Pharmacological Methods Research Articles

Analysis and Validation of the Network Pharmacology of the Mechanism of Glycyrrhetinic Acid for the Treatment of High-Altitude Pulmonary Hypertension

Glycyrrhetinic acid (GA) is a pentacyclic triterpene component in Glycyrrhize glabra L, it has demonstrated an inhibitive effect on high-altitude pulmonary hypertension (HAPH), but the molecular action is still not known. We aimed to explore the mechanism of GA for the treatment of HAPH based on network pharmacology and molecular docking method. Cell experiment validation was also conducted. The targets for GA were screened using the Swiss Target Prediction and Batman databases. The HAPH-related targets were obtained using the GeneCards and OMIM databases. The common targets for diseases and drugs were obtained using a Venn diagram. The core targets were screened using the String database. Then, a component-target-disease diagram and protein–protein interaction (PPI) network mutual assistance diagram were developed using Cytoscape3.9.1 software. GO functional and KEGG pathway enrichment analyses were conducted using the Metascape database. Finally, molecular docking of the target and its corresponding active components were performed using Autodock software. A total of 68 common targets for glycyrrhetinic acid high-altitude pulmonary hypertension were screened out. The core targets include PTGS1, MMP1, SERPINA6, and nitric oxide synthase (NOS2), involving PPAR signal pathway, human cytomegalovirus infection, IL-17 signal pathway, proteoglycans in cancer, and other pathways. The molecular docking affinity was −8.4 kcal·mol−1 in average, indicating that GA has a good binding stability with key target proteins. In the PDGF-BB-induced PASMC proliferation model, PASMC proliferation and the p-p38, p38, p-ERK1/2, and ERK1/2 protein expression were inhibited. The pharmacological mechanism of GA for the treatment of HAPH was characterized by multi-target and multi pathway. GA may serve as a promising therapeutic candidate for HAPH but still needs further in vivo/in vitro experiment.

Exploring the efficacy and molecular mechanism of Danhong injection comprehensively in the treatment of idiopathic pulmonary fibrosis by combining meta-analysis, network pharmacology, and molecular docking methods.

Danhong injection, a compound injection of Chinese herbal medicine, has been widely used in idiopathic pulmonary fibrosis (IPF) at present as an adjuvant treatment. However, the clinical efficacy and molecular mechanism of IPF are still unclear. This study will evaluate and explore the clinical efficacy and molecular mechanism of Danhong injection in the treatment of IPF. In meta-analysis, the computer was used to search 8 databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, CNKI, WanFang, and VIP) to collect the RCTs, and RevMan 5.3 and Stata 14.0 were used for statistical analysis. It has been registered on PROSPERO: CRD42020221096. In network pharmacology, the main chemical components and targets of the chemical components of Danhong injection were obtained in TCMSP and Swiss Target Prediction databases. The main targets of IPF were obtained through Gencards, Disgenet, OMIM, TTD, and DRUGBANK databases. The String platform was used to construct PPI networks. Cytoscape 3.8.2 was used to construct the "Danhong components - IPF targets-pathways" network. The molecular docking verification was conducted by Auto Dock. Twelve RCTs were finally included with a total of 896 patients. The meta-analysis showed that Danhong injection could improve the clinical efficiency ([OR] = 0.25, 95% CI [0.15, 0.41]), lung function, arterial blood gas analysis, inflammatory cytokines, and serum cytokines associated with pulmonary fibrosis of IPF patients, respectively (P < .05). The core active components of Danhong injection on IPF were Luteolin, Quercetin, and Kaempferol, and the core targets were PTGS2, AR, ESR1, PPARG, and RELA. Danhong injection mainly improved IPF through PD-L1 expression and PD-1 checkpoint path in cancer, pathways in cancer, PI3K-Akt signaling pathway, etc. These results provided scientific basis for the clinical use of Danhong injection for the treatment of IPF, and provided a new direction to explore the potential mechanism of action of Danhong injection.

Evaluation of Midwifery Practices among Registered Midwives in Selected Hospitals in Limpopo Province, South Africa

Midwifery practices are defined as the level of midwifery care in which midwives use their expertise, management, and clinical leadership to provide personalized, evidence-based care to women independently and autonomously. Midwifery care includes antepartum, intrapartum, and postpartum care, which are defined by the WHO as the care provided by skilled healthcare professionals to pregnant women and adolescent girls to ensure the best health conditions for the mother and baby during the antepartum, intrapartum and postpartum period. The aim of this study was to evaluate midwifery practices among registered midwives in selected hospitals in Limpopo Province, South Africa. The quantitative, descriptive, and cross-sectional research design was used to assess and describe midwifery practices among registered midwives in selected hospitals in Limpopo Province, South Africa. The population size was 100 registered midwives in the selected hospitals. The sample size of 80 registered midwives was determined using the Slovin formula. Simple random sampling was used to select the sample. A self-developed questionnaire was tested and validated prior to conducting the main study. The findings of the pilot study were used to refine the questionnaire before being used for the main study. Reliability and validity were ensured. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 27 with the assistance of a statistician. The study revealed inadequate provision of midwifery care during antepartum, intrapartum, and postpartum periods due to lack of resources and equipment. The shortage of midwives and the shorter experience in the clinical setting within the midwifery environment were overwhelming. The study concluded that the practices of registered midwives were inadequate due to some challenges they faced during the provision of midwifery care. Inadequate midwifery practices have serious implications for the health and well-being of mothers and newborns. These practices were influenced by various factors, such as inadequate material and human resources and lack and malfunctioning of available equipment. The study recommended that women have access to a variety of pain relief options during labor, including both pharmacological and non-pharmacological methods. In addition, the study recommended implementation of the presence of doulas during labor and childbirth.

Assessment of pharmacotherapy efficacy for the treatment of exacerbations of chronic obstructive pulmonary disease associated with viral infection

Justification. Knowledge of the differences in response to therapy between phenotypes of exacerbations of chronic obstructive pulmonary disease (COPD) is necessary to improve treatment outcomes. Objective: to determine the most effective additional pharmacological methods for virus-associated exacerbations of COPD. Material and methods. The study included patients hospitalized with exacerbations of COPD with viral (n = 60) and viral-bacterial (n = 60) infections, and a comparison group with exacerbations of COPD with bacterial infection (n = 60). The diagnosis of COPD was based on spirometric criteria, viral infection — according to the results of PCR-RV of sputum for RNA of respiratory viruses. Treatment was carried out in real clinical practice. The groups were comparable in the use of systemic glucocorticoids, short-acting bronchodilators. Dyspnea was assessed using the TDI index (primary endpoint), lung function (spirometry, diffusion capacity for carbon monoxide), exercise tolerance (6-minute walk test), length of hospital stay (secondary endpoints). The сorrelations were determined with the use of Cox proportional hazards model. Results. In the groups with virus-associated and viral-bacterial exacerbations, unlike bacterial exacerbations, the following types of treatment were associated with achieving TDI +1 (odds ratio — OR, 95 % confidence interval — CI): fixed triple combination (OR 2.69; 95 % CI 1.48–4.90; p = 0.010 and OR 2.74; 95 % CI 1.29–3.80; p = 0.031), inhalation of 3 % sodium chloride solution (OR 3.64; 95 % CI 1.45–5.42; p = 0.001 and OR 3.23; 95 % CI 2.15–5.43;\ p = 0.042), antiviral drugs (OR 2.91; 95 % CI 1.15–3.62; p = 0.009 and OR 2.76; 95 % CI 1.31–3.90; p = 0.008). As a result of treatment, an increase in DLco/Va, SpO2 after a 6-minute walk, and a decrease in the length of hospital stay were observed. Conclusion. Detection of virus-associated infections is a promising marker for determining indications for prescribing long-acting anticholinergic drugs and beta-adrenomimetics, inhaled corticosteroids, inhalations of hypertonic sodium chloride solution, and antiviral drugs for exacerbations of COPD.

Efficacy and Safety of Dexmedetomidine Compared to Other Needle-Free Pharmacological Sedation Methods in Pediatric Patients Undergoing Imaging Procedures.

Pediatric patients often require sedation during magnetic resonance imaging (MRI) and computed tomography (CT) to ensure stillness and minimize stress. This meta-analysis compared the effectiveness and safety of 3 sedative agents-dexmedetomidine, midazolam, and chloral hydrate-for pediatric MRI/CT sedation. Six studies with a total of 633 patients were included in the analysis. Quality assessment revealed varying levels of bias risk. Dexmedetomidine exhibited a significantly higher successful sedation rate compared to midazolam (risk ratio [RR] = 0.43, 95% confidence interval [CI] [0.29-0.64]), but no statistically significant difference compared to chloral hydrate (RR = 0.94, 95% CI [0.60-1.45]). Chloral hydrate also showed a higher successful sedation rate compared to midazolam (RR = 0.46, 95% CI [0.25-0.83]). The onset of sedation time did not significantly differ between the 3 agents. The dexmedetomidine group had a significantly higher incidence of bradycardia compared to the chloral hydrate group (RR = 0.17, 95% CI [0.05-0.59]), but no significant difference compared to the midazolam group (RR = 0.29, 95% CI [0.06-1.26]). No statistically significant differences were observed in the incidence of nausea and vomiting between the 3 groups. Dexmedetomidine demonstrates effectiveness in pediatric MRI/CT sedation, offering advantages over midazolam and similar efficacy to chloral hydrate. Careful cardiovascular monitoring is essential during administration, particularly in patients with congenital heart disease. Sublingual and intranasal administration of dexmedetomidine is a viable option with high bioavailability. This meta-analysis contributes valuable insights into refining sedation protocols for pediatric imaging procedures, emphasizing efficacy and safety considerations.

Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy

ObjectivesThis study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP.Materials and methodsNetwork pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP.ResultsNetwork pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats.ConclusionApoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Myeloid-derived growth factor ameliorates dextran sodium sulfate-induced colitis by regulating macrophage polarization.

Inflammatory bowel disease (IBD) is characterized by inflammatory conditions in the gastrointestinal tract. According to reports, IBD prevalence is increasing globally, with heavy economic and physical burdens. Current IBD clinical treatment is limited to pharmacological methods; therefore, new strategies are needed. Myeloid-derived growth factor (MYDGF) secreted by bone marrow-derived mononuclear macrophages has beneficial effects in multiple inflammatory diseases. To this end, the present study aimed to establish an experimental IBD mouse model using dextran sulfate sodium in drinking water. MYDGF significantly alleviated DSS-induced colitis, suppressed lymphocyte infiltration, restored epithelial integrity in mice, and decreased apoptosis in the colon tissue. Moreover, the number of M1 macrophages was decreased and that of M2 macrophages was increased by the action of MYDGF. In MYDGF-treated mice, the NF-κB and MAPK pathways were partially inhibited. Our findings indicate that MYDGF could mitigate DSS-induced mice IBD by reducing inflammation and restoring epithelial integrity through regulation of intestinal macrophage polarization via NF-κB and MAPK pathway inhibition. KEY MESSAGES: MYDGF alleviated DSS-induced acute colitis. MYDGF maintains colon epithelial barrier integrity and relieves inflammation. MYDGF regulates colon macrophage polarization. MYDGF partially inhibited the activation of NF-κB and MAPK pathway.

CdS/ZnS quantum dots based on an amphipathic polymer platform for fluorescent probe of dopamine with high sensitivity and selectivity

Due to the widespread presence of dopamine in living organisms and its physiological and pharmacological effects, developing rapid and sensitive methods for detecting dopamine has been of great significance. Fluorescent probes are a commonly used and highly sensitive detection method. In this work, based on a self-developed amphipathic polymer template, CdS/ZnS fluorescent quantum dots (QDs) with a maximum absorption wavelength of 500–550 nm were synthesized and characterized. They exhibited stable fluorescence in the pH range from weak acid to alkaline, and fluorescence quenching occurred at pH = 4.5. The QDs could be applied as fluorescent probes for detecting dopamine, with a limit of detection 0.027 mM and high selectivity, unaffected by common metal ions, amino acids, glucose, etc. Compared to the high activity of dopamine being oxidized easily, this fluorescent QDs and its template polymer PEI played a stabilizing role during the testing process. Therefore, this work provides a promising dopamine fluorescent probe with application prospects.

Exploring the Dual Components and Mechanism of Panax notoginseng-Eucommia ulmoides for Managing Osteoporosis-Associated Lumbar Disc Herniation Using Network Pharmacology

Osteoporosis (OP) combined with lumbar intervertebral disc herniation (LDH) is a complex disease that exhibits limited efficacy in drug treatment, physical therapy, and surgical intervention, while also carrying potential side effects and risks. Traditional Chinese medicine treatment of OP combined with LDH primarily aims to address deficiencies and regulate the body. Several active ingredients found in Panax notoginseng and Eucommia ulmoides, such as quercetin and beta-sitosterol, have demonstrated the ability to enhance osteoblast proliferation and bone matrix synthesis. While historical literature contains mechanistic studies on individual herbs, there is a conspicuous dearth of comprehensive and systematic research on their mechanisms of action. By utilizing network pharmacology method, we identified 35 active ingredients present in Panax notoginseng and Eucommia ulmoides, along with 98 potential targets associated with the treatment of OP combined with LDH using Panax notoginseng-Eucommia ulmoides. Through protein-protein interaction network analysis, we identified 5 essential active ingredients (Quercetin, Beta-carotene, Kaempferol, Beta-sitosterol, and Notoginsenoside Fe) and 5 core targets (Nuclear factor kappa-B 3 [RELA], hypoxia-induciblefactor-1A [HIF-1A], Myelocytomatosis Viral Oncogene homolog [MYC], Transcription Factor AP-1 [JUN], and Estrogen Receptor 1 [ESR1]). The potential targets primarily involve IL-17, AGEs-RAGE, the TNF signaling pathway, and other pathways through which they exert therapeutic effects. The key active ingredient was docked with the core target molecule, resulting in all molecules exhibiting binding energies ≤-5 kcal/mol. This study provides preliminary evidence that treatment with Panax notoginseng-Eucommia ulmoides for OP combined with LDH may lead to improvements in inflammation, oxidative stress, cell proliferation, differentiation, and apoptosis, and cytokine regulation.

The Effect of Foot Massage on Comfort and Pain Intensity After Vaginal Delivery

Childbirth is a mother's subjective experience that is very memorable in her life. It is important to maintain maternal comfort so that the process of adapting to motherhood can run well. Pain during postpartum is one of the factors that prevents mothers from having difficulty adapting during the postpartum period, especially in primapara mothers. A pharmacological method that can be given to increase comfort and reduce the intensity of pain is foot massage. The aim of this study was to determine the effect of foot massage on the comfort and intensity of maternal pain after vaginal delivery during the postpartum period. This type of quasi-experimental research sample consisted of 38 respondents and the sampling technique used simple random sampling. This research was conducted at the Independent Early Midwife Practice in Lubuk Pakam. Respondents consisted of 2 groups, namely the intervention group and the control group. The instruments used were questionnaires, Visual Analog Scale (VAS), Post Partum Comfort Scale (PCS). Data analysis used chi-square/Fisher's exact test, independent-samples t test and one-way analysis of variance (ANOVA). The mean maternal comfort score in the intervention group was higher than the control group (143.45 ± 8.96, 119.00 ± 14.65, respectively) with a value of p = 0.000. The mean pain score in the intervention group was lower than the control group (1.36 ± 1.22, 4.95 ± 2.27) and the p value = 0.000. Foot massage is effective in increasing comfort and reducing the intensity of pain after vaginal delivery. The increase in maternal comfort after intervention was 18.34% and the reduction in pain intensity after vaginal delivery was 73%. In this way, midwives can apply foot massage to every mother after vaginal delivery.

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.

Gender and age peculiarities of autophagy in men and women induced by a comprehensive wellness program: a prospective observational study

Background. Autophagy refers to an evolutionary physiological mechanism of cell self-purification. The use of its positive effects in regenerative and preventive medicine implies this process to be investigated under the conditions of various therapeutic factors.Objective. To investigate the influence of gender, age and somatic-morphological factors on the autophagy processes induced by a comprehensive wellness program as expressed by the marker protein Beclin-1.Methods. A prospective observational study involved 107 patients to be monitored before and after comprehensive wellness procedures. All study participants underwent a wellness program in the clinic of OOO Centr Zdorovie (Maykop, Russia). The study was conducted in the periods of September‒December 2020 and January 2021. The study involved measuring the concentration of Beclin-1 protein in the blood before and 12 days after the wellness procedures. In order to characterize the degree of activation of the autophagy process, the index “delta-Beclin-1” was introduced (difference between the initial level of Beclin-1 protein concentration and the level registered after 12 days). The autophagy response was evaluated in terms of its upward or downward direction (positive/negative delta- Beclin-1 value, respectively). The effect of the comprehensive wellness procedures on the functional systems of the organism was determined in accordance with the laboratory tests (complete blood count, lipid profile), morphometric evaluation, and the assessment of body composition by impedance monitoring. The obtained data were processed using SPSS Statistics 26.0 (IBM, USA).Results. Monitoring of Beclin-1 protein concentration revealed that basic autophagy activity is age-specific and significantly lower in individuals over 60 years as compared to both individuals under 60 years and healthy persons. This correlation with age appears more pronounced in obese individuals (r = -0.59). The basic activity of autophagy in men was 30% lower than in women, however, after a set of wellness procedures the mentioned response in men increased by 7%. The study found that not all patients responded unidirectionally to the comprehensive wellness procedures: 49 out of 77 patients showed an increase in Beclin-1 protein concentration, while 28 — a decrease. Patients who participated in the wellness program demonstrated negative correlation between the level of Beclin-1 protein expression and age, while those responding with an increase in Beclin-1 protein level — with body mass index, weight and fat mass. The source of autophagy activity in men under 60 years can refer to fat mass, and in women — lean body mass, especially in the mature age of period II (36‒60 years).Conclusion. The factors of basic autophagy and autophagy induced by the complex of wellness procedures include age, gender and body weight. These factors obtain different significance at different age periods. A comprehensive wellness program can serve as an alternative to existing pharmacological methods for activating autophagy in humans.

Complementary Approaches to Pain for Children

Pain, an unpleasant sensory and emotional experience, affects children often and is one of the most common reasons to seek care. Pain in the pediatric patient population often goes unrecognized and is not assessed appropriately and adequately, leading to mismanagement and increased use of pharmacological methods to relieve pain. Pediatric surgical nurses must understand the numerous influential factors and assessment strategies in order to contribute to pain management, ensuring the appropriate pain assessment tool is used based on the child's age, cognitive development, culture, and beliefs. Complementary approaches should be included, when possible, to aid in eliminating or controlling pain in children. Alternative options, such as distraction, skin-to-skin contact, guided imagery, and hypnosis, are effective in reducing or eliminating pediatric pain. They can be used alone or in conjunction with traditional treatment plans, even in the perioperative period. Pediatric nurses can benefit from learning, understanding, and using the complementary approaches outlined for pain management in this vulnerable population.

A Review on the Potential Use of Medicinal Plants from the Apiaceae and the Rosaceae Families in Cardiovascular Diseases—Experimental Evidence and Traditional Applications

Cardiovascular diseases are the leading cause of mortality worldwide. The World Health Organization has presented alarming data stating that in 2019, 17.9 million people globally died due to cardiovascular diseases, constituting 32% of all deaths. Despite increasingly advanced pharmacological and procedural treatment methods for these diseases, there is still a quest for new therapeutic possibilities that promise even greater efficacy and safety. The overriding purpose of this study is to provide an insight into the traditional uses of species from the Apiaceae and Rosaceae families as well as to systematize knowledge regarding their scientifically proven cardiovascular activities (animal studies and clinical trials). The review is intended to indicate knowledge gaps for future studies concerning plants used in traditional medicine but without scientific research. As a result, various plant species from both Apiaceae and Rosaceae family have been collected and described based on their study that has proven their effectiveness and uses in cardiovascular diseases. Most of these plants have a hypotensive effect, followed by anti-hyperlipidemic, vasorelaxant, antithrombotic, and diuretic activity. These are the mechanisms that contribute to various cardiovascular diseases, such as heart attack, coronary heart disease, hypertension, and stroke.

Network pharmacology combined with affinity ultrafiltration to elucidate the potential compounds of Shaoyao Gancao Fuzi Decoction for the treatment of rheumatoid arthritis

Ethnopharmacological relevanceShaoyao Gancao Fuzi Decoction (SGFD), has been employed for thousands of years in the treatment of rheumatoid arthritis (RA) with remarkable clinical efficacy. However, the material basis underlying the effectiveness of SGFD still remains unclear. Aim of the reviewThis study aims to elucidate the material basis of SGFD through the application of network pharmacology and biological affinity ultrafiltration. ResultsUPLC-Q-TOF-MS/MS was employed to characterize the components in SGFD, the identified 145 chemical components were mainly categorized into alkaloids, flavonoids, triterpenoids, and monoterpenoids according to the structures. Network pharmacology method was utilized to identify potential targets and signaling pathways of SGFD in the RA treatment, and the anti-inflammatory and anti-RA effects of SGFD were validated through in vivo and in vitro experiments. Moreover, as the significant node in the pharmacology network, TNF-α, a classical therapeutic target in RA, was subsequent employed to screen the interacting compounds in SGFD via affinity ultrafiltration screening method, 6 active molecules (i.e.,glycyrrhizic acid, paeoniflorin, formononetin, isoliquiritigenin, benzoyl mesaconitine, and glycyrrhetinic acid) were exhibited significant interactions. Finally, the significant anti-inflammatory and anti-TNF-α effects of these compounds were validated at the cellular level. ConclusionsIn conclusion, this study comprehensively elucidates the pharmacodynamic material basis of SGFD, offering a practical reference model for the systematic investigation of traditional Chinese medicine formulas.

Knowledge, attitude, and practice toward pharmacological and non- pharmacological methods for labor pain management among midwives

This review focuses on labor pain management during childbirth, encompassing non-pharmacological and pharmaceutical methods. A thorough literature search was conducted across databases like Scopus, PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews. The review, comprising eleven studies, explores topics such as the theoretical framework of labor pain management, midwives' knowledge, attitudes, and practices, pharmacologic and non-pharmacologic methods, factors influencing midwives’ strategies, and identified gaps and challenges. The conclusion highlights existing literature gaps and emphasizes the potential for future research to enhance midwifery practices, informed decision making, and obstetric outcomes.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

BackgroundIntracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated.MethodsC57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism.ResultsMas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH.ConclusionsMas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Elucidating the mechanism of action of Isobavachalcone induced autophagy and apoptosis in non-small cell lung cancer by network pharmacology and experimental validation methods

BackgroundLung cancer is the leading cause of cancer deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer-related mortality. In recent years, there have been numerous treatments for non-small cell lung cancer, but the cure and survival rates are still extremely low. Isobavachalcone (IBC) belongs to the chalcone component of the traditional Chinese medicine Psoralea corylifolia L., and is a unique Protein kinase B (AKT) pathway inhibitor with significant anticancer effects. Previous studies have shown that IBC possess a variety of biological properties, including anti-cancer, anti-inflammatory, and antioxidant properties. This study focused on the use of network pharmacology analysis, molecular docking technology and experimental validation to elucidate the potential mechanisms of IBC for the treatment of NSCLC. MethodsScreening key genes and pathways of IBC action in NSCLC using network pharmacology. The IBC target genes were from The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM databases, the NSCLC target genes were from GeneCards, Online Mendelian Inheritance in Man (OMIM) and The Therapeutic Target database (TTD) databases, both of which were taken as intersecting genes for protein–protein interaction network analysis and enrichment analysis, and the binding energies of the compounds to the core targets were further verified by molecular docking. Cell lines in vitro experiments were then performed to further unravel the mechanism of IBC for NSCLC. ResultsA total of 279 potential targets were retrieved by searching the intersection of IBC and NSCLC targets. Protein-protein interaction (PPI) network analysis indicated that 6 targets, including AKT1, RXRA, NCOA1, RXRB, RARA, PPARG were hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that IBC treatment of NSCLC mainly involves steroid binding, transcription factor activity, Pathways in cancer, cAMP signaling pathway, Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Among them, the AMPK signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of NSCLC. Then, the results of in vitro experiment indicated that IBC could inhibit proliferation of NSCLC cells and induce cell autophagy and apoptosis. The results also showed that IBC could increase the protein expression of AMPK and decrease the protein expression of AKT and mammalian target of rapamycin (mTOR), suggesting that IBC can treat NSCLC by inducing cellular autophagy and apoptosis as well as modulating AMPK and AKT signaling pathways. ConclusionsIn summary, this study provided a new insight into the protective mechanism of IBC against NSCLC through network pharmacology and experimental validation.

Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation

Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including Il2, in Th17 cell differentiation. Inhibiting Hdac4/7 through pharmacological or genetic methods effectively mitigates Th17 cell-mediated intestinal inflammation in a colitis mouse model. Our study uncovers molecular mechanisms where HDAC4 and HDAC7 function distinctively yet cooperatively in regulating ordered gene transcription during Th17 cell differentiation. These findings suggest a potential therapeutic strategy of targeting HDAC4/7 for treating Th17-related inflammatory diseases, such as ulcerative colitis.

The comparison of the effect of non-pharmacological pain relief and pharmacological analgesia with remifentanil on fear of childbirth and postpartum depression: a randomized controlled clinical trial

IntroductionChildbirth may be associated with psychological, social, and emotional effects and provide the background for women’s health or illness throughout their life. This research aimed at comparing the impact of non-pharmacological pain relief and pharmacological analgesia with remifentanil on childbirth fear and postpartum depression.Materials and methodThis randomized clinical trial with two parallel arms was conducted on 66 women with term pregnancy referred to Taleghani Hospital in Tabriz for vaginal delivery during September 2022 to September 2023. First, all of the eligible participants were selected through Convenience Sampling. Then, they were randomly assigned into two groups of pharmacological analgesia with remifentanil and non-pharmacological analgesia with a ratio of 1:1 using stratified block randomization based on the number of births. Before the intervention, fear of childbirth (FOC) was measured using Delivery Fear Scale (DFS) between 4 and 6 cm cervical dilatation. Pain and fear during labor in dilatation of 8 cm were measured in both groups using VAS and DFS. After delivery, FOC was assessed using Delivery Fear Scale (W DEQ Version B) and postpartum depression using the Edinburgh’s postpartum depression scale (EPDS). Significance level was considered 0.05. Mean difference (MD) was compared with Independent T-test and ANCOVA pre and post intervention.ResultsThe mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after the intervention by controlling the effect of the baseline score (MD: -6.33, 95%, Confidence Interval (CI): -12.79 to -0.12, p = 0.04). In the postpartum period, the mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after controlling the effect of the baseline score (MD: -21.89; 95% CI: -35.12 to -8.66; p = 0.002). The mean score of postpartum depression in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group (MD: -1.93, 95% CI: -3.48 to -0.37, p = 0.01). Trial registration: Iranian Registry of Clinical Trials (IRCT): IRCT20170506033834N10. Date of registration: 05/07/2022 Date of first registration: 05/07/2022. URL: https://www.irct.ir/trial/61030; Date of recruitment start date05/07/2022.ConclusionThe study results indicated a reduction in FOC and postpartum depression among parturient women receiving non-pharmacological strategies with active participation in childbirth compared to women receiving pharmacological analgesia. Owing to the possible side effects of pharmacological methods for mother and fetus, non-pharmacological strategies with active participation of the mother in childbirth are recommended to reduce the FOC and postpartum depression.