Association between cognitive function and IL-18 levels in schizophrenia: Dependent on IL18 - 607 A/C polymorphism.

Accumulating evidence suggests that immune system dysregulation is associated with debilitating neurodevelopment in schizophrenia (SZ). Cognitive impairment is a persistent feature that occurs during the onset of SZ and persists throughout the course of the disease. Early studies have found that elevated interleukin (IL)- 18 interacts with IL18 polymorphism and is correlated with psychotic symptoms in SZ. This study aimed to investigate whether elevated IL-18 levels interacted with the -607 A/C polymorphism to determine cognitive decline in patients with chronic SZ. We recruited 693 inpatients and 422 healthy controls to measure IL-18 levels and genotype the - 607 A/C polymorphism. Further, cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We found that IL-18 serum levels were higher in patients than those in healthy controls, and were not associated with IL18 - 607 A/C in combined subjects or either patients or healthy controls, respectively. Moreover, - 607 A/C was correlated with the visuospatial/constructional index only in the patients. In addition, our research found that IL-18 levels were positively correlated to immediate memory only in patients with the C/C genotype, but not in patients with C/A or A/A genotype. This study suggests that the relationship of IL-18 with cognitive function depends on the IL18 - 607 A/C polymorphism of SZ patients.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. METHODS: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. RESULTS: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. CONCLUSION: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974.

Production of retinoic acid by engineered Saccharomyces cerevisiae using an endogenous aldehyde dehydrogenase.

Retinoic acid (RA), a vitamin A (retinol)-derived lipophilic compound, is involved in various physiological functions. The demand for RA is growing in the pharmaceutical industry, but RA biosynthesis is still in its infancy compared to other forms of retinoids such as retinol and retinal, largely due to the lack of efficient retinal dehydrogenases. To achieve effective biosynthesis of RA, the catalytic activities of exogenous retinal dehydrogenases were comparatively analyzed in a previously constructed retinoids-producing Saccharomyces cerevisiae strain, followed by mining of endogenous enzymes with higher retinal dehydrogenase activities using homology-based search. After confirming the retinal oxidation activity of the endogenous aldehyde dehydrogenase Hfd1 using in vivo and in vitro experiments, it was overexpressed in multiple copies, and the resulting strain produced 99.71 mg/L of RA in shake-flask cultures. Finally, 545.28 mg/L of RA was produced in fed-batch fermentation. This study suggests the yeast endogenous Hfd1 as a potent catalyst for RA biosynthesis, and demonstrates the potential of yeast as a platform for RA production.

Selective biosynthesis of retinol in S. cerevisiae.

The vitamin A component retinol has become an increasingly sought-after cosmetic ingredient. In previous efforts for microbial biosynthesis of vitamin A, a mixture of retinoids was produced. In order to efficiently produce retinol at high purity, the precursor and NADPH supply was first enhanced to improve retinoids accumulation in the S. cerevisiae strain constructed from a ß-carotene producer by introducing ß-carotene 15,15'-dioxygenase, following by screening of heterologous and endogenous oxidoreductases for retinal reduction. Env9 was found as an endogenous retinal reductase and its activity was verified in vitro. By co-expressing Env9 with the E. coli ybbO, as much as 443.43 mg/L of retinol was produced at 98.76% purity in bi-phasic shake-flask culture when the antioxidant butylated hydroxytoluene was added to prevent retinoids degradation. The retinol titer reached 2479.34 mg/L in fed-batch fermentation. The success in selective biosynthesis of retinol would lay a solid foundation for its biotechnological production.

Naloxone Alleviate the Severity of Delirium in Hospitalized Patients With Parkinsonism: Three Case Reports.

Purpose: Delirium is common in geriatric with Parkinson's disease (PD). Treatments for delirium have generally been neuroleptics; however, antipsychotics have potential effect to block striatal dopamine D2 receptors and worsen symptom of parkinsonism. We explored whether naloxone can alleviate delirium in PD and other forms of parkinsonism. Patients and Methods: Patients with parkinsonism who met the delirium criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) received naloxone infusions once or twice daily. Treatment effects were evaluated by the delirium rating scale-revised 98 (DRS-R98), including non-cognitive and cognitive subscales; the Richmond agitation-sedation scale (RASS); and the mini mental status examination (MMSE). Results: Two patients with primary parkinsonism, one with vascular PD were observed. The daily dose of naloxone was 2.08 ± 0.64 mg (range: 1-4 mg). Medication time last from 1 h to 7 days without side effects observed. Following with naloxone infusions, DRS-R98 scores decreased within 12 h and MMSE scores increased. The psychotic symptoms, disorientation, and attention deficits were alleviated significantly, while RASS scores decreased with naloxone treatment. Conclusion: Naloxone alleviated psychotic symptoms, improved cognitive dysfunction, and irritability in patients with delirium in the context of PD. The preliminary findings point out that the opioid system may be involved in the pathophysiology of delirium, which may be one of potential treat targets for delirium of PD.

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients. METHODS: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted. RESULTS: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05). CONCLUSIONS: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Establishment of callus and cell suspension cultures of Corydalis saxicola Bunting, a rare medicinal plant.

An efficient procedure has been developed for callus induction and cell suspension cultures of C. saxicola for the first time. Explant selection was carried out among leaf, stem and root to select a suitable type of explants capable of higher callus formation. Leaf explants thus selected showed maximum response to callus induction (67.1%). Modified B5 medium supplemented with 0.5 mg l(-1) 2,4-D plus 2 mg l(-1) BA was the most favorable medium for callus formation with the highest induction rate (94.8%) and greatest fresh weight of callus (1.7 g per explant). Cell suspension cultures were established by transferring 2-8 g fresh callus to 80 ml liquid B5 medium. An inoculum size of 8 g produced the greatest biomass accumulation, dehydrocavidine and berberine productions, which was 13.1 g l(-1), 8.0 mg l(-1) and 4.1 mg l(-1), respectively. In response to various sucrose concentrations from 10 g l(-1) to 80 g l(-1), cultures with 60 g sucrose l(-1) not only produced the highest dry biomass (18.5 g l(-1)) but also the highest formation of dehydrocavidine (11.6 mg l(-1)) and berberine (7.6 mg l(-1)). These prepared cell suspension cultures provided a useful material for further regulation of alkaloid biosynthesis and for enhanced production of valuable alkaloids on a large scale.