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Background: Actin-related protein 2/3 complex subunit 1B (ARPC1B) is reported to be involved in tumorigenesis and progression. However, its role in kidney renal clear cell carcinoma (KIRC), correlation with tumor-infiltrating immune cells, and prognostic significance remain unclear.Methods: Data sets from the TCGA, GTEx, GEPIA, GEO, UALCAN, and CPTAC databases were extracted and analyzed to investigate the expression difference, prognosis, and clinicopathological features of ARPC1B. Single-sample Gene Set Enrichment Analysis (ssGSEA), CIBERSORT, and TISCH2 analysis were used to examine the relationship between ARPC1B expression and tumor immune infiltration in KIRC. The potential function of ARPC1B in KIRC was explored by GO functional annotation and KEGG pathway analysis. The TIDE algorithm was used to predict and analyze the relationship between ARPC1B expression and response to immune checkpoint blockade (ICB). The expression of ARPC1B was further validated by using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).Results: The study showed that ARPC1B expression was an independent prognostic factor of KIRC, with high ARPC1B expression being associated with poor overall survival (OS). Enrichment of GO annotation and pathway analysis showed multiple immune-related functional pathways affected by ARPC1B such as regulation of immune effector process, inflammatory response regulation, antigen processing and presentation, asthma, autoimmune thyroid disease, graft versus host disease, intestinal immune network for IgA production, and type I diabetic mellitus. Moreover, ARPC1B expression positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in KIRC. Importantly, high ARPC1B expression predicted a low response to ICB in KIRC.Conclusion: This study indicates that ARPC1B expression is an independent prognostic biomarker for OS in KIRC patients. High ARPC1B expression is closely associated with MDSCs and Tregs infiltration. These findings suggest that ARPC1B may serve as a biomarker for prognosis and immune infiltration in KIRC, potentially aiding in the development of novel treatment strategies to improve the survival outcomes for KIRC patients.

The present study aimed to investigate the role of JWA gene in the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells and the effect on the MAPK signaling pathway. Human PANC-1 pancreatic cancer cells were cultured in vitro, and small interfering RNA (siRNA) was designed for the JWA gene. The siRNA was transfected into PANC-1 cells. Subsequently, the cell proliferation was measured by MTT assay; cell apoptosis was detected by analyzing BAX and Bcl-2 protein expression; cell migration and invasion were measured using Transwell® chambers; and the protein expression of JWA and ERK1/2, JNK and p38 and their phosphorylated forms were measured by western blotting. By utilizing the MTT assay, the results showed that when JWA protein expression was inhibited, the proliferation of PANC-1 cells was enhanced. In addition, the expression of apoptosis-associated protein (AAP) BAX was substantially decreased, while the expression of the apoptosis inhibitor gene, Bcl-2, was significantly enhanced. Using Transwell chambers, it was found that the number of penetrating PANC-1 cells was significantly increased after transfection with JWA siRNA, suggesting that the migration and invasion of the cells was substantially increased. By studying the association between JWA and the MAPK pathway in PANC-1 cells, it was found that the expression of p-ERK1/2 of the MAPK pathway was significantly downregulated following JWA siRNA transfection. However, the expression levels of ERK1/2, JNK, p38, p-JNK and p-p38 showed no significant differences. In conclusion, it was shown that JWA affects the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells which could be attributed to effects on the expression of ERK1/2 in the MAPK pathway. [ABSTRACT FROM AUTHOR]

The present study evaluated the role of ventrolateral periaqueductal gray (vlPAG)-located orphanin-FQ (OFQ) in the opioid tolerance induced by repeated microinjections of morphine (MOR) into vlPAG. Microinjection of MOR (5 μg/0.5 μl) into vlPAG caused antinociception as quantified with the tail flick and the hot plate tests. When MOR microinjection was repeated twice daily, the antinociceptive effect disappeared within 2 days (tolerance). However, if MOR microinjection was preceded by the OFQ receptor antagonist nocistatin (NST; 1 ng/0.5 μl), the microinjections of MOR did not induce tolerance. If NST microinjections were suspended, subsequent MOR microinjections induced tolerance. In MOR-tolerant rats, a single NST microinjection into vlPAG was enough to restore the antinociceptive effect of MOR. Furthermore, if OFQ (1 ng/0.5 μl) was microinjected into vlPAG, then a MOR microinjection administered 15 min later into vlPAG did not elicit antinociception. Finally, opioid tolerance induced by repeated systemic MOR injections (5 mg/kg, i.p.) was reversed by a single microinjection of NST into vlPAG. This emphasizes the central importance of vlPAG-located OFQ in the MOR tolerance. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Potentiation of GABAA receptor-mediated inhibitory neurotransmission contributes to the anesthetic action of thiopental. However, the inhibiting action of general anesthetic on excitatory neurotransmission also purportedly underlies its effects. The aim of the study was to elucidate the role of glutamate receptors (NMDA and AMPA receptors) in thiopental-induced anesthesia. Intracerebroventricular (i.c.v.) NMDA (50 ng) significantly increased the induction time of loss of righting reflex and decreased sleep time induced by intraperitoneal injection (i.p.) of thiopental (50 mg/kg). Furthermore, NMDA at 50 ng i.c.v. increased the 50% effective dose values for thiopental to produce loss of righting reflex and immobility in response to noxious tail clamp by 25% and 21% (p < 0.05), respectively. However, intrathecal (IT) administration of NMDA or both of i.c.v. or IT administration of AMPA did not show such antagonizing effects on thiopental action at subconvulsive dose. Finally, thiopental (25 mg/kg i.p.) inhibited convulsions induced by NMDA (0.4 μg i.c.v.) or bicuculline (0.6 μg i.c.v.). However, i.p. muscimol (1 mg/kg) blocked the convulsions induced by bicuculline, but not those induced by NMDA at 3 mg/kg. Similarly, i.p. MK-801 (0.1 mg/kg) antagonized NMDA-induced convulsions, but not bicuculline-induced convulsions at 0.3 mg/kg. Therefore, we suggest that the effects of the selective GABAA and NMDA receptors on convulsive behavior are special to their sites of action, and that the inhibitory action of thiopental on NMDA receptors is possibly not mediated by secondary effects of its GABAA receptors agonism. These results above indicate the involvement of NMDA receptors in thiopental-induced anesthesia in mice. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cyclooxygenase (COX), the rate-limiting enzyme in prostaglandins (PG) synthesis, exists in at least two isoforms, COX-1 and COX-2. COX-2 plays an important role in carcinogenesis, and overexpression may increase proliferation, inhibit apoptosis, and enhance the invasiveness of breast cancer cells. Polymorphisms in the regulatory regions of the COX-2 gene may influence function and/or expression and contribute to interindividual variability in susceptibility to cancer. In this study three variants (-1195G/A and -765G/C in the promoter and 8473C/T in 3'UTR) of COX-2 were examined for correlation with breast cancer risk. A case-control study of 615 histologically confirmed breast cancer patients and 643 cancer-free controls frequency-matched for age were selected. Logistic regression analyses revealed that no overall significant associations were detected in the single-locus analysis between three polymorphisms of COX-2 and the risk of breast cancer. However, a significantly increased risk of breast cancer was associated with the combined genotypes containing "more than 3 variant alleles"' (adjusted OR = 1.37, 95% CI 1.01-1.84) compared with the combined genotypes with "0-3 variant alleles." Haplotype analyses showed that haplotypes A-1195G-765T8473 and A-1195C-765T8473 were significantly associated with breast cancer risk (OR = 1.20, 95% CI 1.01-1.43 for A-1195G-765T8473; OR = 9.16, 95% CI 1.14-73.51 for A-1195C-765T8473) compared with the most common haplotype, G-1195G-765T8473. These findings indicate that these three variants in the regulatory regions of COX-2 may contribute to the etiology of breast cancer. [ABSTRACT FROM AUTHOR]

To investigate the relationship between spinal cord norepinephrine,α1 andα2 adrenergic receptors and antinociception of propofol in mice.Kunming mice were used. Antinociceptive tests were investigated with the tail-immersion test and the acetic acid-induced writhing test. The effects of subcutaneous (sc), intrathecal (ith) and intracerebroventricular (icv) injection propofol on pain threshold were observed. The influences of pretreatment with ith 6-hydroxydopamine,α1R antagonist prazosin, orα2R antagonist yohimbine on the antinociception of propofol were studied.Significant antinociception was produced by propofol (25, 50 mg/kg, sc) and propofol (20, 40μg, ith) in tail-immersion test and acetic the acid-induced writhing test (P<0.05 orP<0.01). Icv propofol (10, 20, and 40μg) did not produce any effect on pain threshold in mice (P>0.05). The 6-hydroxydopamine (5 and 10μg), prazosin (5 and 10μg), or yohimbine (5 and 10μg) ith alone did not affect basal tai-flick latency (TFL) in conscious mice, but significantly reduced the TFL as measured by tail-immersion test in propofol (50 mg/kg, sc)-treated mice, compared with basal TFL and vehicle groups (P<0.05 orP<0.01).The spinal cord is a target of propofol antinociception. In mice propofol antinociception is partly mediated by spinal norepinephrine,α1R andα2R. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between ADAM8 tissue expression and patient prognosis in hepatocellular carcinoma (HCC). Methods: ADAM8 expression was analyzed using immunohistochemical staining methods on tissue samples from a consecutive series of 105 HCC patients who underwent resections between 2000 and 2006. The correlation of ADAM8 expression and patients' clinicopathoogical parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: ADAM8 was highly expressed in 54.3% of the HCC patients. The ADAM8 expression level was closely associated with serum AFP elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that a high expression level of ADAM8 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that ADAM8 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. Conclusions: These findings provide evidence that a high expression level of ADAM8 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that ADAM8 may be a potential target of antiangiogenic therapy for HCC. [ABSTRACT FROM AUTHOR]