Inhibitory interaction of flavonoids with organic anion transporter 3 and their structure-activity relationships for predicting nephroprotective effects.

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.

Morphinan Alkaloids from the Leaves of Alphonsea cylindrica and Their Antibacterial Properties.

A phytochemical study has been carried out on CH2Cl2 extract of Alphonsea cylindrica leaves, resulting in the isolation of three new morphinan alkaloids. They are kinomenine (1: ), N-methylkinomenine (2: ), and hydroxymethylkinomenine (3: ). The structures of these compounds were elucidated by extensive spectroscopic analysis (1D and 2D NMR, IR, UV, HRESIMS) and comparison with the data reported in literature for similar alkaloids. Kinomenine (1: ) and N-methylkinomenine (2: ) showed weak inhibition against S. aureus (MIC values of 1: and 2: = 500 µg/mL; pIC50 values in 95% C. I. of: 1: = 2.9 to 3.0; 2: = 2.9 to 3.1), while kinomenine (1: ) also showed weak inhibition against E. coli (MIC values of 1: = 500 µg/mL; pIC50 value in 95% C. I. of: 1: = 2.9) by broth microdilution method. The results obtained can be used as future referencefor the discovery of morphinans and the potential of A. cylindrica as an antibacterial source.

Investigation of Naoluoxintong on the neural stem cells by facilitating proliferation and differentiation in vitro and on protecting neurons by up-regulating the expression of nestin in MCAO rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The classic traditional Chinese compound Naoluoxintong (NLXT) has been proven an effective remedy for ischemic stroke (IS). The protective effect of NLXT on neural stem cells (NSCs), however, remains unclear. AIM OF THE STUDY: To investigate the protective effect of NLXT on NSCs in rats with middle cerebral artery occlusion (MCAO) and the effect of Nestin expression in vivo. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: the sham-operated group, the MCAO model group and the NLXT group. The MCAO model in rats was established by modified Longa wire embolization method. The sham-operated group, the model group and the NLXT groups were divided into three subgroups according to the sampling time points of 1 d, 3 d and 7 d after successful model-making. Immunofluorescence staining, including bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP), ß-tubulinIII/GFAP, BrdU/doublecortin (DCX) and BrdU/neuronal nuclei (NeuN), was used to detect the proliferation and survival of NSCs in the hippocampal after drug administration. Protein expression of Nestin, DCX, GFAP and NeuN in the hippocampal was detected by Western blot (WB). RESULTS: Immunofluorescence experiment of Nestin labeled: on the first day, a few Nestin-positive cells were found in the hippocampal DG area. Afterwards, the number of Nestin-labeled positive cells in the model group increased, while the number of cells in the sham group did not fluctuate significantly. The number of positive cells in each administration group increased more than that in the model and normal group. ß-tubulin III/GFAP double-labeled: a small amount of double labeled cells was expressed in the normal group, and the number subsequently fluctuated little. In the model group, ß-tubulin III/GFAP positive cells increased initially after acute ischemia, and gradually decreased afterwards. In the NLXT-treated group, ß-Tubulin III positive cells were significantly increased on day 1, 3 and 7, while GFAP positive cells had little change. BrdU/DCX double-labeled: initially, a small number of BrdU/DCX-labeled positive cells were observed in the normal group and the model group, but there was no increasing trend over time. The positive cells in the NLXT group increased over time, and those in the seven-day group were significantly higher than those in the one-day and three-day groups. BrdU/NEUN double-labeled: in the normal group, BrdU/NEUN positive cells were enriched and distributed regularly. The number of positive cells in the model group was small and decreased gradually with time, and the decrease was most obvious on the third day. The number of positive cells in the NLXT group was significantly higher than that in the model group, and the number of positive cells in the seven-day group was significantly higher than that in the one-day and three-day groups. WB results reflected those three proteins, Nestin, NeuN and DCX, showed an increase in expression, except GFAP, which showed a decreasing trend. CONCLUSIONS: Preliminarily, NLXT can promote the migration and differentiation of NSCs. It may have a protective effect on the brain by promoting repair of brain tissue damage through upregulation of Nestin after IS.

Three-Pronged Attack by Hybrid Nanoplatform Involving MXenes, Upconversion Nanoparticle and Aggregation-Induced Emission Photosensitizer for Potent Cancer Theranostics.

Inspired by the excellent photothermal conversion ability and inherent nanomedicine platform property of MXenes, efficient reactive oxygen species production and prominent fluorescence emission feature of aggregation-induced emission (AIE)-active photosensitizers (PSs), as well as the extending excitation wavelength capability of upconversion nanoparticles (UCNPs), a versatile nanoplatform comprised of Ti3 C2 nanosheets (NSs), AIE-active PSs and UCNPs is intelligently fabricated. This three-pronged strategy takes advantages of each component simultaneously, and realizes fluorescence imaging/photoacoustic imaging/photothermal imaging triple-modal imaging-guided photothermal/photodynamic synergetic therapy under 808 nm laser irradiation. The introduction of UCNPs actualizes the long wavelength-activation of AIE-active PSs, which significantly increases the tissue penetration depth. Spatially isolation of AIE-active PSs and Ti3 C2 NSs is beneficial for suppressing the fluorescence quenching effect of Ti3 C2 NSs, bringing about ultimately brilliant fluorescence. The covalently bonded polymer surface endows the nanoplatform with excellent physiological stability and efficient tumor accumulation. These outputs reveal a win-win cooperation of multiple inorganic/organic nanocomposites for phototheranostics, and present great potential for future clinical translations.

Use of Complementary and Alternative Medicine and Adherence to Medication Therapy Among Stroke Patients: A Meta-analysis and Systematic Review.

Purpose: To identify the use patterns of complementary and alternative medicine (CAM) and its impact on medication adherence among patients with stroke. Method: A systematic search through Science Direct, Google Scholar, and PubMed was performed to identify potential studies up to June 2021.The primary outcome was CAM use, and the secondary outcome was medication adherence among patients with stroke. Articles included in the review met the following criteria: 1) patients with stroke ≥18 years old on prescribed medications, and 2) medication adherence reported status. Meta-analyses were conducted to estimate the pooled prevalence of complementary and alternative medicine and adherence in stroke patients using a random-effects model. Results: A total of 1,330 studies were screened, of which 22 were included in the final analysis. The type of studies included were cross-sectional surveys, cohort studies, retrospective studies and prospective survey. The pooled prevalence of CAM usage was at 38% (29-48% CI) and medication non-adherence among stroke patients was at 29% (20-48% CI). The most common reason for inadequate stroke therapy and higher dependence on CAM was the patients' lack of knowledge and the regimen complexity of the medication. Other factors for medication non-adherence were forgetfulness, side effects, cost, and lack of doctor-patient communication. Conclusion: A low prevalence of CAM usage and non-adherence to medications was observed among patients with stroke. Studies investigating the association between CAM usage and medication adherence among patients with stroke are scarce and future researches are needed to explore the influence of CAM use on stroke medication adherence.

Prevalence of olfactory dysfunction and quality of life in hospitalised patients 1 year after SARS-CoV-2 infection: a cohort study.

OBJECTIVES: To determine the long-term prevalence of olfactory and/or gustatory dysfunction (OD±GD), associated risk factors and impact on quality of life (QoL) in previously hospitalised patients with COVID-19 1 year after infection. DESIGN: A single-centre cohort study. SETTING: Patients admitted at a large central London hospital with COVID-19 infection between 10 February 2020 and 22 May 2020. PARTICIPANTS: 150 adult subjects with previously confirmed SARS-CoV-2 infection were recruited between 10 December 2020 and 29 January 2021. Participants were predominantly male (102/150, 68.0%); mean age 58.0±15.9 years and 41.2% (56/136) were of black, Asian and minority ethnic backgrounds. MAIN OUTCOME MEASURES: EQ-5D-5L values and Sino-Nasal Outcome Test-22 (SNOT-22) scores. RESULTS: Long-term prevalence of OD±GD was 12.8% (19/149) at median time of 264.5 days following SARS-CoV-2 infection onset. Patients with OD±GD had a significantly higher median total SNOT-22 score (46.1; Q1-Q3: 23.0-60.0; 95% CI 23.0 to 60.0) compared with those without (16.0; Q1-Q3: 5.0-30.5; 95% CI 12.0 to 18.0) (p=0.0002), reflecting poorer QoL, particularly psychological well-being (p=0.0004), which was not alleviated with time (p=0.4977). Median EQ-5D-5L value was not significantly different between patients with OD±GD (0.70; Q1-Q3: 0.38-0.83; 95% CI 0.38 to 0.83) and those without (0.83; Q1-Q3: 0.61-0.94; 95% CI 0.75 to 0.89) (p=0.0627). Age, sex, ethnicity, smoking status, highest C reactive protein value, intubation and ventilation, and oxygen supplementation were not found to influence OD±GD (p>0.05). CONCLUSIONS: 12.8% of previously hospitalised patients with COVID-19 in London still report persistent problems with smell or taste up to a year after infection, impacting their QoL. Increased holistic support including psychological therapy and olfactory rehabilitation for affected patients may help to reduce long-term morbidity.

Effect of bovine serum albumin on the stability and antioxidant activity of blueberry anthocyanins during processing and in vitro simulated digestion.

The application of blueberry anthocyanins (ANs) was limited due to their low in-process stability and bioavailability. In our study, the stability and antioxidant capacity of ANs before and after adding bovine serum albumin (BSA) were examined by simulating various processing, storage (light, sucrose, and vitamin C (Vc)), and in vitro simulated digestion parameters. For this purpose, pH-differential method, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), peroxyl scavenging capacity assay, and cellular antioxidant assay were conducted. BSA at different concentrations, specifically at 0.15 mg/mL, inhibited the degradation of ANs and the loss of antioxidant capacity. The results suggest that BSA has a positive effect on ANs.

Achieving Efficient NIR-II Type-I Photosensitizers for Photodynamic/Photothermal Therapy upon Regulating Chalcogen Elements.

Second near-infrared (NIR-II) window type-I photosensitizers have intrinsic advantages in photodynamic/photothermal therapy (PDT/PTT) of some malignant tumors with deep infiltration, large size, complicated location, and low possibility of surgery/radiotherapy. Herein, three chalcogen-element-based donor-acceptor-type semiconducting polymers (poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4″H)-dione)-alt-2,5-(thiophene)] (PTS), poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4″H)-dione)-alt-2,5-(selenophene)] (PTSe), and poly[2,2″-((E)-4,4″-bis(2-octyldodecyl)-[6,6″-bithieno[3,2-b]pyrrolylidene]-5,5″(4H,4'H)-dione)-alt-2,5-(tellurophene)] (PTTe)) are synthesized and fully characterized, demonstrating strong absorption in the NIR-II region. Upon adjusting the chalcogen elements, the intramolecular charge-transfer characteristics and the heavy-atom effect are tuned to enhance the intersystem crossing rate, improving the photodynamic effect. Moreover, the energy levels and Gibbs free energies are tuned to facilitate the type-I photodynamic process. As a result, PTTe nanoparticles (NPs) produce superoxide anion radicals (O2 •- ) more efficiently and demonstrate higher photothermal conversion efficiency than PTS and PTSe NPs upon NIR-II (1064 nm) laser irradiation, exhibiting unprecedented NIR-II type-I PDT/PTT performance in vitro and in vivo. This work provides ideas for achieving high-performance NIR-II type-I PDT/PTT semiconducting polymers for hypoxic oncotherapy.

Integrating Palliative Care Into a Neurosurgical Intensive Care Unit (NS-ICU): A Quality Improvement (QI) Project.

OBJECTIVES: We conducted a pilot quality improvement (QI) project with the aim of improving accessibility of palliative care to critically ill neurosurgical patients. METHODS: The QI project was conducted in the neurosurgical intensive care unit (NS-ICU). Prior to the QI project, referral rates to palliative care were low. The ICU-Palliative Care collaborative comprising of the palliative and intensive care team led the QI project from 2013 to 2015. The interventions included engaging key stake-holders, establishing formal screening and referral criteria, standardizing workflows and having combined meetings with interdisciplinary teams in ICU to discuss patients' care plans. The Palliative care team would review patients for symptom optimization, attend joint family conferences with the ICU team and support patients and families post-ICU care. We also collected data in the post-QI period from 2016 to 2018 to review the sustainability of the interventions. RESULTS: Interventions from our QI project and the ICU-Palliative Care collaborative resulted in a significant increase in the number of referrals from 9 in 2012 to 44 in 2014 and 47 the year later. The collaboration was beneficial in facilitating transfers out of ICU with more deaths outside ICU on comfort-directed care (96%) than patients not referred (75.7%, p < 0.05). Significantly more patients had a Do-Not-Resuscitation (DNR) order upon transfer out of ICU (89.7%) compared to patients not referred (74.2.%, p < 0.001), and had fewer investigations in the last 48 hours of life (p < 0.001). Per-day ICU cost was decreased for referred patients (p < 0.05). CONCLUSIONS: Multi-faceted QI interventions increased referral rates to palliative care. Referred patients had fewer investigations at the end-of-life and per-day ICU costs.

Targeted Separation of COX-2 Inhibitor from Pterocephalus hookeri Using Preparative High-Performance Liquid Chromatography Directed by the Affinity Solid-Phase Extraction HPLC System.

Pterocephalus hookeri, as a kind of popular traditional Tibetan medicine, is reputed to treat inflammatory related diseases. In the present work, a cyclooxygenase-2 functionalized affinity solid-phase extraction HPLC system was developed and combined with preparative-HPLC for rapidly screening and separating cyclooxygenase-2 ligand from P. hookeri extracts. Firstly, ligands of cyclooxygenase-2 were screened from extracts by affinity solid-phase extraction HPLC system. Then directed by the screening results, the recognized potential active compounds were targeted separated. As a result, the major cyclooxygenase-2 inhibitor of P. hookeri was obtained with a purity of >95%, which was identified as sylvestroside I. To test the accuracy of this method, the anti-inflammatory activity of sylvestroside I was inspected in lipopolysaccharide-induced RAW 264.7 cells. The results show that sylvestroside I significantly suppressed the release of prostaglandin E2 with dose-dependent, which was in good agreement with the screening result of the affinity solid-phase method. This method of integration of screening and targeted separation proved to be very efficient for the recognition and isolation of cyclooxygenase-2 inhibitors from natural products.

Effect of Naoluoxintong on the NogoA/RhoA/ROCK pathway by down-regulating DNA methylation in MCAO rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Naoluoxintong (NLXT) is a traditional Chinese Medicine (TCM) prescription that is clinically used in the treatment of ischemic stroke (IS). However, its therapeutic mechanism remains unclear. AIM OF THE STUDY: To obtain the mechanism of NLXT by observing the protective effects of NLXT on the NogoA/RhoA/Rock pathway in a rat model of IS by regulating DNA methylation. MATERIALS AND METHODS: Rats were divided into five groups using a random number table: normal group, model group, NLXT group, blocker group I (NLXT + SGI-1027) and blocker group II (NLXT + Y27632). The right middle cerebral artery occlusion-reperfusion (MCAO/R) rat model was made, and the regional cerebral blood flow (rCBF) of each group was detected using laser Doppler. The methylation levels of CpG sites of neurite outgrowth inhibitor protein-A (Nogo-A), Nogo receptor (NgR), ras homolog gene family member A (RhoA) and rho-associated coiled-coil protein kinase 2 (ROCK2) genes in rat brain tissue were detected using the bisulfite method. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect NogoA, RhoA, NgR1, NgR2 and ROCK2 mRNA expression in rat brain tissue. NogoA, RhoA, NgR1, NgR2 and ROCK2 proteins were detected using immunoblotting in rat brain tissue. RESULTS: After the modeling of middle cerebral artery occlusion (MCAO), neurological deficit test was made to ensure the success of the modeling. At each time point after surgery, the rCBF of the other groups decreased compared with the normal group (P < 0.01 or P < 0.05). Meanwhile, the rCBF increased in blocker group I as well as blocker group II after 3 days (P < 0.05). There were differences in the DNA methylation sites of NogoA, RhoA, NgR and ROCK2 genes between the model group and the NLXT group (P < 0.05). Compared with the normal group, NogoA, NgR1, NgR2, RhoA and ROCK2 gene expression in the model group increased observably (P < 0.01). In comparison with the model group, NogoA and NgR1 gene expression in the blocker group II was prominently observed on the 1st day. NogoA, NgR1, NgR2, RhoA and ROCK2 gene expression remarkably reduced (P < 0.01) on the 3rd and 7th days. Compared with the normal group, NogoA, RhoA, NgR1, NgR2 and ROCK2 protein expression in the model group increased observably (P < 0.01). In comparison with the model group, NogoA, RhoA, NgR1, NgR2 and ROCK2 protein expression in the other groups declined prominently (P < 0.01). CONCLUSION: NLXT can reduce the DNA methylation level of NogoA pathway after IS, thus inhibit the expression of NogoA/RhoA/ROCK pathway from producing anti-cerebral ischemia pharmacological effect.

MOF-Templated Sulfurization of Atomically Dispersed Manganese Catalysts Facilitating Electroreduction of CO2 to CO.

To reach a carbon-neutral future, electrochemical CO2 reduction reaction (eCO2RR) has proven to be a strong candidate for the next-generation energy system. Among potential materials, single-atom catalysts (SACs) serve as a model to study the mechanism behind the reduction of CO2 to CO, given their well-defined active metal centers and structural simplicity. Moreover, using metal-organic frameworks (MOFs) as supports to anchor and stabilize central metal atoms, the common concern, metal aggregation, for SACs can be addressed well. Furthermore, with their turnability and designability, MOF-derived SACs can also extend the scope of research on SACs for the eCO2RR. Herein, we synthesize sulfurized MOF-derived Mn SACs to study effects of the S dopant on the eCO2RR. Using complementary characterization techniques, the metal moiety of the sulfurized MOF-derived Mn SACs (MnSA/SNC) is identified as MnN3S1. Compared with its non-sulfur-modified counterpart (MnSA/NC), the MnSA/SNC provides uniformly superior activity to produce CO. Specifically, a nearly 30% enhancement of Faradaic efficiency (F.E.) in CO production is observed, and the highest F.E. of approximately 70% is identified at -0.45 V. Through operando spectroscopic characterization, the probing results reveal that the overall enhancement of CO production on the MnSA/SNC is possibly caused by the S atom in the local MnN3S1 moiety, as the sulfur atom may induce the formation of S-O bonding to stabilize the critical intermediate, *COOH, for CO2-to-CO. Our results provide novel design insights into the field of SACs for the eCO2RR.

Characteristics of the interaction mechanisms of procyanidin B1 and procyanidin B2 with protein tyrosine phosphatase-1B: Analysis by kinetics, spectroscopy methods and molecular docking.

Protein tyrosine phosphatase-1B (PTP1B) is a novel and indispensable drug target for the treatment of type 2 diabetes mellitus (T2DM). Procyanidins are flavonoids that exhibit a significant hypoglycemic function. However, the potential inhibitory effects of procyanidins on PTP1B are unclear. In this study, the interaction mechanisms of PTP1B with procyanidin B1 (PB1) and procyanidin B2 (PB2) were investigated through kinetics analysis, UV-visible spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy and molecular docking. The results showed that PB1 and PB2 could inhibit the activity of PTP1B in a mixed inhibition mode, which was one of the reversible inhibition types. Multi-spectral analysis showed that PB1/PB2 formed complexes with PTP1B, which effectively quenched the intrinsic fluorescence of PTP1B based on the static mechanism. The values of the binding constants were KS(PTP1B-PB1) = 4.06 × 102 L·mol-1 and KS(PTP1B-PB2) = 2.53 × 102 L·mol-1, indicating that the binding affinity of PTP1B to PB1 was higher than that for PB2. PB1 and PB2 both changed the secondary structure of the enzyme, thereby decreasing the PTP1B activity. Thermodynamic investigations revealed that the binding of procyanidin B1 and B2 to PTP1B was spontaneous in both cases, and highlighted the key role of hydrophobic interactions. Molecular docking analysis provided further information regarding the interactions between PB1 or PB2 and the amino acid residues of PTP1B. Moreover, PB1 and PB2 were found to down-regulate the expression level of PTP1B in insulin-resistant HepG2 cells. These findings are the first to elucidate the inhibitory effects of PB1 and PB2 on PTP1B, and highlight the role of procyanidins as dietary supplements in regulating T2DM.

Facilitators of and barriers to implementing a traditional Chinese medicine collaborative model of care for axial spondyloarthritis: a qualitative study.

BACKGROUND: Conventional therapy may be inadequate for many patients with axial spondyloarthritis (axSpA). Traditional Chinese medicine (TCM) may be a viable alternative, but its effectiveness for axSpA is unknown. We are currently conducting a pragmatic randomised controlled trial (RCT) to investigate the effectiveness of a TCM collaborative model of care (TCMCMC), which combines usual rheumatologic care with acupuncture for patients with axSpA. This nested qualitative sub-study aims to identify facilitators of and barriers to the implementation of the TCMCMC. METHODS: We conducted individual in-depth interviews with participants who had completed the acupuncture regimen to elicit opinions on the facilitators of and barriers to the implementation of the TCMCMC. The interviews were transcribed and analysed using thematic analysis. RESULTS: Twelve participants were included, with data saturation occurring after 10 interviews. The analysis revealed both a number of important 'facilitators' and 'barriers'. Facilitators to the implementation of the TCMCMC included effectiveness of TCM to relieve symptoms, inadequacy of conventional treatment and positive social perceptions of TCM. Barriers included scepticism towards TCM, inability of TCM to provide instant relief, needle-related discomfort, variable effectiveness of TCM influenced by physicians' skills and experience and the high cost of TCM. Recommendations to overcome barriers included further patient education about TCM. CONCLUSION: Policymakers should take into account the various feasibility factors identified in this study when developing and implementing a TCMCMC. TRIAL REGISTRATION NUMBER: NCT03420404 (ClinicalTrials.gov).

Effect of Blueberry Anthocyanin-Rich Extracts on Peripheral and Hippocampal Antioxidant Defensiveness: The Analysis of the Serum Fatty Acid Species and Gut Microbiota Profile.

The current study investigated the positive effects of blueberry anthocyanin-rich extracts (BAE) on either peripheral or hippocampal antioxidant defensiveness and established the connection of the improved antioxidant status with the altered fatty acid species and gut microbiota profile. High-fat diet-induced oxidative stress in C57BL/6 mice was attenuated by BAE administration, which was reflected by strengthened antioxidant enzymes, alleviated hepatic steatosis, and improved hippocampal neuronal status. Serum lipidomics analysis indicated that the fatty acid species were altered toward the elevated unsaturated/saturated ratio, along with phospholipid species toward enriched n-3 polyunsaturated fatty acid compositions. The modulated antioxidant pattern could be attributed to the increased bacteria diversity, stimulated probiotics (Bifidobacterium and Lactobacillus) and short-chain fatty acid (SCFA) producers (Roseburia, Faecalibaculum, and Parabacteroides) improved by anthocyanins and their metabolites, which improved the colon environment, characterized by promoted SCFAs, restored colonic mucosa, and reorganized microbial structure. Thus, anthocyanin-rich dietary intervention is a promising approach for the defensiveness in human oxidative damage and neurodegeneration.

Impact of complementary and alternative medicines on antiepileptic medication adherence among epilepsy patients.

BACKGROUND: The aim of this study was to assess the knowledge, attitude, and practice of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy. METHODS: A cross-sectional study was carried out on 100 epilepsy patients, aged 18 years or older that did not have any physical or psychiatric illness. A patient-administered questionnaire was used to assess their knowledge, attitude towards, practice, and perceived effectiveness (KAPP) of CAM. Established adherence assessment tools were used to determine patient medication adherence. RESULTS: The prevalence of CAM usage was found to be at 58%. CAM was used more frequently by males (n = 32, 60.4%) than by females (n = 26, 55.3%; p = 0.609). The most commonly used CAM included vitamins and minerals (36%), ginseng (16%), antioxidants (15%), and acupuncture (12%). A significant number of patients had low knowledge of (59%) and a positive attitude (54%) toward complementary and alternative medicine. Main reasons for using CAM were a lower price, better availability, and inadequate seizure control by AEDs. About 43% of the patients who used CAM informed their doctor. Prevalence of non-adherence to AED therapy was found to be 68%. A significant association was found between non-adherence and CAM usage (p < 0.01). CONCLUSION: A high prevalence of CAM usage and non-adherence to AEDs among epilepsy patients was identified. CAM usage was associated with a non-adherence to AED therapy. This study highlights the need to explore CAM usage with patients before making clinical decisions to achieve the best outcomes from AED therapy.

The Antibacterial Agent Identified from Acidocella spp. in the Fluid of Nepenthes gracilis Against Multidrug-Resistant Klebsiella pneumoniae: A Functional Metagenomic Approach.

Aims: The fluid of Nepenthes gracilis harbors diverse bacterial taxa that could serve as a gene pool for the discovery of the new genre of antimicrobial agents against multidrug-resistant Klebsiella pneumoniae. The aim of this study was to explore the presence of antibacterial genes in the fluids of N. gracilis growing in the wild. Methods: Using functional metagenomic approach, fosmid clones were isolated and screened for antibacterial activity against three strains of K. pneumoniae. A clone that exhibited the most potent antibacterial activity was sent for sequencing to identify the genes responsible for the observed activity. The secondary metabolites secreted by the selected clone was sequentially extracted using hexane, chloroform, and ethyl acetate. The chemical profiles of a clone (C6) hexane extract were determined by gas chromatography/mass spectrometry (GC-MS). Results: Fosmid clone C6 from the fluid of pitcher plant that exhibited antibacterial activity against three strains of K. pneumoniae was isolated using functional metagenome approach. A majority of the open reading frames detected from C6 were affiliated with the largely understudied Acidocella genus. Among them, the gene that encodes for coproporphyrinogen III oxidase in the heme biosynthesis pathway could be involved in the observed antibacterial activity. Based on the GC-MS analysis, the identities of the putative bioactive compounds were 2,5-di-tert-butylphenol and 1-ethyl-2-methyl cyclododecane. Conclusions: The gene that encodes for coproporphyrinogen III oxidase in the heme biosynthesis pathway as well as the secondary metabolites, namely 2,5-di-tert-butylphenol and 1-ethyl-2-methyl cyclododecane could be the potential antibacterial molecules responsible for the antibacterial activity of C6.

[Mechanisms of Yiqihuoxue herb Naoluoxintong promotes cerebral vascular regeneration in rats with cerebral ischemia syndrome of Qi deficiency accompanied by blood stasis].

Objective To investigate the effect of Yiqihuoxue herb Naoluoxintong on cerebral vascular regeneration in rats of middle cerebral artery occlusion-reperfusion(MCAO-R)experimental model with Qi deficiency and blood stasis syndrome, and explore the possible mechanisms. Methods A total of 60 SD rats were randomly divided into a control group, a model group and three Naoluoxintong-treated groups [(1 200, 800 and 400 mg/(kg.d)], with 12 rats each. Except for the control group, the other groups were treated with modified suture method combined with multi-factor compound simulation to establish the models with both MCAO-R and syndrome of Qi deficiency accompanied by blood stasis. Neural functional deficit, blood stasis syndrome and Qi deficiency syndrome were scored by quantitative criteria for biological characteristics score. The regional cerebral blood flow (rCBF) was dynamically monitored with laser Doppler scanning. HE staining was used to observe the pathological changes of brain tissue. The mRNA expression levels of Wnt5a, glycogen synthase kinase-3ß (GSK-3ß) were determined by real-time fluorescent quantitative PCR, and the protein expression levels of ß-catenin, vascular endothelial growth factor (VEGF), AngII in the rat brain tissue were detected by Western blotting. Results Naoluoxintong improved neural functional in the model rats, reduced the scores of neural functional deficit, blood stasis syndrome and Qi deficiency syndrome, and restored rCBF simultaneously. Meanwhile, Naoluoxintong high- and middle-dose groups were better than any other model groups in terms of pathological changes, and the up-regulation of Wnt5a mRNA expression in these two groups was the most obvious. However, it had no significant effect on GSK3ß mRNA in the model rats. Expression levels of ß-catenin, VEGF, AngII protein were obviously up-regulated in Naoluoxintong high- and middle-dose groups. Conclusion Naoluoxintong can improve the rCBF with the aid of promoting cerebral vascular regeneration, which might be related to high expression of pro-angiogenic factors that are affected by Wnt signal path activation.

Effect of ultrahigh pressure on structural and physicochemical properties of rice and corn starch in complexes with apple polyphenols.

BACKGROUND: Ultrahigh-pressure (UHP) treatment, a non-thermal processing technology, exerts a bactericidal effect and affects food texture. How UHP treatments influence starch-polyphenol complexes has not yet been reported. Here, we studied the effects of UHP treatment on the structure of common rice starch (CRS)-apple polyphenol (AP) and common corn starch (CCS)-AP mixtures. RESULTS: Overall, UHP treatment decreased the particle size of the CRS-AP and CCS-AP composites. Furthermore, the ΔH values of the CRS-AP and CCS-AP mixtures decreased, and the heating stability was improved after UHP treatment. X-ray diffraction indicated that the relative crystallinity of the mixtures was unaffected by UHP treatment. Fourier-transform infrared spectroscopy proved that no new absorption peaks were observed in the infrared spectra, and the order of starch-AP was decreased after UHP treatment. These results indicated that UHP treatment inhibited the retrogradation of the starch-AP mixture. Our analyses of the microstructures of CRS-AP and CCS-AP mixtures showed increased folding and more pronounced network structures under high-pressure. CONCLUSIONS: These results provide a theoretical basis for further exploring the properties of starch-AP mixtures following UHP treatment and provide insights regarding the use of UHP treatments for food production. © 2020 Society of Chemical Industry.

Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers.

Although radiation is widely used to treat cancers, resistance mechanisms often develop and involve activation of DNA repair and inhibition of apoptosis. Therefore, compounds that sensitize cancer cells to radiation via alternative cell death pathways are valuable. We report here that ferroptosis, a form of nonapoptotic cell death driven by lipid peroxidation, is partly responsible for radiation-induced cancer cell death. Moreover, we found that small molecules activating ferroptosis through system xc- inhibition or GPX4 inhibition synergize with radiation to induce ferroptosis in several cancer types by enhancing cytoplasmic lipid peroxidation but not increasing DNA damage or caspase activation. Ferroptosis inducers synergized with cytoplasmic irradiation, but not nuclear irradiation. Finally, administration of ferroptosis inducers enhanced the antitumor effect of radiation in a murine xenograft model and in human patient-derived models of lung adenocarcinoma and glioma. These results suggest that ferroptosis inducers may be effective radiosensitizers that can expand the efficacy and range of indications for radiation therapy.