ABSTRACT
Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), is still one of the significant threats to human life. In recent years, the continuous exploration of small molecule inhibitors represented by bedaquinoline has brought new vitality into the field of tuberculosis. However, small molecule inhibitors will inevitably occur acquired drug resistance during clinical medication. As a new pharmacological mechanism, targeted protein degradation (TPD) achieves efficacy by destroying rather than inhibiting protein targets. It might be an excellent strategy to develop anti-tuberculosis drugs based on the TPD concept to solve drug resistance. This article reviews the protein degradation pathways of Mtb, such as the Pup proteasome system and the ClpP-ClpC1 complex enzyme system. The future development of these strategies into TPD drugs was prospected and summarized.
ABSTRACT
MicroRNAs (miRNAs) are known to regulate post-transcriptional gene expression. They are involved in carcinogenesis and tumor progression. The aim of this study was to explore the microRNA-mRNA regulatory network in esophageal squamous cell carcinoma (ESCC) using comprehensive computational approaches. In this study we have selected a total of 11 miRNAs from one previously reported study in ESCC. The mRNA targets of these miRNAs were predicted using various algorithms. The expression profiles of these mRNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples. Based on the miRNA-mRNA regulatory relationships, the network was inferred. A total of 23 miRNA-mRNA regulatory interactions, with 11 miRNAs and 13 mRNA targets, were inferred in ESCC. The miRNA-mRNA regulatory network with increased confidence provides insights into the progression of ESCC and may serve as a biomarker for prognosis or the aggressiveness of ESCC. However, the results should be examined with further experimental validation.
Subject(s)
Humans , Carcinoma, Squamous Cell , Genetics , Case-Control Studies , Esophageal Neoplasms , Genetics , Gene Regulatory Networks , MicroRNAs , Genetics , RNA, Messenger , GeneticsABSTRACT
<p><b>BACKGROUND</b>Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia.</p><p><b>METHODS</b>cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups.</p><p><b>RESULTS</b>Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088).</p><p><b>CONCLUSIONS</b>LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blepharospasm , Diagnostic Imaging , Corpus Striatum , Diagnostic Imaging , Cross-Sectional Studies , Dystonic Disorders , Diagnostic Imaging , EchoencephalographyABSTRACT
Objective To explore the permeability of nerve growth factor(NGF)through blood brain barrier and protective effect of NGF by periphery in neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods The models with HIBD were established and NGF 5 ?g/kg was injected intravenously with 125I,and the permeability of NGF was observed by periphery through blood brain barrier of neonatal rats.Then apoptosis in each group was examined in tissues,samples of frontal cortex and CA1 district in cornu ammonis by TUNEL method.Results The contents of 125I-NGF in neonatal rats and ratio with blood content was higher than those of adult rats,then contents of 125I-NGF in neonatal rats with HIBD and ratio with blood content were higher than those of the neonatal rats(Pa