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Objective To observe the effect of electroacupuncture (EA) on the expression of NKCC1, KCC2 and activation of microglia in spinal dorsal horn of paclitaxel (PTX)-induced neuropathic pain rats and its possible mechanism. Methods Male SD rats were randomly divided into the vehicle group (vehicle), the PTX group, the PTX + EA group and the PTX + sham EA group, with 12 rats in each group. The rat model of PTX-induced neuropathic pain was established by intraperitoneal injection of PTX. After modeling, EA was applied to "Zusanli" and "Yanglingquan" for 7 days in the PTX + EA group. Paw withdrawal threshold and paw withdrawal latency were tested at 2 days before and 1, 3, 5, 7, 14 and 21 days after PTX injection. Immunofluorescence and Western blot assay were used to detect expression levels of sodium-potassium-chloride cotransporter 1 (NKCC1), potassium-chloride cotransporters 2 (KCC2) and microglia markers - ionized calcium binding adapter molecule 1 (Iba1) in spinal dorsal horn. Results Compared with the vehicle group, mechanical and thermal hyperalgesia of both hind feet were found in the PTX group, and the expression of NKCC1 and the number of activated microglia in dorsal horn tissue of spinal cord were increased. Compared with the PTX group, mechanical and thermal hyperalgesia were significantly improved in the PTX+EA group at day 14 and 21, and the expression levels of NKCC1 and Iba1 in dorsal horn tissue of spinal cord were decreased. There was no significant difference in KCC2 expression between the four groups. Conclusion Electroacupuncture can effectively relieve paclitaxol-induced neuropathic pain, which may be related to the inhibition of NKCC1 expression and microglia activation in spinal dorsal horn of rats. [ABSTRACT FROM AUTHOR]

Solute carrier family 12 member 8 (SLC12A8) is a nicotinamide mononucleotide transporter. Despite emerging evidence supporting its potential involvement in oncogenesis, a systematic pan-cancer analysis of SLC12A8 has not been performed. Thus, this research aimed to explore the prognostic implications of SLC12A8 and assess its possible immune-related functions across 33 different tumor types. And multiple datasets were retrieved from the databases of TCGA, GTEx, Broad Institute CCLE, TISCH, HPA, and GDSC2. After this data acquisition, bioinformatics analyses were conducted to assess the potential involvement of SLC12A8 in cancer pathogenesis. These analyses focused on examining the relationship between SLC12A8 and prognosis, drug sensitivity, chemotherapy response, immune checkpoints (ICPs), immune cell infiltration, and immunotherapy efficacy across various tumor types. Furthermore, experimental methods such as EdU assay, wound healing assay, and transwell assay were conducted to evaluate the cell proliferative and invasive abilities. Finally, the data analysis demonstrated that SLC12A8 was differentially expressed and predicted unfavorable survival outcomes in the majority of the tumor types in the TCGA dataset. Furthermore, a notable upregulation in the expression of SLC12A8 mRNA and protein was observed in cancer tissues compared to normal tissues. Additionally, the SLC12A8 levels demonstrated a strong association with ICPs, chemokines, immune-activating genes, immune-suppressive genes, chemokine receptors, chemotherapy response, and immunotherapy efficacy. In vitro experiments substantiated that knockdown of SLC12A8 restricted the malignant phenotypes of MDA-MB-231 and BT-549 cells. So SLC12A8 holds promise as a cancer biomarker with the capacity to interact with other ICPs to synergistically regulate the immune microenvironment. Thus, the identification of SLC12A8 contributes to the development of novel therapeutic strategies for enhancing the efficacy of immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In salivary acinar cells, cholinergic stimulation induces elevations of cytosolic [Ca 2+ ] i to activate the apical exit of Cl - through TMEM16A Cl - channels, which acts as a driving force for fluid secretion. To sustain the Cl - secretion, [Cl - ] i must be maintained to levels that are greater than the electrochemical equilibrium mainly by Na + -K + -2Cl - cotransporter-mediated Cl - entry in basolateral membrane. Glucose transporters carry glucose into the cytoplasm, enabling the cells to produce ATP to maintain Cl - and fluid secretion. Sodium-glucose cotransporter-1 is a glucose transporter highly expressed in acinar cells. The salivary flow is suppressed by the sodium-glucose cotransporter-1 inhibitor phlorizin. However, it remains elusive how sodium-glucose cotransporter-1 contributes to maintaining salivary fluid secretion. To examine if sodium-glucose cotransporter-1 activity is required for sustaining Cl - secretion to drive fluid secretion, we analyzed the Cl - currents activated by the cholinergic agonist, carbachol, in submandibular acinar cells while comparing the effect of phlorizin on the currents between the whole-cell patch and the gramicidin-perforated patch configurations. Phlorizin suppressed carbachol-induced oscillatory Cl - currents by reducing the Cl - efflux dependent on the Na + -K + -2Cl - cotransporter-mediated Cl - entry in addition to affecting TMEM16A activity. Our results suggest that the sodium-glucose cotransporter-1 activity is necessary for maintaining the oscillatory Cl - secretion supported by the Na + -K + -2Cl - cotransporter activity in real time to drive fluid secretion. The concerted effort of sodium-glucose cotransporter-1, Na + -K + -2Cl - cotransporter, and apically located Cl - channels might underlie the efficient driving of Cl - secretion in different secretory epithelia from a variety of animal species., (© 2024. The Author(s).)