Malignant astrocytoma (MA) is the most common and severe type of brain tumor. A greater understanding of the underlying mechanisms responsible for the development of MA would be beneficial for the development of targeted molecular therapies. In the present study, the upregulated differentially expressed genes (DEGs) in MA were obtained from the Gene Expression Omnibus database using R/Bioconductor software. DEGs in different World Health Organization classifications were compared using the Venny tool and 15 genes, including collagen type I α1 chain (COL1A1) and laminin subunit γ1 (LAMC1), were revealed to be involved in the malignant progression of MA. In addition, the upregulated DEGs in MA were evaluated using functional annotations of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes with the Database for Annotation, Visualization, and Integrated Discovery tool. The results indicated that invasion-associated enrichment was observed in 'extracellular matrix' (ECM), 'cell adhesion' and 'phosphoinositide 3-kinase-protein kinase B signaling pathway'. Subsequently, the analysis of the protein-protein interactions was performed using STRING and Cytoscape software, which revealed that the ECM component was the invasion-associated module and its corresponding genes included COL1A1, LAMC1 and fibronectin 1. Finally, survival Kaplan-Meier estimate was conducted using cBioportal online, which demonstrated that COL1A1 expression affected the survival of and recurrence in patients with MA. Moreover, the results of in vitro Transwell assay and western blot analysis revealed that the depleted levels of COL1A1 also decreased the expression of several proteins associated with cell invasion, including phosphorylated-signal transducer and activator of transcription 3, matrix metalloproteinase (MMP)-2, MMP-9 and nuclear factor-κB. On the whole, the present study identified the invasion-related target genes and the associated potential pathways in MA. The results indicated that COL1A1 may be a candidate biomarker for the prognosis and treatment of MA.

Chronic pain occurs in ~85–90% of chronic pancreatitis (CP) patients. However, as the pathogenesis of CP pain remains to be fully understood, the current therapies for CP pain remain inadequate. Emerging evidence has suggested that the epigenetic modulations of genes are involved in chronic pain. In the present study, intrapancreatic trinitrobenzene sulfonic acid infusions were used to establish a CP model in rats. Mechanical allodynia was measured with von Frey filaments. Immunofluorescent staining analysis was used to observe the expression changes of histone deacetylase 2 (HDAC2) and µ-opioid receptor (MOR), and intrathecal administration of the selective HDAC2 inhibitor AR-42 was used to assess the underlying mechanisms. The expression levels of c-Jun N-terminal kinase (JNK) in the thoracic spinal cord were detected by western blotting, and the mRNA expression levels of interleukin (IL)1-β, IL-6 and tumor necrosis factor (TNF)-α were detected by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that HDAC2 expression was upregulated during the course of CP induction, while MOR activity in the thoracic spinal dorsal horn was significantly suppressed. Intrathecal infusion of AR-42 significantly attenuated CP-induced mechanical allodynia, with rescued MOR activity. Additionally, HDAC2 facilitated the release of inflammatory cytokines, including IL-1β, IL-6 and TNF-α. These results suggested that the underlying mechanisms of HDAC2 regulating MOR activity under CP induction may occur via promoting the release of inflammatory cytokines, thus activating the JNK signaling pathway. The present study suggested that the epigenetic-regulated disturbance of MOR is dependent on the endogenous analgesia system in CP, which may a provide novel therapeutic strategy for treating pain in CP.

Morphologic features and electrical membrane properties of neurons in the substantia gelatinosa (SG) of the caudal spinal trigeminal nucleus (the medullary dorsal horn; MDH) were examined in the rat. Intracellular recording and biocytin-injection combined with histochemical staining were performed in horizontal slices. Twenty-four SG (lamina II) neurons were recorded stably and stained successfully. Both projection neurons (PNs; n = 9) that sent axons to regions outside the MDH and intrinsic neurons (INs; n = 15) that sent axons only to the MDH were observed. The INs were divided into those with dense axonal arborization (INDAs; n = 7) and those with sparse axonal arborization (INSAs; n = 8). In the PNs, the dendrites with spines spread to all MDH layers (laminae I-III). The main axons sent collaterals within the SG and rostrally, caudally, or medially to laminae I and III of the MDH, interpolar spinal trigeminal nucleus, spinal tract of the trigeminal nerve, or upper cervical cord segments. In the INDAs, the dendrites arising from the rostral and caudal pole of the cell bodies mainly extended rostrally and caudally parallel to the rostrocaudal axis of the SG: the dendritic trees were elongated and oval in shape and were confined within the SG. The axonal field of each INDA, a dense mesh of axonal processes, was elongated and oval in shape and almost was confined within the SG. In the INSAs, a small, round cell body was located in the center of each dendritic field, which usually was limited within the SG. Axonal processes ran radially to spread to all layers of the MDH, constituting round or oval axonal fields. The three groups of SG neurons showed more or less different intracellular responses to current injections. In particular, adaptation of spike frequency, hyperpolarizing sag, and rebound excitation were observed in the PNs and INSAs but not in the INDAs. Slow ramp depolarization and slow afterdepolarization were recorded only in INDAs.

Down syndrome (DS) or trisomy 21 is a genetic condition often accompanied by chronic pain caused by congenital abnormalities and/or conditions, such as osteoarthritis, recurrent infections, and leukemia. Although DS patients are more susceptible to chronic pain as compared to the general population, the pain experience in these individuals may vary, attributed to the heterogenous structural and functional differences in the central nervous system, which might result in abnormal pain sensory information transduction, transmission, modulation, and perception. We tried to elaborate on some key questions and possible explanations in this review. Further clarification of the mechanisms underlying such abnormal conditions induced by the structural and functional differences is needed to help pain management in DS patients.

A pair of new 8-oxa-bicyclo[3,2,1]oct-3-en-2-one derivative enantiomers, (�)-acutalourin [(�)-1], a new racemic linear sesquiterpenoid acutalourone (2), along with five known caffeic acid derivatives (3-7), were isolated from Argyreia acuta Lour. The structures were determined by a combination of spectro-scopic data interpretation. The absolute stereochemistry of (+)-acutalourin and (À )-acutalourin were proposed by comparison of their experimental electronic circular dichroism (ECD) curves with the time-dependent density functional theory (TDDFT)-calculated curves.