Sesquiterpene lactones from Tithonia diversifolia with ferroptosis-inducing activities.

Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

Electroencephalography Monitoring for Preventing Postoperative Delirium and Postoperative Cognitive Decline in Patients Undergoing Cardiothoracic Surgery: A Meta-Analysis.

Background: Patients undergoing cardiothoracic surgery frequently encounter perioperative neurocognitive disorders (PND), which can include postoperative delirium (POD) and postoperative cognitive decline (POCD). Currently, there is not enough evidence to support the use of electroencephalograms (EEGs) in preventing POD and POCD among cardiothoracic surgery patients. This meta-analysis examined the importance of EEG monitoring in POD and POCD. Methods: Cochrane Library, PubMed, and EMBASE databases were searched to obtain the relevant literature. This analysis identified trials based on the inclusion and exclusion criteria. The Cochrane tool was used to evaluate the methodological quality of the included studies. Review Manager software (version 5.3) was applied to analyze the data. Results: Four randomized controlled trials (RCTs) were included in this meta-analysis, with 1096 participants. Our results found no correlation between EEG monitoring and lower POD risk (relative risk (RR): 0.81; 95% CI: 0.55-1.18; p = 0.270). There was also no statistically significant difference between the EEG group and the control group in the red cell transfusions (RR: 0.86; 95% CI: 0.51-1.46; p = 0.590), intensive care unit (ICU) stay (mean deviation (MD): -0.46; 95% CI: -1.53-0.62; p = 0.410), hospital stay (MD: -0.27; 95% CI: -2.00-1.47; p = 0.760), and mortality (RR: 0.33; 95% CI: 0.03-3.59; p = 0.360). Only one trial reported an incidence of POCD, meaning we did not conduct data analysis on POCD risk. Conclusions: This meta-analysis did not find evidence supporting EEG monitoring as a potential method to reduce POD incidence in cardiothoracic surgery patients. In the future, more high-quality RCTs with larger sample sizes are needed to validate the relationship between EEG monitoring and POD/POCD further.

Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L­serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L­serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L­serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L­serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.

The therapeutic mechanism of Compound Lurong Jiangu Capsule for the treatment of cadmium-induced osteoporosis: network pharmacology and experimental verification.

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain. Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP. Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB). Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes. Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.

Injectable, stable, and biodegradable hydrogel with platelet-rich plasma induced by l-serine and sodium alginate for effective treatment of intrauterine adhesions.

The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l-serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l-Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

INTRODUCTION: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. PATIENT CONCERNS: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. DIAGNOSIS: The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. INTERVENTIONS: After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. OUTCOMES: Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. CONCLUSION: NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Applying machine-learning models to differentiate benign and malignant thyroid nodules classified as C-TIRADS 4 based on 2D-ultrasound combined with five contrast-enhanced ultrasound key frames.

Objectives: To apply machine learning to extract radiomics features from thyroid two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasound (CEUS) images to classify and predict benign and malignant thyroid nodules, classified according to the Chinese version of the thyroid imaging reporting and data system (C-TIRADS) as category 4. Materials and methods: This retrospective study included 313 pathologically diagnosed thyroid nodules (203 malignant and 110 benign). Two 2D-US images and five CEUS key frames ("2nd second after the arrival time" frame, "time to peak" frame, "2nd second after peak" frame, "first-flash" frame, and "second-flash" frame) were selected to manually label the region of interest using the "Labelme" tool. A total of 7 images of each nodule and their annotates were imported into the Darwin Research Platform for radiomics analysis. The datasets were randomly split into training and test cohorts in a 9:1 ratio. Six classifiers, namely, support vector machine, logistic regression, decision tree, random forest (RF), gradient boosting decision tree and extreme gradient boosting, were used to construct and test the models. Performance was evaluated using a receiver operating characteristic curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and F1-score were calculated. One junior radiologist and one senior radiologist reviewed the 2D-US image and CEUS videos of each nodule and made a diagnosis. We then compared their AUC and ACC with those of our best model. Results: The AUC of the diagnosis of US, CEUS and US combined CEUS by junior radiologist and senior radiologist were 0.755, 0.750, 0.784, 0.800, 0.873, 0.890, respectively. The RF classifier performed better than the other five, with an AUC of 1 for the training cohort and 0.94 (95% confidence interval 0.88-1) for the test cohort. The sensitivity, specificity, accuracy, PPV, NPV, and F1-score of the RF model in the test cohort were 0.82, 0.93, 0.90, 0.85, 0.92, and 0.84, respectively. The RF model with 2D-US combined with CEUS key frames achieved equivalent performance as the senior radiologist (AUC: 0.94 vs. 0.92, P = 0.798; ACC: 0.90 vs. 0.92) and outperformed the junior radiologist (AUC: 0.94 vs. 0.80, P = 0.039, ACC: 0.90 vs. 0.81) in the test cohort. Conclusions: Our model, based on 2D-US and CEUS key frames radiomics features, had good diagnostic efficacy for thyroid nodules, which are classified as C-TIRADS 4. It shows promising potential in assisting less experienced junior radiologists.

Circadian disruption during fetal development promotes pathological cardiac remodeling in male mice.

Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.

Eighteen iridoids from the roots and rhizomes of Valeriana jatamansi and their protective effects against α-hemolysin.

Thirteen previously undescribed iridoids (1-13), together with five known iridoids (14-18) were isolated from the roots and rhizomes of Valeriana jatamansi Jones. Their structures with absolute configurations were elucidated by analysis of MS, NMR, optical rotation and their experimental and calculated electronic circular dichroism spectra. All of the isolated compounds were tested for their protective effects against α-hemolysin-induced cell death in A549 cells. Compounds 14, 16 and 17 showed moderate protective effects, and compounds 15 and 18 showed weak protective effects.

Dimeric ent-kauranoids isolated from Isodon japonica var. Glaucocalyx and their anti-inflammatory activities.

The phytochemical investigation of the aerial parts of Isodon japonica var. glaucocalyx afforded four undescribed (glaucocalyxin O-R, 1-4) and six known ent-kauranoids (5-10). Their structures were established using NMR and MS measurements. Compounds 1 and 2 are dimeric ent-kaurane-type diterpenoids. Moreover, the plausible biogenetic pathways for compounds 1 and 2 were proposed as Michael addition between two monomers. Eight compounds were assayed for their anti-inflammatory activity by evaluating NO production in LPS-induced RAW 267.4 cells, and compounds 7, 8 and 9 exhibited relatively remarkable anti-inflammatory activities at 10 µM.

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443.

OBJECTIVE: To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration. METHODS: HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR. RESULTS: HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05). CONCLUSION: HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443 / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration.@*METHODS@#HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR.@*RESULTS@#HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05).@*CONCLUSION@#HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

[Characteristics of Microplastic-derived Dissolved Organic Matter(MPDOM) and the Complexation Between MPDOM and Sulfadiazine/Cu2].

Microplastic-derived dissolved organic matter(MPDOM) during the aging process could be complexed with organic pollutants, heavy metals, and other contaminants and thus affect their migration and transformation. In this study, two types of microplastics, polyethylene terephthalate(PET) and polystyrene(PS), were selected to investigate the spectral properties of MPDOM and their effect on the complexation between MPDOM and sulfadiazine(SDZ)/copper ion(Cu2+) using the fluorescence quenching method, various spectroscopic analysis techniques, and the Ryan-Weber quenching model. The results of UV-vis absorption spectroscopy analysis showed that the molecular weight of the two MPDOMs decreased; the aromaticity and humification increased; and the carboxyl, carbonyl, hydroxyl, and ester substituents on aromatic rings increased after aging. The fluorescence quenching process between MPDOM and SDZ/Cu2+ was static quenching. After quenching, the aromaticity and humification of the two MPDOMs were similar, and the molecular weights were comparable. Combined with three-dimensional fluorescence spectra and parallel factor analysis, two humic-like components and one protein-like component were identified. In addition, the protein-like components of MPDOM reacted preferentially with SDZ and were more sensitive to Cu2+. The results of the Ryan-Weber quenching model revealed that the binding ability of humic-like components to PET-DOM was higher in both SDZ and Cu2+ quenching systems, but the binding ability of MPDOM in the SDZ quenching system was generally stronger than that in the Cu2+ system.

Infrared Imageries of Human Body Activated by Tea Match the Hypothesis of Meridian System.

Human meridian (Jingluo) system was hypothesized by traditional Chinese medicine (TCM) for thousands of years, suggesting 12 normal meridian channels going through respective organs, carrying fluid and energy, and laying thermal effects. Some treatments based on meridians have been proved effective. However, existence of meridians has never been confirmed, let alone the lack of measurement for meridian phenotypes. Thermal effect is one of the major phenotypes of meridian metabolism. Infrared photograph was employed to display the picture of meridians since 1970. Unfortunately, no satisfactory results have been obtained. It is possible that only when a certain meridian is activated will there be thermal effect for successful infrared photograph. In this study, 13 types of tea were selected out of the herbs to activate the hypothesized 12 meridians for imagery taking. Forty-two volunteers took part in the experiment lasted for 13 days. Different tea was tested in different day. Infrared imageries of the human bodies were taken immediately after each tea was drunk. The highest temperatures of the fingers, palms, and above the organs were derived from the imageries and analyzed. The temperatures of the organs and fingers possibly connected by 12 hypothesized meridians rose together significantly following the meridian hypothesis. Infrared imageries showed quite clear shapes of the organs activated by different kinds of tea, e.g., heart and kidneys by yellow tea, etc. Some high temperature lines also matched the hypothetic meridians. Our work displayed the probable imageries of all the 12 hypothetic meridians for the first time, and proved with data that different foods may activate different organs following the meridian hypothesis, shedding light on a possible new method of targeted drug designs. Measurements of meridian phenotypes can be developed based on this method of activation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00090-x.

Effects of continuous cropping on fungal community diversity and soil metabolites in soybean roots.

IMPORTANCE: Soybean yield can be affected by soybean soil fungal communities in different tillage patterns. Soybean is an important food crop with great significance worldwide. Continuous cultivation resulted in soil nutrient deficiencies, disordered metabolism of root exudates, fungal pathogen accumulation, and an altered microbial community, which brought a drop in soybean output. In this study, taking the soybean agroecosystem in northeast China, we revealed the microbial ecology and soil metabolites spectrum, especially the diversity and composition of soil fungi and the correlation of pathogenic fungi, and discussed the mechanisms and the measures of alleviating the obstacles.

Mechanism of albiflorin in improvement of Alzheimer's disease based on network pharmacology and in vitro experiments / 中国中药杂志

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aβ_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways. The results of network pharmacological analysis showed that albiflorin acted on key targets such as mitogen-activated protein kinase-1(MAPK1 or ERK2), albumin(ALB), epidermal growth factor receptor(EGFR), caspase-3(CASP3), and sodium-dependent serotonin transporter(SLC6A4), and signaling pathways such as MAPK, cAMP, and cGMP-PKG. The results of molecular docking showed that albiflorin had strong binding affinity to MAPK1(ERK2). In vitro experiments showed that compared with the blank group, the model group showed decreased cell viability, decreased expression level of B-cell lymphoma 2(Bcl-2), increased Bcl-2-associated X protein(Bax), and reduced phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and the relative expression ratio of p-ERK1/2 to ERK1/2. Compared with the model group, the albiflorin group showed potentiated cell viability, up-regulated expression of Bcl-2, down-regulated Bax, and increased phosphorylation level of ERK1/2 and the relative expression ratio of p-ERK1/2 to ERK1/2. These results suggest that the mechanism of albiflorin against AD may be related to its activation of the MAPK/ERK signaling pathway and its inhibition of neuronal apoptosis.

Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice / 中国中药杂志

This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aβ deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.

Applying contrast-enhanced ultrasound model to distinguish atypical focal adenomyosis from uterine leiomyomas.

Background: Different from conventional ultrasound, contrast-enhanced ultrasound (CEUS) is better in observing microperfusion. For atypical focal adenomyosis and uterine leiomyomas that are difficult to be distinguished by conventional ultrasound, this study aims to further improve the differential diagnosis performance by using CEUS model. Methods: After screening the cases with difficulties in identifying focal myometrium lesions through conventional ultrasound, the number of cases covered in the focal adenomyosis group and leiomyomas group were 60 and 30 in derivation cohort, 14 and 7 in validation cohort. The qualitative and quantitative characteristics of CEUS were analyzed according to the surgical pathology. The qualitative characteristics include: the enhancement level based on the myometrium, the contrast enhancement pattern, the enhanced time of the lesion based on the myometrium, post-contrast lesion border, the distribution of the contrast agent, and the wash-out time based on the myometrium. The quantitative characteristics include: arrive time (AT), time to peak (TTP), peak intensity (PI), ΔAT, ΔTTP, ΔPI, |ΔAT|, |ΔTTP|, |ΔPI| and lesion temporal variability. Multiple logistic regression analysis was used to screen the independent risk factors, and a risk prediction model for the differential diagnosis of the two diseases was established. The area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the diagnostic performance of the model. The validation cohort was used to further evaluate the diagnostic performance of the model. Results: Through the multivariate analysis, it concluded that short-term vessels first enhanced enhancement mode, unclear boundary, lesion temporal variability under CEUS >9.5 s, uneven contrast agent distribution could be independent risk factors for the diagnosis of adenomyosis [AUC =0.908, 95% confidence interval (CI): 0.833-0.982]. We also determined the sensitivity (98.33%), specificity (70.00%), positive predictive value (PPV) (86.76%), negative predictive value (NPV) (95.45%), and accuracy (87.78%) of this model. Based on pathological diagnosis, the sensitivity and specificity of the model in the validation cohort were both 85.71%, with NPV of 75% and PPV of 92.3%. The area under the ROC curve was 0.898 (95% CI: 0.742-1.000). Conclusions: The establishment of CEUS model has certain clinical application value in differentiating atypical focal adenomyosis from leiomyomas.