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Background and purpose: Remimazolam is a newly developed benzodiazepine drug with water-soluble, esterase degradation, and ultra-short-acting properties. The dose for general anesthesia induction in obese patients was not known. This study aimed to determine the optimal dose of remimazolam in combination with sufentanil for the induction of general anesthesia in obese patients.Methods: It was a prospective observational study. We recruited 46 patients scheduled for bariatric surgery from October 2022 to December 2023. One patient refused to provide informed consent, and six patients were receiving psychotropic medication. Thirty-nine patients were enrolled. The Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale was used to assess the patient’s response. The dose of sufentanil was 0.5 µg/kg (lean body weight [LBW]). The initial dose of remimazolam was 0.3 mg/kg (LBW). The dose of remimazolam was modified using the up-and-down allocation technique. Successful sedation (negative group) was characterized by achieving a MOAA/S score ≤ 1 within 3 min of commencing remimazolam infusion. If negative, the next patient received a low-level dose at a ratio of 0.9. Failed sedation (positive group) was defined as a MOAA/S score of >1 within 3 min of commencing remimazolam infusion. The patients in the positive group received propofol 0.5 mg/kg as a remedial measure, and the next dose was increased to a higher level. The primary outcome was to determine the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam in combination with sufentanil 0.5 µg/kg for induction in obese patients. The secondary outcome was to determine the occurrence of adverse effects such as hypotension, hypertension, and intraoperative awareness.Results: The ED50 and ED95 values of remimazolam (LBW) combined with sufentanil (0.5 µg/kg) (LBW) were 0.115 mg/kg (95% CI: 0.072–0.137) and 0.179 mg/kg (95% CI: 0.150–0.434), respectively, and the time of loss of consciousness in the negative group was 120.13 ± 25.03 s. The cardiovascular system was stable during the induction period. The incidence of post operative nausea and vomiting (PONV) was 38.5% in 39 patients. Respiratory depression, allergic reaction, intraoperative awareness, and delayed emergence were not observed in any patient.Conclusion: Remimazolam combined with sufentanil (0.5 µg/kg) (LBW) can be effectively used for general anesthesia induction in obese patients. The ED50 and ED95 values of remimazolam (LBW) were 0.115 mg/kg and 0.179 mg/kg, respectively.Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200065602.

BackgroundQianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce.ObjectiveTo explore QGHJ’s osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration.MethodsQGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs’ responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays.ResultsUPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ’s key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs’ viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress.ConclusionIn T2DOP rat and BMSCs oxidative stress models, QGHJ’s bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment’s heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis.Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies.Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM.Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.

Introduction: The accurate diagnosis of pneumatosis intestinalis (PI) is increasing despite patients’ limited identification of etiologic factors. Recently a patient with lung squamous carcinoma who developed pneumatosis intestinalis following methylprednisolone administration for immune-related adverse events was treated at our hospital. Subsequent a literature review and an analysis of the FDA Adverse Event Reporting System (FAERS) database enabled the identification of additional cases of pneumatosis intestinalis.Methods: A literature review of the MEDLINE/PubMed and Web of Science Core Collection databases using standard pneumatosis intestinalis search terms to identify published cases of immune checkpoint inhibitors (ICIs) or steroids causing pneumatosis intestinalis were performed. A separate retrospective pharmacovigilance study of FAERS enabled the extraction of unpublished cases of pneumatosis intestinalis between the first quarter of 2005 and the third quarter of 2022. Disproportionality and Bayesian analyses were performed to identify signal detection in reported odds ratios, proportional reporting ratios, information components, and empirical Bayesian geometric means.Results: Ten case reports of steroid-related pneumatosis intestinalis were retrieved from six published studies. The implicated drug therapies included pre-treatment with steroids before chemotherapy, combination therapy with cytotoxic agents and steroids, and monotherapy with steroids. In the FAERS pharmacovigilance study, 1,272 cases of immune checkpoint inhibitors or steroid-related pneumatosis intestinalis were incidentally reported. The signal detected in five kinds of immune checkpoint inhibitors and six kinds of steroids implied a positive correlation between the drugs and adverse events.Conclusion: Steroids might be the etiologic factors in the current case of pneumatosis intestinalis. Reports supporting the role of steroids in suspected cases of pneumatosis intestinalis can be found in literature databases and the FAERS database. Even so, as documented in FAERS, immune checkpoint inhibitors-induced pneumatosis intestinalis should not be excluded.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Background: The Yizhiqinxin formula (YZQX) has been used to treat Alzheimer’s disease (AD) or major depression disorder (MDD). However, its specific underlying mechanisms and therapeutic targets remain unclear.Methods: The ingredients and putative targets of YZQX were screened using the TCMSP and Drugbank databases. Next, the GEO database was used to retrieve relevant differentially expressed genes (DEGs) in AD or MDD and normal tissues. The PPI network was established, merged, and further screened to identify the main ingredients and core targets of YZQX against AD and MDD comorbidities. We performed enrichment analysis of core targets to identify biological processes and pathways. Finally, AutoDock software was used to validate the binding affinity between the crucial targets of direct action and their corresponding ingredients.Results: A total of 43 ingredients were identified from YZQX, of which 43 were screened to yield 504 targets. By establishing the PPI network, 92 targets were regarded as targets of YZQX against AD and MDD comorbidities in the core network. Promising targets (HSP90AA1, ESR1, AKT1, VCAM1, EGFR, CDK1, MAPK1, CDK2, MYC, HSPB1, and HSPA5) and signaling pathways (PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, MAPK signaling pathway, etc.) were filtered and refined to elucidate the underlying mechanism of YZQX against AD and MDD comorbidities. Molecular docking confirmed the ingredients of YZQX (quercetin and kaempferol) could bind well to multiple crucial targets.Conclusion: The ingredients of YZQX, such as quercetin and kaempferol, might treat AD and MDD comorbidities by acting on multiple targets and pathways.

Background: The aim of the study was to investigate the protective effect of canagliflozin (CANA) on myocardial metabolism and heart under stress overload and to further explore its possible molecular mechanism.Methods: High-salt diet was used to induce heart failure with preserved ejection fraction (HFpEF), and then, the physical and physiological indicators were measured. The cardiac function was evaluated by echocardiography and related indicators. Masson trichrome staining, wheat germ agglutinin, and immunohistochemical staining were conducted for histology analysis. Meanwhile, oxidative stress and cardiac ATP production were also determined. PCR and Western blotting were used for quantitative detection of related genes and proteins. Comprehensive metabolomics and proteomics were employed for metabolic analysis and protein expression analysis.Results: In this study, CANA showed diuretic, hypotensive, weight loss, and increased intake of food and water. Dahl salt-sensitive (DSS) rats fed with a diet containing 8% NaCl AIN-76A developed left ventricular remodeling and diastolic dysfunction caused by hypertension. After CANA treatment, cardiac hypertrophy and fibrosis were reduced, and the left ventricular diastolic function was improved. Metabolomics and proteomics data confirmed that CANA reduced myocardial glucose metabolism and increased fatty acid metabolism and ketogenesis in DSS rats, normalizing myocardial metabolism and reducing the myocardial oxidative stress. Mechanistically, CANA upregulated p-adenosine 5′-monophosphate-activated protein kinase (p-AMPK) and sirtuin 1 (SIRT1) and significantly induced the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a).Conclusion: CANA can improve myocardial hypertrophy, fibrosis, and left ventricular diastolic dysfunction induced by hypertension in DSS rats, possibly through the activation of the AMPK/SIRT1/PGC-1a pathway to regulate energy metabolism and oxidative stress.

Background: Multiple systematic reviews (SRs) have been conducted to evaluate the efficacy and safety of Chinese herbal medicine (CHM) in patients with Alzheimer’s disease (AD). Here, we aim to perform an overview to assess the methodological quality and quality of evidence of the SRs to provide convincing data on the treatment of AD with CHM.Method: Six electronic databases including Chinese and English were searched, until April 31, 2021. Two researchers independently screen documents and extract data according to the predesigned rules. A Measure Tool to Assessment System Reviews 2 (AMSTAR-2) was used to investigate the methodological quality, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence for outcomes.Results: Twelve qualified SRs including 163 randomized controlled trials were reviewed. The methodological quality of the included SRs was considered extremely low assessed through AMSTAR-2. Compared with western medicines (WM) alone, CHM as an adjuvant treatment has shown significant effects in improving Mini-mental State Examination, Alzheimer’s Disease Assessment Scale-Cognitive, and Clinical Dementia Rating scores. The same is true for CHM alone. Regarding the effect on Activities Daily Living, neither the single CHM nor the combination with WM has an obvious effect. For the total effective rate, both single CHM and the combination with WM shown significant effects. Nine SRs suggested that CHM as adjuvant therapy or single-use had fewer adverse events than WM. Additionally, the quality of evidence for the main outcome was reviewed as low or extremely low according to GRADE profiler data.Conclusion: Current evidence suggests that CHM may be beneficial in improving the cognitive function of AD patients. However, we should be cautious about the evidence due to methodological flaws and low quality. High-quality RCTs are further needed to confirm the efficacy and safety of CHM for AD.

MicroRNAs (miRNAs) have emerged as potential therapeutic targets for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Traditional Chineses Medicine (TCM) plays an important role in the prevention or treatment of NAFLD/NASH. However, miRNA targets of TCM against NASH still remain largely unknown. Here, we showed that Yiqi-Bushen-Tiaozhi (YBT) recipe effectively attenuated diet-induced NASH in C57BL/6 mice. To identify the miRNA targets of YBT and understand the potential underlying mechanisms, we performed network pharmacology using miRNA and mRNA deep sequencing data combined with Ingenuity Pathway Analysis (IPA). Mmu-let-7a-5p, mmu-let-7b-5p, mmu-let-7g-3p and mmu-miR-106b-3p were screened as the main targets of YBT. Our results suggested that YBT might alleviate NASH by regulating the expression of these miRNAs that potentially modulate inflammation/immunity and oxidative stress. This study provides useful information for guiding future studies on the mechanism of YBT against NASH by regulating miRNAs.

Patients with advanced cancer often undergo myelosuppression after receiving chemotherapy. However, severe myelosuppression results in treatment delay, and some can even be life-threatening. At present, cancer patients undergoing chemotherapy urgently need effective intervention strategies to prevent myelosuppression. Fortunately, ginsenoside Rg3 has shown promise as an anti-myelosuppression agent. Therefore, this study was conducted to evaluate the effectiveness of ginsenoside Rg3 in preventing chemotherapy-induced myelosuppression in cancer patients. The PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Weipu (VIP), and Wanfang databases were searched in this study. A total of 18 trials which reported on 2,222 subjects were identified. All trials concerning the use of ginsenoside Rg3 for the prevention of chemotherapy-induced myelosuppression (the decline of leukocyte, hemoglobin, platelet, and neutrophil counts) were randomized-controlled trials. Dichotomous data were expressed as odds ratio (OR) with their respective 95% confidence intervals (CI). The Cochrane evidence-based medicine systematic evaluation was used to evaluate the methodological quality of the included trials. The Review Manager 5.3 and Stata 12.0 software were used to perform the statistical analyses. The trial sequential analysis (TSA) was used to evaluate information size and prevention benefits. The results revealed obvious ginsenoside Rg3-induced improvement in the leukocyte (OR, 0.46; 95% CI, 0.37–0.55), hemoglobin (OR, 0.64; 95% CI, 0.53–0.77), platelet (OR, 0.60; 95% CI, 0.48–0.75) and neutrophil (OR, 0.62; 95% CI, 0.43–0.90) counts at toxic grades I–IV, and leukocyte (OR, 0.39; 95% CI, 0.28–0.54) counts at toxic grades III–IV. The sensitivity analysis revealed that the results were robust. The Egger’s test indicated that there was no publication bias in the results. Overall, this study suggested that ginsenoside Rg3 is beneficial for alleviating the chemotherapy-induced decrease in leukocyte, hemoglobin, platelet, and neutrophil counts. However, the confirmation of the ginsenoside Rg3 can be recommended for myelosuppression patients was limited due to poor methodological quality. Thus, more rigorously designed randomized-controlled trials (RCTs) are required to assess the efficacy of ginsenoside Rg3 for myelosuppression.

BackgroundPharmacological treatments play a significant role in treating mild to moderate Alzheimer’s disease (AD), but the optimal doses of various drugs used for these treatments are unknown. Our study compared the efficacy, acceptability, and safety of different doses of pharmacological treatments for mild to moderate AD.MethodsRandomized controlled trials (RCTs) were identified by searching the PubMed, EMBASE, and Cochrane Library databases (all RCTs published from the date of inception of the databases until September 19, 2019). Trials comparing the efficacy, acceptability, and safety of pharmacological interventions involving donepezil, galantamine, rivastigmine, memantine, huperzine A, and Ginkgo biloba extract EGb761, alone or in combination, were identified. The primary outcomes were efficacy, acceptability, and safety.ResultsOur meta-analysis included 37 studies involving 14,705 participants. In terms of improving cognitive function, galantamine 32 mg, galantamine 24 mg, donepezil 5 mg, and donepezil 10 mg were more effective than other interventions, with the surface under the cumulative ranking curve (SUCRA) values of 93.2, 75.5, 73.3, and 65.6%, respectively. According to the SUCRA values, EGb761 240 mg was considered to be the optimal intervention in terms of both acceptability and safety. With regard to clinical global impression, rivastigmine 12 mg had the highest probability of being ranked first (83.7%). The rivastigmine 15 cm2 patch (SUCRA = 93.7%) may be the best choice for daily living. However, there were no interventions that could significantly improve neuropsychiatric symptoms, compared with the placebo.ConclusionsDifferent doses of the tested pharmacological interventions yielded benefits with regard to cognition, acceptability, safety, function, and clinical global impressions, but not effective behaviors.

Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.

Simvastatin (SV) enhances glutamate release and synaptic plasticity in hippocampal CA1 region upon activation of α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we examined the effects of SV on the functional activity of α7nAChR on CA1 pyramidal cells using patch-clamp recording and explored the underlying mechanisms. We found that the treatment of hippocampal slices with SV for 2 h induced a dose-dependent increase in the amplitude of ACh-evoked inward currents (IACh) and the level of α7nAChR protein on the cell membrane without change in the level of α7nAChR phosphorylation. These SV-induced phenotypes were suppressed by addition of farnesol (FOH) that converts farnesyl pyrophosphate, but not geranylgeraniol. Similarly, the farnesyl transferase inhibitor FTI277 was able to increase the amplitude of IACh and enhance the trafficking of α7nAChR. The treatment with SV enhanced phosphorylation of CaMKII and PKC. The SV-enhanced phosphorylation of CaMKII rather than PKC was blocked by FOH, Src inhibitor PP2 or NMDA receptor antagonist MK801 and mimicked by FTI. The SV-enhanced phosphorylation of PKC was sensitive to the IP3R antagonist 2-APB. The SV-increased amplitude of IACh was suppressed by PKC inhibitor GF109203X and Go6983, or CaMKII inhibitor KN93. The SV- and FTI-enhanced trafficking of α7nAChR was sensitive to KN93, but not GF109203X or Go6983. The PKC activator PMA increased α7nAChR activity, but had no effect on trafficking of α7nAChR. Collectively, these results indicate that acute treatment with SV enhances the activity and trafficking of α7nAChR by increasing PKC phosphorylation and reducing farnesyl-pyrophosphate to trigger NMDA receptor-mediated CaMKII activation.