Exploring the Mechanism of Yiwei Decoction in the Intervention of a Premature Ovarian Insufficiency Rat Based on Network Pharmacology and the miRNA-mRNA Regulatory Network

Objective: our aim is to explore the mechanism of action of Yiwei decoction (YWD) in addressing premature ovarian insufficiency (POI) through a combination of transcriptomics and network pharmacology. By doing so, we hope to identify important pathways of action, key targets, and active components that contribute to the efficacy of YWD. Materials and Methods: group A comprised of the model + traditional Chinese medicine group, while group B was the model control group and group C was the normal control group. After gavage, serum AMH and E2 levels were measured by using ELISA. HE staining was used to study the impact of YWD on ovarian follicle recovery in POI rats. Additionally, RNA-seq sequencing technology was employed to analyze the transcription levels of mRNAs and miRNAs in the ovarian tissues of each group, and the resulting data were examined using R. YWD used UPLC-Q-TOF-HRMS to analyze its active ingredients. Upon obtaining the sequencing results, the miRWalk database was utilized to forecast the targets of DEmiRNAs. Network pharmacology was then applied to predict the targets of active ingredients present in YWD, ultimately constructing a regulatory network consisting of active ingredients-mRNA-miRNA. The coexpression relationship between mRNAs and miRNAs was calculated using the Pearson correlation coefficient, and high correlation coefficients between miRNA-mRNA were confirmed through miRanda sequence combination. Results: the application of YWD resulted in improved serum levels of AMH and E2, as well as an increased number of ovarian follicles in rats with POI. However, there was a minimal impact on the infiltration of ovarian lymphocytes. Through GSEA pathway enrichment analysis, we found that YWD may have a regulatory effect on PI3K-Akt, ovarian steroidogenesis, and protein digestion and absorption, which could aid in the treatment of POI. Additionally, our research discovered a total of 6 DEmiRNAs between groups A and B, including 2 new DEmiRNAs. YWD contains 111 active compounds, and our analysis of the active component-mRNA regulatory network revealed 27 active components and 73 mRNAs. Furthermore, the coexpression network included 5 miRNAs and 18 mRNAs. Our verification of MiRanda binding demonstrated that 12 of the sequence binding sites were stable. Conclusions: our research has uncovered the regulatory network mechanism of active ingredients, mRNA, and miRNA in YWD POI treatment. However, further research is needed to determine the effect of the active ingredients on key miRNAs and mRNAs

Exploring the Mechanism of Yiwei Decoction in the Intervention of a Premature Ovarian Insufficiency Rat Based on Network Pharmacology and the miRNA-mRNA Regulatory Network

Objective: our aim is to explore the mechanism of action of Yiwei decoction (YWD) in addressing premature ovarian insufficiency (POI) through a combination of transcriptomics and network pharmacology. By doing so, we hope to identify important pathways of action, key targets, and active components that contribute to the efficacy of YWD. Materials and Methods: group A comprised of the model + traditional Chinese medicine group, while group B was the model control group and group C was the normal control group. After gavage, serum AMH and E2 levels were measured by using ELISA. HE staining was used to study the impact of YWD on ovarian follicle recovery in POI rats. Additionally, RNA-seq sequencing technology was employed to analyze the transcription levels of mRNAs and miRNAs in the ovarian tissues of each group, and the resulting data were examined using R. YWD used UPLC-Q-TOF-HRMS to analyze its active ingredients. Upon obtaining the sequencing results, the miRWalk database was utilized to forecast the targets of DEmiRNAs. Network pharmacology was then applied to predict the targets of active ingredients present in YWD, ultimately constructing a regulatory network consisting of active ingredients-mRNA-miRNA. The coexpression relationship between mRNAs and miRNAs was calculated using the Pearson correlation coefficient, and high correlation coefficients between miRNA-mRNA were confirmed through miRanda sequence combination. Results: the application of YWD resulted in improved serum levels of AMH and E2, as well as an increased number of ovarian follicles in rats with POI. However, there was a minimal impact on the infiltration of ovarian lymphocytes. Through GSEA pathway enrichment analysis, we found that YWD may have a regulatory effect on PI3K-Akt, ovarian steroidogenesis, and protein digestion and absorption, which could aid in the treatment of POI. Additionally, our research discovered a total of 6 DEmiRNAs between groups A and B, including 2 new DEmiRNAs. YWD contains 111 active compounds, and our analysis of the active component-mRNA regulatory network revealed 27 active components and 73 mRNAs. Furthermore, the coexpression network included 5 miRNAs and 18 mRNAs. Our verification of MiRanda binding demonstrated that 12 of the sequence binding sites were stable. Conclusions: our research has uncovered the regulatory network mechanism of active ingredients, mRNA, and miRNA in YWD POI treatment. However, further research is needed to determine the effect of the active ingredients on key miRNAs and mRNAs

Objective parameter definitions from iTUG and SPA tests.

<p>A reference for calculation procedure is presented for each parameter.</p><p>iTUG: instrumented Timed-up-and-go</p><p>SPA: spontaneous physical activity</p><p>S-St: sit-to-stand</p><p>St-S: stand-to-sit</p><p>ROM: range of motion</p><p>* St-S and St-S transition were defined based on the change of trunk tilt in the sagittal plane both in the iTUG and SPA assessments.</p><p>†Turn transition was defined based on the change of trunk twisting angle in the iTUG assessment.</p><p>‡ Gait speed was computed using information from the detected step time and the amplitude of acceleration during each gait cycle.</p><p>Objective parameter definitions from iTUG and SPA tests.</p

Exploring the Mechanism of Yiwei Decoction in the Intervention of a Premature Ovarian Insufficiency Rat Based on Network Pharmacology and the miRNA-mRNA Regulatory Network

Objective: our aim is to explore the mechanism of action of Yiwei decoction (YWD) in addressing premature ovarian insufficiency (POI) through a combination of transcriptomics and network pharmacology. By doing so, we hope to identify important pathways of action, key targets, and active components that contribute to the efficacy of YWD. Materials and Methods: group A comprised of the model + traditional Chinese medicine group, while group B was the model control group and group C was the normal control group. After gavage, serum AMH and E2 levels were measured by using ELISA. HE staining was used to study the impact of YWD on ovarian follicle recovery in POI rats. Additionally, RNA-seq sequencing technology was employed to analyze the transcription levels of mRNAs and miRNAs in the ovarian tissues of each group, and the resulting data were examined using R. YWD used UPLC-Q-TOF-HRMS to analyze its active ingredients. Upon obtaining the sequencing results, the miRWalk database was utilized to forecast the targets of DEmiRNAs. Network pharmacology was then applied to predict the targets of active ingredients present in YWD, ultimately constructing a regulatory network consisting of active ingredients-mRNA-miRNA. The coexpression relationship between mRNAs and miRNAs was calculated using the Pearson correlation coefficient, and high correlation coefficients between miRNA-mRNA were confirmed through miRanda sequence combination. Results: the application of YWD resulted in improved serum levels of AMH and E2, as well as an increased number of ovarian follicles in rats with POI. However, there was a minimal impact on the infiltration of ovarian lymphocytes. Through GSEA pathway enrichment analysis, we found that YWD may have a regulatory effect on PI3K-Akt, ovarian steroidogenesis, and protein digestion and absorption, which could aid in the treatment of POI. Additionally, our research discovered a total of 6 DEmiRNAs between groups A and B, including 2 new DEmiRNAs. YWD contains 111 active compounds, and our analysis of the active component-mRNA regulatory network revealed 27 active components and 73 mRNAs. Furthermore, the coexpression network included 5 miRNAs and 18 mRNAs. Our verification of MiRanda binding demonstrated that 12 of the sequence binding sites were stable. Conclusions: our research has uncovered the regulatory network mechanism of active ingredients, mRNA, and miRNA in YWD POI treatment. However, further research is needed to determine the effect of the active ingredients on key miRNAs and mRNAs

Objective parameter definitions from gait and postural balance tests.

<p>A reference for calculation procedure is presented for each parameter.</p><p>COG: center of gravity</p><p>AP: anterior-posterior</p><p>ML: medial-lateral</p><p>RCI: reciprocal compensatory index</p><p>OL: open-loop</p><p>* Steady-state walking was the first stride of the group of six strides with an SD below the median SD of the all analyzed strides ±6% [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124763#pone.0124763.ref013" target="_blank">13</a>].</p><p>Objective parameter definitions from gait and postural balance tests.</p

Patient Survey on Satisfaction and Impact of 123I-Ioflupane Dopamine Transporter Imaging

<div><p>Patients were surveyed to assess the impact of dopamine transporter imaging on diagnostic confidence, change in treatment plan, effect on medication compliance, and subjective well-being. Surveys were sent to 140 patients who completed dopamine transporter imaging an average of 18 months prior. Sixty-five surveys from patients (46%) were returned. Questions assessed patients’ perceived impact of the imaging on their care. Increased diagnostic confidence following imaging was reported by 69% of patients. Changes to treatment plan from imaging were reported by 24% of patients. Overall satisfaction with the study and its impact was reported by 70% of patients. Dopamine transporter imaging increased diagnostic confidence among patients and overall patient satisfaction with the impact of imaging on clinical care was high.</p></div

Differences in gait and postural balance parameters between PD and healthy control groups.

<p>The symbol * indicates a significant difference using <i>t</i>-test or U test (0.01 was used as the significance level). Due to similarity between conditions, only normal habitual gait and the eyes-open condition for the balance test are presented. Mean (SD) are presented.</p><p>PD: Parkinson’s disease</p><p>CI: confidence interval</p><p>COG: center of gravity</p><p>AP: anterior-posterior</p><p>ML: medial-lateral</p><p>RCI: reciprocal compensatory index</p><p>OL: open-loop.</p><p>Differences in gait and postural balance parameters between PD and healthy control groups.</p

A Pilot Clinical Trial to Objectively Assess the Efficacy of Electroacupuncture on Gait in Patients with Parkinson's Disease Using Body Worn Sensors

<div><p>Background</p><p>Gait disorder, a key contributor to fall and poor quality of life, represents a major therapeutic challenge in Parkinson’s disease (PD). The efficacy of acupuncture for PD remains unclear, largely due to methodological flaws and lack of studies using objective outcome measures.</p><p>Objective</p><p>To objectively assess the efficacy of electroacupuncture (EA) for gait disorders using body-worn sensor technology in patients with PD.</p><p>Methods</p><p>In this randomized pilot study, both the patients and assessors were masked. Fifteen PD patients were randomly assigned to an experimental group (n = 10) or to a control group (n = 5). Outcomes were assessed at baseline and after completion of three weekly EA treatments. Measurements included gait analysis during single-task habitual walking (STHW), dual-task habitual walking (DTHW), single-task fast walking (STFW), dual-task fast walking (DTFW). In addition, Unified Parkinson's Disease Rating Scale (UPDRS), SF-12 health survey, short Falls Efficacy Scale-International (FES-I), and visual analog scale (VAS) for pain were utilized.</p><p>Results</p><p>All gait parameters were improved in the experimental group in response to EA treatment. After adjustment by age and BMI, the improvement achieved statistical significant level for gait speed under STHW, STFW, and DTFW (9%-19%, p<0.05) as well as stride length during DTFW (9%, p = 0.037) and midswing speed during STFW (6%, p = 0.033). No significant changes were observed in the control group (p>0.110). The highest correlation between gait parameters and UPRDS scores at baseline was observed between gait speed during STFW and UPDRS II (r = -0.888, p = 0.004). The change in this gait parameter in response to active intervention was positively correlated with baseline UPDRS (r = 0.595, p = 0.057). Finally, comparison of responses to treatment between groups showed significant improvement, prominently in gait speed (effect size 0.32–1.16, <i>p</i> = 0.001).</p><p>Conclusions</p><p>This study provides the objective proof of concept for potential benefits of non-pharmaceutical based EA therapy on enhancing gait in patients with PD.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/results?term=NCT02556164&Search=Search" target="_blank">NCT02556164</a></p></div

Changes in therapy by indication and result of dopamine transporter imaging.

<p>Abbreviations: PD = Parkinson’s disease; ET = essential tremor; MSA = multiple system atrophy; RLS = restless leg syndrome</p><p>*Start ET treatment (n = 2), adjusting antipsychotic (n = 1), starting neuromodulatory drugs (n = 1)</p><p>Changes in therapy by indication and result of dopamine transporter imaging.</p

Baseline characteristics of the study population.

<p>Baseline characteristics of the study population.</p