Excitatory neurons in the lateral parabrachial nucleus mediate the interruptive effect of inflammatory pain on a sustained attention task.

BACKGROUND: Attentional deficits are among the most common pain-induced cognitive disorders. Pain disrupts attention and may excessively occupy attentional resources in pathological states, leading to daily function impairment and increased disability. However, the neural circuit mechanisms by which pain disrupts attention are incompletely understood. METHODS: We used a three-choice serial reaction time task (3CSRTT) to construct a sustained-attention task model in male C57BL/6J mice. Formalin or complete Freund's adjuvant was injected into a paw to establish an inflammatory pain model. We measured changes in 3CSRTT performance in the two inflammatory pain models, and investigated the neural circuit mechanisms of pain-induced attentional deficits. RESULTS: Acute inflammatory pain impaired 3CSRTT performance, while chronic inflammatory pain had no effect. Either inhibition of the ascending pain pathway by blockade of the conduction of nociceptive signals in the sciatic nerve using the local anesthetic lidocaine or chemogenetic inhibition of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) neurons in the lateral parabrachial nucleus (LPBN) attenuated the acute inflammatory pain-induced impairment of 3CSRTT performance, while chemogenetic activation of CaMKIIα neurons in the LPBN disrupted the 3CSRTT. Furthermore, the activity of CaMKIIα neurons in the LPBN was significantly lower on Day 2 after complete Freund's adjuvant injection than on the day of injection, which correlated with the recovery of 3CSRTT performance during chronic inflammatory pain. CONCLUSIONS: Activation of excitatory neurons in the LPBN is a mechanism by which acute inflammatory pain disrupts sustained attention. This finding has implications for the treatment of pain and its cognitive comorbidities.

[Proliferation of MicroRNA-365 and E74-like Factor 4 in Cervical Cancer Cells and Its Clinical Significance].

Objective To investigate the expressions,roles,and clinical significance of microRNA-365(miR-365)and E74-like factor 4(ELF4)in cervical cancer. Methods The expressions of miR-365 in normal cervical tissues(n=34),cervical intraepithelial neoplasia 1(CIN 1)(n=31),cervical intraepithelial neoplasia2-3(CIN 2-3)(n=37),squamous cell carcinoma of the cervix(SCC)(n=33),and three cervical cancer cell lines(C33A cells,Hela cells,and SiHa cells)were detected by real-time quantitative polymerase chain reaction(qPCR).Bioinformatic prediction and luciferase reporter gene assay were performed to verify whether ELF4 was a direct target of miR-365.Western blot and immunohistochemistry were used to detect ELF4 expression in cervical cancer cells and in different pathological cervix tissues.CCK8 assay was used to detect the effect of overexpression or inhibition of miR-365 on the proliferation of cervical cancer cells at different time points.The relationships among the miR-365 expression,ELF4 expression,and clinicopathological parameters of cervical cancer were analyzed by correlation analysis. Results qPCR results showed that compared with the normal cervical cell HcerEpic,the expressions of miR-365 in CIN1,CIN2-3,and cervical cancer tissues gradually decreased with the increased pathologic grade,and its expressions also decreased in different cervical cancer cell lines.The luciferase reporter gene assay confirmed that ELF4 was the direct target of miR-365.Western blot showed that the expression of ELF4 increased in all three cervical cancer cell lines compared with normal cervical epidermal cell(P=0.013,P=0.002,P=0.004).Immunohistochemistry showed that ELF4 expression was up-regulated in CIN and cervical cancer tissues.CCK8 assay showed that overexpression of miR-365 inhibited cell proliferation,while inhibition of miR-365 promoted the proliferation of three cervical cancer cells(P<0.05).Further analysis confirmed that there was a negative correlation between the expression levels of miR-365 and ELF4 in CIN2-3 and SCC(r=-0.351,P=0.045;r=-0.349,P=0.035).Clinical analysis showed that the expressions of both miR-365 and ELF4 were correlated with tumor size,pathological grade,and clinical stage in SCC(all P < 0.05).Conclusion The decreased expression of miR-365 in human cervical cancer cells relieves its inhibitory effect on ELF4,which promotes the proliferation of cervical cancer cells and the formation of tumor.

Efficient Capture and Effective Sensing of Cr2O72- from Water Using a Zirconium Metal-Organic Framework.

Highly efficient decontamination of heavily toxic Cr2O72- from water remains a serious task for public health and ecosystem protection. An easily regenerative and reused sorbent with suitable porosity may address this task. Herein, a series of water-stable and ecofriendly metal-organic frameworks (MOFs) with large surface areas were assessed for their ability to adsorb and separate Cr2O72- from aqueous solutions. Among these tested MOFs, NU-1000 shows an extraordinary capability to efficiently capture (within 3 min) Cr2O72- with a sorption capacity of up to 76.8 mg/g, which is the largest one for the neutral MOF-based Cr2O72- sorbents. NU-1000 also shows remarkable selectivity for Cr2O72- capture and can effectively reduce the Cr(VI) concentration from 24 ppm to 60 ppb, which is below the acceptable limit for the drinking water standard (100 ppb by the U.S. Environmental Protection Agency). Moreover, this adsorbent can be easily regenerated by Soxhlet extraction with an acidic methanol solution (2.5 M HCl) and can be reused at least three times without a significant loss of it adsorption ability. More intriguingly, NU-1000 can also serve as an efficient photoluminescent probe for the selective detection of Cr2O72- in aqueous media. The Cr2O72- detection limit is as low as 1.8 µM, and the linear range is from 1.8 to 340 µM. Our work shows that NU-1000 is a unique material combining both efficient sorption and exceptional fluorescent sensing of Cr2O72- in aqueous media.

KLF5 promotes cervical cancer proliferation, migration and invasion in a manner partly dependent on TNFRSF11a expression.

Although the transcription factor Krüppel-like factor 5 (KLF5) plays important roles in both inflammation and cancer, the mechanism by which this factor promotes cervical carcinogenesis remains unclear. In this study, we demonstrated a potential role for tumour necrosis factor receptor superfamily member 11a (TNFRSF11a), the corresponding gene of which is a direct binding target of KLF5, in tumour cell proliferation and invasiveness. Coexpression of KLF5 and TNFRSF11a correlated significantly with tumorigenesis in cervical tissues (P < 0.05) and manipulation of KLF5 expression positively affected TNFRSF11a mRNA and protein expression. Functionally, KLF5 promoted cancer cell proliferation, migration and invasiveness in a manner dependent partly on TNFRSF11a expression. Moreover, in vivo functional TNFRSF11a-knockdown mouse studies revealed suppression of tumorigenicity and liver metastatic potential. Notably, tumour necrosis factor (TNF)-α induced KLF5 expression by activating the p38 signalling pathway and high KLF5 and TNFRSF11a expression increased the risk of death in patients with cervical squamous cell carcinoma. Our results demonstrate that KLF5 and TNFRSF11a promote cervical cancer cell proliferation, migration and invasiveness.

Changes of TIZ expression in epithelial ovarian cancer cells.

OBJECTIVE: To study the change of TIZ expression in epithelial ovarian cancer cells. METHODS: HO8910 cells were transinfected with siRNA to inhibit the expression of TIZ. pcDNA3.1-TIZ vectors were combined to increase the TIZ expression level. The cell viability, colony forming efficiency and cycle distribution of HO8910, HO8910/NC, HO8910/pcDNA3.1-NC, HO8910/TIZ-573 and H08910/pcDNA3.1-TIZ were compared, and the invasion rate, migration rate and adhesion rate between 5 groups of cells were compared. RESULTS: Compared with those of HO8910, HO8910/NC and HO8910/pcDNA3.1-NC, the cell viability, colony forming efficiency and cell cycle distribution of HO8910/TIZ-573 were increased, while the indexes of H08910/pcDNA3.1-NC were decreased with statistical significant difference (P<0.05). There was no statistical significant difference in the invasion rate, migration rate and adhesion rate between 5 groups of cells (P>0.05). CONCLUSIONS: The expression of TIZ can inhibit the proliferation of epithelial ovarian cancer cells.