Pharmacological Methods Research Articles

Norepinephrine triggers glutamatergic long-term potentiation in hypothalamic paraventricular nucleus magnocellular neuroendocrine cells through postsynaptic β1-AR/PKA signaling pathway in vitro in rats.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM). HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Asiatic acid induces lung cancer toxicity by triggering SRC-mediated ferroptosis

Ferroptosis is a recently discovered form of regulated cell death that shows promise as a novel approach for inducing tumor cell death in cancer treatment, with significant research potential. Asiatic acid (AA), a key component of the traditional Chinese medicine Centella asiatica, has been identified as having potential therapeutic benefits for various diseases, particularly cancer. Non-small cell lung cancer (NSCLC) is a challenging and prevalent form of cancer to treat. In our study, we utilized network pharmacology, molecular docking, and experimental methods to investigate the potential of AA in treating NSCLC and to elucidate its role in inhibiting cancer through the ferroptosis pathway. Through network pharmacology analysis, we identified that AA targets the core NSCLC protein SRC through the ferroptosis pathway. Our experiments demonstrated that treatment with AA led to increased iron accumulation, mitochondrial membrane potential, and expression of ferroptosis markers glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long chain family member 4 (ACSL4) in NSCLC cells, confirming the induction of ferroptosis. In conclusion, AA has the potential to target SRC and induce NSCLC cell death through the ferroptosis pathway, offering a promising approach for cancer treatment.

Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification.

Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown. In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments. Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes. Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes. This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.

Chemistry, Analysis, and Biological Aspects of Daprodustat, A New Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor: A Comprehensive Review.

The National Health and Nutrition Examination Survey (NHANES) carried out a survey between 2007-10 and found that as compared to the general population, the prevalence of anemia in chronic kidney disease (CKD) patients was twice high. Daprodustat is an investigational novel drug for the treatment of renal anemia. The objective of this study is to provide a comprehensive review of chemistry, synthesis, pharmacology, pharmacokinetic, and bioanalytical methods for the analysis of Daprodustat. To improve understanding, a review was carried out by creating a database of relevant prior research from electronic sources such as ScienceDirect and PubMed. The methodology is shown in the flowchart of the literature selection process. The drug was approved in 2020 for therapeutic purposes in Japan. It is a novel drug approved for the treatment of anemia in chronic kidney disease for oral administration. It is intended for adults who have undergone dialysis for a minimum of four months and are experiencing anemia as a result of chronic kidney disease. This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat.

Unveiling the efficacy and mechanism of Danggui-Shaoyao-San in treating nephrotic syndrome: A meta-analysis and network pharmacology study

Aim of the studyThe purpose of this study was to investigate the efficacy and mechanism of DSS in treating nephrotic syndrome through meta-analysis and network pharmacology methods. Materials and methodsTo conduct a comprehensive search for randomized controlled trials on the efficacy of Danggui Shaoyao San (DSS) in the treatment of nephrotic syndrome, we searched across eight electronic databases from their establishment to May 1, 2023. The Cochrane Collaboration's Risk of Bias 2 tool was used to evaluate the quality of evidence regarding bias risk and outcomes. Statistical analysis was performed using RevMan software (version 5.4). Furthermore, network pharmacology was employed to validate the underlying mechanism. ResultsThis study included 14 articles that involved 1256 patients with nephrotic syndrome. The clinical efficacy of DSS against nephrotic syndrome was significantly higher than that of Western medical treatment alone. In comparison with the control groups, which were administered Western medicines alone, the use of DSS significantly increased plasma albumin levels (mean difference [MD] = 4.32, 95 % confidence interval [CI] [2.37, 6.24], p < 0.00001) and reduced 24 h urinary protein excretion (MD = −0.92, 95 % CI [−1.11, −0.73], p < 0.00001), total cholesterol levels (MD = −1.23, 95 % CI [−1.76, −0.70], p < 0.00001), triglyceride levels (MD = −0.37, 95 % CI [−0.54, −0.20], p < 0.00001). Furthermore, the combination of DSS with Western medicines achieved better control of adverse reactions in comparison with the control groups (relative risk = 0.37, 95 % CI [0.29, 0.49], p < 0.00001). Network pharmacology analysis identified 39 important active compounds and 18 core target genes involved in the treatment of primary nephrotic syndrome by DSS. Gene Ontology enrichment analysis identified 2126 biological processes, 64 cellular components, and 115 molecular functions, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified 149 signaling pathways. Key active compounds include ginsenoside Rg5, ginsenoside Rg1, schisandrin A, berberine, gallic acid, quercetin, and β-sitosterol, while potential core target genes include IL6, AKT1, TNF, VEGFA, IL1B, and TP53. KEGG pathway analysis indicated that DSS is involved in multiple mechanisms, such as neural development, synaptic plasticity, programmed cell death, inflammation, and immunity. ConclusionsDSS has higher efficacy and safety in the treatment of nephrotic syndrome and acts on nephrotic syndrome via mechanisms that involve multiple targets, components, and pathways.

Cholecystokinin-expressing neurons of the ventromedial hypothalamic nucleus control energy homeostasis

The hypothalamus is the primary center of the brain that regulates energy homeostasis. The ventromedial hypothalamus (VMH) plays a central role in maintaining energy balance by regulating food intake, energy expenditure, and glucose levels. However, the cellular and molecular mechanisms underlying its functions are still poorly understood. Cholecystokinin (CCK) is one of many genes expressed in this hypothalamic nucleus. Peripheral CCK regulates food intake, body weight, and glucose homeostasis. However, current research does not explain the function of CCK neurons in specific nuclei of the hypothalamus and their likely roles in network dynamics related to energy balance and food intake. This study uses genetic and pharmacological methods to examine the role of CCK-expressing neurons in the VMH (CCKVMH). Namely, using a previously generated BAC transgenic line expressing Cre recombinase under the CCK promoter, we performed targeted manipulations of CCKVMH neurons. Histological and transcriptomic database analysis revealed extensive distribution of these neurons in the VMH, with significant heterogeneity in gene expression related to energy balance, including co-expression with PACAP and somatostatin. Pharmacogenetic acute inhibition via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) resulted in increased food intake and altered meal patterns, characterized by higher meal frequency and shorter intermeal intervals. Furthermore, diphtheria toxin-mediated ablation of CCKVMH neurons led to significant weight gain and hyperphagia over time, increasing meal size and duration. These mice also exhibited impaired glucose tolerance, indicative of disrupted glucose homeostasis. Our findings underscore the integral role of CCKVMH neurons in modulating feeding behavior, energy homeostasis, and glucose regulation. This study enhances our understanding of the neurohormonal mechanisms underlying obesity and metabolic disorders, providing potential targets for therapeutic interventions.

METTL3 drives heart failure by regulating Spp1 and Fos m6A modification in myocardial infarction

Abstract Background While m6A modification has been reported in myocardial infarction (MI), the detailed mechanism by which METTL3 regulates the progression of the disease has not yet been elucidated, and it remains unclear why m6A modification increases after MI. Purpose To investigate the role and mechanism of METTL3 in regulating its targets through m6A methylation in MI. The research results will not only add new content to the basic mechanism of myocardial protection but also provide new ideas and new targets for the prevention and treatment of MI. Methods Through MeRIP-seq and extensive bioinformatics analysis, the target genes SPP1 and FOS with the most significant m6A modification and differential expression in MI were screened. We successfully constructed heart specific Mettl3 knockout mice (Mettl3CKO) to verify that METTL3 promotes the deterioration of cardiac function after MI. We performed complementary molecular methods to assess protein quantity and interactions to identify mechanisms regulating this response. We manipulated select molecular pathways using both genetic and pharmacological methods to validate these mechanisms. Results Here, we showed that METTL3 exerted methyltransferase activity-dependent functions in gene regulation in MI, and a significant transcription factor HuR assisted the function of METTL3. and demonstrated that METTL3 was critical for the promotion of heart failure after MI. More specifically, METTL3 directly interacted with HuR through its nuclear localization domain in the cell nucleus under normoxia condition. When hypoxia developed, METTL3 separated from HuR and deposited m6A into 5’UTR of Spp1 and Fos mRNA to maintain their stability. In contrast, HuR bound to the ARE domain of 3’UTR of Spp1 and Fos mRNA to take them to the cytosol, maintaining their stability. Moreover, HIF-1α directly interacted with the HRE domain of Mettl3 to promote its transcription, and HuR bound to the ARE domain of 3’UTR of Mettl3 mRNA to maintain its stability to promote following translation. Conclusions Collectively, our studies revealed previously unappreciated functions of METTL3 with the help of HuR, and a direct target of HIF-1α under normoxia condition, which together contribute to its essential function in MI, suggesting therapeutic potential for targeting the METTL3/HuR/Spp1(Fos) mRNA axis.Figure1

Daridorexant as a new dual orexin receptor antagonist for insomnia - a literature review

Introduction and purpose of review: Insomnia is a prevalent disorder responsible for multiple negative effects on human health. Its treatment involves both non pharmacological and pharmacological methods, however many common insomnia medications are recommended not to be used long term. Daridorexant is a new dual orexin receptor inhibitor, recently approved by the EMA for use in the European Union. The aim of this study is to present current knowledge concerning daridorexantsafety, efficacy and general characteristics. Methods: Pubmed database literature review has been performed. Relevant studies regarding daridorexant and insomnia have been assessed. Product characteristics available on EMA, FDA and Idorsia Pharmaceuticals websites have also been inspected. Current state of knowledge: Studies suggest that daridorexant is generally safe and significantly improves the night-time and daytime functioning of people suffering from insomnia, by enabling them to fall asleep in shorter periods of time and stay asleep for longer. It increases time spent in both REM and non-REM phases proportionally and does not disturb physiological sleep architecture. It shows no residual effects in the morning and can be used long-term, with no reduced efficacy and with no signs of physical dependence or withdrawal symptoms. It rarely leads to serious adverse effects and is contraindicated only in a few groups of patients. Conclusions: Daridorexant is a recently approved dual orexin receptor inhibitor with a promising long-term use safety and efficacy profile. As it is a new medication, further investigation concerning the side effects observed over time should be advised.

Transcutaneous auricular vagus nerve stimulation mitigates gouty inflammation by reducing neutrophil infiltration in BALB/c mice

Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation.

Ocular adverse events associated with GLP-1 receptor agonists: a Real-World Study Based on the FAERS database and network pharmacology.

This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) by analyzing data from the FDA Adverse Event Reporting System (FAERS) and employing network pharmacology methods. FAERS data from the first quarter of 2004 to the first quarter of 2024 were analyzed, focusing on reports of ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis using the Reporting Odds Ratio (ROR) was employed to identify signals of ocular AEs. Additionally, a drug-gene interaction network was constructed using data from multiple public databases to elucidate potential mechanisms underlying these AEs. Analysis of 17,785,793 reports from the FAERS database revealed significant associations between semaglutide, lixisenatide, and ocular AEs. The ROR for semaglutide was 1.25 (95% CI, 1.20-1.31) and for lixisenatide was 1.96 (95% CI, 1.70-2.27), indicating an increased risk of ocular AEs. Frequently reported ocular AEs included blurred vision, visual impairment, and diabetic retinopathy. Time-to-onset analysis indicated that some AEs could manifest as early as 10 days after treatment initiation. Gene enrichment analysis further highlighted a potential link between GLP-1-related genes and ocular AEs. The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Unraveling Cordia myxa’s anti-malarial potential: integrative insights from network pharmacology, molecular modeling, and machine learning

Malaria is a potentially fatal infective illness caused due to parasites that belong to the Plasmodium genus, which are transferred to humans with the help of the stings of affected female Anopheles mosquitoes, and it persists as a serious public wellness problem worldwide. Cordia myxa is a medicinal plant that possesses various medicinal characteristics like antimicrobial, anti-inflammation, antioxidant, and antidiabetic activities, which makes it an important natural resource for the therapy of different maladies in traditional medicine. In this investigation, a certain network pharmacology method has been utilized to identify the potent active components, possible targets as well as signaling pathways present in C. myxa in relation to malaria therapy. The active compounds were submitted to molecular docking approaches to validate their successful activity against the potential targets. The study concluded that three constituents named cosmosiin, stigmastanol, robinetin, and quercetin were highly active and could regulate the expression of Interleukin 6 (IL6) and Cysteine-aspartic acid protease 3 (CASP3), which may act as a potential therapeutic target for malaria treatment. These analyses are validated by molecular dynamics simulation which reflects on the overall structural stability of the intermolecular conformation and interactions. These results can also be witnessed in simulation-based trajectories binding free energies, which concluded the significant role of electrostatic and van der Waals energies in total intermolecular interactions. Finally, we utilized machine learning to predict the anti-malarial activity of C. myxa compounds, comparing them with approved drugs. Using the Chemprop model and MAIP predictions, we assessed ten compounds, revealing their potential as lead anti-malarial agents. This study establishes a groundwork for comprehending the function of the anti-malaria action of C. myxa.

Based on Spectrum-Effect Relationship, Network Pharmacology, and Molecular Docking, the Material Basis and Mechanism of Antioxidant Effect of Miao Medicine Indigofera stachyoides Lindl Were Studied.

Indigofera stachyoides Lindl (IS.Lindl, Xuerensen in Chinese) is a traditional medicine frequently utilized by ethnic minorities; nevertheless, the chemicals responsible for these effects have not been identified. Ultraperformance liquid chromatography (UPLC) was utilized to establish the fingerprints of various origins. Free radical scavenging in 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and 2,2-biazobis(3-ethyl-phenylpropylthiazole-6-sulfonate) diammonium salt (ABTS) assays was used to evaluate the antioxidant activity. Partial least-squares regression analysis (PLSR) and gray correlation analysis (GRA) were utilized to determine the spectral-effect relationship in order to screen the antioxidant pharmacodynamic components. The corresponding targets were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrated Traditional Chinese Medicine (ITCM). Disease-related targets for antioxidants were collected from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The PPI interaction network analysis, GO enrichment analysis, and KEGG pathway analysis were established using the online analysis platform, and Autodock software assisted in aligning the components with important targets. The fingerprint profile revealed 32 common peaks, and eight standards were identified using standard comparison, with similarity ranging from 0.920 to 0.995. The primary antioxidant components include proanthocyanidin B1, epicatechin, and proanthocyanidin B3. Important targets include EGFR, CASP3, IL6, PTGS2, and TNF. Important signaling pathways include the AGE-RAGE signaling pathways in diabetic complications, the MAPK signaling pathway, the IL-17 signaling pathway, and the pathways in cancer. The results of molecular docking technology showed that the main active ingredients of the drug could bind well to the core target. In this study, we successfully established the spectral-effect relationship of IS.Lindl and clarified the effective substances of IS.Lindl. Through network pharmacology and molecular docking methods, it was clear that IS.Lindl plays an antioxidant role through multicomponent, multitarget, and multipathway synergy.

Modern Possibilities for Reconstruction of Nerves of the Head and Neck

The main etiological factors of nerve damage to the head and neck include injuries, oncological diseases, iatrogenic injuries during surgical interventions. An important task of treatment is to restore the lost function of the nervous head and neck, the functions of which certainly determine the quality of life of the patient. The article presents modern methods of nerve reconstruction of the head and neck. The methods of reconstructive surgery of the facial, trigeminal, inferior alveolar, lingual, recurrent laryngeal nerves are described. This article also describes the types of rehabilitation after reconstructive operations on the nerves of the head and neck using pharmacological and non-pharmacological treatment methods such as botulinum therapy, neuromuscular retraining, taping, post-isometric relaxation, acupuncture, phonophoresis, gymnastics.

Pharmacologic and Nonpharmacologic Management of Neuropathic Pain.

Disorders of the somatosensory nervous system that cause neuropathic pain are treated in a variety of ways. Herein, we introduce a stepwise approach to treating neuropathic pain. We then summarize the available data and guidelines for treating neuropathic pain, both with pharmacologic and nonpharmacologic methods, and provide a synthesized algorithm highlighting the similarities and differences between recent guidelines on the management of neuropathic pain. Pharmacologic treatments are primarily antiseizure medications (e.g., gabapentinoids, sodium channel blockers) and antidepressant medications (e.g., tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), though other medications and interventional pharmacologic therapies can also be considered. There are a wide variety of nonpharmacologic treatments for neuropathic pain including neuromodulation, nerve stimulation, physiotherapy, movement therapies, lifestyle modification, nutritional supplements, acupuncture, and mind-body techniques.

Mechanism of action of "cistanche deserticola-Polygala" in treating Alzheimer's disease based on network pharmacology methods and molecular docking analysis.

This article used network pharmacology, molecular docking, GEO analysis, and Gene Set Enrichment Analysis to obtain 38 main chemical components and 66 corresponding targets involved in Alzheimer's disease (AD) treatment in "Cistanche deserticola-Polygala". Through further Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis, we obtained AD signalling pathways, calcium signalling pathways, and other signalling pathways related to the treatment of AD with "Cistanche deserticola-Polygala". Molecular docking showed that most of the core chemical components had good binding ability with the core targets. This article aims to reveal the mechanism of "Cistanche deserticola-Polygala" in treating AD and provide a basis for the treatment of AD with "Cistanche deserticola-Polygala".

From Life's Essential 8 to metabolic syndrome: insights from NHANES database and network pharmacology analysis of quercetin.

Metabolic syndrome (MetS), or syndrome X, is a collection of metabolic illnesses that affect the body's health, particularly insulin resistance and obesity. The prevalence of MetS is on the rise, particularly among younger individuals. Quercetin, a natural flavonoid found in many traditional Chinese medicines, can impact various pathways to disrupt the pathological advancement of MetS with few negative effects. The American Heart Association recently introduced a cardiovascular health assessment termed Life's Essential 8 (LE8), which might impact the treatment of MetS. Quercetin targets and their functions in MetS pathways were identified using a network pharmacology method and molecular docking techniques. The study examined quercetin's direct and indirect interactions with proteins linked to the pathogenic processes of MetS. Data were collected regarding the American Heart Association's LE8 cardiovascular health indicators, which include health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure). The study assessed the connection between LE8 and the occurrence of MetS, taking into account dietary quercetin consumption as a variable of interest. The negative correlation between MetS and LE8 indicates that individuals with higher LE8 scores are less likely to develop MetS. Individuals in the fully adjusted highest group (LE8 ≥ 80) demonstrated a 79% lower likelihood of developing MetS than those in the lowest group (OR = 0.21; 95% CI, 0.17-0.26, p < 0.0001). Network pharmacology and molecular docking results show that quercetin may exert its therapeutic effects by modulating various biological response processes, including those related to xenobiotic stimuli, bacterial molecules, lipopolysaccharides, and oxidative stimuli. These processes involve key pathways associated with diabetic complications, such as the AGE-RAGE signaling pathway, pathways related to diabetic complications, and pathways involved in lipids and atherosclerosis. Therefore, quercetin may reduce cardiovascular risk, improve glucose-lipid metabolism, and alleviate insulin resistance and other biological processes by influencing multiple aspects of the lipid profile, blood glucose, and insulin resistance, ultimately impacting the links between LE8 score and MetS. This study discovered that an optimal LE8 score is a marker of adopting a lifestyle of wellness and is connected with a reduced likelihood of developing MetS. Quercetin acts on core targets such as IL6, BCL2, TP53, IL1B, MAPK1, and CCL2, and then plays a therapeutic role in regulating lipid metabolism, anti-inflammation, immunomodulation, autophagy, etc., through the pathways of diabetic complications, lipids, atherosclerosis, etc., and has the characteristics of multi-targets, multi-pathways, and multi-functions in regulating interventions for MetS.

How Labor Induction Methods have Evolved Throughout History, from the Egyptian Era to the Present Day: Evolution, Effectiveness, and Safety.

Induction of labor is currently used for one in ten pregnancies globally. Methods used for induction have shown major changes over time. Medical interventions trace their origins back to ancient civilizations, with evidence suggesting that they began over 5,000 years ago in ancient Egypt. During this era, the Egyptians employed natural remedies such as castor oil and date fruits for the induction of labor. These early practices highlight the rich history and long-standing tradition of using natural substances in medical treatments, laying the foundation for the development of modern obstetric practices. After that, Hippocrates practised mammary stimulation and mechanical cervical dilatation about 2500 years ago in Greece. Since then, there has been a marked change, especially over the last century, with the development of safer and more effective methods. Mechanical methods were the main method until the early 20th century, which were then substituted by pharmacological methods with more experiments in the mid to late 20th century. Nowadays, effectiveness, safety, cost and client satisfaction are the main determinants of the methods used. This review summarizes how labor induction practices have evolved from the Egyptian era to the present-day randomized controlled trials and meta-analysis evidence, paying attention to their effectiveness, safety, and future directions.

MODERN APPROACHES TO BIRTH CONTROL: MANAGING PAIN AND MINIMISING COMPLICATIONS

The thesis focuses on modern approaches to birth control, concentrating on methods of pain management and minimizing complications. Pharmacological and non-pharmacological methods of pain management are reviewed, as well as psychological techniques to reduce anxiety and fear in women during labor. The importance of birth preparation and antenatal education is mentioned, as well as the role of modern fetal monitoring and an interdisciplinary approach in ensuring safety and comfort. The article highlights the importance of individualized care for each woman and the need for comprehensive management of the pregnant woman to optimize the birth experience.

Network Pharmacology and Molecular Docking to Explore the Mechanism of Action of Danxiong Huoxue Tablets for the Prevention and Treatment of Heterotopic Ossification

Background: Danxiong Huoxue tablets have been used clinically to prevent and treat Heterotopic Ossification (HO) after total hip arthroplasty, but its therapeutic mechanism is not clear. background: Danxiong Huoxue Tablets has been used clinically to prevent and treat heterotopic ossification (HO) after total hip arthroplasty, but its therapeutic mechanism is not clear. Objectives: This study investigated the potential mechanism of action of Danxiong Huoxue tablets against HO using network pharmacology and molecular docking methods. Methods: The TCMID and SymMap databases and the existing literature were used to screen the active ingredients and targets of Danxiong Huoxue tablets, and the targets of heterotopic ossification were obtained from Gene Cards, DisGeNET, and PharmGkb databases. The PPI network diagram was constructed using the String database and Cytoscape 3.9.1 software. Finally, the core targets were analyzed by GO and KEGG enrichment and validated by molecular docking. Results: A total of 39 active ingredients and 328 corresponding targets of Danxiong Huoxue tablets were identified, which were enriched in signaling pathways, such as PI3K/Akt and MAPK. Molecular docking verified that there was good binding activity between the core targets and the corresponding components. Conclusion: Danxiong Huoxue tablets may prevent and treat HO by acting on key targets, such as SRC, AKT1, JUN, and TNF, and regulating the PI3K/Akt signaling pathway and MAPK signaling pathway.

Integrating protein interaction and pathway crosstalk network reveals a promising therapeutic approach for psoriasis through apoptosis induction

Psoriasis is a complex inflammatory skin disease manifested by altered proliferation and differentiation of keratinocytes with dysfunctional apoptosis. This study aimed to identify regulatory factors and comprehend the underlying mechanisms of inefficient apoptosis to open up promising therapeutic approaches. Incorporating human protein interactions, apoptosis proteins, and physical relationships of psoriasis-apoptosis proteins helped us to generate a psoriasis-apoptosis interaction (SAI) network. Subsequently, topological and functional analyses of the SAI network revealed effective proteins, functional modules, hub motifs, dysregulated pathways and transcriptional gene regulatory factors. Network pharmacology, molecular docking and molecular dynamics simulation methods identified the potential drug-target interactions. RELA, MAPK1, MAPK3, MMP9, IL1B, AKT1 and STAT1 were revealed as effective proteins. The MAPK1-MAPK3-RELA motif was identified as a hub regulator in the crosstalk between 41 pathways. Among all pathways, “lipid and atherosclerosis” was found to be the predominant pathway. Acetylcysteine, arsenic-trioxide, β-elemene, bortezomib and curcumin were identified as potential drugs to inhibit pathway crosstalk. Experimental verifications were performed using the literature search, GSE13355 and GSE14905 microarray datasets. Drug-protein-pathway interactions associated with apoptosis were deciphered. These findings highlight the role of hub motif-mediated pathway-pathway crosstalk associated with apoptosis in the complexity of psoriasis and suggest crosstalk inhibition as an effective therapeutic approach.