The BDNF-TrkB signaling pathway in the rostral anterior cingulate cortex is involved in the development of pain aversion in rats with bone cancer via NR2B and ERK-CREB signaling.

Patients with bone cancer pain (BCP) are more prone to aversion. which not only causes mental distress but also aggravates BCP. However, the mechanism of BCP-related aversion is still unclear. Previous studies have demonstrated that the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway of the rostral anterior cingulate cortex (rACC) plays an important role in the regulation of emotions related to chronic pain, such as neuropathic pain or inflammatory pain; however, few studies have investigated the role of this pathway in cancer pain. This study explored the role of BDNF in cancer pain-related aversion in the rACC and to determine whether N-methyl D-aspartate receptor subtype 2B (NR2B) and extracellular signal-regulated kinase (ERK)-cAMP response element-binding (CREB) signaling are involved in cancer pain-related aversion. A Sprague-Dawley rat model of BCP (one of the classic BCP models) was established, and the changes in pain aversion were detected by mechanical stimulation-induced conditioned place avoidance. Our findings confirmed that rats with BCP exhibited intense pain aversion accompanied by the up-regulated BDNF expression in the rACC. Additionally, the pain aversion of BCP rats was reduced while blocking the BDNF-TrkB. Furthermore, the expression of NR2B and phosphorylated ERK (pERK)/phosphorylated CREB (pCREB) were up-regulated with the development of pain aversion, whereas the use of NR2B blocker Ro25-6981, or ERK inhibitor U0126 could reduce the pain aversion. The expression of NR2B and pERK/pCREB were up-regulated after exogenous BDNF was injected into the rACC, whereas the expression levels of NR2B and pERK/pCREB were down-regulated after blocking the BDNF-TrkB signaling. In conclusion, the BDNF-TrkB signaling in the rACC mediates the generation of aversion in rats with BCP, which requires the involvement of NR2B and the ERK-CREB signaling pathway.

Surface modified silver/magnetite nanocomposite activating hydrogen peroxide for efficient degradation of chlorophenols.

The mixed-valent magnetite (Fe3O4) played a critical role in H2O2-based Fenton-like system for the removal of chlorophenols, but high activity and cycle stability of the Fe3O4-based catalysts are still a huge challenge. Herein, a series of surface hydroxyl- and carboxyl-modified Ag0/Fe3O4 nanocomposite catalysts were prepared and used to activate H2O2 for degradation chlorophenols pollutants. Under the optimized condition, nearly 100% degradation ratio were achieved within 2-30 min for 2,4-dichlorophenol, 2,3-dichlorophenol, 3,4-dichlorophenol, 2,4,6-trichlorophenol, p-nitrophenol, and 98% degradation ratio for 2,5-dichlorophenol, 2,6-dichlorophenol and 3,5-dichlorophenol,. Moreover, wide pH applicability was obtained for the Ag0/Fe3O4-H2O2 system, where 95% degradation ratio of 2,4-dichlorophenol was still obtained at pH 6.0. The excellent activity of Ag0/Fe3O4 catalyst can be ascribed to the incorporation of Ag0 nanoparticles that accelerated the Fe(III)/Fe(II) transformation with the assistance of surface hydroxyl and carboxyl groups. Detailed mechanism study indicated a pseudo-second-order kinetic model, where the oxidative degradation and reductive degradation pathways coexisted in the system. The surface-modified Ag0/Fe3O4-H2O2 provide a practical catalyst system for the removal of phenol contaminants with high reaction rate, wide pH adaptability, and validity for a series of chlorophenols.

A Panel of Urinary Long Non-coding RNAs Differentiate Bladder Cancer from Urocystitis.

Liquid biopsy is becoming a promising method for non-invasive cancer detection. In several proof-of-concept studies, long non-coding RNAs (lncRNAs) were found to be potential biomarkers for bladder cancer detection. The objective of this study was to discover a panel of cell-free, urinary lncRNAs as liquid biopsy biomarkers to non-invasively differentiate bladder cancer from chronic urocystitis. To this end, we collected urine samples from both bladder cancer patients and urocystitis patients. These samples were divided into discovery group and validation group. In the discovery group, the expression levels of 16 cell-free urinary lncRNAs were measured by qPCR to discover candidate biomarkers. The diagnostic performance of the candidate lncRNA biomarkers was then evaluated, which led to a panel of lncRNA biomarkers for bladder cancer detection. The performance of this panel of biomarkers was further evaluated in the validation group to see if these lncRNA biomarkers could discriminate the bladder cancer patients from urocystitis patients. We found that all of the 16 lncRNAs evaluated in this study demonstrated significant difference (p<0.05) of expression between bladder cancer patients and urocystitis patients. Nine lncRNAs provided decent diagnostic performance with area under the receiver operating characteristic (ROC) curve (AUC) reaching 0.70 or higher. We then selected the top four lncRNAs, namely UCA1-201, HOTAIR, HYMA1 and MALAT1, to form a panel of urinary biomarkers. Using this panel, bladder cancer patients could be discriminated from urocystitis patients, with sensitivity and specificity reaching 95.7% and 94.3%, respectively. Finally, we confirmed the applicability of the four-lncRNA panel in an independent validation study that included 60 bladder cancer patients and 60 urocystitis patients. Our study paves the way for further studies aimed at large-scale clinical tests of developing lncRNA biomarkers in urine for bladder cancer diagnostics.

Preparation of porous semi-IPN temperature-sensitive hydrogel-supported nZVI and its application in the reduction of nitrophenol.

Nanoscale zero-valent iron (nZVI) particles supported on a porous, semi-interpenetrating (semi-IPN), temperature-sensitive composite hydrogel (PNIPAm-PHEMA). nZVI@PNIPAm-PHEMA, was successfully synthesized and characterized by FT-IR, SEM, EDS, XRD and the weighing method. The loading of nZVI was 0.1548 ±â€¯0.0015 g/g and the particle size was 30-100 nm. NZVI was uniformly dispersed on the pore walls inside the PNIPAm-PHEMA. Because of the well-dispersed nZVI, the highly porous structure, and the synergistic effect of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA showed excellent reductive activity and wide pH applicability. 95% of 4-NP in 100 mL of 400 mg/L 4-NP solution with initial pH 3.0-9.0 could be completely reduced into 4-AP by about 0.0548 g of fresh supported nZVI at 18-25 °C under stirring (110 r/min) within 45 min reaction time. A greater than 99% 4-NP degradation ratio was obtained when the initial pH was 5.0-9.0. The reduction of 4-NP by nZVI@PNIPAm-PHEMA was in agreement with the pseudo-first-order kinetics model with Kobs values of 0.0885-0.101 min-1. NZVI@PNIPAm-PHEMA was able to be recycled, and about 85% degradation ratio of 4-NP was obtained after its sixth reuse cycle. According to the temperature sensitivity of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA exhibited very good storage stability, and about 88.9% degradation ratio of 4-NP was obtained after its storage for 30 days. The hybrid reducer was highly efficient for the reduction of 2-NP, 3-NP, 2-chloro-4-nitrophenol and 2-chloro-4-nitrophenol. Our results suggest that PNIPAm-PHEMA could be a good potential carrier, with nZVI@PNIPAm-PHEMA having potential value in the application of reductive degradation of nitrophenol pollutants.

Neuroprotective potential of ketamine prevents developing brain structure impairment and alteration of neurocognitive function induced via isoflurane through the PI3K/AKT/GSK-3ß pathway.

BACKGROUND: The aim of the current experimental study was to scrutinize the neuroprotective effect of ketamine on the isoflurane (iso)-induced cognitive dysfunction in rats via phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3ß (GSK-3ß) pathway. MATERIALS AND METHODS: Sprague-Dawley rats were used for the current experimental study. The rats were divided into six groups and rats were treated with ketamine and memantine. For the estimation of cognitive function study, we used the Morris water test. Pro-inflammatory cytokines such as IL-1ß, IL-6, tumor necrosis factor-α (TNF-α), and caspase-6; the antioxidant parameters malondialdehyde, glutathione, superoxide dismutase, catalase, and protein carbonyl; acetylcholinesterase, amyloid ß, and brain-derived neurotrophic factor were estimated, respectively. The protein expression of AKT, GSK-3ß, p21WAF1/CIP1, and p53 was also estimated, respectively. RESULTS: Ketamine significantly enhanced cognitive function and showed anti-inflammatory and antioxidant effects, and exhibited the neuroprotective effect of ketamine against the isoflurane-induced cognitive impairment. Additionally, ketamine significantly (P<0.005) suppressed IL-1ß, TNF-α, IL-6, caspase-6 and p21WAF1/CIP1, p53 expression and up-regulated the PI3K/AKT/GSK-3ß expression in the group of iso-induced rats. CONCLUSION: We can conclude that ketamine prevented the cognitive impairment induced by isoflurane anesthesia through anti-apoptotic, anti-inflammatory, and antioxidant effects via the PI3K/AKT/GSK-3ß pathway.

MITF-M regulates melanogenesis in mouse melanocytes.

BACKGROUND: Although the impact of the microphthalamia-associated transcription factor (Mitf) signaling pathway on melanocytes progression has been extensively studied, the specific molecular mechanisms behind MITF-M-enhanced melanin production in melanocytes still need to be clarified. METHODS: In this study, we analyzed the levels of Mitf-M in skin tissues of different coat mice in order to further reveal the relationship between Mitf-M and skin pigmentation. To address the function of Mitf-M on melanogenesis, we have used an overexpression system and combined morphological and biochemical methods to investigate its localization in different coat color mice and pigmentation-related genes' expression in mouse melanocytes. RESULTS: The qRT-PCR assay and Western blotting analysis revealed that Mitf-M mRNA and protein were synthesized in all tested mice skin samples, with the highest expression level in brown skin, a moderate expression level in grey skin and the lowest expression level in black skin. Simultaneously, immunofluorescence staining revealed that MITF-M was mainly expressed in the hair follicle matrix and inner and outer root sheath in the skin tissues with different coat colors. Furthermore, overexpression of MITF-M led to increased melanin content and variable pigmentation-related gene expression. CONCLUSION: These results directly demonstrate that MITF-M not only influences melanogenesis, but also determines the progression of melanosomal protein in mouse melanocytes.

FGF21 regulates melanogenesis in alpaca melanocytes via ERK1/2-mediated MITF downregulation.

Fibroblast growth factor 21 (FGF21) is known as a metabolic regulator to regulate the metabolism of glucose and lipids. However, the underlying mechanism of FGF21 on melanin synthesis remains unknown. Therefore, the current study investigates the effect of FGF21 on melanogenesis in alpaca melanocytes. We transfected the FGF21 into alpaca melanocytes, then detected the melanin contents, protein and mRNA levels of pigmentation-related genes in order to determine the melanogenesis-regulating pathway of FGF21. The results showed that FGF21 overexpression suppressed melanogenesis and decreased the expression of the major target genes termed microphthalmia-associated transcription factor (MITF) and its downstream genes, including tyrosinase (TYR) and tyrosinase-related protein 2 (TRP2). However FGF21 increased the expression of phospho-extracellular signal-regulated kinase (p-Erk1/2). In contrast, FGF21-siRNA, a small interference RNA mediating FGF21 silencing, abolished the inhibition of melanogenesis. Altogether, FGF21 may decrease melanogenesis in alpaca melanocytes via ERK activation and subsequent MITF downregulation, which is then followed by the suppression of melanogenic enzymes and melanin production.