Comparison of Intravenous and Inhalational Anesthetic on Postoperative Cognitive Outcomes in Elderly Patients Undergoing Cancer Surgery: Systematic Review and Meta-analysis.

PURPOSE: Previous studies have documented consistent findings on the long-term cognitive effects such as postoperative cognitive dysfunction (POCD), delirium and delayed recovery among elderly undergoing cancer surgery. This review was conducted to compare the effect of intravenous and inhalational anesthetic on the postoperative cognitive outcomes among elderly patients undergoing cancer surgery. DESIGN: Systematic review and meta-analysis METHODS: We searched Medline, EMBASE, PubMed Central, ScienceDirect, Google Scholar, and Cochrane library from inception until May 2021. We carried out a meta-analysis with a random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. FINDINGS: In total, we analyzed 10 studies including 2,333 participants. Half of the studies had high risk of bias. For the cognitive score, the pooled SMD was -0.87 [95% CI: -3.97 to 2.24] indicating no statistically significant difference between inhalational and intravenous anesthetic. For POCD, the pooled RR was 1.24 (95% CI: 0.83-1.84); for postoperative delirium, the pooled RR was 2.26 (95% CI: 0.79-6.44); for delayed neurocognitive recovery, the pooled RR was 1.49 (95% CI: 1.09-2.03). CONCLUSION: Inhalational anesthetics did not show a significant difference in postoperative cognitive outcomes, except delayed neurocognitive recovery, compared to intravenous anesthetic following cancer surgery.

Upregulation of RIN3 induces endosomal dysfunction in Alzheimer's disease.

BACKGROUND: In Alzheimer's Disease (AD), about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways. Among them, the Ras and Rab Interactor 3(RIN3) is a guanine nucleotide exchange factor (GEF) for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD (LOAD) and sporadic early onset AD (sEOAD). However, how RIN3 is linked to AD pathogenesis is currently undefined. METHODS: Quantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron (BFCNs). Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells. Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry. RIN3-interacting partners were validated by co-immunoprecipitation, immunofluorescence and yeast two hybrid assays. Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein (APP) and ß-secretase 1 (BACE1). Immunoblotting was used to detect protein expression, processing of APP and phosphorylated forms of Tau. RESULTS: We have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain. Basal forebrain cholinergic neurons (BFCNs) cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement. In addition, via its proline rich domain, RIN3 recruited BIN1(bridging integrator 1) and CD2AP (CD2 associated protein), two other AD risk factors, to early endosomes. Interestingly, overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments (CTFs) in PC12 cells. Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level. Therefore, upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau. These effects by RIN3 was rescued by the expression of a dominant negative Rab5 (Rab5S34N) construct. Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling. CONCLUSION: RIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse. Through interacting with BIN1 and CD2AP, increased RIN3 expression alters axonal trafficking and procession of APP. Together with our previous studies, our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking.

miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/ß-Catenin Pathway by Targeting Wnt1.

PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/ß-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/ß-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/ß-catenin pathway by targeting Wnt1.

Antioxidant activity of whole grain highland hull-less barley and its effect on liver protein expression profiles in rats fed with high-fat diets.

PURPOSE: Whole grain exhibits potential for regulating lipid levels, possibly because of its antioxidant activity. This study aims to investigate the antioxidant activity of whole grain highland hull-less barley (WHLB) and its effect on liver protein expression profiles in rats fed with high-fat diets. METHODS: Antioxidant activity of WHLB was investigated in vitro by analyzing phenolic and pentosan contents and oxygen radical absorbance capacity (ORAC). Proteins involved in lipid regulation were investigated in vivo by analyzing liver protein expression profiles in Sprague-Dawley rats fed with high-fat diet (HFD) with or without WHLB. RESULTS: WHLB possessed high total phenolic content (259.90 mg/100 g), total pentosan content (10.74 g/100 g), and ORAC values (418.05 ± 5.65 µmol/g). Rats fed with WHLB diet exhibited significantly (P < 0.05) lower liver lipid levels than those fed with the control HFD diet. Seven differentially expressed proteins were detected through liver proteome analysis and were found to be correlated with 11 pathways, including lipid metabolism, through annotation with Kyoto Encyclopedia of Genes and Genomes. Quantitative real-time polymerase chain reaction analysis showed that rats given with WHLB diet exhibited down-regulated expression of heat shock protein 60 (HSP60) and phosphatidylethanolamine binding protein 1 (PEBP1) and up-regulated expression of enoyl-coenzyme A hydratase (ECH) and peroxiredoxin 6 (PRDX6). CONCLUSIONS: HSP60, PEBP1, ECH, and PRDX6 may be involved in the lipid regulatory effect of WHLB. Moreover, the regulation of PRDX6 may be related to the antioxidant activity of WHLB.

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

Andrographolide (ANDRO) has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains) were subjected to 3 and 21% of O2 for various times (0-12 h) to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

Hypolipidaemic effect and mechanism of paprika seed oil on Sprague-Dawley rats.

BACKGROUND: Details regarding the functional properties of paprika seed oil are relatively scarce. In this study the hypolipidaemic effects and mechanisms of paprika seed oil on Sprague-Dawley rats are explored, which may improve the usage of paprika seed source and provide a theoretical basis of paprika seed oil for the alleviation of hyperlipidaemia. RESULTS: In capsaicin and paprika seed oil (PSO) groups, total cholesterol (TC) and total triglyceride (TG) in serum and liver lipids of rats were significantly decreased (P < 0.05). The contents of serum HDL cholesterol were increased and the contents of serum LDL cholesterol were decreased (P < 0.05). Real-time PCR analyses revealed that the hepatic mRNA expression of fatty acid synthetase (FAS) is decreased and the expression levels of HSL is increased (P < 0.05). The mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is decreased and the expression levels of low-density lipoprotein receptor (LDLR) is significantly improved (P < 0.05). The cholesterol 7-hydroxylase (CYP7A1) expression is regulated to control the cholesterol-to-bile acid transformation and cholesterol excretion is promoted. Capsaicin and unsaturated fatty acid PSO can activate and improve the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and peroxisome proliferators-activated receptors (PPARα). CONCLUSION: The hypolipidaemic effects of paprika seed oil (PSO) may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMG-CoAR, CYP7A1 and FAS, meanwhile, promoting the metabolism and excretion of lipids via up-regulating the expression of LDLR, HSL, TRPV1 and PPARα. © 2017 Society of Chemical Industry.

Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway.

The present study investigated the effects of andrographolide on postoperative cognitive dysfunction (POCD) in aged rats to gain insight of the underlying mechanism, which may provide theoretical basis for the clinical application of andrographolide to prevent POCD in older patients. Thirty aged male rats were randomly assigned to 3 groups: Control, model and andrographolide groups. The Morris water maze test was used to examine the spatial memory and learning ability of the rats postoperatively. The histological alterations of neuronal cells in the hippocampus were visualized by H&E staining. The serum levels of neuron-specific enolase (NSE), human soluble protein-100ß (S-100ß) and the inflammation factors of interluekin (IL)-1ß, IL-6 and TNF-α involved in the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway were detected by ELISA. The NF-κB/MAPK signaling pathway-associated proteins in rat serum were detected by western blotting. Following andrographolide treatment, the rats significantly gained learning ability after surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery. Andrographolide decreased NSE, S-100ß, and the inflammation factors, IL-6, IL-1ß and TNF-α in serum. Andrographolide reduced NF-κB/MAPK pathway-associated protein expression. Andrographolide ameliorated POCD in aged rats following surgery. The underlying mechanism may be associated with the downregulation the inflammatory factors and NF-κB/MAPK-associated protein expression.

The Effects of Different Methods of Anaesthesia for Laparoscopic Radical Gastrectomy with Monitoring of Entropy.

AIM: To investigate the effects of methods of total intravenous anaesthesia (TIVA) and combined intravenous and inhaled anaesthesia (CIIA) for laparoscopic radical gastrectomy under the same anaesthetic depth monitored by entropy indices. PATIENTS AND METHODS: One hundred patients undergoing laparoscopic radical gastrectomy were randomly distributed into group I (anaesthetized by TIVA) and group II (anaesthetized by CIIA), each group including 50 patients. TIVA was performed with propofol and remifentanil by means of target controlled infusion (TCI) for the patients in group I. CIIA was performed for patients in group II by inhalation of sevoflurane and continuous infusion of remifentanil after anaesthesia induction, with state entropy (SE) maintained in the range of 45-60 and difference regarding response entropy (RE) and SE less than 10.3. The concentrations of epinephrine, norepinephrine and dopamine in plasma from radial artery blood samples were measured and the durations of surgical operation, breathing recovery, extubation, awakening, and postoperative orientation recovery recorded; and 48 h postoperative adverse reactions at the following times: the time at which the patient becomes calm for 5 min after entering the operating theatre (T0); upon completion of pneumoperitoneum (PPT) (T1); 15 min after PPT (T2); intraoperative detection (T3), immediately after extubation (T4); and 15 min after extubation (T5). RESULTS: Comparing the measurements of epinephrine, norepinephrine and dopamine in plasma of the above two groups at the same time, the difference between the measurements at T0 and T2, and T5 were not statistically significant (p>0.05), whereas those at T1, T3, and T4 were statistically significant (p<0.05). Specifically, the measurements for group I were significantly higher than those for group II; the differences regarding the duration of breathing recovery, extubation, and awakening in both groups were not statistically significant (p>0.05). The postoperative orientation recovery duration for group II was significantly less than that that for group I (p<0.05); none of the patients in either group had intraoperative awareness, and the incidence of adverse reactions, such as nausea, vomit, and agitation in both groups was not statistically significantly different (p>0.05). CONCLUSION: At the same anaesthetic depth, the CIIA method outperforms the TIVA method in suppressing the stress response and obtaining smooth awakening after laparoscopic radical gastrectomy for patients with gastric cancer; therefore, the CIIA method has a better anaesthetic effect.

Combinatorial screening of potentiometric Pb(II) sensors from polysulfoaminoanthraquinone solid ionophore.

A potentiometric Pb(II)-selective sensor was fabricated by a combinatorial screening of electrically conducting polysulfoaminoanthraquinone (PSA) nanoparticles as a solid ionophore, ion exchangers (oleic acid (OA) and NaTPB), plasticizers in a polyvinyl chloride (PVC) matrix, membrane thickness, inner filling ion species, and concentration. The membrane sensor with the composition of PSA/PVC/DOP (dioctyl phthalate)/OA (1.0:33:61:5.0) exhibited the best performance, including a slope of 29.3 mV decade(-1) in the concentration range 10(-6.3)-10(-1.6) M, detection limit of 1.6 × 10(-7) M, response time of 16 s, lifetime of five months, and good response reversibility. The proposed sensor has demonstrated good selectivity for Pb(II) over other monovalent, divalent and trivalent interfering ions, and could be used in a pH range of 3.62-5.22. The Pb(II) sensor has been successfully applied for the determination of Pb(II) concentration in real-world samples and also as an indicator electrode for potentiometric titration of lead ions.

Lead-ion potentiometric sensor based on electrically conducting microparticles of sulfonic phenylenediamine copolymer.

A potentiometric sensor to detect lead ions using newly synthesized conducting copolymer microparticles as an ionophore in self-supporting poly(vinyl chloride) membrane matrix plasticized with dioctyl phthalate was developed. The copolymer microparticles containing many ligating functional groups including amino, imino and sulfonic groups were synthesized by a chemical oxidative copolymerization of m-phenylenediamine (mPD) and p-sulfonic-m-phenylenediamine (SPD) in pure water. Due to the presence of -NH-, -N=, -NH2, and -SO3H ligating groups on the microparticles, a linear Nernstian response is obtained within a Pb(II) activity range from 1.00 × 10(-6) M to 1.00 × 10(-3) M. The Pb(II)-sensor containing the mPD/SPD (95/5) copolymer microparticles with the maximal electrical conductivity demonstrates a superior detection limit down to 1.26 × 10(-7) M, short response time to 14 s, and long lifetime of up to 4 months. The Pb(II)-sensor also exhibits a selective response to Pb(II) over 9 other metal ions and a pH independent plateau between 2.7 and 5.0. These advantages could make for a robust sensor performing credible analysis of Pb(II) concentration in real-world samples at trace levels.

Lead ion-selective electrodes based on polyphenylenediamine as unique solid ionophores.

A novel membrane electrode for Pb(II) ion detection based on semi-conducting poly(m-phenylenediamine) microparticles as a unique solid ionophore was fabricated. The electrode exhibited significantly enhanced response towards Pb(II) over the concentration range from 3.16×10(-6) to 0.0316 M at pH 3.0-5.0 with a low detection limit of 6.31×10(-7) M, a high sensitivity displaying a near-Nernstian slope of 29.8 mV decade(-1) for Pb(II). The electrode showed a long lifetime of 5 months and a short response time of 14s. A systematical investigation on the effect of anion excluder and various foreign ions on the selectivity of the electrode by a fixed interference method suggests that all other metal ions hardly ever interfere with the determination of Pb(II) except high concentration Hg(II). The electrode was successfully used as an indicator electrode in the potentiometric titration of Pb(II) with EDTA. Furthermore, the electrode has been used to satisfactorily analyze four types of real-world samples like spiked human urine, spiked tap water, and river water containing interfering ions like Na(I), Ca(II), Mg(II), Zn(II), Pd(II), Fe(III), K(I), Cu(II) and Hg(II) up to 8.04×10(-4) M, demonstrating fast response, high selectivity, good recovery (96.6-121.4%), good repeatability (RSD 0.31-6.45%), and small relative error (5.0%).