Complex insoluble dietary fiber alleviates obesity and liver steatosis, and modulates the gut microbiota in C57BL/6J mice fed a high-fat diet.

BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.

Bioinformatics-based analysis of mechanistic differences in vascular endothelial injury ischemic stroke induced by atrial fibrillation and atherosclerosis.

Studies of the intracranial vasculature in patients with ischemic stroke caused by atherosclerosis (AS) and cardiac embolism have revealed significantly different degrees of AS, plaque, and vascular stenosis. And the endothelium has a great influence on the vasculature throughout the circulatory system, especially in the brain. This study aimed to investigate the mechanistic differences in endothelial injury between atrial fibrillation (AF)- and AS-induced ischemic stroke. All target genes of AF, AS, and the vascular endothelial cell (VC) were obtained from the GeneCards database; the differential genes of AF and AS separately associated with the VC were established by a Venn diagram. A protein-protein interaction network was created, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to perform genomic enrichment and functional enrichment analysis. Hub genes were selected by Maximal Clique Centrality algorithm ranking and correlation linkage in the STRING database, and then, clinical serum samples were used to verify the quantitative expressions in the AF, AF stroke, AS, and AS stroke groups. Fifty-five AF-VC-related genes and ninety-three AS-VC-related genes were screened, which differed in biological function, cellular composition, and molecular function. The genes correlation between AF and vascular endothelial cells (VCs) was KRAS and PTPN11, and those correlation between AS and VCs was IL-4, IFNG, IL-17A, and CSF-2. IL-4 and CSF-2 may be relevant proteins involved in the differences in stroke mechanisms between AF and AS, and they may act by further influencing the function of their downstream cells. This study provides a preliminary theoretical basis for investigating the differences in mechanisms of endothelial injury between AF- and AS-induced ischemic stroke.

Association between Sleep and Alzheimer's Disease: A Bibliometric Analysis from 2003 to 2022.

INTRODUCTION: Alzheimer's disease (AD) often presents with sleep disorders, which are also an important risk factor for AD, affecting cognitive function to a certain extent. This study aimed to reveal the current global status, present hotspots, and discuss emerging trends of sleep and AD using a bibliometric approach. METHODS: Research and review articles related to sleep and AD from 2003 to 2022 were extracted from the Web of Science Core Collection. VOSviewer 1.6.18.0, Scimago Graphica, and CiteSpace 6.2.R2 were used to map the productive and highly cited countries, institutions, journals, authors, references, and keywords in the field. RESULTS: Overall, 4,008 publications were included in this bibliometric analysis. The number of publications and citations showed an increasing trend over the past two decades. The USA and China had the largest and second largest, respectively, number of publications and citations and cooperated with other countries more closely. Ancoli-Israel Sonia published the most papers, and Holtzman David M was co-cited most frequently. The most productive journal was Journal of Alzheimer's Disease, and Neurology was the most frequently cited journal. The risk factors, ß-amyloid (Aß), tau, neuroinflammation, astrocytes, glymphatic system, orexin, functional connectivity, and management have been the main research directions of researchers over the past few years and may be the future trend of valuable research. CONCLUSION: We identified hotspots and emerging trends including risk factors, Aß, tau, neuroinflammation, the glymphatic system, orexin, and management, which may help identify new therapeutic targets and improve clinical efficacy of sleep and AD.

Anchoring Al- and/or Mg-oxides to magnetic biochars for Co-uptake of arsenate and fluoride from water.

The co-occurrence of arsenic and fluoride in the water environment has led to many health concerns for living beings. Simultaneous removal of such ions is crucial to the safety of water resources, and biochar has been extensively engaged to address this issue. Here four magnetic biochars (mBCs) including pristine magnetic biochar and three aluminum (Al) and/or magnesium (Mg) oxides-anchored magnetic biochar (i.e., Al-mBC, Mg-mBC, and MgAl-mBC) were prepared via a facile pyrolysis method and then comprehensively evaluated as adsorbents for enhanced co-uptake of arsenate (AsV) and fluoride (F-) from synthetic water. The mBC shows a high specific surface area of 205 m2 g-1, which dropped to 116, 80, and 114 m2 g-1 upon the anchoring of Al, Mg, and Mg + Al, respectively. Our results suggest that the adsorption of either AsV or F- is highly pH-dependent, and pH 4-6 is the optimal range for maximum adsorption. The adsorption isotherm data indicate that the MgAl-mBC adsorbent outranks all other mBCs for co-uptake of both AsV and F-. The adsorption capacity maxima of MgAl-mBC are 34.45, and 21.59 mg g-1 for AsV and F-, respectively (pH = 5, T = 10 °C), also highly outstripping other biochars reported in the literature. The magnetic feature of these mBCs enables us to fast reclaim and regenerate the exhausted adsorbents by an external magnet and dilute NaOH. The Al- and Mg-anchored mBCs are expected to be used as highly efficient adsorbents for environmental remediation of waters contaminated by both AsV and F-.

Compressive spectral imaging system for soil classification with three-dimensional convolutional neural network.

Compressive spectral imaging systems have promising applications in the field of object classification. However, for soil classification problem, conventional methods addressing this specific task often fail to produce satisfying results due to the tradeoff between the invariance and discrepancy of each soil. In this paper, we explore a liquid crystal tunable filters (LCTF)-based system and propose a three-dimensional convolutional neural network (3D-CNN) for soil classification. We first obtain a set of soil compressive measurements via a low spatial resolution detector, and soil hyperspectral images are reconstructed with improved resolution in spatial as well as spectral domains by a compressive sensing (CS) method. Furthermore, different from previous spectral-based object classification methods restricted to extract features from each type independently, on account of the potential of spectral property on individual solid, our method proposes to apply the principal component analysis(PCA) to achieve a dimensionality reduction in the spectral domain. Then, we explore a differential perception model for flexible feature extraction, and finally introduce a 3D-CNN framework to solve the multi-soil classification problem. Experimental results demonstrate that our algorithm not only is able to accelerate the ability of feature discriminability but also performs against conventional soil classification methods.

Fourier ptychographic microscopy reconstruction with multiscale deep residual network.

Fourier ptychographic microscopy (FPM) is a newly developed microscopic technique for large field of view, high-resolution and quantitative phase imaging by combining the techniques from ptychographic imaging, aperture synthesizing and phase retrieval. In FPM, an LED array is utilized to illuminate the specimen from different angles and the corresponding intensity images are synthesized to reconstruct a high-resolution complex field. As a flexible and low-cost approach to achieve high-resolution, wide-field and quantitative phase imaging, FPM is of enormous potential in biomedical applications such as hematology and pathology. Conventionally, the FPM reconstruction problem is solved by using a phase retrieval method, termed Alternate Projection. By iteratively updating the Fourier spectrum with low-resolution-intensity images, the result converges to a high-resolution complex field. Here we propose a new FPM reconstruction framework with deep learning methods and design a multiscale, deep residual neural network for FPM reconstruction. We employ the widely used open-source deep learning library PyTorch to train and test our model and carefully choose the hyperparameters of our model. To train and analyze our model, we build a large-scale simulation dataset with an FPM imaging model and an actual dataset captured with an FPM system. The simulation dataset and actual dataset are separated as training datasets and test datasets, respectively. Our model is trained with the simulation training dataset and fine tuned with the fine-tune dataset, which contains actual training data. Both our model and the conventional method are tested on the simulation test dataset and the actual test dataset to evaluate the performances. We also show the reconstruction result of another neural network-based method for comparison. The experiments demonstrate that our model achieves better reconstruction results and consumes much less time than conventional methods. The results also point out that our model is more robust under system aberrations such as noise and blurring (fewer intensity images) compared with conventional methods.

Mechanisms of multiple neurotransmitters in the effects of Lycopene on brain injury induced by Hyperlipidemia.

BACKGROUND: Lycopene is a kind of carotenoid, with a strong capacity of antioxidation and regulating the bloodlipid. There has been some evidence that lycopene has protective effects on the central nervous system, but few studies have rigorously explored the role of neurotransmitters in it. Therefore, the present study was designed to investigate the effects of several neurotransmitters as lycopene exerts anti-injury effects induced by hyperlipidemia. METHODS: Eighty adult SD rats, half male and half female, were randomly divided into eight groups on the basis of serum total cholesterol (TC) levels and body weight. There was a control group containing rats fed a standard laboratory rodent chow diet (CD); a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) group; a positive group (CCT + F) fed CCT, supplemented with 10 mg·kg·bw- 1·d- 1 fluvastatin sodium by gastric perfusion; and lycopene groups at five dose levels (CCT + LYCO) fed with CCT and supplied lycopene at doses of 5, 25, 45, 65, and 85 mg·kg·bw- 1·d- 1. The levels of TC, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), oxidized low density lipoprotein (ox-LDL), low-density lipoprotein receptor (LDLR), nerve growth factor (NGF), glutamic acid (Glu), Gamma aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), N-methyl-D-aspartate (NMDA1R), GABAA, 5-HT1, D1, and apoptosis-related proteins Caspase3, bax, and bcl-2 were measured after the experiment. Nissl staining was adopted to observe the morphological changes in neurons. RESULTS: At the end of the experiment, the levels of TC, TG, LDL-C, IL-1, TNF-α, and ox-LDL in the serum and brain as well as the content of Glu, DA, NMDA, and D1 in the brain of rats in the CCT group were higher than those in the control group (P<0.05); the levels of LDLR, NGF, GABA, 5-HT, GABAA, 5-HT1, and neuron quantities in the hippocampal CA1 and CA3 areas were lower than those in the control group (P<0.05). Compared to the CCT group, levels of TC, TG, LDL-C, IL-1, TNF-α, and ox-LDL in the serum and brain, as well as the content of Glu, DA and the expression of pro-apoptotic Caspase3 in the brain decreased in the rats with lycopene (25 mg to 85 mg) added to the diet (P<0.05); the levels of LDLR, NGF, GABA, 5-HT, GABAA, and 5-HT1 as well as the expression of anti-apoptotic bcl-2 and the neuron quantity in hippocampal CA1 and CA3 areas increased (P<0.05); further, the hippocampal cells were closely arranged. Lycopene dose was negatively correlated with the levels of TC, TG, and LDL-C in the serum and brain as well as levels of IL-1, TNF-α, ox-LDL, Glu/GABA, NMDA1R, and Caspase3 (P<0.05); it was positively correlated with the levels of LDLR, NGF, 5-HT, 5-HT1, GABAA, bcl-2, and the neuron quantity in hippocampal CA1 and CA3 areas (P<0.05). CONCLUSIONS: Lycopene exerts anti-injury effects in the brain as-induced by hyperlipidemia. It can inhibit the elevation of serum TC, TG, and LDL-C in rats with hyperlipidemia while indirectly affecting the levels of TC, TG, and LDL-C in the brain, leading to a reduction in ox-LDL, IL-1, and TNF-α in the brain. This inhibits the release of Glu, which weakens nerve toxicity and downregulates pro-apoptotic Caspase3. Lycopene also plays an anti-injury role by promoting the release of the inhibitory neurotransmitter GABA and 5-HT, which enhances the protective effect, and by upregulating the anti-apoptotic bcl-2.

Correction to: Mechanisms of multiple neurotransmitters in the effects of Lycopene on brain injury induced by Hyperlipidemia.

Following publication of the original article [1] it came to the attention of the Research Integrity Group that the following corrections were required.

Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.

BACKGROUND: The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. METHOD: One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aß), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. RESULTS: Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P < 0.05) and the expression of IL-1, TNF-α and GFAP in the brains had increased (P < 0.05). In the second week, the expression of FFA and APP in the brains, and the amount of apoptotic neurons, had increased (P < 0.05). In the third week, the levels of VEGF, Ox-LDL and Aß had increased, and the expression of Claudin-5 had decreased in the brains (P < 0.05). In the fourth week, the levels of TC, LDL-C and the amount of apoptotic neurons had increased (P < 0.05). The correlation analysis showed a positive correlation among FFA, TNF-α, VEGF, ox-LDL, Aß, GFAP and neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P < 0.05). CONCLUSION: Hyperlipidemia may activate astrocytes by means of high levels of TG that will have direct toxic effects on the cerebral vessels and neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aß, induce the secretion of VEGF, reduce the expression of tight junction protein Claudin-5 and change the permeability of blood-brain barriers to factors that could damage cerebral vessels and neurons.

Large-leaf yellow tea protein derived-peptides alleviated dextran sodium sulfate-induced acute colitis and restored intestinal microbiota balance in C57BL/6 J mice.

Large-leaf yellow tea (LYT)-derived peptides (TPP) are rich in amino acids required for damage repair, such as Glu, Arg, and Pro, and can be used to alleviate acute colitis. However, its effect and mechanisms against colitis remain unclear. This study utilized TPP to intervene in dextran sodium sulfate-induced acute colitis in C57BL/6 J mice. Results confirmed that TPP ameliorated acute colitis symptoms by inhibiting pro-inflammatory cytokines, restoring gut microbiota dysbiosis, particularly by increasing the abundance of beneficial bacteria Akkermansia and Lactobacillus while declining harmful microbiota Escherichia-Shigella. Besides, TPP intervention reshaped the gut microbiota phenotype by increasing the aerobic phenotype and reducing the potentially pathogenic phenotype. Levels of short-chain fatty acids, including acetic acid, propanoic acid, isobutyric acid, and butyric acid, were also enhanced in a dose-dependent manner to help restore gut microbiota equilibrium. This study supports using TPP as a viable plant protein-derived dietary resource for alleviating inflammatory bowel disease.

Melatonin as an add-on treatment for epilepsy: A systematic review and meta-analysis.

PURPOSE: Epilepsy, one severe prevalent brain disorder, primarily relies on drug treatment. However, approximately one-third of patients with epilepsy do not achieve effective control with current medications, underscoring the need for more innovative treatment approaches. Notably, melatonin has gained attention for its anti-seizure properties and favourable safety profile. This systematic review aimed to evaluate the efficacy and safety of melatonin as an add-on treatment for epilepsy. METHODS: We searched for articles published before June 2023 in Web of Science, Cochrane Library, and PubMed. We used RevMan 5.4 software to compute relative risks (RRs) and 95 % confidence intervals (CIs). Key outcomes included total sleep time, wakefulness after sleep onset, sleep latency, seizure frequency, seizure severity, and safety. The quality of randomised controlled studies (RCTs) was assessed using the Cochrane Risk of Bias tool. RESULTS: Of the 264 publications retrieved, 10 RCTs were included in the meta-analysis. Add-on melatonin treatment improved sleep latency (RR: 0.56; 95 %CI: 0.10-1.02; P = 0.02) and seizure severity (RR: 0.33; 95 %CI: 0.04-0.62; P = 0.03) compared with placebo treatment. Adverse events (increased headache severity in children with a history of migraines, bronchitis, ear infections, agitation, and urinary frequency) were reported in only one trial. CONCLUSION: This systematic review found that add-on melatonin therapy improved sleep latency and seizure severity in patients with epilepsy. However, several of the included studies did not systematically assess sleep quality, seizures, and safety and lacked long-term follow-up data. Further RCTs with extended follow-up periods are required to definitively determine the efficacy and safety of melatonin.

Macrophage-derived CD36 + exosome subpopulations as novel biomarkers of Candida albicans infection.

Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

Combiner and HyperCombiner networks: Rules to combine multimodality MR images for prostate cancer localisation.

One of the distinct characteristics of radiologists reading multiparametric prostate MR scans, using reporting systems like PI-RADS v2.1, is to score individual types of MR modalities, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced, and then combine these image-modality-specific scores using standardised decision rules to predict the likelihood of clinically significant cancer. This work aims to demonstrate that it is feasible for low-dimensional parametric models to model such decision rules in the proposed Combiner networks, without compromising the accuracy of predicting radiologic labels. First, we demonstrate that either a linear mixture model or a nonlinear stacking model is sufficient to model PI-RADS decision rules for localising prostate cancer. Second, parameters of these combining models are proposed as hyperparameters, weighing independent representations of individual image modalities in the Combiner network training, as opposed to end-to-end modality ensemble. A HyperCombiner network is developed to train a single image segmentation network that can be conditioned on these hyperparameters during inference for much-improved efficiency. Experimental results based on 751 cases from 651 patients compare the proposed rule-modelling approaches with other commonly-adopted end-to-end networks, in this downstream application of automating radiologist labelling on multiparametric MR. By acquiring and interpreting the modality combining rules, specifically the linear-weights or odds ratios associated with individual image modalities, three clinical applications are quantitatively presented and contextualised in the prostate cancer segmentation application, including modality availability assessment, importance quantification and rule discovery.

Comparison of sea buckthorn fruit oil nanoemulsions stabilized by protein-polysaccharide conjugates prepared using ß-glucan from various sources.

To understand the influence of ß-glucans structure on the emulsifying properties of protein-polysaccharide conjugates, sodium caseinate (NaCas) was utilized to form glycosylation conjugates with varying degrees of glycosylation (10.68-17.50%) using three ß-glucans from bacteria, yeast, and oats. This process induced alterations in the secondary structure of protein. The nanoemulsions prepared with the glycosylated conjugates exhibited superior stability compared to those formulated solely with NaCas, particularly under conditions of drastic pH fluctuations and extended storage periods. The nanoemulsion prepared with the NaCas-Salecan conjugate demonstrated exceptional stability at pH 4 and 6, or storage for 20 days. Additionally, it significantly attenuated the oxidation of unsaturated fatty acids and exhibited the lowest levels of aggregation, flocculation, and free fatty acid release rate during in vitro digestion. This study suggested the potential of the NaCas-Salecan conjugates in enhancing the stability of nanoemulsions and facilitating the colorectal-targeted delivery of sea buckthorn fruit oil.

Active learning using adaptable task-based prioritisation.

Supervised machine learning-based medical image computing applications necessitate expert label curation, while unlabelled image data might be relatively abundant. Active learning methods aim to prioritise a subset of available image data for expert annotation, for label-efficient model training. We develop a controller neural network that measures priority of images in a sequence of batches, as in batch-mode active learning, for multi-class segmentation tasks. The controller is optimised by rewarding positive task-specific performance gain, within a Markov decision process (MDP) environment that also optimises the task predictor. In this work, the task predictor is a segmentation network. A meta-reinforcement learning algorithm is proposed with multiple MDPs, such that the pre-trained controller can be adapted to a new MDP that contains data from different institutes and/or requires segmentation of different organs or structures within the abdomen. We present experimental results using multiple CT datasets from more than one thousand patients, with segmentation tasks of nine different abdominal organs, to demonstrate the efficacy of the learnt prioritisation controller function and its cross-institute and cross-organ adaptability. We show that the proposed adaptable prioritisation metric yields converging segmentation accuracy for a new kidney segmentation task, unseen in training, using between approximately 40% to 60% of labels otherwise required with other heuristic or random prioritisation metrics. For clinical datasets of limited size, the proposed adaptable prioritisation offers a performance improvement of 22.6% and 10.2% in Dice score, for tasks of kidney and liver vessel segmentation, respectively, compared to random prioritisation and alternative active sampling strategies.

A Meta-analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Pregabalin and Gabapentin in the Treatment of Postherpetic Neuralgia.

OBJECTIVE: To systematically evaluate the clinical efficacy of pregabalin and gabapentin in the treatment of postherpetic neuralgia (PHN), including the difference in pain control and occurrence of adverse reactions. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for randomized controlled trials (RCTs) comparing the efficacy of pregabalin and gabapentin in patients with PHN. Data from studies meeting the inclusion criteria were extracted and the Cochrane Risk of Bias risk assessment tool was used to evaluate the quality of the included studies. Revman 5.3 and Stata17 were used to perform the meta-analysis and to detect publication bias. RESULTS: A total of 14 RCTs with 3545 patients were included in this study, including 926 in the pregabalin treatment group, 1256 in the gabapentin treatment group, and 1363 in the placebo control group. Pregabalin was better than gabapentin in alleviating pain and improving the global perception of change in pain and sleep (P < 0.05). Gabapentin was associated with a lower incidence of adverse events than pregabalin (P < 0.05). Funnel plot and Begg's and Egger's tests showed no significant publication bias. CONCLUSION: Pregabalin appears to have a better overall therapeutic effect than gabapentin for patients with PHN, but gabapentin has a lower incidence of adverse reactions and a better safety profile. Clinicians should comprehensively consider patient factors and fully evaluate the advantages and disadvantages of each treatment option to select the most suitable drugs for patient use. Considering the limited quantity and quality of the existing literature, high-quality RCTs are needed to confirm the advantages of pregabalin over gabapentin in the treatment of PHN and guide clinical decision-making.

Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: In recent years, as one of the drugs for the treatment of acute ischemic stroke (AIS), the clinical application of tenecteplase is still controversial. Therefore, we aimed to evaluate the safety and efficacy of tenecteplase versus alteplase to guide clinical practice. METHODS: A search of PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023 was conducted to identify eligible articles. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 and Stata 17 were used to perform the meta-analysis and detect publication bias, and risk ratios (RRs) with 95% confidence intervals (95% CIs) were reported for each outcome measure. RESULTS: A total of 1326 records were retrieved in this meta-analysis. As a result of the limited reports on tenecteplase in patients with AIS and the lack of high-quality randomized controlled trials (RCTs), and considering the impact of publication bias, we did not include any of these studies published before 2015. Ultimately we included 16 RCTs with a total of 7508 patients, including 3940 patients treated with alteplase and 3568 patients treated with tenecteplase. Tenecteplase was associated with better early neurological improvement (RR 0.10; 95% CI 0.00-0.19; P = 0.04), recanalization of blood vessels (RR 0.24; 95% CI 0.07-0.40; P = 0.01), and 90-day excellent neurological recovery (RR 0.12; 95% CI 0.01-0.24; P = 0.04). In addition, there were no significant differences in other efficacy and safety outcomes between the two groups. The funnel plot and Begg's as well as Egger's tests showed no significant publication bias. CONCLUSIONS: This meta-analysis showed that tenecteplase was not inferior to alteplase in early thrombolytic therapy in patients with AIS, and was even better than alteplase on some efficacy outcomes with no significant differences in safety. However, as a result of some inherent limitations of this study, more high-quality prospective clinical studies are needed to confirm these results.

In recent years, there has been controversy surrounding the use of tenecteplase, a drug for treating acute ischemic stroke (AIS). To help doctors make better decisions, we compared the safety and effectiveness of tenecteplase with another drug called alteplase. We looked at various research articles from PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023. After careful analysis, we found 16 relevant studies with a total of 7508 patients, including those treated with alteplase and tenecteplase. Our findings showed that tenecteplase was as effective as alteplase in providing early thrombolytic therapy for patients with AIS. In fact, tenecteplase even showed better results in some aspects of treatment, without compromising safety. However, we acknowledge some limitations in our study and recommend more high-quality clinical studies to validate these results.

Bioinformatics and network pharmacology analysis of drug targets and mechanisms related to the comorbidity of epilepsy and migraine.

OBJECTIVE: The present study aimed to explore the mechanisms underlying the comorbidity of epilepsy and migraine, identify potential common targets for drug intervention, and provide insight into new avenues for disease prevention and treatment using an integrated bioinformatic and network pharmacology approach. METHODS: Disease targets in epilepsy and migraine were screened using the DisGeNET database to identify intersecting gene targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) enrichment analyses were then performed using the WebGestalt database. Furthermore, the STRING database was used to construct a protein-protein interaction (PPI) network, and Cytoscape software was used to analyze the protein molecular signals at the intersection of epilepsy and migraine. The Drugbank database was used to identify common targets for antiepileptic drugs in epilepsy and migraine to further analyze the disease-gene-target-drug interaction network. Finally, molecular docking simulations were performed to verify the hypothesis that migraine and epilepsy share common diseases and drug targets. RESULTS: A total of 178 common targets for epilepsy and migraine were identified using the DisGeNET database, and the 24 genes most related to the diseases were screened using the Score_gda gene scoring system. GO enrichment analysis indicated that common targets were mainly enriched in biological processes and molecular functions, including membrane potential regulation, inorganic ion transmembrane transport, axonal signaling, and ion channel activity. KEGG pathway enrichment analysis indicated that the mechanism of action might be related to neuroactive ligand receptors, AGE-RAGE, cAMP, and VEGF signaling pathways. The PPI network construction and analysis results showed that the PPI grid had 23 central nodes and 24 connected edges, with an average node degree of 2.09 and an average clustering coefficient of 0.384. The 10 genes with potentially important roles in epilepsy and migraine were CACNA1A, KCNQ2, KCNA1, SCN1A, PRRT2, SCN8A, KCNQ3, SCN2A, GRIN2A, and GABRG2. Drugbank database results indicated that antiepileptic drugs, including lamotrigine, topiramate, valproic acid, carbamazepine, gabapentin, and perampanel, also had common targets with migraine. The three most important targets exhibited strong binding affinity with drugs in the molecular docking simulations. CONCLUSION: Our systematic and comprehensive analyses of disease-gene-target-drug interaction networks identified several biological processes and molecular functions common to migraine and epilepsy, most of which were related to neuroactive ligand-receptor interactions. These data provide a new theoretical basis and reference for the clinical treatment of comorbid epilepsy and migraine and may aid in the development of novel pharmacological strategies.

The efficacy and safety of third-generation antiseizure medications and non-invasive brain stimulation to treat refractory epilepsy: a systematic review and network meta-analysis study.

Background: The new antiseizure medications (ASMs) and non-invasive brain stimulation (NIBS) are controversial in controlling seizures. So, this network meta-analysis aimed to evaluate the efficacy and safety of five third-generation ASMs and two NIBS therapies for the treatment of refractory epilepsy. Methods: We searched PubMed, EMBASE, Cochrane Library and Web of Science databases. Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM), perampanel (PER), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) were selected as additional treatments for refractory epilepsy in randomized controlled studies and other cohort studies. Randomized, double-blind, placebo-controlled, add-on studies that evaluated the efficacy or safety of medication and non-invasive brain stimulation and included patients with seizures were uncontrolled by one or more concomitant ASMs were identified. A random effects model was used to incorporate possible heterogeneity. The primary outcome was the change in seizure frequency from baseline, and secondary outcomes included the proportion of patients with ≥50% reduction in seizure frequency, and the rate of treatment-emergent adverse events. Results: Forty-five studies were analyzed. The five ASMs and two NIBS decreased seizure frequency from baseline compared with placebo. The 50% responder rates of the five antiseizure drugs were significantly higher than that of placebo, and the ASMs were associated with fewer adverse events than placebo (p < 0.05). The surface under the cumulative ranking analysis revealed that ESL was most effective in decreasing the seizure frequency from baseline, whereas CNB provided the best 50% responder rate. BRV was the best tolerated. No significant publication bias was identified for each outcome index. Conclusion: The five third-generation ASMs were more effective in controlling seizures than placebo, among which CNB, ESL, and LCM were most effective, and BRV exhibited better safety. Although rTMS and tDCS did not reduce seizure frequency as effectively as the five drugs, their safety was confirmed. Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/ (CRD42023441097).

Corylin inhibits the progression of Non-small cell lung cancer cells by regulating NF-κB signaling pathway via targeting p65.

BACKGROUND: Lung cancer is characterized by high-risk and high mortality, among which non-small cell lung cancer (NSCLC) conquers a dominant position. Previous studies have reported that corylin has anti-inflammatory, anti-oxidant, and anti-tumor effects; however, its role in NSCLC cells remains unclear. HYPOTHESIS: Corylin inhibits the progression of NSCLC cells. METHODS: A lentivector NF-κB luciferase reporter was constructed by molecular cloning. Corylin was screened and identified as an NF-κB pathway inhibitor by luciferase reporter assay. Corylin inhibited the expression of NF-κB downstream genes, which was detected by qRT-PCR. The effect of corylin on NSCLC cells was detected by colony formation assay, cell apoptosis, cell proliferation, in vitro invasion, and cell scratch assay. Corylin inhibited p65 nuclear translocation and was detected by molecular docking, immunofluorescence assay, and Western blot analysis. RESULTS: We constructed a lentiviral expression vector, containing an NF-κB luciferase reporter and established a stable A549 cell line for its expression. Using this cell line, corylin was screened and identified as an NF-κB pathway inhibitor. It was found that corylin inhibited the expression of NF-κB downstream genes and inhibited the proliferation and migration of NSCLC cells. Meanwhile, it was also found that corylin significantly reversed the increased proliferation of NSCLC cell lines induced by p65 overexpression. Molecular docking analysis showed that corylin could bind to p65 by hydrogen bonding. Further study showed that corylin inhibited the NF-κB signaling pathway by blocking p65 nuclear translocation. CONCLUSIONS: Our study screened and identified corylin as an NF-κB inhibitor and elucidated the molecular mechanism by which corylin inhibits the growth of NSCLC cells. The present study provides a novel strategy for improving the prognosis and treatment of NSCLC patients.