Effects of Intranasal Insulin Pretreatment on Preoperative Sleep Quality and Postoperative Delirium in Patients Undergoing Valve Replacement for Rheumatic Heart Disease.

Background: Postoperative delirium (POD) is a common neurological complication associated with valve replacement. Preoperative sleep disturbance is a risk factor for POD development, and nasal insulin modulates the sleep-wake cycle. This study investigated the beneficial effects of intranasal insulin pretreatment on preoperative sleep quality and reducing POD in patients undergoing valve replacement for rheumatic heart disease. Patients and Methods: This prospective, single-center, randomized controlled trial (RCT) included 76 adult patients aged 18-65 years undergoing valve surgery with cardiopulmonary bypass who were randomly allocated to receive intranasal insulin or normal saline interventions two days before surgery. POD incidence was on postoperative days 1 (T3), 2 (T4), and 3 (T5). Before the first intervention (T0), 1 d before surgery (T1), and before anesthesia on the day of surgery (T2), sleep quality was assessed and serum cortisol concentrations were measured. At T1 and T2, sleep quality related indicators monitored by sleep monitoring watches from the previous night were recorded. Results: Compared with the normal saline group, 3 days after surgery, the insulin group showed a significantly reduced incidence of POD; significantly increased deep sleep, REM sleep, deep sleep continuity, and total sleep quality scores at T1 and T2; and significantly reduced serum cortisol concentration, PSQI scale, light sleep ratio, and wakefulness at T1 and T2. Conclusion: The administration of 20 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can improved preoperative sleep quality significantly and reduced POD incidence in patients with rheumatic heart disease undergoing valve replacement. Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier ChiCTR2100048515; July 9, 2021).

Super-Multiple Deletion Analysis of Type III Effectors in Ralstonia solanacearum OE1-1 for Full Virulence Toward Host Plants.

Ralstonia solanacearum species complex (RSSC) posses extremely abundant type III effectors (T3Es) that are translocated into plant cells via a syringe-like apparatus assembled by a type III secretion system (T3SS) to subvert host defense initiated by innate immunity. More than 100 T3Es are predicted among different RSSC strains, with an average of about 70 T3Es in each strain. Among them, 32 T3Es are found to be conserved among the RSSC and hence called the core T3Es. Here, we genetically characterized contribution of abundant T3Es to virulence of a Japanese RSSC strain OE1-1 toward host plants. While all the T3Es members of AWR family contributed slightly to virulence, those of the GALA, HLK, and SKWP families did not influence full virulence of OE1-1. Mutant OE1-1D21E (with deletion of all 21 T3Es members of four families) exhibited slightly impaired virulence, while mutant OE1-1D36E (deleting all 21 T3Es of 4 families and 15 core T3Es) exhibited substantially reduced virulence. Mutant OE1-1D42E (deleting all 21 T3Es of 4 families, 15 core T3Es and 6 extended core T3Es) failed to cause any disease on tobacco plants with leaf infiltration but retained faint virulence on tobacco plants with petiole inoculation. The proliferation of mutant OE1-1D42E in tobacco stems was substantially impaired with about three orders of magnitude less than that of OE1-1, while no impact in tobacco leaves if directly infiltrated into leaves. On the contrary, the OE1-1D42E mutant retained faint virulence on eggplants with leaf infiltration but completely lost virulence on eggplants with root-cutting inoculation. The proliferation of OE1-1D42E mutant both in eggplant leaves and stems was substantially impaired. Intriguingly, mutant OE1-1D42E still caused necrotic lesions in tobacco and eggplant leaves, indicating that some other than the 42 removed effectors are involved in expansion of necrotic lesions in host leaves. All taken together, we here genetically demonstrated that all the core and extended core T3Es are nearly crucial for virulence of OE1-1 toward host plants and provided currently a kind of T3Es-free strain that enables primary functional studies of individual T3Es in host cells.

Effect of prebiotics, inorganic salts and amino acids for cell envelope proteinase production from Lactobacillus plantarum LP69.

BACKGROUND: Cell-envelope proteinases (CEPs) can improve the texture and organoleptic characteristics of dairy products, and may also cause the release of bioactive peptides, which contribute to improving the host’s health. Thus, the CEPs with high activity produced by L. plantarum has great potential in the development of functional dairy products. METHODS: A single factor experiment was used to investigate the effects of prebiotics (inulin, stachyose, isomaltooligosaccharide, xylooligosaccharides, galactooligosaccharides and fructooligosaccharides), inorganic salts (Na2HPO4, NaH2PO4, K2HPO4, KH2PO4, CH3COONa and C6H14N2O7) and amino acids (arginine, leucine, serine, lysine, alanine and glutamic acid) on the activity of cell envelope proteinases (CEPs), specific activity, protein content, OD600 value and pH in MRS broth fermented by Lactobacillus plantarum LP69. RESULTS: The optimum concentration of inulin (0.7%), isomaltooligosaccharide (0.5%), Na2HPO4 (0.4%), CH3COONa (0.4%), leucine (20 mg/L), serine (20 mg/L) for L. plantarum LP69 was estimated with the activity of CEP in the range 17.36–21.47 U/mL, protein content in the range 19.18–22.53 mg/mL, specific activity in the range 0.77–1.12 U/mg. CONCLUSIONS: Inulin, isomaltooligosaccharide, Na2HPO4, CH3COONa, leucine and serine are superior to other selected substances, and have a significant influence on the CEP activity and specific activity of L. plantarum LP69. This would provide a reference for further optimization of CEP-producing media of L. plantarum LP69.

Characterization of Goat Milk Hydrolyzed by Cell Envelope Proteinases from Lactobacillus plantarum LP69: Proteolytic System Optimization, Bioactivity, and Storage Stability Evaluation.

Despite the widespread application of lactic acid bacterium in dairy production through its contribution to acidification, development of sensorial properties, and health-promoting effects, relatively little information is available on the cell envelope proteinases (CEPs) of Lactobacillus plantarum, especially on the proteolytic system and the production of bioactivity peptides. In this study, CEPs from a novel L. plantarum LP69 were involved in goat milk hydrolysis and generated a product with high activity that showed a degree of hydrolysis of 15.68 ± 0.74%, Angiotensin I-Converting Enzyme (ACE)-inhibitory rate of 83.25 ± 1.05%, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate of 64.91 ± 1.27%, and hydroxyl radical scavenging rate of 89.17 ± 1.13%. The optimized hydrolysis conditions were time of 4.5 h, temperature of 41 °C, initial pH of 8.5, and enzyme to substrate ratio (E/S) of 12% (w/w) by orthogonal experiments. Application of a stabilizer greatly promoted milk stability. A well-designed stabilizer consists of 0.05% carrageenan, 0.15% gellan gum, and 0.15% sucrose esters, which significantly raised the milk stability coefficient, R, from 70.67% to 98.57%. The storage stability of milk was evaluated during 84 days at room temperature or 4 °C. Our study depicts the contribution of CEPs from L. plantarum LP69 in goat milk, exploring a new way for the development of a functional milk product.

Cellulase-Assisted Extraction of Polysaccharides from White Hyacinth Bean: Characterization of Antioxidant Activity and Promotion for Probiotics Proliferation.

Food-derived polysaccharides have advantages over synthetical compounds and have attracted interest globally for decades. In this study, we optimized the cellulase-assisted extraction of polysaccharides from white hyacinth bean (PWBs) with the aid of response surface methodology (RSM). The optimum extraction parameters were a pH of 7.79, a cellulase of 2.73%, and a ratio of water to material of 61.39, producing a high polysaccharide yield (3.32 ± 0.03)%. The scavenging ability of PWBs varied on three radicals (hydroxyl > 2,2-diphenyl-1-picrylhydrazyl (DPPH) > superoxide). Furthermore, PWBs contributed to the proliferation of three probiotic bacteria (Lactobacillus acidophilus LA5, Bifidobacterium bifidum BB01, and Lactobacillus bulgaricus LB6). These investigations of PWBs provide a novel bioresource for the exploitation of antioxidant and probiotic bacterial proliferation.

Combined treatment with artesunate and bromocriptine has synergistic anticancer effects in pituitary adenoma cell lines.

Prolactinomas are the most prevalent functional pituitary adenomas. The preferred treatments for prolactinomas are dopamine agonists (DAs) such as bromocriptine (BRC), but DAs still have the challenges of tumor recurrence and drug resistance. This study demonstrates that the synergy of function and mechanism between artesunate (ART) and BRC inhibits prolactinoma cell growth in vitro. We found that low-dose ART combined with BRC synergistically inhibited the growth of GH3 and MMQ cell lines, caused cell death, attenuated cell migration and invasion, and suppressed the expression of extracellular prolactin. The induction of apoptosis after co-treatment was confirmed by immunofluorescent staining, assessment of caspase-3 protein expression, and flow cytometry. Expression of miR-200c, a carcinogenic factor in pituitary adenoma, was reduced following co-treatment with ART and BRC. This was accompanied by increased expression of the antitumor factor Pten. Transfection experiments with miR-200c analogs and inhibitors confirmed that miR-200c expression was inversely associated with Pten expression. We suggest that ART and BRC used in combination exert synergistic apoptotic and antitumor effects by suppressing miR-200c and stimulating Pten expression.

Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats.

AIM: To evaluate preventative effects of ischemic preconditioning (IP) in a rat model of intestinal injury induced by ischemia-reperfusion (IR). METHODS: Male Sprague-Dawley rats (250-300 g) were fasted for 24 h with free access to water prior to the operation. Eighteen rats were randomly divided into three experimental groups: S group (n = 6), rats were subjected to isolation of the superior mesenteric artery (SMA) for 40 min, then the abdomen was closed; IR group (n = 6), rats were subjected to clamping the SMA 40 min, and the abdomen was closed followed by a 4-h reperfusion; IP group (n = 6) rats underwent three cycles of 5 min ischemia and 5 min reperfusion, then clamping of the SMA for 40 min, then the abdomen was closed and a 4-h reperfusion followed. All animals were euthanized by barbiturate overdose (150 mg/kg pentobarbital sodium, i.v.) for tissue collection, and the SMA was isolated via median abdominal incision. Intestinal histologic injury was observed. Malondialdehyde (MDA), myeloperoxidase (MPO) and tumor necrosis factor (TNF)-α concentrations in intestinal tissue were measured. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression, as well as nuclear factor (NF)-κB activity and expression in intestinal tissue were also determined. RESULTS: Compared with the IR group, IP reduced IR-induced histologic injury of the intestine in rats (2.00 ± 0.71 vs 3.60 ± 0.84, P < 0.05). IP significantly inhibited the increase in MDA content (5.6 ± 0.15 µmol/L vs 6.84 ± 0.18 µmol/L, P < 0.01), MPO activity (0.13 ± 0.01 U/L vs 0.24 ± 0.01 U/L, P < 0.01), and TNF-α levels (7.79 ± 2.35 pg/mL vs 10.87 ± 2.48 pg/mL, P < 0.05) in the intestinal tissue of rats. IP also markedly ameliorated the increase in ICAM-1 (204.67 ± 53.27 vs 353.33 ± 45.19, P < 0.05) and VCAM-1 (256.67 ± 58.59 vs 377.33 ± 41.42, P < 0.05) protein expression in the intestinal tissues. Additionally, IP remarkably decreased NF-κB activity (0.48 ± 0.16 vs 0.76 ± 0.22, P < 0.05) and protein expression (320.23 ± 38.16 vs 520.76 ± 40.53, P < 0.01) in rat intestinal tissue. CONCLUSION: IP may protect against IR-induced intestinal injury by attenuation of the neutrophil-endothelial adhesion cascade via reducing ICAM-1 and VCAM-1 expression and TNF-α-induced NF-κB signaling pathway activity.

The marine metabolite SZ-685C induces apoptosis in primary human nonfunctioning pituitary adenoma cells by inhibition of the Akt pathway in vitro.

Nonfunctioning pituitary adenoma (NFPA) is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403) which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay) to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs) and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI) double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI) apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN) were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.

BMI, apolipoprotein B/apolipoprotein A-I ratio, and insulin resistance in patients with prolactinomas: a pilot study in a Chinese cohort.

Deranged metabolic profiles and insulin resistance (IR) have been documented in patients with prolactinomas. Few data are yet available on the apolipoprotein (apo) B/apoA-I ratio and its relationship with IR in patients with prolactinomas. This study was aimed to evaluate the level of apoB/apoA-I ratio and its association with IR in a Chinese subgroup with prolactinomas. Twenty-three prolactinoma patients and 20 healthy controls were enrolled in this study. The clinical anthropometric parameters and laboratory evaluation were collected. Insulin sensitivity was estimated using homeostatic model assessment [homeostasis model assessment of insulin resistance (HOMA-IR)]. Waist circumference and body weight index (BMI) were significantly higher in patients with prolactinomas than those in the controls (p < 0.05). Meanwhile, the prevalence of general and abdominal obesity seemed more pronounced in male patients compared to that in healthy subjects (57.14 vs. 0 % and 71.43 vs. 16.7 %, respectively). Furthermore, fasting glucose, insulin, HOMA-IR, triglyceride, and apoB/apoA-I ratio were also significantly higher in prolactinoma patients, but with lower level of apoA-I (p < 0.05). Univariate regression analysis revealed that prolactin, waist circumference, BMI, and presence of hypogonadism were significantly associated with IR (p < 0.05). However, only BMI [odds ratio (OR) = 1.937, 95 % confidence interval (CI) 1.112-3.375, p = 0.02] and prolactin (OR = 5.173, 95 % CI 1.073-24.94, p = 0.041) were shown to be independent predictors for the presence of IR in multivariate logistic analysis. This study confirmed the altered metabolic profile, including body weight gain, IR, disordered lipids, and apolipoproteins in prolactinoma patients. Prolactin and BMI were independently associated with IR. The effect of apoB/apoA-I ratio on IR is warranted to be determined in further studies.

L-dopa induces under-damped visually guided motor responses in Parkinson's disease.

Parkinson's disease preferentially affects internally generated movements, e.g., movements recalled from memory, while externally cued movements are relatively preserved. However, L-dopa may have effects on visually guided movements as well as error-related processing. Fourteen Parkinson's disease (PD) subjects (on and off L-dopa medication) as well as ten normal controls performed a tracking task using a joystick. During discrete 30 s blocks, the visual feedback of the actual tracking errors were attenuated, amplified or unaltered. Second order dynamical system models, with the desired trajectory as the input and the actual motor performance as the output, were used to characterize the motor performance by the each subject under each condition. Although the overall root-mean-square tracking error did not significantly differ between groups, the nature of the motor performance differed significantly across groups. A clear dissociation was made between manipulations of error feedback--which altered the natural frequency of the models--and the effects of L-dopa, which affected damping. Compared to normal controls, PD subjects were significantly overdamped before medication and underdamped after medication. We interpret our results as being suggestive of L: -dopa normalization of compensatory overactive cerebellar activity in PD.

Catalytic functions of Mo/Ni/MgO in the synthesis of thin carbon nanotubes.

The functions and structures of Mo/Ni/MgO catalysts in the synthesis of carbon nanotubes (CNTs) have been investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Thin 2-5-walled CNTs with high purities (over 90%) have been successfully synthesized by catalytic decomposition of CH(4) over Mo/Ni/MgO catalysts at 1073 K. It has been found that the yield of CNTs as well as the outer diameter or thickness correlates well with the contents of these three elements. The three components Mo, Ni, and MgO are all necessary to synthesize the thin CNTs at high yields since no catalytic activity was observed for CNT synthesis when one of these components was not present. The outer diameter of the CNTs increases from 4 to 13 nm and the thickness of graphene layers also increases with increasing Mo content at a fixed Ni content, while the inner diameter stays at 2-3 nm regardless of their contents. Furthermore, the average outer diameter is in good agreement with the average particle size of metal catalyst. That is, the thickness or the outer diameter can be controlled by selecting the composition of the Mo/Ni/MgO catalysts. XRD analyses have shown that Mo and Ni form a Mo-Ni alloy before CNT synthesis, while the Mo-Ni alloy phase is separated into Mo carbide and Ni. These alloy particles are supported on MgO cubic particles 15-20 nm in width. It has been found that only small Mo-Ni alloy particles 2-16 nm in size catalyze CNT synthesis, with larger particles over 15 nm exhibiting no activity. Mo carbide and Ni should play different roles in the synthesis of the thin CNTs, in which Ni is responsible for the dissociation of CH(4) into carbon and Mo(2)C works as a carbon reservoir.