Non-invasive treatments improve patient outcomes in chronic tinnitus: a systematic review and network meta-analysis.

OBJECTIVE: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. METHODS: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. RESULTS: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. CONCLUSIONS: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. LEVEL OF EVIDENCE: How common is the problem? Level 2. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1. What will happen if we do not add a therapy? (Prognosis) Level 1. Does this intervention help? (Treatment Benefits) Level 1. What are the COMMON harms? (Treatment Harms) Level 1. What are the RARE harms? (Treatment Harms) Level 1. Is this (early detection) test worthwhile? (Screening) Level 1I.

Post-marketing safety concerns with lumateperone: a pharmacovigilance analysis based on the FDA adverse event reporting system (FAERS) database.

Objective: Lumateperone, a novel antipsychotic drug that was granted by the Food and Drug Administration (FDA) approval in December 2019, remains insufficiently explored for its adverse event profile. This study used the FDA Adverse Event Reporting System (FAERS) database to explore its potential safety issues. Methods: This study conducted a retrospective analysis of FAERS data from the fourth quarter of 2019 to the third quarter of 2023, extracting reports related to lumateperone. Disproportionality analysis using Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithms was employed to detect signals of adverse events (AEs). Results: Our research processed 4,777 pertinent AE disclosures related to lumateperone, unveiling 125 signals that satisfied both ROR and BCPNN evaluative benchmarks across 26 System Organ Classes (SOCs). Intriguingly, 108 of these signals were categorized as unanticipated, spotlighting notable psychiatric manifestations such as mania (ROR = 73.82, 95% CI = 57.09-95.46; IC = 6.16, IC025 = 4.49), and hypomania (ROR = 34.74, 95% CI = 15.54-77.64; IC = 5.10, IC025 = 3.43), alongside non-psychiatric phenomena like urinary retention (ROR = 3.59, 95% CI = 1.80-7.19; IC = 1.84, IC025 = 0.18) and serotonin syndrome (ROR = 8.69, 95% CI = 4.81-15.72; IC = 3.11, IC025 = 1.45). Conclusion: This research provides real-world safety data on lumateperone post-marketing and is an important supplement to the information from clinical trial studies. Healthcare professionals should be vigilant for the risk of a manic switch in patients with bipolar depression who are administered lumateperone. More epidemiological studies are needed in the future to explore and further evaluate the risk-benefit issue of lumateperone.

Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study.

BACKGROUND: Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. METHODS: Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. RESULTS: The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. CONCLUSION: This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.

Neurodevelopmental disorders as a risk factor for temporomandibular disorder: evidence from Mendelian randomization studies.

Objective: This study aims to clarify the incidence rate of temporomandibular joint disease in patients with mental disorders. Methods: Data extracted from the Psychiatric Genomics Consortium and FinnGen databases employed the Mendelian Randomization (MR) method to assess the associations of three neurodevelopmental disorders (NDDs)-Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette's Disorder (TD)-as exposure factors with Temporomandibular Disorder (TMD). The analysis used a two-sample MR design, employing the Inverse Variance Weighted (IVW) method to evaluate the relationships between these disorders and Temporomandibular Disorder. Sensitivity analysis and heterogeneity assessments were conducted. Potential confounding factors like low birth weight, childhood obesity, and body mass index were controlled for. Results: The study found that ADHD significantly increased the risks for TMD (OR = 1.2342, 95%CI (1.1448-1.3307), p < 0.00001), TMD (including avohilmo) (OR = 1.1244, 95%CI (1.0643-1.1880), p = 0.00003), TMD-related pain (OR = 1.1590, 95%CI (1.0964-1.2252), p < 0.00001), and TMD-related muscular pain associated with fibromyalgia (OR = 1.1815, 95%CI (1.1133-1.2538), p < 0.00001), while other disorders did not show significant causal relationships. Conclusion: This study reveals the elevated risk of various TMD aspects due to ADHD. Furthermore, we discuss the link between low vitamin D levels ADHD and TMD. Future research should address these limitations and delve further into the complex interactions between ADHD, ASD, TD, and TMD.

Unveiling the muscle-brain axis: A bidirectional mendelian randomization study investigating the causal relationship between sarcopenia-related traits and brain aging.

BACKGROUND: Observational studies suggest an association between sarcopenia-related traits and brain aging, but whether this association reflects a causal relationship remains unclear. This study aims to employ Mendelian randomization (MR) methods to investigate the causal impact of sarcopenia-related traits on brain aging. METHODS: This study presents a comprehensive analysis of genome-wide association study (GWAS) summary data associated with sarcopenia-related traits. The data were derived from a large-scale cohort, encompassing measures such as grip strength, lean body mass, and walking pace. Measurements of brain aging were obtained from neuroimaging genetics, utilizing meta-analysis (ENIGMA) to combine magnetic resonance imaging (MRI) data from 33,992 participants. The primary methodology employed in this analysis was the inverse-variance-weighted method (IVW). Additionally, sensitivity analyses were conducted, to assess heterogeneity and pleiotropy. RESULT: Appendicular lean mass(ALM) is negatively correlated with Pallidum aging; Whole body fat-free mass shows a negative correlation with Amygdala aging; Leg fat-free mass (left) and Leg fat-free mass (right) are negatively correlated with Pallidum aging; Usual walking pace is positively correlated with Nucleus Accumbens aging. Cerebellum WM aging is negatively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Hippocampus aging is negatively correlated with Hand grip strength (left) and Hand grip strength (right). Ventricles aging is positively correlated with Usual walking pace; Nucleus Accumbens aging is positively correlated with Leg fat-free mass (left) and Leg fat-free mass (right); Putamen aging is positively correlated with ALM. CONCLUSION: Our study confirms that reduced muscle mass speeds up brain aging. Walking too fast raises the risk of brain aging, while maintaining or increasing appendicular lean mass, overall muscle mass, and muscle mass in both legs lowers the risk of brain aging.

Medical cost of environmental pollution: evidence from the Chinese Social Survey.

Environmental pollution impairs residents' health, while the pursuit of health is highly correlated to medical costs. Understanding how environmental pollution affects medical costs is closely linked to the welfare of society. Based on theoretical analysis, this paper uses data from 5112 households of the Chinese Social Survey (CSS) in 2019, constructs a composite indicator to quantify environmental pollution using respondents' evaluations, and empirically investigates the causal effect of environmental pollution on household medical cost and the mechanism. The conclusions are shown as follows. First, environmental pollution can increase household medical costs, and this estimation result still holds after dealing with the endogeneity problem and other robustness tests. Second, there is heterogeneity in the impact of environmental pollution on household medical costs, households in the upper socioeconomic class, with heavy pension burdens or with strong health insurance coverage are more sensitive to environmental pollution and incur relatively higher household medical costs. Third, environmental pollution reduces residents' satisfaction with their spiritual life, which adversely affects their physical and mental health and can increase household medical costs. Residents' satisfaction with their spiritual life is an important mechanism for environmental pollution to affect household health care expenditures. Therefore, governments should enhance the enforcement of environmental protection and governance, strengthen the awareness of green issues and health education, and increase the supply of facilities for leisure and sports, thus reducing medical costs due to environmental pollution and easing the medical burden of residents.

Relationship between composite dietary antioxidant index and depression among overweight and obese adults.

BACKGROUND: The use of specific dietary patterns to alleviate depressive symptoms has gained increasing recognition. The Composite Dietary Antioxidant Index (CDAI) is a crucial criterion for assessing antioxidant diets. We examined the relationship between CDAI and depression among overweight and obese adults through a cross-sectional study conducted in the United States. METHODS: We used weighted multivariate logistic regression models with subgroup analysis to study the relationship between CDAI and depression. Generalized additive models were used to determine whether there was a nonlinear association between them. We developed a two-piece linear regression model to calculate the inflection point utilizing a recursive strategy. RESULTS: After adjusting for confounding variables, the odds ratios (ORs; 95 % CI) for the correlation between CDAI and depression were 0.75 (0.67, 0.84). A saturation effect emerged for the overweight group, following which we calculated the inflection point for the overweight population, which displayed ORs (95 % CI) of 0.62 (0.47, 0.80) before the inflection point of 0.83 and the ORs (95 % CI) of 1.01 (0.77, 1.31) after 0.83. The interaction was statistically significant in the sex stratification of the obese population. CONCLUSIONS: Our study highlighted a negative association between CDAI and depression among overweight and obese adults. Saturation effects and sex differences were observed in the overweight population.

Integrated UPLC-MS, network pharmacology, and intestinal flora analysis to determine the treatment effect of Qiangzhi decoction on comorbid Tourette syndrome and RRTI.

Background: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI. However, the mechanism of QZD on TS and RRTI remains unclear. This study aimed to determine the treatment effect of QZD on comorbid TS and RRTI by integrating ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), network pharmacology, and intestinal flora analysis. Methods: The components of QZD were first identified by UPLC-quadrupole (Q)-orbitrap-MS/MS. The mechanism of QZD on comorbid RRTI and TS was investigated by a series of network pharmacological methods, including target prediction and bioinformatics analysis. Finally, a comorbid TS and RRTI rat model was established by intraperitoneal injection of 3,3-iminodipropionitrile (IDPN), cyclophosphamide (CTX), and lipopolysaccharide (LPS). Alteration of gut microbiota in the alleviation of TS and RRTI by QZD was investigated via intestinal flora analysis. Results: The results of UPLC-Q-orbitrap-MS/MS showed that QZD had 96 types of chemical components. The network pharmacology results demonstrated that targets of QZD involved in the treatment of TS and RRTI involved 1045 biological processes (BPs), 109 cellular components (CCs), and 133 molecular functions (MFs), including synaptic and transsynaptic signaling, chemical synaptic transmission, neurotransmitter receptor activity, G protein-coupled amine receptor activity, and serotonin receptor activity, among others. Firmicutes, Bacteroidetes, Coprococcus, and Lachnospiraceae played crucial roles in gut microbiota of a QZD-treated comorbid TS and RRTI model. Conclusions: Our results revealed QZD provided a multicomponent, multitarget, and multipathway synergistic treatment of comorbid TS and RRTI.

A J-shaped association between Dietary Inflammatory Index (DII) and depression: A cross-sectional study from NHANES 2007-2018.

BACKGROUND: Growing evidence indicates that depression is more common in people who partake in a pro-inflammatory diet. The objective of our study was to assess the association between the Dietary Inflammatory Index (DII) and depression through a cross-sectional study of the National Health and Nutrition Examination Survey from 2007 to 2018. METHODS: We used weighted multivariable logistic regression models with subgroup analysis to explore the relationship between DII and depression. Generalized additive models were used to test whether there was a nonlinear association. Then, we constructed a two-piece linear regression model and performed a recursive algorithm to calculate the inflection point. RESULTS: The study enrolled a total of 30,627 individuals from the United States. In the regression model with full confounding variables adjusted, the OR (95 % CI) for the association between DII and depression was 1.05 (1.04, 1.06). A J-shaped association was found between DII and depression, with a turning point of 2.74. After the turning point, the OR (95 % CI) was 1.60 (1.51, 1.69). Only the interaction in the cardiovascular disease (CVD) analysis was statistically significant. CONCLUSION: Our study highlighted a J-shaped association between DII and depression in a nationally representative sample of adults from the United States.

Pupil calibration for pyramid wavefront sensors based on a wavefront corrector.

The pyramid wavefront sensor (PWS) presents numerous advantages, such as high energy utilization, exceptional spatial resolution, and adjustability. Precise calibration of the pupil's position and size in advance is essential for accurately extracting wavefront slope information from the captured pupil image by the PWS. What we believe to be a novel calibration method is proposed using a wavefront corrector to enhance the sharpness of the pupil images in the PWS. An experimental setup using a crystal spatial light modulator (SLM) is established to validate this method. Both physical experiments and simulated results demonstrate that our proposed method can achieve accurate calibration of the pupil image with an error within 4 pixels for pupil size and not exceeding 3 pixels for position, meeting practical application requirements. The proposed PWS calibration method exhibits excellent repeatability and robustness, making it directly applicable in astronomical adaptive optics systems.

Quality of evidence supporting the role of non-steroidal anti-inflammatory drugs for the treatment of anxious depression: a protocol for an overview of systematic reviews and meta-analyses.

INTRODUCTION: There have been several studies showing the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for anxious depression. We aimed to summarise the evidence and evaluate the methodological quality regarding the effectiveness and safety of NSAIDs for anxious depression from systematic reviews/meta-analyses (SRs/MAs). METHODS AND ANALYSIS: Two researchers searched seven databases for SRs/MAs, which are randomised controlled trials on NSAIDs for anxious depression. Two investigators used the Assessment System for Evaluating Methodological Quality 2, the Risk of Bias in Systematic reviews tool, the list of preferred reporting items for SRs/MAs and the Grading of Recommendations, Assessment, Development and Evaluation system to assess the included SRs/MAs. ETHICS AND DISSEMINATION: The findings of the study will be disseminated through peer-reviewed journals, and national and international conference presentations.

A critical overview of systematic reviews and meta-analyses of light therapy for non-seasonal depression.

Light therapy has increasingly been used in relieving non-seasonal depression. We aimed to summarize the evidence and evaluate the methodological quality regarding the effectiveness and safety of light therapy for non-seasonal depression from systematic reviews/meta-analyses (SRs/MAs). In this study, five databases were searched from their inceptions to January 24, 2022. SRs/MAs on light therapy treatment for non-seasonal depression were included. Methodological quality assessment was performed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and evidence quality assessment was performed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). Six SRs/MAs on light therapy treatment for non-seasonal depression were included. The AMSTAR-2 showed that the methodological level of five included SRs/MAs were evaluated as critically low quality, and one included SRs/MAs were rated as low quality. According to the evaluation results of GRADE, the quality of evidence was mostly unsatisfactory. The results and descriptions in the included SRs/MAs suggest that light therapy is effective as a non-pharmacological intervention for the treatment of non-seasonal depression. However, the generally unsatisfied evidence quality and methodological quality of the SRs/Mas indicate that these results must be interpreted with caution.

Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival.

Background: To investigate the prognostic significance of N7-methylguanosine (m7G) regulators and immune infiltration in liver hepatocellular carcinoma (LIHC). Methods: The research measured predictive m7G genes in LIHC samples from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Data on the stemness index based on mRNA expression (mRNAsi), gene mutations, and corresponding clinical characteristics were obtained from TCGA and ICGC. Lasso regression was used to construct the prediction model to assess the m7G prognostic signals in LIHC. Based on these genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key biological functions and pathways. The correlation between m7G RNA methylation regulators and the prognosis and immune infiltration of LIHC was evaluated. Results: There were 21 m7G-related differentially expressed genes (DEGs) in LIHC and healthy tissues, and LIHC patients could be divided into two categories by consensus clustering of these DEGs. A five-gene predictive approach was employed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Patients in the low-risk group showed a significantly higher survival rate compared with those in the high-risk group (P=0.001). Validations using the ICGC database. Also, univariate and multivariate Cox regression analyses suggested that the risk score produced by the predictive model is an independent predictor for LIHC [hazard ratio (HR): 1.848, 95% confidence interval (CI): 1.286-2.656; HR: 2.597, 95% CI: 1.358-4.965]. The ROC curves of the ICGC cohort revealed that the five-gene prediction model performed well [area under the curve (AUC) =0.642 at 1 year, AUC =0.686 at 2 years, and AUC =0.667 at 3 years]. Immuno-oncology scoring revealed that in the high-risk group, among 16 immune cells, the expressions of neutrophils and natural killer (NK) cells were low and that of regulatory T-cells (Tregs) was high. Conclusions: LIHC occurrence and progression are linked to m7G-related genes. Corresponding prognostic models help forecast the prognosis of LIHC patients. m7G-related genes and associated immune cell infiltration in the TME may serve as potential therapeutic targets in LIHC, which requires further trials. In addition, the m7G-related gene signature offers a viable alternative to predict LIHC, and these m7G-related genes show a prospective research area for LIHC targeted treatment in the future.

Charged Tubular Supramolecule Boosting Multivalent Interactions for the Drastic Suppression of Aß Fibrillation.

Anti-Aß therapy has dominated clinical trials for the prevention and treatment of Alzheimer's disease (AD). However, suppressing Aß aggregation and disintegrating mature fibrils simultaneously remains a great challenge. In this work, we developed a new strategy using a charged tubular supramolecule (CTS) with pillar[5]arene as the backbone and modifying amino and carboxyl groups at the tubular terminals (noted as CTS-A, CTS-A/C, and CTS-C, respectively) to suppress Aß fibrillation for the first time. According to the spectroscopic and microscopic characterizations, Aß40 fibrillation can be efficiently suppressed by CTS-A in a very low inhibitor:peptide (I:P) molar ratio (1:10). A greatly alleviated cytotoxic effect of Aß peptides after the inhibition or disaggregation process is further disclosed. The well-organized supramolecular structure drives multivalent interaction and gains enhanced efficiency on amyloid fibrillar modulation. These results open a new path for the design of supramolecules in the application of AD treatment.

Establishment and evaluation of a compound fear behavior model of Tourette's syndrome in rats.

BACKGROUND: Tourette syndrome (TS) is a common childhood disorder characterized by unwanted movements or vocal sounds called tics. It is often accompanied by other psychobehavioral disorders, including fearful behavior. The establishment and evaluation of rat models of TS and comorbid fear can provide an experimental basis for the treatment of TS and its comorbid fear disorder. METHODS: Sixteen rats were randomly divided into a model group (n=8) and control group (n=8). In the model group, rats were injected intraperitoneally with iminodipropionitrile (IDPN) for 1 week to establish the TS model, which was followed by acoustic and electrical stimulation for 3 weeks to establish the rat models of TS and comorbid fear. The control group received intraperitoneal injection of saline for 1 week, and no further intervention was given in the last 3 weeks. The behavioral changes of the rats were observed and analyzed by the open field test (OFT). Protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA), and tyrosine hydroxylase (TH) and microRNA-134 (miRNA-134) in the brain tissue were detected by using polymerase chain reaction (PCR). RESULTS: One rat in the model group died on the 24th day. Compared with the control group, the model group had significantly higher scores of locomotor activity, stereotyped behavior, and motor behavior, along with prolonged freezing time and significantly lower expression of miRNA-134. The differences in the expressions of PKA, cAMP, DA, and TH in brain tissue were not statistically significant. CONCLUSIONS: The rat models of TS and comorbid fear have similar changes in behaviors and miRNA-134 level to those in clinical settings and therefore can be used as a reliable animal model to study the mechanism of action of TS and comorbid fear.

Network pharmacology study on the mechanism of Qiangzhifang in the treatment of panic disorder.

BACKGROUND: Panic disorder (PD) is a kind of mental illness characterized by the symptom of recurring panic attacks. Qiangzhifang (QZF) is a novel decoction developed by Professor Zhaojun Yan based on a unique system of syndrome differentiation and clinical experience. It has achieved remarkable results after long-term clinical practice, but its mechanism of action is still unclear. This study aims to use network pharmacology and molecular docking to explore the mechanism of QZF in the treatment of PD. METHODS: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a literature search, and Encyclopedia of Traditional Chinese Medicine (ETCM) to find active ingredients and targets of QZF. We searched for PD targets in GeneCards, Online Mendelian Inheritance in Man (OMIM), the Comparative Toxicogenomics Database (CTD), and DrugBank. We established a PD target database, constructed a protein-protein interaction (PPI) network, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis in order to screen possible pathways of action and analyze the mechanism. RESULTS: This study identified 84 effective components of QZF, 691 potential targets, 357 PD targets, and 97 intersectional targets. Enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that QZF was associated with 118 biological processes (BPs), 18 cellular components (CCs), 35 molecular functions (MFs) [false discovery rate (FDR) <0.01], and 62 pathways (FDR <0.01). QZF mainly acts on its targets AKT1, FOS, and APP through active ingredients such as quercetin, ß-sitosterol, 4-(4'-hydroxybenzyloxy)benzyl methyl ether, harmine, 1,7-dimethoxyxanthone, and 1-hydroxy-3,7-dimethoxyxanthone to regulate serotonin, gamma-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and other signal pathways to treat PD. CONCLUSIONS: Through network pharmacology and molecular docking technology, we predicted the possible mechanism of QZF in the treatment of PD, revealed the interaction targets and potential value of QZF, and provided a basis for its clinical application.

Voltage-Driven Flipping of Zwitterionic Artificial Channels in Lipid Bilayers to Rectify Ion Transport.

We developed a voltage-sensitive artificial transmembrane channel by mimicking the dipolar structure of natural alamethicin channel. The artificial channel featured a zwitterionic structure and could undergo voltage-driven flipping in the lipid bilayers. Importantly, this flipping of the channel could lead to their directional alignment in the bilayers and rectifying behavior for ion transport.

Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted gene coexpression network analysis.

BACKGROUND: To date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of high-throughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD. METHODS: In this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases. Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors. RESULTS: As a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors. CONCLUSIONS: Our research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.

Network pharmacology study on the mechanism of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel for anxiety disorders.

BACKGROUND: Although anxiety disorders are one of the most common mental illness in population, antianxiety drugs often only have single action targets, require long-term use, and are associated with many adverse reactions and dependencies. Professor Yan Zhaojun from Shandong Provincial Hospital of Traditional Chinese Medicine (TCM) has applied the modified Renshu Powder, a TCM formula, to treat anxiety disorders, with satisfactory outcomes. Here, we investigated the mechanism of action of two core herbs (prepared Rehmannia root and Chinese arborvitae kernel) in the Renshu Powder in the treatment of anxiety disorders by using network pharmacology approaches. METHODS: Candidate compounds of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel were extracted via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. The targets of action of the main compounds were collected using the SwissTargetPrediction database. Targets associated with anxiety disorders were retrieved from DisGeNET, Online Mendelian Inheritance in Man (OMIM), DrugBank, GeneCards, and Comparative Toxicogenomics Database (CTD) databases. The compound-target interaction network was constructed by Cytoscape 3.7.2 software, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses the data by using Metascape. RESULTS: The main active compounds of the herb pair included arachidonic acid, stigmasterol, and beta-sitosterol. The key targets included Nitric Oxide Synthase 3 (NOS3), Epidermal growth factor (EGF), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Caspase 3 (CASP3), Mitogen-Activated Protein Kinase 1 (MAPK1), Peroxisome proliferator-activated receptor gamma (PPARG), RELA Proto-Oncogene, NF-KB Subunit (RELA), Estrogen Receptor 1 (ESR1), Solute Carrier Family 6 Member 4 (SLC6A4), and Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN). Anxiety disorder-related GO analysis mainly involved synaptic signaling, neurotransmitter receptor activity, and G protein-coupled neurotransmitter receptor activity. The KEGG pathways involved neuroactive ligand-receptor interaction, serotonergic synapse, PI3K/AKT/mTOR signaling pathway, and MAPK signaling pathway. CONCLUSIONS: The mechanism of action of the prepared Rehmannia root-Chinese arborvitae kernel in treating anxiety disorders involves multiple ingredients, multiple targets, and pathways.

Utilizing network pharmacology to explore the underlying mechanism of Qiangzhi decoction in treating Tourette's syndrome.

BACKGROUND: Tourette's syndrome (TS) is a neurodevelopmental condition characterized by multiple motor and vocal tics. Qiangzhi decoction (QD), a well-known herbal decoction, has been used in treating TS in China for decades. We have found relevance between the indications of QD and the classic symptoms of TS. The pharmacological mechanisms of QD in treating TS are still unclear. METHODS: The active compounds of QD were extracted from multi-database, including TCMSP (the Traditional Chinese Medicine Systems Pharmacology database), and potential targets of the compounds were compiled by target fishing. The TS target database was established, and then the protein-protein interaction (PPI) network was constructed to analyze the interactions between the potential targets of compounds in QD and targets associated with TS and screened the core targets by topology. The DAVID bioinformatics database was used to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: 59 active molecules and 585 potential targets of QD were selected. The consequences of the DAVID enrichment analysis show that 36 cellular biological processes (FDR <0.01) and 65 pathways (FDR <0.01) of QD chiefly took part in the convoluted treating effects relevant to the dopamine system, inflammation, and infection, and miRNA pathway. Fourteen core targets of QD were found as potential targets of the treatment of TS. CONCLUSIONS: QD could relieve the symptoms of TS through the molecular mechanisms predicted by network pharmacology. This study supplies insight into how network pharmacology can predict traditional Chinese herbal medicine's possible molecular mechanisms (TCHM).