Optimal dose of perineural dexamethasone for the prolongation of analgesia for peripheral nerve blocks: protocol for a systematic review and meta-analysis.

INTRODUCTION: Perineural use of dexamethasone is demonstrated to extend the analgesia duration of peripheral nerve blocks (PNB), but its optimal dose remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of perineural dexamethasone in the prolongation of analgesia for PNB. METHODS AND ANALYSIS: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from their inception to 1 March 2023. Language will be restricted to English. Randomised controlled trials that compared the efficacy and safety of different doses of perineural dexamethasone for PNB in adult patients will be included. Retrospective studies, reviews, meta-analyses, case reports, conference abstracts, comments and studies regarding paediatric surgeries will be excluded. The duration of analgesia will be defined as the primary outcome. Secondary outcomes will include pain scores, the total analgesic requirement over 48 hours and the incidence of adverse effects. Two reviewers will independently perform the study selection, data extraction and quality assessment. RevMan V.5.3 software will be used for data analysis. The quality of evidence will be assessed using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: No ethical approval is required. The results of this study will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022385672.

GARP: A family of glycine and alanine-rich proteins that helps spider mites feed on plants.

Spider mites (Tetranychidae) are destructive agricultural pests which have evolved strategies to overcome plant defenses, such as the ability to puncture the leaves of their hosts to feed. The expression of many genes with unknown functions is altered during feeding, but little is known about the role of these genes in plant-mite interactions. Here, we identified 3 novel gene families through analysis of genomic and transcriptomic data from 3 spider mite species. These GARP family genes encode glycine and alanine-rich proteins; they are present in mites (Acariformes) but absent in ticks (Parasitiformes) in the subclass Acari, indicating that these genes have undergone a significant expansion in spider mites and thus play important adaptive roles. Transcriptomic analysis revealed that the expression of GARP genes is strongly correlated with feeding and the transfer to new hosts. We used RNA interference to silence GARP1d in the two-spotted spider mite Tetranychus urticae, which inhibited feeding and egg laying and significantly increased mortality when the mites were transferred to soybean shoots; a similar effect was observed after TuVATPase was silenced. However, no changes in mite mortality were observed after TuGARP1d-silenced mites were placed on an artificial diet, which was different from the effect of TuVATPase silencing. Our results indicate that GARP family members play important roles in mite-plant interactions. Additional studies are needed to clarify the mechanisms underlying these interactions.

Developmental exposure to nonylphenol induced rat axonal injury in vivo and in vitro.

Increasing evidence indicates that developmental exposure to nonylphenol (NP) causes damage to the central nervous system (CNS). As the most unique and primary component of neuron, axon is an essential structure for the CNS function. Here, we investigated whether developmental exposure to NP affected rat axonal development in vivo and in vitro. Our results showed that developmental exposure to NP 10, 50, and 100 mg/(kg day) caused an obvious decrease in axonal length and density in the hippocampus. Developmental exposure to NP also altered the expression of CRMP-2 and p-CRMP-2, and activated Wnt-Dvl-GSK-3ß cascade in the hippocampus, the crucial signaling that regulates axonal development. Even months after the exposure, impairment of axonal growth and alteration of this cascade were not fully restored. In the primary cultured neurons, 30, 50, and 70 µM NP treatment decreased axonal length and impaired axonal function. Similar to in vivo results, it also activated Wnt-Dvl-GSK-3ß cascade in cultured neurons. SB-216763, a specific GSK-3ß inhibitor, recovered the shortening of axon and the impairment of axonal function induced by NP. Taken together, our results support the idea that exposure to NP induces axonal injury in the developing neurons. Furthermore, the activation of Wnt-Dvl-GSK-3ß cascade contributes to the axonal injury induced by NP.

Autophagy activation alleviates nonylphenol-induced apoptosis in cultured cortical neurons.

Emerging evidence indicates that nonylphenol (NP), a widely diffused and stable environmental contaminant, causes damage to the central nervous system (CNS). Although NP could cross the blood-brain barrier (BBB) and accumulate in key brain regions, little is known about the direct effects of NP on neurons. In this study, we aimed to investigate the direct effects of NP exposure on induction of apoptosis and autophagy in primary cortical neurons. Results showed that exposure to NP decreased the cell viability in a concentration-dependent manner. The exposure led to both the increase of TUNEL-positive neurons and the activation of caspase-3. Increased levels of endoplasmic reticulum (ER) stress-related proteins, GRP78, CHOP, ATF4, and casepase-12, were observed in neurons exposed to NP. At the same time, the exposure decreased Bcl-2/Bax ratio and mitochondrial transmembrane potential, and increased the release of Cytochrome-C. In addition, NP exposure enhanced LC3-II conversion, decreased levels of SQSTM1/p62, and increased levels of Beclin-1 and LAMP2. NP exposure also reduced the protein levels of p-mTOR, and did not change the levels of total mTOR. Furthermore, to investigate the role of autophagy in NP-induced apoptosis, both the autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (RAP) were applied to modulate autophagy activation in primary cortical neurons. The inhibition of autophagy caused by CQ enhanced NP-induced apoptosis; conversely, RAP-induced autophagy remarkably suppressed it. In conclusion, our findings demonstrate that NP exposure induced apoptosis with a concomitant increase of autophagic flux in primary cortical neurons, which supports the idea that this potential neurotoxin has direct effects of on neurons. Both ER stress and mitochondrial pathways may be involved in NP-induced apoptosis in neurons. Furthermore, our results also suggest that autophagy activation might be a protective strategy to ameliorate NP-induced apoptosis in neurons.

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

The aim of the present study was to compare the antioxidant and antiproliferative effects on cancer cells between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and its fraction PII that were separated by Biologic low pressure (LP) chromatography system followed by DEAE cellulose column chromatography. Results of in vitro experiments showed that the reducing power and the scavenging capacity of KCCP towards hydroxyl radicals (OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased in a concentration dependent manner and were stronger than that of fraction PII. Results of the antiproliferative effect of KCCP and fraction PII on cervical cancer HeLa cells, esophagus cancer Eca109 cells, and mouse ascites hepatomas H22 cells indicated that both KCCP and its fraction PII possessed inhibitory activity on all the tested cancer cells at a dose- and time-dependent manner, with KCCP showing higher inhibitory activity than that of fraction PII. The present study demonstrates that KCCP and its fraction PII have antioxidant properties that may help fight cancers.