Transcriptome and Animal Model Integration Reveals Inhibition of Calcium Homeostasis-Associated Gene ITPKB Alleviates Amyloid Plaque Deposition.

Alzheimer's disease (AD) is a severe neurological illness that causes memory loss and is a global problem. The calcium hypothesis recently steadily evolved in AD. The prospective targets for calcium homeostasis therapy, however, are limited, and gene expression-level research connected to calcium homeostasis in AD remains hazy. In this study, we analyzed the microarray dataset (GSE132903) taken from the Gene Expression Omnibus (GEO) database to investigate calcium homeostasis-related genes for AD. Using immunoblot analysis, we examined the association of ITPKB with inflammation in AD. Additionally, the immunofluorescence technique was employed to assess the impact of pharmacological inhibition of ITPKB on the amyloid-ß (Aß) plaque deposition in APP/PS1 mice. This article's further exploration of calcium homeostasis-related genes has propelled the validation of the calcium homeostasis theory in AD.

Effect of pre-infusion of hypertonic saline on postoperative delirium in geriatric patients undergoing shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: Neuroinflammation may be a potential mechanism of postoperative delirium (POD) in geriatric patients, and hypertonic saline (HS) has immunomodulatory properties. The purpose of this study was to investigate whether HS could reduce the incidence of POD in elderly patients and its effect on neutrophil activation and inflammatory cytokine expression. METHODS: We studied the effect of pre-infusion of 4 mL/kg 3% hypertonic saline vs. 4 mL/kg 0.9% normal saline on POD in patients undergoing shoulder arthroscopy in a prospective, randomized, double-blind, controlled trial. Neutrophil surface molecules (CD11b, CD66b and CD64) were analyzed by flow cytometry. Circulating concentrations of inflammatory factors IL-1ß, IL-6, TNF-α and neurological damage factor S100ß were assessed by enzyme immunoassay. The Confusion Assessment Method-Chinese Revision (CAM-CR) was applied for the assessment of POD 1-3 days after surgery. RESULTS: The incidence of POD in group H was significantly lower than that in group N (7.14% vs 26.83%, P = 0.036). The expression levels of inflammatory cytokines ( IL-6 and TNF-α) and neutrophil surface markers (CD11b and CD66b) were significantly lower in group H than in group N at 24 h after surgery (P = 0.018, P < 0.001, P < 0.001, P = 0.024). There were no significant differences in postoperative pain, nausea and vomiting, infection, phlebitis, and patients satisfaction between the two groups. CONCLUSION: Pre-infusion of HS can reduce the incidence of POD and the immune-inflammatory response. TRIAL REGISTRATION: Chinese Clinical Trial Registry (14/4/2022, registration number: ChiCTR2200058681.

taVNS Alleviates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Via Activating Basal Forebrain Cholinergic Neurons.

Postoperative cognitive dysfunction (POCD) is a common complication of central nervous system after anesthesia or surgery. Sevoflurane, an inhalation anesthetic, may inhibit cholinergic pathway that induce neuronal death and neuroinflammation, ultimately leading to POCD. Transauricular vagus nerve stimulation (taVNS) has neuroprotective effects in POCD rats, but the mechanisms related to cholinergic system have not been revealed. Sprague-Dawley rats were anesthetized with sevoflurane to construct the POCD model. The immunotoxin 192-IgG-saporin (192-sap) selectively lesioned cholinergic neurons in the basal forebrain, which is the major source of cholinergic projections to hippocampus. After lesion, rats received 5 days of taVNS treatment (30 min per day) starting 24 h before anesthesia. Open field test and Morris water maze were used to test the cognitive function. In this study, rats exposed to sevoflurane exhibited cognitive impairment that was attenuated by taVNS. In addition, taVNS treatment activated cholinergic system in the basal forebrain and hippocampus, and downregulated the expression of apoptosis- and necroptosis-related proteins, such as cleaved Caspase-3 and p-MLKL, in the hippocampus. Meanwhile, the activation of Iba1+ microglial by sevoflurane was reduced by taVNS. 192-sap blocked the cholinergic system activation in the basal forebrain and hippocampus and inhibited taVNS-mediated neuroprotection and anti-inflammation effects in the hippocampus. Generally, our study indicated that taVNS might alleviate sevoflurane-induced hippocampal neuronal apoptosis, necroptosis and microglial activation though activating cholinergic system in the basal forebrain.

Downregulation of RPS15A by miR-29a-3p attenuates cell proliferation in colorectal carcinoma.

miR-29a-3p has been reported to function as a tumor suppressor in several cancers. However, the biological function role of miR-29a-3p in colorectal carcinoma (CRC) has not been well investigated. In this study, we found that miR-29a-3p was at lower level expression in CRC tissues and cell lines. Experimental up-regulation miR-29a-3p with mimic could inhibit cell proliferation, but induced cell cycle arrest at G0/G1 phase and apoptosis in CRC cells. MiR-29a-3p overexpression significantly down-regulated the expression levels of CDK4, Cyclin D1, and Bax, but up-regulated the expression levels of p21 and Bcl-2 in DLD-1 cells. Moreover, ribosomal protein S15A (RPS15A) was predicted and confirmed as a direct target gene of miR-29a-3p. Furthermore, restoration of RPS15A could rescue the phenotypic changes caused by miR-29a-3p. The findings demonstrate miR-29a-3p inhibits CRC cell function possibly by targeting RPS15A, which might be exploited therapeutically in CRC.