-term prospective follow-up studies to provide more substantive clinical evidence for Tai Chi exercise prescriptions.

No abstract