Effects of hypoxic compound exercise to promote HIF-1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila.

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.

Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 coactivator, identifying wingless/integrated (WNT) signaling as a highly enriched AR-regulated pathway in the genitalia. Transcription factor (TF) hits were then assayed for sexually dimorphic expression at two critical time points and also cross-referenced to a database of clinically relevant copy number variations to identify 252 TFs exhibiting copy variation in patients with LGU phenotypes. A subset of 54 TFs was identified for which LGU phenotypes are statistically overrepresented as a proportion of total observed phenotypes. The 252 TF hitlist was then subjected to a functional screen to identify hits whose silencing affects genital mesenchymal growth rates. Overlap of these datasets results in a refined list of 133 TFs of both functional and clinical relevance to LGU development, 31 of which are top priority candidates, including the well-documented renal progenitor regulator, Sall1. Loss of Sall1 was examined in vivo and confirmed to be a powerful regulator of LGU development.

Adipose Tissue Exosome circ_sxc Mediates the Modulatory of Adiposomes on Brain Aging by Inhibiting Brain dme-miR-87-3p.

Aging of the brain usually leads to the decline of neurological processes and is a major risk factor for various neurodegenerative diseases, including sleep disturbances and cognitive decline. Adipose tissue exosomes, as adipocyte-derived vesicles, may mediate the regulatory processes of adipose tissue on other organs, including the brain; however, the regulatory mechanisms remain unclear. We analyzed the sleep-wake behavior of young (10 days) and old (40 days) Drosophila and found that older Drosophila showed increased sleep fragmentation, which is similar to mammalian aging characteristics. To investigate the cross-tissue regulatory mechanisms of adiposity on brain aging, we extracted 10-day and 40-day Drosophila adipose tissue exosomes and identified circRNAs with age-dependent expression differences by RNA-seq and differential analysis. Furthermore, by combining data from 3 datasets of the GEO database (GSE130158, GSE24992, and GSE184559), circ_sxc that was significantly downregulated with age was finally screened out. Moreover, dme-miR-87-3p, a conserved target of circ_sxc, accumulates in the brain with age and exhibits inhibitory effects in predicted binding relationships with neuroreceptor ligand genes. In summary, the current study showed that the Drosophila brain could obtain circ_sxc by uptake of adipose tissue exosomes which crossed the blood-brain barrier. And circ_sxc suppressed brain miR-87-3p expression through sponge adsorption, which in turn regulated the expression of neurological receptor ligand proteins (5-HT1B, GABA-B-R1, Rdl, Rh7, qvr, NaCP60E) and ensured brain neuronal synaptic signaling normal function of synaptic signaling. However, with aging, this regulatory mechanism is dysregulated by the downregulation of the adipose exosome circ_sxc, which contributes to the brain exhibiting sleep disturbances and other "aging" features.

Cardiac Timeless Trans-Organically Regulated by miR-276 in Adipose Tissue Modulates Cardiac Function.

The interconnection between cardiac function and circadian rhythms is of great importance. While the role of the biological clock gene Timeless (Tim) in circadian rhythm has been extensively studied, its impact on cardiac function remains largely been unexplored. Previous research has provided experimental evidence for the regulation of the heart by adipose tissue and the targeting of miR-276a/b on Timeless. However, the extent to which adipose tissue regulates cardiac Timeless genes trans-organically through miR-276a/b, and subsequently affects cardiac function, remains uncertain. Therefore, the objective of this study was to investigate the potential trans-organ modulation of the Timeless gene in the heart by adipose tissue through miR-276a/b. We found that cardiac-specific Timeless knockdown and overexpression resulted in a significant increase in heart rate (HR) and a significant decrease in Heart period (HP), diastolic intervals (DI), systolic intervals (SI), diastolic diameter (DD), and systolic diameter (SD). miR-276b systemic knockdown resulted in a significant increase in DI, arrhythmia index (AI), and fractional shortening (FS) significantly increased and SI, DD and SD significantly decreased. Adipose tissue-specific miR-276a/b knockdown and miR-276a overexpression resulted in a significant increase in HR and a significant decrease in DI and SI, which were improved by exercise intervention. This study presents a novel finding that highlights the significance of the heart circadian clock gene Timeless in heart function. Additionally, it demonstrates that adipose tissue exerts trans-organ modulation on the expression of the heart Timeless gene via miR-276a/b.

The Effects of Laughter Yoga on Perceived Stress, Positive Psychological Capital, and Exercise Capacity in Lung Cancer Chemotherapy Patients: A Pilot Randomized Trial.

BACKGROUND: Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Although chemotherapy is effective in improving clinical symptoms, it causes a variety of acute and chronic side effects, seriously aggravating the psychological stress of patients. Laughter Yoga as a new type of aerobic exercise can effectively reduce stress levels and increase positive mood in patients. This study aimed to examine the effects of laughter yoga on perceived stress, positive psychological capital, and exercise capacity in lung cancer patients. METHODS: This study was a randomized, single-blind, parallel-group trial. The study enrolled 84 lung cancer chemotherapy patients from a general hospital in central China. These patients were randomly allocated to control and intervention groups (n = 42 per group) after baseline assessments. Patients in the control group received routine care and those in the intervention group received laughter yoga intervention. Perceived stress, positive psychological capital, and exercise capacity were assessed at baseline, immediately post-intervention. RESULTS: During the implementation of the study, there were 2 dropouts in each of the intervention and control groups. Ultimately, 80 patients in the control and intervention groups completed the trial. Patients who received laughter yoga intervention had significantly higher scores in positive psychological capital (P < .01, Cohen's d = 0.692) and exercise capacity (P < .01, Cohen's d = 0.659). Discernible differences were also observed in perceived stress (P < .01, Cohen's d = 1.087) between the 2 groups. CONCLUSIONS: The results of this study suggest that laughter yoga is an effective way and may produce beneficial effects on perceived stress, positive psychological capital and exercise capacity.

Operation Status of the Mutual Aid Human Milk Bank for Preterm Infants and Data Analysis.

Objectives: This study aimed to investigate the matching degree between the donated supply and demand, clinical characteristics of both donors and recipients, along with the operation cost. Methods: From January 1, 2018 to December 31, 2021, the data on human milk donation and usage, the clinical characteristics of donors and recipients, and the cost of each operating center were collected from the Manual Donation Registration Form and Information Management System of the selected human milk bank. Results: During the four years that the human milk bank was in operation, the volume of donated milk was slightly greater than the volume of consumed milk. A total of 1364 donors donated 2434.63 liters of qualified human milk, for RMB 1,791,000 (USD 257, 202), ie, RMB 385.3 (USD 55.3)/L; 97.8% of the donors were preterm puerperae, and 59% of the donors donated between 1 week and 1 month after delivery. All recipients were preterm infants and received donated human milk for a duration of 9.4 days on average. During the four years of operation, the proportion of donors who had previously received donated milk among all donors showed an overall increasing trend, while the incidence of NEC in preterm infants gradually decreased. Conclusions: The increasingly optimized structure of donors, the more economical operation, and the fact that the use of donated milk may not affect breastfeeding of the recipients have made it a human milk bank operation mode worthy of promotion.

Effects of sublingual colostrum application on oral and intestinal flora of extremely low birth weight infants.

BACKGROUND: The aim of this study is to analyze the effects of colostrum application on the establishment of normal flora in the intestinal tracts and oral cavities of extremely low birth weight infants (ELBWI). METHODS: A prospective cohort study design was adopted following the STROBE guidelines (Supplementary File 1). Colostrum was administered immediately after obtaining maternal breast milk using a special sterile cotton swab. There were no specific treatments for infants who did not receive colostrum. This experiment was completed on day 5 post-birth and the patients were divided into the colostrum and control groups, corresponding to whether or not colostrum was administered. Throat swabs and stool samples were collected on days 1 and 5 post-birth. RESULTS: Using the conventional bacteria cultivation technique, the detection rate of bacteria in 98 cases of meconium at birth was 15.31%. On day 5, the detection rates of Staphylococcus in the colostrum and control groups were 36.54% and 34.78%, with no significant difference between them (P = 0.856), and that of Enterococcus was 26.92% and 13.04%, respectively, with no statistically significant difference (P = 0.089). Likewise, at birth, the detection rate of bacteria in 98 cases of throat swabs was 27.55%. On day 5, the detection rate of Streptococcus in the colostrum and control groups was 78.85% and 50.00%, respectively, recording a statistically significant difference this time (P = 0.003). CONCLUSION: Colostrum application had limited effects on intestinal flora colonization but contributes to physiological oral flora colonization.

The Utilization of Sodium Concentration in Human Milk from Pump-Dependent Mothers of Preterm Infants as a Measure of Milk Production.

Objective: This study investigated changes in sodium concentrations in human milk from mothers of premature infants using different breast pumps for 14 days postpartum, and the correlation between the sodium concentration in mother's own milk (MOM) and the volume pumped. Study Design: This randomized controlled study recruited 66 mothers of premature infants delivered in our hospital from February to December 2018, and we assigned them to three groups using an envelope method. In intervention group 1, a hospital-grade electric breast pump was used from postpartum day 1 to 14; in intervention group 2, a hospital-grade electric breast pump was used on postpartum days 1 to 5 and a normal personal electric breast pump on postpartum days 6 to 14; in the control group, a personal normal electric breast pump was used from postpartum day 1 to 14. Data recorded included the breast milk volume pumped and milk sodium concentration. Results: The average daily volume of MOM pumped differed statistically (p < 0.05) between the intervention and control groups at postpartum days 7 and 14. The average daily volume pumped did not differ between intervention groups 1 and 2 by postpartum day 14 (p > 0.05). However, the time taken for the sodium concentrations to normalize differed significantly (p < 0.01). At postpartum day 5, the sodium concentrations of 73% of intervention group 1 and 2 mothers were within normal limits, and they were maintained until day 14. In comparison, only 41% of the controls had normal MOM sodium levels on day 5, and they were still high on day 7 in 27.3% of controls. Conclusions: In the early stage of lactation initiation (within 5 days postpartum), using a hospital-grade electric breast pump promotes lactation in mothers who deliver prematurely and the sodium concentrations normalize more quickly. Sodium can be used as an objective biomarker of MOM to evaluate the possibility of delayed lactation in mothers of premature infants, and it could assist interventions in the early postpartum period. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200061384.

Eriodictyol regulated ferroptosis, mitochondrial dysfunction, and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer cells.

This study aimed to investigate the antitumor effect and the underlying molecular mechanism of eriodictyol on ovarian cancer cells. CaoV3 and A2780 were exposed to eriodictyol at different concentrations of 0-800 µM. Cell apoptosis and viability were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay and Cell Counting Kit-8 (CCK-8) assay, respectively. Mitochondrial membrane potential was evaluated by flow cytometers with a JC-1 detection kit. Fe2+ content was evaluated using an iron assay kit. The section of tumor tissues was observed using hematoxylin-eosin (H&E) staining and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was detected by immunohistochemistry (IHC) staining. Eriodictyol suppressed cell viability and induced cell apoptosis of CaoV3 and A2780 cells. Half maximal inhibitory concentration (IC50 ) value of CaoV3 at 24 and 48 h was (229.74 ± 5.13) µM and (38.44 ± 4.68) µM, and IC50 value of A2780 at 24 and 48 h was (248.32 ± 2.54) µM and (64.28 ± 3.19) µM. Fe2+ content and reactive oxygen species production were increased and protein levels of SLC7A11 and GPX4 were decreased by eriodictyol. Besides, eriodictyol reduced the ratio of JC-1 fluorescence ratio, glutathione and malondialdehyde contents but elevated Cytochrome C level. Nrf2 phosphorylation were obviously downregulated by eriodictyol. Finally, eriodictyol suppressed tumor growth, aggravated mitochondrial dysfunction and downregulated Nrf2 expression in tumor tissue in mice. Eriodictyol regulated ferroptosis, mitochondrial dysfunction and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer.

Stable Expression of dmiR-283 in the Brain Promises Positive Effects in Endurance Exercise on Sleep-Wake Behavior in Aging Drosophila.

Sleep-wake stability is imbalanced with natural aging, and microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and aging; however, the biological functions of miRNAs in regulating aging-related sleep-wake behavior remain unexplored. This study varied the expression pattern of dmiR-283 in Drosophila and the result showed that the aging decline in sleep-wake behavior was caused by the accumulation of brain dmiR-283 expression, whereas the core clock genes cwo and Notch signaling pathway might be suppressed, which regulate the aging process. In addition, to identify exercise intervention programs of Drosophila that promote healthy aging, mir-283SP/+ and Pdf > mir-283SP flies were driven to perform endurance exercise for a duration of 3 weeks starting at 10 and 30 days, respectively. The results showed that exercise starting in youth leads to an enhanced amplitude of sleep-wake rhythms, stable periods, increased activity frequency upon awakening, and the suppression of aging brain dmiR-283 expression in mir-283SP/+ middle-aged flies. Conversely, exercise performed when the brain dmiR-283 reached a certain accumulation level showed ineffective or negative effects. In conclusion, the accumulation of dmiR-283 expression in the brain induced an age-dependent decline in sleep-wake behavior. Endurance exercise commencing in youth counteracts the increase in dmiR-283 in the aging brain, which ameliorates the deterioration of sleep-wake behavior during aging.

Variety-Specific Flowering of Sugarcane Induced by the Smut Fungus Sporisorium scitamineum.

Sugarcane smut is the most severe sugarcane disease in China. The typical symptom is the emerging of a long, black whip from the top of the plant cane. However, in 2018, for the first time we observed the floral structures of sugarcane infected by smut fungus in the planting fields of China. Such smut-associated inflorescence in sugarcane was generally curved and short, with small black whips emerging from glumes of a single floret on the cane stalk. Compatible haploid strains, named Ssf1-7 (MAT-1) and Ssf1-8 (MAT-2), isolated from teliospores that formed black whips in inflorescence of sugarcane were selected for sexual mating assay, ITS DNA sequencing analysis and pathogenicity assessment. The isolates Ssf1-7 and Ssf1-8 showed stronger sexual mating capability than the reported Sporisorium scitamineum strains Ss17 and Ss18. The ITS DNA sequence of the isolates Ssf1-7 and Ssf1-8 reached 100% similarity to the isolates of S. scitamineum strains available in GenBank. Inoculating Ssf1-7 + Ssf1-8 to six sugarcane varieties, i.e., GT42, GT44, GT49, GT55, LC05-136 and ROC22, resulted in different smut morphological modifications. The symptoms of floral structure only occurred in LC05-136, indicating that the flowering induction by S. scitamineum is variety-specific. Furthermore, six selected flowering-related genes were found to be differentially expressed in infected Ssf1-7 + Ssf1-8 LC05-13 plantlets compared to uninfected ones. It is concluded that the flowering induction by S. scitamineum depends on specific fungal race and sugarcane variety, suggesting a specific pathogen-host interaction and expression of some flowering-related genes.

Regular Exercise in Drosophila Prevents Age-Related Cardiac Dysfunction Caused by High Fat and Heart-Specific Knockdown of skd.

Skuld (skd) is a subunit of the Mediator complex subunit complex. In the heart, skd controls systemic obesity, is involved in systemic energy metabolism, and is closely linked to cardiac function and aging. However, it is unclear whether the effect of cardiac skd on cardiac energy metabolism affects cardiac function. We found that cardiac-specific knockdown of skd showed impaired cardiac function, metabolic impairment, and premature aging. Drosophila was subjected to an exercise and high-fat diet (HFD) intervention to explore the effects of exercise on cardiac skd expression and cardiac function in HFD Drosophila. We found that Hand-Gal4>skd RNAi (KC) Drosophila had impaired cardiac function, metabolic impairment, and premature aging. Regular exercise significantly improved cardiac function and metabolism and delayed aging in HFD KC Drosophila. Thus, our study found that the effect of skd on cardiac energy metabolism in the heart affected cardiac function. Exercise may counteract age-related cardiac dysfunction and metabolic disturbances caused by HFD and heart-specific knockdown of skd. Skd may be a potential therapeutic target for heart disease.

Unmet Care Needs and Related Factors of Lung Transplant Patients at Home.

The purpose of this study was to explore the relationship among unmet care needs, social support, and anxiety in patients with lung transplantation. We conducted a cross-sectional study; 173 lung transplant patients who met the inclusion criteria completed questionnaires including the Organ Transplant Recipient Care Needs Scale, the Perceived Social Support Scale, and the Anxiety Self-Rating Inventory. Pearson's correlations and multiple linear regression analyses were used to test the relationship between the selected variables. The results showed a moderate level of unmet care needs at home for lung transplant patients. Education level, transplant-related complications, perceived social support, and anxiety were significantly correlated with unmet care needs of lung transplant patients at home (p < .05), explaining 23.8% of the total variance for unmet care needs. Further research is required to explore interventions to reduce the level of unmet care needs of lung transplant patients.

Exercise Training Upregulates Cardiac mtp Expression in Drosophila melanogaster with HFD to Improve Cardiac Dysfunction and Abnormal Lipid Metabolism.

Current evidence suggests that the heart plays an important role in regulating systemic lipid homeostasis, and high-fat diet (HFD)-induced obesity is a major cause of cardiovascular disease, although little is known about the specific mechanisms involved. Exercise training can reportedly improve abnormal lipid metabolism and cardiac dysfunction induced by high-fat diets; however, the molecular mechanisms are not yet understood. In the present study, to explore the relationship between exercise training and cardiac mtp in HFD flies and potential mechanisms by which exercise training affects HFD flies, Drosophila was selected as a model organism, and the GAL4/UAS system was used to specifically knock down the target gene. Experiments revealed that HFD-fed Drosophila exhibited changes in body weight, increased triglycerides (TG) and dysregulated cardiac contractility, consistent with observations in mammals. Interestingly, inhibition of cardiac mtp expression reduced HFD-induced cardiac damage and mitigated the increase in triglycerides. Further studies showed that in HFD +w1118, HFD + Hand > w1118, and HFD+ Hand > mtpRNAi, cardiac mtp expression downregulation induced by HFD was treated by exercise training and mitochondrial ß-oxidation capacity in cardiomyocytes was reversed. Overall, knocking down mtp in the heart prevented an increase in systemic TG levels and protected cardiac contractility from damage caused by HFD, similar to the findings observed after exercise training. Moreover, exercise training upregulated the decrease in cardiac mtp expression induced by HFD. Increased Had1 and Acox3 expression were observed, consistent with changes in cardiac mtp expression.

Regular Exercise Rescues Heart Function Defects and Shortens the Lifespan of Drosophila Caused by dMnM Downregulation.

Although studies have shown that myomesin 2 (MYOM2) mutations can lead to hypertrophic cardiomyopathy (HCM), a common cardiovascular disease that has a serious impact on human life, the effect of MYOM2 on cardiac function and lifespan in humans is unknown. In this study, dMnM (MYOM2 homologs) knockdown in cardiomyocytes resulted in diastolic cardiac defects (diastolic dysfunction and arrhythmias) and increased cardiac oxidative stress. Furthermore, the knockdown of dMnM in indirect flight muscle (IFM) reduced climbing ability and shortened lifespan. However, regular exercise significantly ameliorated diastolic cardiac dysfunction, arrhythmias, and oxidative stress triggered by dMnM knockdown in cardiac myocytes and also reversed the reduction in climbing ability and shortening of lifespan caused by dMnM knockdown in Drosophila IFM. In conclusion, these results suggest that Drosophila cardiomyocyte dMnM knockdown leads to cardiac functional defects, while dMnM knockdown in IFM affects climbing ability and lifespan. Furthermore, regular exercise effectively upregulates cardiomyocyte dMnM expression levels and ameliorates cardiac functional defects caused by Drosophila cardiomyocyte dMnM knockdown by increasing cardiac antioxidant capacity. Importantly, regular exercise ameliorates the shortened lifespan caused by dMnM knockdown in IFM.

The impact of breast milk feeding on early brain development in preterm infants in China: An observational study.

BACKGROUND: The prevailing consensus from large epidemiological studies is that breastfeeding is associated with improved IQ and cognitive functioning in later childhood and adolescence. Current research is exploring the association between breastfeeding and early brain development in preterm infants. OBJECTIVE: To explore the differences in brain gray matter between breastmilk-fed and formula-fed preterm infants using structural and functional magnetic resonance imaging. METHODS: A convenience sample of breastmilk-fed preterm infants(n = 34) and formula-fed infants (n = 22) aged approximately 32 weeks. At near term-equivalent age, MR scanning was performed. Gray matter structural and functional differences between the two groups were assessed using MATLAB software for voxel-based morphometry (VBM) and amplitude of low-frequency fluctuation (ALFF) analysis. RESULTS: Maternal and neonatal demographic characteristics showed no significant difference between the two groups. Breastmilk-fed infants had greater regional gray matter volume on MRI than formula-fed infants in multiple brain regions, including the bilateral frontal lobe (BA11, BA46), right temporal lobe (BA37), and left caudate nucleus, at a statistical threshold of p<0.01 (AlphaSim corrected) with a cluster size of >40 voxels. Compared with formula-fed infants, breastmilk-fed infants showed increased brain activation on fMRI in the right superior temporal gyrus (BA41). CONCLUSION: Breastmilk-fed infants had greater regional gray matter development and increased regional gray matter function compared with formula-fed infants at near term-equivalent age, suggesting breastmilk feeding in the early period after birth may have some degree of influence on early brain development in preterm infants.

Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB.

It is well-established that SPIB is essential for the survival of mature B cells, playing a key role in diffuse large B-cell lymphoma, colorectal cancer, and lung cancer. However, no study has hitherto conducted a systematic pan-cancer analysis on SPIB. Herein, we analyzed the differential expression of SPIB in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases and found that SPIB was significantly upregulated in most cancers. In addition, SPIB was positively or negatively associated with prognosis in different cancers. We found that SPIB was significantly associated with tumor immune infiltration and immune checkpoint genes in more than 35 tumors by TIMER database analysis. In addition, SPIB was negatively correlated with Tumor mutational burden (TMB) and Microsatellite instability (MSI) in most tumors. Finally, GO/KEGG enrichment analysis revealed the possible involvement of SPIB in NF-kappa B and B-cell receptor signaling pathways. In conclusion, our comprehensive pan-cancer analysis of SPIB reveals its important role in tumor immunity, suggesting it has huge prospects for clinical application in cancer therapy.

Protective effect of active components of Eucommia ulmoides leaves on gastric ulcers in rats: Involvement of the PI3K/Akt/NF-κB pathway.

Eucommia ulmoides leaves are widely developed as food and medicines in China and Japan. Its main components have anti-inflammatory properties against gastric ulcers. The purpose of this study was to assess the protective role of an extract derived from the active components of Eucommia ulmoides leaves (EUL 50) against a gastric ulcer and analyze the underlying antiulcer mechanism. The main components of EUL 50 were identified using an ultra-performance liquid chromatography (UPLC) method. Network pharmacology and molecular docking were performed to predict the possible mechanism of action of EUL 50 in the treatment of gastric ulcers. The rats received EUL 50 intragastric administration twice a day for 3 days. Hydrochloric acid/ethanol (HCl/EtOH) was utilized to induce gastric ulcers, followed by histopathological and histochemical evaluation of the ulcer tissues and determination of the main oxidative stress parameters and inflammatory cytokines. The expression of PI3K/Akt/NF-κB pathway-related proteins was measured. Neochlorogenic acid, chlorogenic acid, rutin, and so on were identified as the major components of EUL 50 by UPLC. The prediction results identified the PI3K/Akt/NF-κB signaling pathway as the main possible protective mechanism against gastric ulcers. Furthermore, in a dose-dependent manner, EUL 50 reduced gastric tissue damage. In addition, the high dose of EUL 50 administration resulted in remarkable reductions in the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1ß (IL-1ß) by 22.64%, 42.61%, 57.78%, and 56.51%, respectively, and suppression of the phosphorylation of Akt, p65, IKKα, and IκBα by 60.87%, 67.65, 74.58%, and 59.57%, respectively, and increased the antioxidant enzyme activity. EUL 50 is rich in flavonoids and organic acids that can act on the PI3K/Akt/NF-κB signaling pathway; as a result, oxidative stress and inflammation are considerably reduced, and gastric ulcers caused by HCl/EtOH are reduced. PRACTICAL APPLICATION: As a medicinal and food substance, Eucommia ulmoides leaves are widely used in the development of health products. EUL 50, a moderately polar part of E. ulmoides leaves, was obtained by extraction and enrichment and was found to have a better protective effect against HCl/EtOH-induced gastric ulcers. This finding can enrich the traditional application of E. ulmoides leaves and provide a basis for their health product development.