[Two novel cephalotaxine-type alkaloids from Cephalotaxus sinensis].

Silica gel, octadecyl-silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was performed to isolate nine cephalotaxine-type alkaloids from Cephalotaxus sinensis: 8-oxodeoxyharringtonine(1), 8-oxonordeoxyharringtonine(2), cephafortunine A(3), 8-oxocephalotaxine(4), deoxyharringtonine(5), acetylcephalotaxine(6), cephalotaxine(7), epicephalotaxine(8), and cephalotaxinone(9). Compounds 1 and 2 were identified for the first time and their structures were determined by high-resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR), and electronic circular dichroism(ECD). Compounds 1-3 and 5 significantly inhibited the transcription of nuclear factor kappa B(NF-κB), with the half-maximal inhibitory concentration(IC_(50)) of(3.91±0.70),(2.99±0.45),(7.84±0.51), and(1.46±0.17) µmol·L~(-1), respectively.

Adjunctive Nonconvulsive Electrotherapy for Patients with Depression: a Systematic Review.

The efficacy and safety of adjunctive nonconvulsive electrotherapy (NET) for patients with depression are undetermined. This systematic review was conducted to examine the efficacy and safety of adjunctive NET for patients with depression. Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO and the Cochrane Library) databases were systematically searched from their inception until Jan 27, 2021 by three independent investigators. One randomized controlled trial (RCT) with 3 treatment arms (n = 108) and two observational studies (single-group, before-after design, n = 31) were included. In the RCT, the antidepressant efficacy of NET on depression was similar to that of electroconvulsive therapy (ECT) (P > 0.05) but with significantly fewer neurocognitive impairments as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (P < 0.05). In two observational studies, the 17-item Hamilton Depression Rating Scale (HAMD-17) scores decreased significantly from baseline to post-NET (all Ps < 0.05), without adverse neurocognitive effects. In the RCT, adverse drug reactions (ADRs) were not separately reported among the 3 treatment arms but a similar rate of discontinuation was reported. The currently available limited evidence from 3 studies suggests that NET as an adjunctive treatment may be a safe, well-tolerated, effective therapy for depression without serious neurocognitive impairments.

A Preliminary Study of Adjunctive Nonconvulsive Electrotherapy for Treatment-Refractory Depression.

Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.

Enantioselective total syntheses of (+)-stemofoline and three congeners based on a biogenetic hypothesis.

The powerful insecticidal and multi-drug-resistance-reversing activities displayed by the stemofoline group of alkaloids render them promising lead structures for further development as commercial agents in agriculture and medicine. However, concise, enantioselective total syntheses of stemofoline alkaloids remain a formidable challenge due to their structural complexity. We disclose herein the enantioselective total syntheses of four stemofoline alkaloids, including (+)-stemofoline, (+)-isostemofoline, (+)-stemoburkilline, and (+)-(11S,12R)-dihydrostemofoline, in just 19 steps. Our strategy relies on a biogenetic hypothesis, which postulates that stemoburkilline and dihydrostemofolines are biogenetic precursors of stemofoline and isostemofoline. Other highlights of our approach are the use of Horner-Wadsworth-Emmons reaction to connect the two segments of the molecule, an improved protocol allowing gram-scale access to the tetracyclic cage-type core, and a Cu-catalyzed direct and versatile nucleophilic alkylation reaction on an anti-Bredt iminium ion. The synthetic techniques that we developed could also be extended to the preparation of other Stemona alkaloids.

Serum BDNF Levels are Not Associated with the Antidepressant Effects of Nonconvulsive Electrotherapy.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and in the antidepressant response. This study examined whether changes in serum BDNF levels are associated with the antidepressant effects of nonconvulsive electrotherapy (NET). METHODS: For BDNF analyses, serum samples were collected from 20 patients with treatment-refractory depression (TRD) and from 20 healthy controls. Serum samples were also collected from patients following a course of NET. RESULTS: Although significantly lower baseline serum BDNF levels were observed in TRD patients than in healthy controls, no changes in serum BDNF levels were found in TRD patients after a course of NET compared to baseline. No significant association was found between serum BDNF levels and depression severity. CONCLUSION: Serum BDNF levels appear to have no clinical utility in the prediction of the antidepressant effects of NET in patients with TRD. Future studies of higher quality and with larger sample sizes are needed to confirm these findings.

Enhanced removal of Cr(VI) in the Fe(III)/natural polyphenols system: role of the in situ generated Fe(II).

This study developed a cost-effective and eco-friendly method by coupling plant extracts (take green tea for example) and Fe(III) to reduce Cr(VI) and precipitate Cr(III). At acidic pH, 1.43 mM Fe(III) combined with 1.33 g/L green tea extracts could reduce 93% of Cr(VI) in 180 min, which was much larger than ˜50% by green tea extracts alone. Moreover, 52% of Cr(III) could automatically precipitate out as mixed Fe(III)-Cr(III) (oxy)-hydroxide solids. In the viewpoint of mechanism, polyphenols in green tea extracts were the reactive constituents and transformed Fe(III) to Fe(II), by which step the aqueous Fe(II) level was maintained to continuously reduce Cr(VI) to Cr(III), and thus accelerating Cr(VI) reduction. The generated Fe(III) partially participated in the reaction with polyphenols again and some Fe(III) formed precipitates with Cr(III). Overall, the electron transfers in the polyphenol-Fe-Cr cyclic reactions made Fe(III) used for multiple times, thus accelerated Cr(VI) reduction. The applicability of the combined process was further verified by removing 100% and 70% of Cr(VI) from electroplating wastewater and contaminated soil, respectively. As polyphenols can be derived from plant wastes and Fe(III) is naturally abundant, this study provides a promising method for in situ remediation of Cr(VI)-contaminated sites.

Characteristics of the Water- and Alkali-Soluble Hemicelluloses Fractionated by Sequential Acidification and Graded-Ethanol from Sweet Maize Stems.

Sweet maize stems were treated with hot water and potassium hydroxide to fractionate hemicellulosic polymers. The results showed that the water-soluble hemicelluloses were mainly composed of glucose (27.83%), xylose (27.32%), and galactose (16.81%). In comparison, alkali-soluble hemicelluloses fractionated by acidification and a graded ethanol solution (10%, 20%, 35%, 50%, 65%, and 80%) were mainly composed of xylose (69.73 to 88.62%) and arabinose (5.41 to 16.20%). More highly branched hemicelluloses tended to be precipitated in a higher concentration of ethanol solution, as revealed by the decreasing xylose to arabinose ratio from 16.43 to 4.21. Structural characterizations indicated that alkali-soluble hemicelluloses fractionated from sweet maize stems were mainly arabinoxylans. The results provided fundamental information on hemicelluloses composition and structure and their potential utilization in the fields of biofuels, biochemicals, and biomaterials.

A simple blood microdialysis in freely-moving rats for pharmacokinetic-pharmacodynamic modeling study of Shengmai injection with simultaneous determination of drug concentrations and efficacy levels in dialysate.

Microdialysis is a powerful in vivo sampling technique for pharmacokinetic-pharmacodynamic (PK-PD) modeling of drugs in pre-clinical and clinical studies. However, the noticeable limitations of previous studies using microdialysis were that animals anesthesia in the whole experiment and the combination of microdialysis and blood sampling for drug and (or) effect detection, which can obviously influence PK and PD behavior of drugs. In this study, a simple blood microdialysis sampling system in freely-moving rats was established for simultaneous study of PK and PD of Shengmai injection (SMI) effect on inducing real-time nitric oxide (NO) release on isoproterenol (ISO) induced myocardial ischemia rats. The LC-MS/MS and HPLC with fluorescence detection (HPLC-FLD) methods were developed to determine ginsenside Rg1, Rg2, Re, Rf, Rb1, Rd and Rc, the main effective components of SMI, and NOx-, the main oxidation products of NO, in dialysates respectively. Through simultaneous determination of drug concentrations and NO efficacy levels in dialysate, the developed methods were successfully applied to set up concentration-time and effect-time profiles followed by PK-PD modeling of SMI effect on inducing NO release after intravenous administration of 10.8 mL kg-1 SMI in myocardial ischemia rats. The PK-PD modeling characterized the dose-effect relationships of SMI and behaved good prediction ability. The established blood microdialysis in freely-moving rats is an appealing technology for rational PK-PD studies when selecting suitable blood endogenous micromolecule as effect marker.

[Meta-analysis on effect of compound Danshen injection in treating neonatal hypoxic-ischemic encephalopathy].

To systematically evaluate the clinical efficacy and safety of compound Danshen injection in treating hypoxic-ischemic encephalopathy (HIE) of newborns. Computer retrievals were made in PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and China info (before May 2014) and relevant literature references, and manual retrievals were made for journals and conference papers, in order to collect randomized or semi-randomized controlled trials concerning compound Danshen injection in the treatment of neonatal HIE. The quality of included references was evaluated according to literatures recommended by Cochrane Handbook. RevMan 5. 3 software was applied in the statistical treatment. Finally, a total of 13 randomized controlled trials were included, covering 1,211 patients (including 639 patients in the compound Danshen injection-treated group and 572 patients in the control group). Meta-analysis results showed that the routine treatment combined with compound Danshen injection can improve the treatment efficiency of neonatal HIE [RR = 1.28; 95% CI (1.21-1.36)], reduce the mortality rate [RR = 0.42; 95% CI (0.23-0.75)] and the incidence of long-term neurological sequelae [RR = 0.48; 95% CI (0.35-0.65)], with statistical differences. No fatal side effect was observed in all of included trials. So far, limited evidences in this study proved that the application of compound Danshen injection in the treatment of neonatal HIE can enhance the clinical efficiency. However, because of the low quality of the included trials, more well-designed and large-scale multi-center randomized controlled trials shall be made in the future.