Roles of Matrix Metalloproteinases 2 and 9 in Uterine Leiomyosarcoma.

BACKGROUND/AIM: Uterine leiomyosarcoma (uLMS) is a rare, highly malignant, and invasive cancer, with early metastasis. Mismatch repair (MMR) proteins and matrix metalloproteinases (MMPs) are associated with the occurrence, proliferation, and invasion of most malignant cancers; however, their abnormal expression in uLMS remains poorly clarified. PATIENTS AND METHODS: Immunohistochemistry was performed to assess MMR protein and MMP2/9 expression as well as Ki67 marker proliferation in benign and malignant uterine smooth muscle tumors. Data from 28 cases of uterine leiomyoma and 31 cases of uLMS were analyzed. RESULTS: Tumor tissues from patients with uLMS had higher expression levels of MMP2 (p<0.001), MMP9 (p<0.05), and Ki67 (p<0.001) than those from patients with uterine leiomyoma; MMR protein expression showed the opposite trend (p<0.05). uLMS proliferation and metastasis correlated positively with MMP2 (p=0.012 and 0.015, respectively) but negatively with MMP9 (p=0.021 and 0.04, respectively). MMR protein expression did not correlate with uLMS proliferation or metastasis (p>0.05). CONCLUSION: Expression levels of MMP2 and MMP9 were upregulated in malignant uLMS tumors when compared with those in benign uterine leiomyoma tumors. Increased MMP2 expression might promote uLMS invasion and migration. MMP9 overexpression might be related to uLMS occurrence; however, it protects against uLMS invasion and metastasis. MMP2 and MMP9 may be potential predictors of uLMS cell proliferation, metastasis, and prognosis. These findings could be helpful in developing new strategies for diagnosing and treating uLMS.

A multifunctional 'golden cicada' nanoplatform breaks the thermoresistance barrier to launch cascade augmented synergistic effects of photothermal/gene therapy.

BACKGROUND: Photothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional "Golden Cicada" nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG). RESULTS: Down-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT. CONCLUSIONS: In short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects.

Alkane Solvent-Derived Acylation Reaction Driven by Electric Fields.

Electric field acceleration of alkyl hydroperoxide activation to acylate amines in the scanning tunneling microscope-based break-junction is reported. Alkyl hydroperoxide mixtures, generated from hydrocarbon autoxidation in air, were found to be competent reagents for the functionalization of gold surfaces. Intermolecular coupling on the surface in the presence of amines was observed, yielding normal alkylamides. This novel mode of alkyl hydroperoxide activation to generate acylium equivalents was found to be responsive to the magnitude of the bias in the break junction, indicating an electric field influence on this novel reactivity.

Toxic mechanism of the Mongolian medicine "Hunqile-7" based on metabonomics and the metabolism of intestinal flora.

The traditional Mongolian medicine Hunqile-7 (HQL-7), which is mainly used to relieve pain in clinic, has certain toxicity. Therefore, toxicological investigation of HQL-7 is of great significance to its safety assessment. In this study, the toxic mechanism of HQL-7 was explored based on a combination of metabolomics and intestinal flora metabolism. UHPLC-MS was used to analyze the serum, liver and kidney samples of rats after intragastric administration of HQL-7. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16s rRNA V3-V4 region of bacteria. The experimental results confirm that the bagging algorithm improved the classification accuracy. The toxic dose, toxic intensity, and toxic target organ of HQL-7 were determined in toxicity tests. Seventeen biomarkers were identified and the metabolism dysregulation of these biomarkers may be responsible for the toxicity of HQL-7 in vivo. Several kinds of bacteria was demonstrated to be closely related to the physiological indices of renal and liver function, indicating liver and kidney damage induced by HQL-7 may be related to the disturbance of these intestinal bacteria. Overall, the toxic mechanism of HQL-7 was revealed in vivo, which not only provides a scientific basis for the safe and rational clinical use of HQL-7, but also opens up a new field of research on big data for Mongolian medicine.

A cooperative nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic pyroptosis.

Efficient cancer immunotherapy depends on selective targeting of high bioactivity therapeutic agents to the tumours. However, delivering exogenous medication might prove difficult in clinical practice. Here we report a cooperative Nano-CRISPR scaffold (Nano-CD) that utilizes a specific sgRNA, selected from a functional screen for triggering endogenous GDSME expression, while releasing cisplatin to initiate immunologic cell death. Mechanistically, cascade-amplification of the antitumor immune response is prompted by the adjuvantic properties of the lytic intracellular content and enhanced by the heightened GDSME expression, resulting in pyroptosis and the release of tumor associated antigens. Neither of the single components provide efficient tumour control, while tumor growth is efficiently inhibited in primary and recurrent melanomas due to the combinatorial effect of cisplatin and self-supplied GSDME. Moreover, Nano-CD in combination with checkpoint blockade creates durable immune memory and strong systemic anti-tumor immune response, leading to disease relapse prevention, lung metastasis inhibition and increased survival in mouse melanomas. Taken together, our therapeutic approach utilizes CRISPR-technology to enable cell-intrinsic protein expression for immunotherapy, using GDSME as prototypic immune modulator. This nanoplatform thus can be applied to modulate further immunological processes for therapeutic benefit.

Design, Synthesis, and Biological Evaluation of Heterocyclic-Fused Pyrimidine Chemotypes Guided by X-ray Crystal Structure with Potential Antitumor and Anti-multidrug Resistance Efficacy Targeting the Colchicine Binding Site.

Herein, a series of quinazoline and heterocyclic fused pyrimidine analogues were designed and synthesized based on the X-ray co-crystal structure of lead compound 3a, showing efficacious antitumor activities. Two analogues, 15 and 27a, exhibited favorable antiproliferative activities, which were more potent than lead compound 3a by 10-fold in MCF-7 cells. In addition, 15 and 27a exhibited potent antitumor efficacy and tubulin polymerization inhibition in vitro. 15 reduced the average tumor volume by 80.30% (2 mg/kg) in the MCF-7 xenograft model and 75.36% (4 mg/kg) in the A2780/T xenograft model, respectively. Most importantly, supported by structural optimization and Mulliken charge calculation, X-ray co-crystal structures of compounds 15, 27a, and 27b in complex with tubulin were resolved. In summary, our research provided the rational design strategy of colchicine binding site inhibitors (CBSIs) based on X-ray crystallography with antiproliferation, antiangiogenesis, and anti-multidrug resistance properties.

Analyzing the Therapeutic Mechanism of Mongolian Medicine Zhonglun-5 in Rheumatoid Arthritis Using a Bagging Algorithm with Serum Metabonomics.

Rheumatoid arthritis (RA) is a complex autoimmune disorder. Zhonglun-5 (ZL), a traditional Mongolian medicine, exhibits an excellent clinical effect on RA; however, its molecular mechanism remains unclear. In this study, rat serum metabolomic analysis was performed to identify potential biomarkers for RA and investigate its treatment mechanism. A Dionex Ultimate 3000 ultrahigh-performance liquid chromatography system coupled with a Q-Exactive Focus Orbitrap mass spectrometer was used for metabonomics analysis. Bootstrap aggregation (bagging) classification algorithm was applied to process data from control (CG), model (MG), and treatment administration groups. The classification accuracy was 100.00% (6/6) in the decision tree model and 83.33% (5/6) in the K-nearest neighbor (KNN) model, accompanied by 18 training samples and 6 testing samples. Using volcanic map analysis, 24 biomarkers were identified between CG and MG, including those related to glycosphingolipid biosynthesis, arachidonic acid, fatty acids, amino acids, bile acids, vitamins, and sphingolipids. A set diagram of the heatmap and drug-biomarker network of potential biomarkers was constructed. After ZL administration, the levels of these biomarkers returned to normal, indicating that ZL had a therapeutic effect in rats with RA. This study established a solid theoretical foundation to promote further research on the clinical applicability of ZL.

The Application Value of CT Three-Dimensional Microscope Reconstruction Technology in the Diagnosis of Cervical Cancer.

In order to study the application value of CT three-dimensional microscope reconstruction technology in the diagnosis of cervical cancer. In this paper, 232 patients with newly diagnosed stage IA-II A2 and some stage III C: cervical cancer (stage IB1-IIA2 of stage f go in 2009) were selected, and 204 patients with stage IB1-IIA2 of stage 2009 fig 0 were selected. The original data of DICOM were obtained by CT scanning and imported into mics10.01 software to complete lymph node reconstruction. The short diameter value > 10 mm is used as the standard to judge whether the lymph node is metastatic. Referring to the 2018fig 0 staging standard, if it indicates that the lymph node is positive, it is IIICr stage. The gold standard is the diagnosis of III CP according to the surgical and pathological results, and then the diagnostic efficiency of III C stage is evaluated. The experimental results showed that 65 cases were diagnosed as IIIC stage, and 70 cases were diagnosed as IIICp stage. There was consistency between IIICr and IIICp stage, and the kappa value was 0.340. Using CT multiphase enhanced scanning and three-dimensional reconstruction technology to diagnose cervical cancer has high detection rate and high accuracy of staging diagnosis, which is worthy of clinical application.

Flos Carthami Exerts Hepatoprotective Action in a Rat Model of Alcoholic Liver Injury via Modulating the Metabolomics Profile.

This study was intended to identify the shifts in the metabolomics profile of the hepatic tissue damaged by alcohol consumption and verify the potential restorative action of flos carthami (the flowers of Carthamus tinctorius, FC) in the protection of alcohol-induced injury by attenuating the level of identified metabolites. Rats were treated with FC and subsequently subjected to alcohol administration. The serum samples were subjected to liquid chromatography-mass spectrometry (LC-MS)-based metabolomics followed by statistical and bioinformatics analyses. The clustering of the samples showed an obvious separation in the principal component analysis (PCA) plot, and the scores plot of the orthogonal partial least squares-discriminant analysis (OPLS-DA) model allowed the distinction among the three groups. Among the 3211 total metabolites, 1088 features were significantly different between the control and alcohol-treated groups, while 367 metabolites were identified as differential metabolites between the alcohol- and FC-treated rat groups. Time series clustering approach indicated that 910 metabolites in profile 6 were upregulated by alcohol but subsequently reversed by FC treatment; among them, the top 10 metabolites based on the variable importance in projection (VIP) scores were 1-methyladenine, phenylglyoxylic acid, N-acetylvaline, mexiletine, L-fucose, propylthiouracil, dopamine 4-sulfate, isoleucylproline, (R)-salsolinol, and monomethyl phthalate. The Pearson correlation analysis and network construction revealed 96 hub metabolites that were upregulated in the alcohol liver injury model group but were downregulated by FC. This study confirmed the hepatoprotective effects of FC against alcohol-induced liver injury and the related changes in the metabolic profiles, which will contribute to the understanding and the treatment of alcohol-induced acute liver injury.

Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy.

Epidermal growth factor receptor (EGFR) is of great significance in mediating cell signaling transduction and tumor behaviors. Currently, third-generation inhibitors of EGFR, especially osimertinib, are at the clinical frontier for the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC). Regrettably, the rapidly developing drug resistance caused by EGFR mutations and the compensatory mechanism have largely limited their clinical efficacy. Given the synergistic effect between EGFR and other compensatory targets during tumorigenesis and tumor development, EGFR dual-target inhibitors are promising for their reduced risk of drug resistance, higher efficacy, lower dosage, and fewer adverse events than those of single-target inhibitors. Hence, we present the synergistic mechanism underlying the role of EGFR dual-target inhibitors against drug resistance, their structure-activity relationships, and their therapeutic potential. Most importantly, we emphasize the optimal target combinations and design strategies for EGFR dual-target inhibitors and provide some perspectives on new challenges and future directions in this field.

A programmable hierarchical-responsive nanoCRISPR elicits robust activation of endogenous target to treat cancer.

Despite promising progress of cancer gene therapy made, these therapeutics were still limited by the diversity of gene sizes and types. CRISPR/dCas9 mediated activation of tumor endogenous gene has shown great potential to surmount hinders of genetic varieties during the process of cancer gene therapy. However, the blood interference along with complicated tumor extra/intracellular microenvironment substantially compromise the performance of CRISPR/dCas9-based therapeutics in vivo. Methods: In this study, we constructed a programmable hierarchical-responsive nanoCRISPR (PICASSO) that can achieve sequential responses to the multiple physiological barriers in vivo. The core-shell structure endows PICASSO with long blood circulation capacity and tumor target accumulation as well as efficient cellular uptake and lysosomal escape, leading to high-performance of CRISPR/dCas9-mediated gene activation, which favors the antitumor efficacy. Results: Owing to these properties, PICASSO facilitated CRISPR/dCas9 mediated efficient transcriptional activation of various types of endogenous gene, and long non-protein-coding genes (LncRNA) containing targets ranging in size from ~1 kb to ~2000 kb in tumor cells. Intravenous administration of PICASSO to the tumor-bearing mice can achieve effective transcriptional activation of therapeutic endogenous gene, resulting in remarkable CRISPR/dCas9-mediate tumor inhibition with minimal adverse effect. Conclusions: Taken together, these characteristics allow PICASSO to unleash the potential of CRISPR/dCas9-based therapeutics in oncological treatment. The study provides a simple and versatile strategy to break through the restriction of sizes and types against cancer by utilization of tumor endogenous gene.

An Improved Stacked Autoencoder for Metabolomic Data Classification.

Naru3 (NR) is a traditional Mongolian medicine with high clinical efficacy and low incidence of side effects. Metabolomics is an approach that can facilitate the development of traditional drugs. However, metabolomic data have a high throughput, sparse, high-dimensional, and small sample nature, and their classification is challenging. Although deep learning methods have a wide range of applications, deep learning-based metabolomic studies have not been widely performed. We aimed to develop an improved stacked autoencoder (SAE) for metabolomic data classification. We established an NR-treated rheumatoid arthritis (RA) mouse model and classified the obtained metabolomic data using the Hessian-free SAE (HF-SAE) algorithm. During training, the unlabeled data were used for pretraining, and the labeled data were used for fine-tuning based on the HF algorithm for gradient descent optimization. The hybrid algorithm successfully classified the data. The results were compared with those of the support vector machine (SVM), k-nearest neighbor (KNN), and gradient descent SAE (GD-SAE) algorithms. A five-fold cross-validation was used to complete the classification experiment. In each fine-tuning process, the mean square error (MSE) and misclassification rates of the training and test data were recorded. We successfully established an NR animal model and an improved SAE for metabolomic data classification.

Neonatal exposure to chlordecone alters female social behaviors and central estrogen alpha receptor expression in socially monogamous mandarin voles.

Chlordecone (CD) is one of the common persistent organic pollutants in nature and has a profound impact on the environment and on public health. Accumulating evidence has demonstrated that neonatal exposure of CD influences adult physiology and behavior due to its estrogenic properties. Using socially monogamous mandarin voles as an experimental animal model, the present study aimed to evaluate the impact of neonatal exposure to CD on female social behaviors and central estrogen receptor alpha (ERα) expression in adulthood. After receiving a single subcutaneous injection with sesame seed oil (female control group), 17 beta-estradiol (E2 group), or CD group on postnatal Day 1, the social behaviors of adult animals and ERα expression in specific brain regions were assessed. The data indicated that CD or E2-treated female animals displayed increased affiliative behaviors and decreased aggressive behaviors with regard to the unfamiliar females in the social interaction test. In addition, CD or E2-treated female voles exhibited significant preferences to females over males in the sexual preference test. Moreover, CD-treated female animals exhibited higher levels of ERα expression in the bed nucleus of the stria terminalis, the central amygdala, the medial amygdala and the medial preoptic area compared with those of the control voles. The results suggested that neonatal exposure to CD may masculinize female social behaviors, possibly via CD-induced changes in the ERα expression of relevant brain regions.

A meta-analysis on associations of FTO, MTHFR and TCF7L2 polymorphisms with polycystic ovary syndrome.

BACKGROUND: We aimed to better clarify the relationship between FTO/MTHFR/TCF7L2 polymorphisms and PCOS in a larger combined population by performing a meta-analysis. METHODS: Eligible articles were retrieved from Pubmed, Embase, Web of Science and CNKI. Review Manager Version was used to perform statistical analyses. RESULTS: Forty-six studies were included for this meta-analysis. FTO rs9939609 polymorphism was found to be significantly associated with PCOS under dominant, recessive, over-dominant and allele comparisons, MTHFR rs1801131 polymorphism was found to be significantly associated with PCOS under recessive and allele comparisons, and MTHFR rs1801133 polymorphism was also found to be significantly associated with PCOS under dominant, recessive and allele comparisons in general population. In subgroup analyses, we found that positive results were mainly driven by the Asians. CONCLUSIONS: Collectively, this meta-analysis proved that FTO rs9939609, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms may serve as predisposing factors of PCOS, especially for Asians.

Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b2+ and b3+ Fragment Ions.

Infrared multiple photon dissociation action spectroscopy was performed on the AlaOrn b2+ and AlaAlaOrn b3+ fragment ions from ornithine-containing tetrapeptides. Infrared spectra were obtained in the fingerprint region (1000-2000 cm-1) using the infrared free electron lasers at the Centre Laser Infrarouge d'Orsay (CLIO) facility in Orsay, France, and the free electron lasers for infrared experiments (FELIX) facility in Nijmegen, the Netherlands. A novel terminal ornithine lactam AO+ b2+ structure was synthesized for experimental comparison and spectroscopy confirms that the b2+ fragment ion from AOAA forms a lactam structure. Comparison of experimental spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory shows that AO+ b2+ forms a terminal lactam protonated either on the lactam carbonyl oxygen or the N-terminal nitrogen atom. Several low-lying conformers of these isomers are likely populated following IRMPD dissociation. Similarly, a comparison of the experimental IRMPD spectrum with calculated spectra shows that AAO+ b3+-ions also adopt a lactam structure, again with multiple different protonation sites, during fragmentation. This study provides spectroscopic confirmation for the lactam cyclization proposed for the "ornithine effect" and represents an alternative bn+ structure to the oxazolone and diketopiperazine/macrocycle structures most often formed.

Diagnosis of Breast Hyperplasia and Evaluation of RuXian-I Based on Metabolomics Deep Belief Networks.

Breast cancer is estimated to be the leading cancer type among new cases in American women. Core biopsy data have shown a close association between breast hyperplasia and breast cancer. The early diagnosis and treatment of breast hyperplasia are extremely important to prevent breast cancer. The Mongolian medicine RuXian-I is a traditional drug that has achieved a high level of efficacy and a low incidence of side effects in its clinical use. However, for detecting the efficacy of RuXian-I, a rapid and accurate evaluation method based on metabolomic data is still lacking. Therefore, we proposed a framework, named the metabolomics deep belief network (MDBN), to analyze breast hyperplasia metabolomic data. We obtained 168 samples of metabolomic data from an animal model experiment of RuXian-I, which were averaged from control groups, treatment groups, and model groups. In the process of training, unlabelled data were used to pretrain the Deep Belief Networks models, and then labelled data were used to complete fine-tuning based on a limited-memory Broyden Fletcher Goldfarb Shanno (L-BFGS) algorithm. To prevent overfitting, a dropout method was added to the pretraining and fine-tuning procedures. The experimental results showed that the proposed model is superior to other classical classification methods that are based on positive and negative spectra data. Further, the proposed model can be used as an extension of the classification method for metabolomic data. For the high accuracy of classification of the three groups, the model indicates obvious differences and boundaries between the three groups. It can be inferred that the animal model of RuXian-I is well established, which can lay a foundation for subsequent related experiments. This also shows that metabolomic data can be used as a means to verify the effectiveness of RuXian-I in the treatment of breast hyperplasia.

Microwave extraction optimization using the response surface methodology of Fructus Meliae Toosendan polysaccharides and its antioxidant activity.

Polysaccharides are the main active component of the Mongolian medicine Fructus Meliae Toosendan, but their effective extraction and antioxidant effects have not been reported. Therefore, the optimization of the microwave extraction of polysaccharides from Fructus Meliae Toosendan (FMTP) using the response interface method was carried out. Single-factor tests on four main factors (the solid-liquid ratio, microwave power, extraction time, and number of extractions) affecting the polysaccharide extraction rate in the microwave extraction process were carried out. Then, using the FMTP content as a response index, central composite tests on the four factors were conducted, and an optimization analysis using the response surface method was completed. Consequently, we obtained the optimum conditions for FMTP microwave extraction: a solvent-material ratio of 30.00 mL/mg, extraction power of 700 W, extraction time of 20 min, and two extractions. The FMTP extraction rate was 15.75% at the optimum conditions, consistent with the theoretical predictions. The crude polysaccharide was further purified to obtain high-purity FMTP polysaccharide, having a weight-average molecular mass of 1288 Da. The antioxidant activities of FMTP were evaluated using the hydroxyl superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and nitrite free radical scavenging assays and reducing power assay. The data show that FMTP has considerable antioxidant activity. Thus, polysaccharides from Fructus Meliae Toosendan could be used as a potential antioxidant agent in medicine or as a functional food.

K Nearest Neighbor Algorithm Coupled with Metabonomics to Study the Therapeutic Mechanism of Sendeng-4 in Adjuvant-Induced Rheumatoid Arthritis Rat.

As a traditional Mongolian medicine, Sendeng-4 (SD) has been widely used to treat rheumatoid arthritis (RA) in Inner Mongolia and exhibits a good curative effect. Unfortunately, due to geographical factors, it is difficult to popularize this drug throughout the whole country, and the mechanism of action of SD has been unclear. In this study, a serum metabolite profile analysis was performed to identify potential biomarkers associated with adjuvant-induced RA and investigate the mechanism of action of SD. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed for the metabonomics analysis. K nearest neighbor (KNN) models were established in both positive and negative spectra for classifying data from the control, model, and SD administration groups. Accuracy rate for classification was 95.8% in positive ion mode and 91.7% in negative ion mode. Orthogonal partial least squares discriminant analysis (OPLS-DA) enabled the identification of 12 metabolites as potential biomarkers of adjuvant-induced RA. After treatment with SD, the levels of uridine triphosphate, calcitroic acid, dynorphin B (6-9), and docosahexaenoic acid were restored to normal, indicating that SD likely ameliorated RA by regulating the levels of these biomarkers. This study identified early biomarkers of RA and elucidated the underlying mechanism of action of SD, which is worth further investigation for development as a clinical therapy.

Further Investigation of the Intermolecular Diels-Alder Cycloaddition for the Synthesis of Bicyclo[2.2.2]diazaoctane Alkaloids.

The convergent synthesis of bicyclo[2.2.2]diazaoctane structures using an intermolecular Diels-Alder cycloaddition between a pyrazinone and commercially available fumarate or maleate precursors is reported. High reactivity and stereoselection is observed with both dienophile substrates. Structure validation was achieved by conversion of cycloadducts into known [2.2.2]diazabicyclic compounds or into crystalline derivatives suitable for X-ray analysis. The cycloadduct derived from reaction of pyrazinone and maleic anhydride underwent selective anhydride ring opening and intersected an established precursor in the synthesis of brevianamide B.

Study the therapeutic mechanism of Amomum compactum in gentamicin-induced acute kidney injury rat based on a back propagation neural network algorithm.

Acute kidney injury (AKI) is a major global public health problems, as it causes high morbidity and serious injury to renal function. However, the etiology for AKI is not very clear. In this study, a serum metabolite profile analysis was performed to identify potential biomarkers for gentamicin-induced AKI and to investigate the mechanism of action of Amomum compactum (AC) used for treatment. A metabonomics approach by ultra-performance liquid chromatography together with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to perform the analysis. Back propagation (BP) neural network models were established for classifying data from the control, model, and AC-treated groups. Accuracy rate for classification was 91.7% in positive ion mode and 87.5% in negative ion mode. By orthogonal partial least squares discriminant analysis (OPLS-DA), 29 metabolites were identified as potential biomarkers of gentamicin-induced AKI. Most of them are related to phospholipid metabolism. After treatment with AC, the levels of sphingomyelin, sphingosine, phytosphingosine, and arachidonic acid were restored to normal. The results indicate that AC plays a protective role in rats with gentamicin-induced AKI via regulation of the phospholipid metabolic pathway. In this work, early biomarkers of AKI has been identified and underlying therapeutic mechanism of AC has been understood, therefore, AC can be further investigated and tested for clinical application.