Neuroinflammation is a striking hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Previous studies have shown the contribution of glial cells such as astrocytes in TDP-43-linked ALS. However, the role of microglia in TDP-43-mediated motor neuron degeneration remains poorly understood. In this study, we show that depletion of TDP-43 in microglia, but not in astrocytes, strikingly upregulates cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production through the activation of MAPK/ERK signaling and initiates neurotoxicity. Moreover, we find that administration of celecoxib, a specific COX-2 inhibitor, greatly diminishes the neurotoxicity triggered by TDP-43-depleted microglia. Taken together, our results reveal a previously unrecognized non-cell-autonomous mechanism in TDP-43-mediated neurodegeneration, identifying COX-2-PGE2 as the molecular events of microglia- but not astrocyte-initiated neurotoxicity and identifying celecoxib as a novel potential therapy for TDP-43-linked ALS and possibly other types of ALS.

The 30K proteins are involved with important functions in the growth and development of Bombyx mori. In this study, the synthesis and regulation of 30K proteins were examined during the degeneration of Bombyx silk glands. On day 3 of the fifth instar, the protein level of 30Kc19 was low, whereas the silk proteins were rapidly synthesized. However, synthesis and accumulation of the 30Kc19 protein significantly increased at the prepupal stage and on day 1 of the pupal stage. At this stage, the silk gland cells were filled with 30Kc19 and genomic DNA. Moreover, the transcript levels of the 30K-encoding genes, including 30Kc6, 30Kc12, 30Kc19 and 30Kc23 were up-regulated during the degeneration of the Bombyx silk glands. During the time that the levels of the 30Kc19 protein were significantly up-regulated, it is notable that the transcript levels of the BmAtg8, BmAtg6 and BmDronc genes dramatically increased to regulate the programmed cell death of this gland. On day 1 of the pupal stage, intense fragmentation of genomic DNA occurred in the silk gland cells, and the putative active form of caspase was detected in the cytoplasm, showing the complete degradation of the silk glands in one day. In conclusion, the 30K proteins are synthesized in high concentrations, while proteolysis mediates silk gland degeneration in Bombyx by a caspase-dependent pathway. We propose that the 30K proteins may be nutrients and energy vectors to be absorbed by the developing tissues of pupae or moths.

Introduction This meta-analysis was performed to assess the possible benefits of staple line oversewing during laparoscopic sleeve gastrectomy. Methods A comprehensive search up to February 2017 was conducted on PubMed, the Web of Science™ and Embase™. All eligible studies were included, and the outcomes of staple line bleeding and leak, overall complications and operative time were pooled. Results A total of 7 randomised controlled trials involving 845 patients (428 cases and 417 controls) were analysed. There was no significant difference in staple line bleeding (relative risk [RR]: 0.858, 95% confidence interval [CI]: 0.343-2.143, p=0.742), leak (RR: 0.650, 95% CI: 0.257-1.644, p=0.363) or overall complications (RR: 0.913, 95% CI: 0.621-1.342, p=0.644) between the oversewing group and the patients who did not have oversewing. Oversewing of the staple line was associated with a longer operative time (weighted mean difference: 14.400, 95% CI: 7.198-21.602, p=0.000). Conclusions Oversewing the staple line during laparoscopic sleeve gastrectomy does not decrease the risk of staple line bleeding, leakage or overall complications but it does prolong the operative time.