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The communication between calcitonin gene-related peptide (CGRP) and cytokines plays a prominent role in maintaining trigeminal ganglion (TG) and trigeminovascular sensitization. However, the underlying regulatory mechanism is elusive. In this study, we explored the hypothesis that Src family kinases (SFKs) activity facilitates the crosstalk between CGRP and cytokines in sensitizing TG. Mouse TG tissue culture was performed to study CGRP release by enzyme-linked immunosorbent assay, cytokine release by multiplex assay, cytokine gene expression by quantitative polymerase chain reaction, and phosphorylated SFKs level by western blot. The results demonstrated that a SFKs activator, pYEEI (YGRKKRRQRRREPQY(PO3H2)EEIPIYL) alone, did not alter CGRP release or the inflammatory cytokine interleukin-1β (IL-1β) gene expression in the mouse TG. In contrast, a SFKs inhibitor, saracatinib, restored CGRP release, the inflammatory cytokines IL-1β, C-X-C motif ligand 1, C-C motif ligand 2 (CCL2) release, and IL-1β, CCL2 gene expression when the mouse TG was pre-sensitized with hydrogen peroxide and CGRP respectively. Consistently with this, the phosphorylated SFKs level was increased by both hydrogen peroxide and CGRP in the mouse TG, which was reduced by a CGRP receptor inhibitor BIBN4096 and a protein kinase A (PKA) inhibitor PKI (14–22) Amide. The present study demonstrates that SFKs activity plays a pivotal role in facilitating the crosstalk between CGRP and cytokines by transmitting CGRP receptor/PKA signaling to potentiate TG sensitization and ultimately trigeminovascular sensitization. [ABSTRACT FROM AUTHOR]

Freshwaters in China are affected by point and non-point sources of pollution. The Wujiang District (Suzhou City, China) has a long history of canals, rivers, and lakes that are currently facing various water quality issues. In this study, the water quality of four rivers and a lake in Wujiang was assessed to quantify pollution and explore its causes. Seventy-five monthly samples were collected from these water bodies (five locations/samples per area) from August to October 2020 and were compared with nine control samples collected from a water protection area. Fifteen physicochemical, microbiological, and molecular–microbiological parameters were analyzed, including nutrients, total and fecal coliforms, and fecal markers. Significant monthly variation was observed for most parameters at all areas. Total phosphorus, phosphates, total nitrogen, ammonium–nitrogen, and fecal coliforms mostly exceeded the acceptable limits set by the Chinese Ministry of Environmental Protection. The LiPuDang Lake and the WuFangGang River were the most degraded areas. The studied parameters were correlated with urban, agricultural, industrial, and other major land use patterns. The results suggest that fecal contamination and nutrients, associated with certain land use practices, are the primary pollution factors in the Wujiang District. Detailed water quality monitoring and targeted management strategies are necessary to control pollution in Wujiang's watersheds. [ABSTRACT FROM AUTHOR]