Effects of cannabidiol and Δ9-tetrahydrocannabinol on cytochrome P450 enzymes: a systematic review.

Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included 'cannabidiol', 'tetrahydrocannabinol', and 'cytochrome P450'. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included. Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, cause changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.

Dual-Polymer Functionalized Melanin-AgNPs Nanocomposite with Hydroxyapatite Binding Ability to Penetrate and Retain in Biofilm Sequentially Treating Periodontitis.

Periodontitis is the leading cause of adult tooth missing. Thorny bacterial biofilm and high reactive oxygen species (ROS) levels in tissue are key elements for the periodontitis process. It is meaningful to develop an advanced therapeutic system with sequential antibacterial/ antioxidant ability to meet the overall goals of periodontitis therapy. Herein, a dual-polymer functionalized melanin-AgNPs (P/D-MNP-Ag) with biofilm penetration, hydroxyapatite binding, and sequentially treatment ability are fabricated. Polymer enriched with 2-(Dimethylamino)ethyl methacrylate (D), can be protonated in an acid environment with enhanced positive charge, promoting penetration in biofilm. The other polymer is rich in phosphate group (P) and can chelate Ca2+, promoting the polymer to adhere to the hydroxyapatite surface. Melanin has good ROS scavenging and photothermal abilities, after in situ reduction Ag, melanin-AgNPs composite has sequentially transitioned between antibacterial and antioxidative ability due to heat and acid accelerated Ag+ release. The released Ag+ and heat have synergistic antibacterial effects for bacterial killing. With Ag+ consumption, the antioxidant ability of MNP recovers to scavenge ROS in the inflammatory area. When applied in the periodontitis model, P/D-MNP-Ag has good therapeutical effects to ablate biofilm, relieve inflammation state, and reduce alveolar bone loss. P/D-MNP-Ag with sequential treatment ability provides a reference for developing advanced oral biofilm eradication systems.

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho-1/Gpx4 pathway to prevent α-synuclein-induced ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine.

BACKGROUND: Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. METHODS: This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. RESULTS: Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). CONCLUSION: Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. TRIAL REGISTRATION: NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Futoquinol improves Aß25-35-induced memory impairment in mice by inhibiting the activation of p38MAPK through the glycolysis pathway and regulating the composition of the gut microbiota.

Futoquinol (Fut) is a compound extracted from Piper kadsura that has a nerve cell protection effect. However, it is unclear whether Fut has protective effects in Alzheimer's disease (AD). In this study, we aimed to explore the therapeutic effect of Fut in AD and its underlying mechanism. UPLC-MS/MS method was performed to quantify Fut in the hippocampus of mice brain. The cognition ability, neuronal and mitochondria damage, and levels of Aß1-42, Aß1-40, p-Tau, oxidative stress, apoptosis, immune cells, and inflammatory factors were measured in Aß25-35-induced mice. The content of bacterial meta-geometry was predicted in the microbial composition based on 16S rDNA. The protein levels of HK II, p-p38MAPK, and p38MAPK were detected. PC-12 cells were cultured in vitro, and glucose was added to activate glycolysis to further explore the mechanism of action of Fut intervention in AD. Fut improved the memory and learning ability of Aß25-35 mice, and reduced neuronal damage and the deposition of Aß and Tau proteins. Moreover, Fut reduced mitochondrial damage, the levels of oxidative stress, apoptosis, and inflammatory factors. Fut significantly inhibited the expression of HK II and p-p38MAPK proteins. The in vitro experiment showed that p38MAPK was activated and Fut action inhibited after adding 10 mM glucose. Fut might inhibit the activation of p38MAPK through the glycolysis pathway, thereby reducing oxidative stress, apoptosis, and inflammatory factors and improving Aß25-35-induced memory impairment in mice. These data provide pharmacological rationale for Fut in the treatment of AD.

Cultural Dimensions Moderate the Association between Loneliness and Mental Health during Adolescence and Younger Adulthood: A Systematic Review and Meta-Analysis.

Cultural factors, such as country or continent, influence the relationship between loneliness and mental health. However, less is known about how cultural dimensions moderate this relationship during adolescence and younger adulthood, even if these dimensions manifest as country or continent differences. This study aims to examine the potential influence of Hofstede's cultural dimensions on this relationship using a three-level meta-analysis approach. A total of 292 studies with 291,946 participants aged 10 to 24 were included in this study. The results indicate that cultural dimensions, such as individualism vs. collectivism, indulgence vs. restraint, power distance, and long-term vs. short-term orientation, moderated the associations between loneliness and social anxiety, stress, Internet overuse, and negative affect. The association between loneliness and mental health was not moderated by cultural dimensions, such as masculinity and uncertainty avoidance. These findings suggest that culture's influence on the association between loneliness and mental health is based on a domain-specific mechanism.

A large deletion conferring pale green leaves of maize.

BACKGROUND: The structural basis of chloroplast and the regulation of chloroplast biogenesis remain largely unknown in maize. Gene mutations in these pathways have been linked to the abnormal leaf color phenotype observed in some mutants. Large scale structure variants (SVs) are crucial for genome evolution, but few validated SVs have been reported in maize and little is known about their functions though they are abundant in maize genomes. RESULTS: In this research, a spontaneous maize mutant, pale green leaf-shandong (pgl-sd), was studied. Genetic analysis showed that the phenotype of pale green leaf was controlled by a recessive Mendel factor mapped to a 156.8-kb interval on the chromosome 1 delineated by molecular markers gy546 and gy548. There were 7 annotated genes in this interval. Reverse transcription quantitative PCR analysis, SV prediction, and de novo assembly of pgl-sd genome revealed that a 137.8-kb deletion, which was verified by Sanger sequencing, might cause the pgl-sd phenotype. This deletion contained 5 annotated genes, three of which, including Zm00001eb031870, Zm00001eb031890 and Zm00001eb031900, were possibly related to the chloroplast development. Zm00001eb031870, encoding a Degradation of Periplasmic Proteins (Deg) homolog, and Zm00001eb031900, putatively encoding a plastid pyruvate dehydrogenase complex E1 component subunit beta (ptPDC-E1-ß), might be the major causative genes for the pgl-sd mutant phenotype. Plastid Degs play roles in protecting the vital photosynthetic machinery and ptPDCs provide acetyl-CoA and NADH for fatty acid biosynthesis in plastids, which were different from functions of other isolated maize leaf color associated genes. The other two genes in the deletion were possibly associated with DNA repair and disease resistance, respectively. The pgl-sd mutation decreased contents of chlorophyll a, chlorophyll b, carotenoids by 37.2%, 22.1%, and 59.8%, respectively, and led to abnormal chloroplast. RNA-seq revealed that the transcription of several other genes involved in the structure and function of chloroplast was affected in the mutant. CONCLUSIONS: It was identified that a 137.8-kb deletion causes the pgl-sd phenotype. Three genes in this deletion were possibly related to the chloroplast development, which may play roles different from that of other isolated maize leaf color associated genes.

Cost-minimization analysis of DTaP-IPV-Hib combination vaccine in China: A nationwide cross-sectional study.

Combination vaccines can reduce the vaccination visit, simplify the vaccination schedule and efficiently improve management. This study was primarily designed to evaluate the economic impact of integrating the diphtheria-tetanus-acellular pertussis inactivated poliomyelitis and Haemophilus influenzae type B (DTaP-IPV-Hib) combination vaccine into the China National Immunization Program. A cost-minimization analysis (CMA) compared the costs associated with direct medical, direct nonmedical, and indirect social costs in four schemes was conducted. A budgetary impact analysis assessed the alternative schemes' financial impact on the healthcare budget. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct nonmedical (cost for transportation) and indirect costs (loss of productivity) were derived from parents' questionnaires. Replacement of the current vaccination scheme with DTaP-IPV-Hib combination vaccine, resulted in net increases in direct medical costs of 77.64% for alternative scheme 1, 146.54% for alternative scheme 2, and 294.67% for alternative scheme 3, respectively. However, the direct nonmedical and indirect costs and the cost of the alternative schemes were 18.18%, 36.36%, and 63.64% lower than the current scheme for alternative scheme 1, alternative scheme 2, and alternative scheme 3, respectively. From the societal perspective, when compared with the current scheme, the budgetary impact of the three alternative schemes were +66 million Chinese Yuan (CNY) (4.81%), +103 million CNY (7.53%), and +305million CNY (22.35%), respectively. The CMA considered a broader perspective of social costs and indicated that the alternative schemes would result in an overall saving of parents' transportation and work loss costs to bring their children for vaccination, translating into a total cost saving of 18.18%, 36.36%, 63.64%, comparing to the current scheme. Thus, fully or partly using the DTaP-IPV-Hib combination vaccine is cost-saving in the context of China.

Double-sided asymmetric metasurfaces achieving sub-microscale focusing from a GaN green laser diode.

We proposed and demonstrated a highly efficient sub-microscale focusing from a GaN green laser diode (LD) integrated with double-sided asymmetric metasurfaces. The metasurfaces consist of two nanostructures in a GaN substrate: nanogratings on one side and a geometric phase based metalens on the other side. When it was integrated on the edge emission facet of a GaN green LD, linearly polarized emission was firstly converted to the circularly polarized state by the nanogratings functioning as a quarter-wave plate, the phase gradient was then controlled by the metalens on the exit side. In the end, the double-sided asymmetric metasurfaces achieve a sub micro-focusing from linearly polarized states. Experimental results show the full width at half maximum of the focused spot size is about 738 nm at the wavelength 520 nm and the focusing efficiency is about 72.8%. Our results lay a foundation for the multi-functional applications in optical tweezers, laser direct writing, visible light communication, and biological chip.

COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis.

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination. Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N = 257 817). Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.

Transcriptome analysis reveals the fruit color variation in Ailanthus altissima.

Anthocyanins are responsible for the intensity of color in plants; however, the systematic mechanisms underlying the color differences in the fruit of Ailanthus altissima remain unknown. Therefore, this study aims to analyze the transcriptomes of the white and red fruit of A. altissima by screening and validating the key genes involved in flavonoid and anthocyanin biosynthesis. Samples of A. altissima fruit were collected 30, 45, and 60 days after flowering, and their pigment and sugar content were determined. The anthocyanin content was significantly higher in red than in white fruits. Transcriptome analysis was also performed on the fruit samples, 73,807 unigenes were assembled and annotated to seven databases. Twenty-one co-expressed modules were identified via weighted gene co-expression network analysis, of which two were associated with flavonoids and anthocyanins. Furthermore, in three growth stages, 126, 30, and 124 differentially expressed genes were screened between white and red fruit. Genes involved in flavonoid and anthocyanin metabolism were identified. AaDFR (A. altissima bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase) and AaANS (A. altissima anthocyanidin synthase) were associated with flavonoid and anthocyanin metabolism. Members of the AaDFR and AaANS families were also identified, and their basic physicochemical characteristics, conserved domains, motif compositions, phylogenetics, and expression levels were analyzed. The overexpression of AaDFR and AaANS in transgenic Arabidopsis significantly increased the content of seed and foliar flavonoids and anthocyanins. The study elucidated the different mechanisms underlying fruit color development and provided insight into A. altissima plants breeding with commercially desirable properties.

Mindfulness Training Improves Attention: Evidence from Behavioral and Event-related Potential Analyses.

Mindfulness meditation helps to improve attentional capacity. However, the neural correlates that indicate the mechanism through which mindfulness improves attention are unclear. To address this gap, we aimed to assess the effects of mindfulness training on sustained attentional capacity. Event-related potentials (ERPs) associated with the modified sustained attention response task (mSART) were used in this study. A total of 45 college students were randomly assigned to either the mindfulness group (n = 21) or the control group (n = 24). Participants in the mindfulness group received a three-week mindfulness training. The self-report results showed that the mindfulness group reported higher mindfulness scores (observing and non-judgment of inner experiences) after the training. The mindfulness group also scored lower on the state anxiety than the control group. Behavioral results also showed that self-caught mind wandering in the mindfulness group significantly decreased after the training, and the mindfulness group showed a faster response after the training. The ERP results showed that N2 amplitudes in the post-test were significantly greater than those in the pre-test in the mindfulness group. We did not find any interactions between group and time for P3. The findings suggest that mindfulness training can effectively improve sustained attentional capacity, as indicated by reduced mind wandering and increased N2 responses.

Association of childhood threat and deprivation with depressive symptoms and the moderating role of current economic status among middle-aged and older adults in China.

PURPOSE: To investigate the independent impact of threat-related and deprivation-related adverse childhood experiences (ACEs) on depressive symptoms among middle-aged and older adults, and to evaluate the moderating role of current economic status in these associations. METHODS: This cross-sectional study included 11,048 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. We captured five threat-related ACEs and five deprivation-related ACEs by questionnaires. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale. Current economic status was reflected by annual per capita household consumption expenditure. We performed logistic regression analyses to evaluate the independent association of childhood threat and deprivation with depressive symptoms, and conducted stratified analyses and tests for interaction to explore the moderation effect of current economic status in such associations. RESULTS: Compared with the nonexposed group, the experience of both childhood threat and deprivation were independently associated with greater risks of depressive symptoms later in life (odds ratio [OR] 1.75, 95% CI 1.49-2.05 for ≥ 2 threat-related ACEs; OR 2.02, 95% CI 1.67-2.43 for ≥ 2 deprivation-related ACEs). High current economic status significantly ameliorated the impact of childhood deprivation, but not threat, on depressive symptoms (P value for interaction 0.038). CONCLUSIONS: Both threat-related and deprivation-related ACEs were associated with the risk of depressive symptoms among middle-aged and older adults, while current economic status was a significant moderator in such risks only for childhood deprivation. The findings implied that prioritising targeted interventions for individuals with ACEs, especially for childhood deprivation victims who were economically disadvantaged in adulthood, may help mitigate depressive symptoms in later life.

Comparison between human olfactory sensitivity in the fasted and fed states: A systematic review and meta-analysis.

INTRODUCTION: Olfaction is tightly regulated by internal status such as hunger level. The influence of fasted and fed states on olfactory sensitivity in humans has reached mixed results. This study aims to systematically review, integrate and meta-analyze evidence of the impact of fasting on olfactory sensitivity in humans and to explore the impact of potential moderators. METHOD: Electronic databases (PubMed, PsycINFO, Web of Science, COCHRANE and Ovid) were searched for studies with human participants investigating the effect of fasting on olfactory sensitivity. Studies were included in the review if they measured odor threshold both at fasted and sated status. The data extraction was determined based on the change in odor threshold from the fasted state to the fed state. Meta-analysis was conducted using a random-effect model to estimate the standardized mean difference transformed olfactory sensitivity change between fasted and fed states with 95% confidence interval (CI). RESULTS: Thirteen studies (12 articles) were included in the meta-analysis with a total of 550 participants. Olfactory sensitivity was higher in the fasted state compared to the fed state (SMD = -0.251, 95% CI = -0.426, -0.075, Z = -2.804, p = 0.005). Separated analyses for food and non-food odors revealed a significant elevated sensitivity to non-food odors during the fasted state compared to the fed state. The meta-regression analysis revealed that fasting time positively moderate the increased olfactory sensitivity from the fasted to fed states (ß = -0.013, 95% CI = -0.023, -0.002, p = 0.016). CONCLUSION: Fasting improves human olfactory sensitivity to non-food odors, and this effect increases with longer fasting time. Future research design on olfactory sensitivity should take both the fasted state and fasting period of the participants into consideration.

PGC-1α-siRNA suppresses inflammation in substantia nigra of PD mice by inhibiting microglia.

Background and purpose: Parkinson's disease is a common degenerative disease of the central nervous system with complex pathogenesis. More and more studies have found that inflammatory response promotes the occurrence and development of the disease, in which the activation of microglia plays an important role. PGC-1α (peroxisome proliferator activated receptor-γ coactivator-1α) is the main factor in mitochondrial biogenetic, and is closely related to the inflammatory response. Our immunofluorescence test results showed that PGC-1α and microglia (Iba1) have double-labeled phenomenon. The expression of microglia in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) group increased, and PGC-1α/Iba1 double label increased. To test whether lowering the expression of PGC-1α can reduce the activation of microglia and protect the substantia nigra dopaminergic neurons, we constructed PGC-1α interference lentivirus.Methods: Immunofluorescence, western blot, and ELISA were used to detect microglial phenotype.Results: The results showed that PGC-1α interfering with lentivirus can transfect microglial cells in substantia nigra, and the PGC-1α protein level decreased in substantia nigra accordingly; TH protein expression had no statistical difference compared with MPTP group; PGC-1α interfering lentivirus reduced microglia number and activation, and at the same time the expression of iNOS and Arg1 significantly reduced compared with MPTP group. The IL-6 expression in blood detected using ELISA was significantly reduced compared with MPTP group.Conclusion: PGC-1α downregulation inhibited microglia activity, and both M1 and M2 microglial activities are reduced.

A Pilot Human Cadaveric Study on Accuracy of the Augmented Reality Surgical Navigation System for Thoracolumbar Pedicle Screw Insertion Using a New Intraoperative Rapid Registration Method.

To evaluate the feasibility and accuracy of AR-assisted pedicle screw placement using a new intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy in cadavers. Five cadavers with intact thoracolumbar spines were employed in this study. Intraoperative registration was performed using anteroposterior and lateral views of preoperative CT scanning and intraoperative 2D fluoroscopic images. Patient-specific targeting guides were used for pedicle screw placement from Th1-L5, totaling 166 screws. Instrumentation for each side was randomized (augmented reality surgical navigation (ARSN) vs. C-arm) with an equal distribution of 83 screws in each group. CT was performed to evaluate the accuracy of both techniques by assessing the screw positions and the deviations between the inserted screws and planned trajectories. Postoperative CT showed that 98.80% (82/83) screws in ARSN group and 72.29% (60/83) screws in C-arm group were within the 2-mm safe zone (p < 0.001). The mean time for instrumentation per level in ARSN group was significantly shorter than that in C-arm group (56.17 ± 3.33 s vs. 99.22 ± 9.03 s, p < 0.001). The overall intraoperative registration time was 17.2 ± 3.5 s per segment. AR-based navigation technology can provide surgeons with accurate guidance of pedicle screw insertion and save the operation time by using the intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy.

Relationship between IDH1/2 and TERT promoter mutation and the prognosis of human glioma patients.

Objective: To investigate the relationship between isocitrate dehydrogenase (IDH) 1/2 mutation, telomerase reverse transcriptase (TERT) gene promoter mutation and the prognosis of human glioma patients. Methods: One hundred fifteen patients with human glioma, treated surgically in The First Affiliated Hospital of Hebei North University from January 2019 to January 2020, were included. All patients were followed up until January 31, 2022. The mutations of IDH1/2 and TERT promoter were analyzed, and risk factors affecting survival of the patients with glioma were assessed. Results: IDH1 gene mutation occurred in 82 cases, IDH2 gene mutation occurred in five cases and TERT promoter mutation occurred in 54 cases. Univariate analysis showed that tumor WHO grade, resection range, preoperative Karnofsky performance status score, postoperative radiotherapy and chemotherapy, IDH1/2 gene and TERT promoter mutation influenced postoperative survival of patients with glioma (P<0.05). Kaplan-Meier survival curve showed that IDH1/2 gene and TERT promoter mutation were significantly different from those of wild-type patients (P<0.05). Conclusion: IDH1/2 gene and TERT promoter mutations are more frequent in patients with human glioma. These related factors can be used as molecular markers to aid in the prognosis of patients with glioma.

[Effect of aqueous extract of Corni Fructus on Aß_(25-35)-induced brain injury and neuroinflammation in mice with Alzheimer's disease].

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

[Platycladi Semen oil ameliorates Aß_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota].

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aß_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aß_(25-35), 200 µmol·L~(-1), 0.15 µL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aß_(1-42)/Aß_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aß_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aß_(1-42)/Aß_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aß_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

Genome-wide identification of BAM (ß-amylase) gene family in jujube (Ziziphus jujuba Mill.) and expression in response to abiotic stress.

BACKGROUND: Elevated temperature and drought stress have substantial impacts on fruit quality, especially in terms of sugar metabolism and content. ß-Amylase (BAM) plays a critical role in regulating jujube fruit sugar levels and abiotic stress response. Nevertheless, little is known about the regulatory functions of the BAM genes in jujube fruit. RESULTS: Nine jujube BAM genes were identified, clustered into four groups, and characterized to elucidate their structure, function, and distribution. Multiple sequence alignment and gene structure analysis showed that all ZjBAM genes contain Glu-186 and Glu-380 residues and are highly conserved. Phylogenetic and synteny analysis further indicated that the ZjBAM gene family is evolutionarily conserved and formed collinear pairs with the BAM genes of peach, apple, poplar, Arabidopsis thaliana, and cucumber. A single tandem gene pair was found within the ZjBAM gene family and is indicative of putative gene duplication events. We also explored the physicochemical properties, conserved motifs, and chromosomal and subcellular localization of ZjBAM genes as well as the interaction networks and 3D structures of ZjBAM proteins. A promoter cis-acting element analysis suggested that ZjBAM promoters comprise elements related to growth, development, phytohormones, and stress response. Furthermore, a metabolic pathways annotation analysis showed that ZjBAMs are significantly upregulated in the starch and sucrose metabolism, thereby controlling starch-maltose interconversion and hydrolyzing starch to maltose. Transcriptome and qRT-PCR analyses revealed that ZjBAMs respond positively to elevated temperature and drought stress. Specifically, ZjBAM1, ZjBAM2, ZjBAM5, and ZjBAM6 are significantly upregulated in response to severe drought. Bimolecular fluorescence complementation analysis demonstrated ZjBAM1-ZjAMY3, ZjBAM8-ZjDPE1, and ZjBAM7-ZjDPE1 protein interactions that were mainly present in the plasma membrane and nucleus. CONCLUSION: The jujube BAM gene family exhibits high evolutionary conservation. The various expression patterns of ZjBAM gene family members indicate that they play key roles in jujube growth, development, and abiotic stress response. Additionally, ZjBAMs interact with α-amylase and glucanotransferase. Collectively, the present study provides novel insights into the structure, evolution, and functions of the jujube BAM gene family, thus laying a foundation for further exploration of ZjBAM functional mechanisms in response to elevated temperature and drought stress, while opening up avenues for the development of economic forests in arid areas.