Optimization of the quantitative protocol for organic acid in fecal samples using gas chromatography-mass spectrometry.

Organic acids (OAs) play important roles in a variety of intracellular metabolic pathways, such as the tricarboxylic acid cycle, fatty acid oxidation, glycolysis. The accurate detection of OAs in fecal samples was crucial for comprehending the metabolic changes associated with various metabolic disease. However, the analytical protocol detecting OAs profiling in feces have received scant attention. In this work, an optimized protocol based on chromatography-mass spectrometry for simultaneous quantification of 23 OAs in rat feces was developed. The optimal conditions involved using a 40-mg fecal sample mixed with isopropyl alcohol, acetonitrile, and deionized water (3:2:2 vol ratio) with a total volume of 1500 µL, followed by ultrasonic extraction and a derivatization reaction with an 80 µL derivative agent. The protocol showed an acceptable linearity (R2 ≥ 0.9906), the satisfactory precision (RSD% ≤ 14.87%), the low limits of detection (0.001 to 1 µg/mL) and the limit of quantification (0.005 to 1.5 µg/mL). Moreover, the dried residues of the extracted solution showed the better stability of OAs at -20 °C, which was more suitable for a large-scale sample analysis. Finally, the developed protocol was successfully applied to compare the difference of OAs profiling in fecal samples harvested from normal and nonalcoholic fatty liver disease rats, which was beneficial to find out the metabolic change of OAs profiling and explain the related mechanism of the disease.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Erratum: MicroRNA-30a-3p acts as a tumor suppressor in MHCC-97H hepatocellular carcinoma cells by targeting COX-2: Erratum.

[This corrects the article DOI: 10.7150/jca.52298.].

Mesenchymal stem cells derived from adipose tissue accelerate the progression of colon cancer by inducing a MTCAF phenotype via ICAM1/STAT3/AKT axis.

Previous studies have shown that the risk of colon cancer is greatly increased in people with obesity, and fat content in colorectal cancer tissue is increased in people with obesity. As an important part of tumor microenvironment, adipose-derived mesenchymal stem cells (MSCs) are also another important source of cancer-associated fibroblasts (CAFs), which may be one of the important mechanisms of affecting tumor progression. However, the mechanism is poorly defined. In the present study, CAFs were transformed from MSCs [MSC-transformed CAFs (MTCAFs)] by co-culturing with HCT116 cells. Bioinformatics and Western blotting analysis indicated a positive correlation between intercellular adhesion molecule-1(ICAM-1) and the progression of colon cancer. In clinical colon cancer specimens, we found that ICAM-1 was highly expressed and related to shorter disease-free survival, which might act as an indication for the progression of clinical colon cancer. Our data showed that ICAM-1 secreted from MTCAFs could positively promote the proliferation, migration, and invasion of colon cancer cells by activating signal transducer and activator of transcription 3 (STAT3) and Serine/threonine-protein kinase (AKT) signaling and that blocking ICAM-1 in MTCAFs reversed these effects. We further verified that ICAM-1 secreted from MTCAFs promoted tumor progression in vivo. Taken together, ICAM-1 plays a critical role in regulating tumor growth and metastasis, which could be a potential therapeutic target in colon cancer.

A multi-platform metabolomics reveals possible biomarkers for the early-stage esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancies. This work aimed to identify potential biomarkers for early screening for ESCC and characterize the systemic metabolic disturbances underlying ESCC using multi-platform metabolomics analysis. METHODS: We divided 239 patients (the early-stage ESCC patients, n = 132; Healthy controls, n = 107) into discovery and validation sets after matching age and sex. Integrated statistical and multi-platform serum metabolomics analyses were used to screen and validate significant metabolites linked to ESCC patients. RESULTS: Multi-platform metabolomics analyses showed that amino acid and lipid metabolism were crucial in the etiology of ESCC. Five metabolites, tryptophan (Trp), citrulline, l-carnitine, lysine, and acetyl-carnitine, were selected as potential biomarkers to establish a diagnosis panel, which showed high accuracy in distinguishing ESCC patients from healthy controls (area under the receiver operating characteristic curve, 0.873, 95% confidence interval [CI]: 0.825-0.925). CONCLUSIONS: This work laid the groundwork for understanding the etiology of ESCC. The diagnostic panel showed potential usefulness in early-stage ESCC diagnosis in clinical practice.

Mesenchymal stem cells derived from adipose accelerate the progression of colon cancer by inducing a MT-CAFs phenotype via TRPC3/NF-KB axis.

BACKGROUND: There is increasing evidence that mesenchymal stem cells (MSCs) help shape the tumor microenvironment and promote tumor progression, and ion channels might play a critical role in this process. The objective of the present study was to explore the function and mechanism of MT-CAFs on progression of colon cancer. METHODS: Here, a gene chip was used for a general analysis of gene expression changes in MSC-transformed CAF cells (MT-CAFs). Bioinformatic tool and western blot screened out the ion channel protein TRPC3 with significantly increased expression, and identify the function through two-photon microscope. The progression of cancer was detected via MTS, transwell and Wound Healing. ELISA deected the secretion of inflammation factors. TRPC3/NF-KB axis was identified by western blot and immunofluorescence. RESULTS: TRPC3 can caused calcium influx, which further activated the NF-KB signaling pathway. Knockdown or inhibition of TRPC3 in MSCs significantly reduced the activation of NF-KB, and decreased the growth, migration, and invasion of MT-CAFs. After TRPC3 knockdown, the ability of MT- CAFs to promote tumor migration and invasion was impaired. Conversely, the upregulation of TRPC3 expression in MT-CAFs had the opposite effect. In vivo, TRPC3 expressed on MSCs also contributed to the tumorigenesis and progression of cancer cells. In addition, the Oncomine and GEPIA databases showed that TRPC3 expression is higher in colon cancer tissues compared with normal colon tissues, and was positively correlated with the expression of the CAF genes alpha-smooth muscle (α-SMA/ACTA2) and fibroblast activation protein Alpha. The disease-free survival of patients with positive TRPC3 expression in MSCs was significantly shorter than those with negative expression. CONCLUSIONS: These results indicate that TRPC3 expressed on MT-CAFs plays a critical role in tumor progression via the NF-KB signaling pathway, and is correlated with poor prognosis in colon cancer patients. Therefore, TRPC3 may be a novel therapeutic target for the treatment of colon cancer.

Regorafenib Induces the Apoptosis of Gastrointestinal Cancer-Associated Fibroblasts by Inhibiting AKT Phosphorylation.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and are essential for tumorigenesis and development. Regorafenib is a multikinase inhibitor that targets CAFs and suppresses tumor growth. In this study, we investigated the effects of regorafenib on gastrointestinal CAFs and the underlying molecular mechanisms. First, we established two in vivo tumor models, the cancer cell line HCT116 with and without mesenchymal stem cells (MSCs), and treated them with regorafenib. We found that application of regorafenib potently impaired tumor growth, an effect that was more pronounced in tumors with a high stromal ratio, thus demonstrating that regorafenib can inhibit CAF proliferation and induce CAF apoptosis in vivo. Moreover, we showed that regorafenib affected macrophage infiltration by reducing the proportion of CAFs in tumors. Second, we induced MSCs into CAFs with exosomes to establish an in vitro model. Then, we used 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt and flow cytometry to detect the effects of regorafenib on proliferation and apoptosis of CAFs and western blot to determine the expression level of apoptosis-related proteins. We found that regorafenib inhibited proliferation of CAFs and induced apoptosis in CAFs in vitro. Furthermore, western blot results showed that regorafenib downregulated the expression of B cell lymphoma-2 (Bcl-2) and concurrently upregulated the expression of Bcl-2-associated X (Bax), and regorafenib inhibited the phosphorylation pathway of AKT in CAFs. In conclusion, our results provide a model in which regorafenib induces CAF apoptosis by inhibiting the phosphorylation of AKT and regorafenib affects macrophage infiltration by reducing the proportion of CAFs in tumor tissues.

Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5.

Tumor-infiltrating CD8+T lymphocytes are mostly associated with a favorable prognosis in numerous cancers, including hepatocellular carcinoma (HCC). Biejiajian Pill (BJJP) is a common type of traditional Chinese medicine that is widely used in the treatment of HCC in China. Previous studies showed that BJJP suppressed the growth of HCC cells both in vivo and in vitro, by exerting direct cytotoxic effects on tumor cells. The present study demonstrated that in addition to direct cytotoxicity, BJJP inhibits the growth of tumor cells by promoting the infiltration of CD8+T cells into the tumor in H22-bearing mice. Mechanistically, chemokine ligand 5 (CCL5) was identified as one of the most highly expressed chemokines by tumor cells in vivo after treatment with BJJP. Additionally, CCL5 was knocked down in H22 cells and the results showed that knockdown of the gene significantly impaired the infiltration of CD8+T cells in vivo. Furthermore, the effects of BJJP on human HCC cell lines were assessed in vitro. Similarly, cells treated with BJJP had higher expression of CCL5 mRNA, which was consistent with increased levels of CCL5 protein in human tumor cells. These findings provide new insights into the anticancer effects of BJJP, which regulated the expression of CCL5 and the infiltration of CD8+T cells. The results, therefore, suggest that BJJP has great potential application in clinical practice.

Gastric Cancer Cell-Derived Exosomes Can Regulate the Biological Functions of Mesenchymal Stem Cells by Inducing the Expression of Circular RNA circ_0004303.

As an important component of the dynamic tumor microenvironment, mesenchymal stem cells (MSCs) can interact with tumor cells to promote tumor growth. Treatment with tumor cell-derived exosomes can change the biological functions of MSCs. We want to study the mechanism by which exosomes derived from gastric cancer cells affect the biological functions of MSCs. After MSCs were treated with adenocarcinoma gastric cells (AGS) cell-derived exosomes, circular RNAs differentially expressed in MSCs were verified using existing RNA microarray results combined with quantitative real-time polymerase chain reaction (qRT-PCR). Then, circular RNAs were knocked down or overexpressed by plasmids, and the functions of circular RNAs were evaluated by Migration and invasion assay. Dual luciferase reporter assay was used to evaluate the potential mechanism of circular RNAs. After treatment with exosomes secreted by AGS, the results showed that some circular RNAs expressed by human adipose-derived MSCs showed significant differences. The elevated circ_0004303 promoted the migration and invasion of human adipose-derived MSCs in vitro. Circ_0004303 upregulated the expression of activated leukocyte cell adhesion molecule (ALCAM) by acting as a miR-148a-3p sponge, thereby enhancing the migration and invasion functions of human adipose-derived MSCs. Therefore, exosomes secreted by AGS can affect the expression of circular RNAs in human adipose-derived MSCs. Hsa_circ_0004303 can regulate the migration and invasion of human adipose-derived MSCs via the miR-148a-3P/ALCAM axis. This study suggests that tumor cells can promote the migration and homing of MSCs in adjacent tissues by secreting exosomes.

Gas chromatography/mass spectrometry analysis of organic acid profiles in human serum: A protocol of direct ultrasound-assisted derivatization.

RATIONALE: Low-molecular-weight organic acids that generally contain one to three carboxyl groups are involved in many important biological processes; therefore, it is important to develop a quantitative method for analyzing organic acids in serum in order to allow an evaluation of metabolic changes. In this study, we evaluated a protocol for detecting 26 organic acids in serum based on ultrasound-assisted derivatization by gas chromatography/mass spectrometry (GC/MS). METHODS: Serum samples were prepared using ultrasound-assisted silane derivatization before GC/MS analysis to quantify concentrations of organic acids. Additionally, we investigated the variables affecting derivatization yields, including the extraction solvent, derivatization reagents, and derivatization conditions (reaction temperature, duration, and sonication parameters). The protocol was ultimately applied to detect organic acid profiles related to obesity. RESULTS: We used acetone as the extraction solvent and determined suitable derivatization conditions, as follows: BSTFA + 1% TMCS, 50°C, 10 min, and 100% ultrasound power. The protocol showed satisfactory linearity (r = 0.9958-0.9996), a low limit of detection (0.04-0.42 µmol/L), good reproducibility (coefficient of variation (CV) %: 0.32-13.76%), acceptable accuracy (recovery: 82.97-114.96%), and good stability within 5 days (CV%: 1.35-12.01% at room temperature, 1.24-14.09% at 4°C, and 1.01-11.67% at -20°C). Moreover, the protocol was successfully applied to obtain the organic acid profiles from obese and healthy control subjects. CONCLUSIONS: We identified and validated a protocol for ultrasound-assisted derivatization prior to GC/MS analysis for detecting 26 kinds of organic acids in serum. The results suggest the efficacy of this protocol for clinical applications to determine metabolic changes related to fluctuations in organic acid profiles.

MicroRNA-30a-3p acts as a tumor suppressor in MHCC-97H hepatocellular carcinoma cells by targeting COX-2.

MicroRNAs (miRNAs) are small, noncoding RNAs which can bind to target mRNAs and regulate gene expression. Increasing evidences suggest that miRNAs play an important role in driving hepatocellular carcinoma (HCC) progression by regulating tumor cell proliferation, apoptosis, invasion, and migration. In this study, we demonstrated that the expression of microRNA-30a-3p (miR-30a-3p) was reduced in HCC cell lines in comparison to immortalized liver cell line, LO2. Augmented miR-30a-3p level markedly inhibited MHCC-97H cell growth, migration and invasion in vitro. MiR-30a-3p was also found to inhibit tumor growth in vivo using tumor-bearing mice. Mechanismly, COX-2 was discovered to be a direct and functional target of miR-30a-3p in MHCC-97H cells. Raised miR-30a-3p expression reduced the transcriptional level of COX-2 in MHCC-97H cells, while genetically upregulated COX-2 expression was able to reverse the function of miR-30a-3p-mediated suppression of MHCC-97H cells growth, migration and invasion. In addition, we found that using a COX-2 inhibitor, celecoxib, could enhance the anti-metastatic role of miR-30a-3p in MHCC-97H cells. Lastly, we found that decreased COX-2 protein level affected PGE2 production, leading to lower Bcl-2, Caspase-3, MMP2 and MMP9 expression but higher Bax and E-cadherin expression, which in turn culminated in higher rates of cell death and lower rates of cell migration. Taken together, our findings demonstrate that miR-30a-3p could be a target for the treatment of hepatocellular carcinoma cells progression.

Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3ß/Snail Signaling Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the most usual cancers globally. In China, Biejiajian pill (BJJP), Traditional Chinese Medicine clinical prescription, is broadly utilized for the prevention and therapy of HCC. However, the mechanisms by which BJJP exerts its effects on the prevention of tumor invasion and metastasis are still largely unknown. In this study, in vitro multiple hepatic cancer cell lines and an in vivo xenograft mice model were used to validate the preventive effects and molecular mechanisms of BJJP in HCC. We established that BJJP significantly repressed the proliferation, metastasis and infiltration of HCC cells. Furthermore, BJJP remarkably suppressed HCC cell migration, as well as invasion via epithelial-mesenchymal transition (EMT) by modulating Snail expression, which was associated with the repression of Akt/GSK-3ß/Snail signaling axis activation. In vivo HCC xenograft results indicated that BJJP delayed HCC development and efficiently inhibited lung metastasis. Taken together, BJJP was shown to be an effective therapeutic agent against HCC through repression of the Akt/GSK-3ß/Snail signaling cascade and EMT.

A novel ISM-SAM strategy, based on gas chromatography/mass spectrometry analysis, to compensate for matrix effects in the determination of pyruvic acid.

RATIONALE: The matrix effect is tricky in gas chromatography/mass spectrometry (GC/MS) analyses. Although several methods have been proposed to solve this problem, the results were unsatisfactory. Even fewer studies have assessed the performance of corrective methods. Hence, our study focused on assessing several common corrective methods, and then proposed a new strategy to correct for the matrix effect in GC/MS analyses. METHODS: In GC/MS analyses, the internal standard method (ISM) was employed to overcome the matrix effect during the detection of pyruvic acid (PA) in serum samples from a healthy adult female. The accuracy of the ISM was evaluated by comparing it with the standard addition method (SAM). To employ the ISM-SAM strategy, correction factors (CFs) were established by combining the ISM and the SAM based on different groups. The CFs were used to normalize data onto the results of subsequent analyses. RESULTS: When using the ISM to detect levels of PA, a serious bias is observed, thereby affecting the conclusions reached. In contrast, more reliable data can be obtained after normalizing results by undertaking the ISM-SAM strategy. The feasibility of this strategy was verified by comparing it with the results of the SAM alone. The ISM-SAM strategy was successfully applied to quantify the PA levels in healthy people and nephrotic syndrome patients. CONCLUSIONS: Our results indicated that a false outcome was presented when only the ISM was used to adjust the data, and important information would be missed if the correction strategy was not carried out. Therefore, ISM-SAM, as an available correction method, should be adapted to improve the reliability of research results.

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

INTRODUCTION: Shuanghuanglian (SHL) oral liquid is a well-known traditional Chinese medicine preparation administered for respiratory tract infections in China. However, the underlying pharmacological mechanisms remain unclear. The present study aims to determine the potential pharmacological mechanisms of SHL oral liquid based on network pharmacology. METHODS: Network pharmacology-based strategy including collection and analysis of putative compounds and target genes, network construction, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) enrichment, identification of key compounds and target genes, and molecule docking was performed in this study. RESULTS: A total of 82 bioactive compounds and 226 putative target genes of SHL oral liquid were collected. Of note, 28 hub target genes including 4 major hub target genes: estrogen receptor 1 (ESR1), nuclear receptor coactivator 2 (NCOA2), nuclear receptor coactivator 1 (NCOA1), androgen receptor (AR) and 5 key compounds (quercetin, luteolin, baicalein, kaempferol and wogonin) were identified based on network analysis. The hub target genes mainly enriched in pathways including PI3K-Akt signaling pathway, human cytomegalovirus infection, and human papillomavirus infection, which could be the underlying pharmacological mechanisms of SHL oral liquid for treating diseases. Moreover, the key compounds had great molecule docking binding affinity with the major hub target genes. CONCLUSION: Using network pharmacology analysis, SHL oral liquid was found to contain anti-virus, anti-inflammatory, and "multi-compounds and multi-targets" with therapeutic actions. These findings may provide a valuable direction for further clinical application and research.

Metabolomics studies in gastrointestinal cancer: a systematic review.

Introduction: This systemic review provides an overview of metabolic perturbations and possible mechanisms in gastrointestinal cancer. The authors discuss emerging challenges of technical and clinical applications.Areas covered: In this systemic review, the authors summarized the currently available results of metabolomic biomarkers linked to GI cancer, and discussed the altered metabolism pathways including carbohydrate metabolism, amino acid metabolism, lipids, and nucleotide metabolism and other metabolisms. Furthermore, future efforts need to adhere to normalize analysis procedures, validate with the larger cohort and utilize multiple-omics technologies. The search was conducted in PubMed with the following search terms (biomarker, gastrointestinal cancer, colorectal cancer, and esophageal cancer) from 2013 to 2019.Expert opinion: This systemic review summarized the currently available results of metabolomic biomarkers linked to gastrointestinal cancer, and discussed the altered metabolism pathways. The authors believe that metabolomics will benefit deeper understandings of the pathogenic mechanism, discovery of biomarkers and aid the search for drug targets as we move toward the era of personalized medicine. Personalized medication for tumors can improve the curative effect, avoid side effects and medical resource waste. As a promisingtool, metabolomics that targets the entire cancer-specific metabolite network should be applied more widely in cancer research.

[Molecular mechanisms of anti-inflammatory action of AMPK].

AMP-activated protein kinase (AMPK), an evolutionarily conserved serine/threonine protein kinase, is known as the "cellular energy regulator" and a key molecule to maintain the energy balance of cells and organism. Recent studies have shown that AMPK exerts anti-inflammatory effects mainly through activating SIRT1, PGC-1α, p53, FoxO3a and p300, and down-regulating the activity of various inflammatory related proteins such as NF-κB and AP-1. This article reviews the molecular mechanisms of the anti- inflammatory effects of AMPK, and provides some clues for the development of AMPK-targeted therapeutics to treat inflammation and related diseases.

Carrier Transport Improvement of CH3NH3PbI3 Film by Methylamine Gas Treatment.

Recently, perovskite solar cells with high photovoltaic performance based on methylammonium lead halide have attracted great interest due to the superior physical properties of the perovskite optical absorption layer. Here, we investigate the interface carrier transport properties of CH3NH3PbI3 film by applying the reported treatment with methylamine gas, to reveal the possible mechanism of high performance perovskite-sensitized solar cell results. It is found that the crystal structure and surface morphology are effectively improved by the room-temperature repair of methylamine atmosphere. The preferred 110 orientation results in a slightly larger band gap, which may contribute to the better energy level matching and carrier transport. Further investigations on relaxation time and electron mobility confirm the significantly enhanced carrier diffusion length, revealing the important role of optimized crystallization on charge transport properties, which may be helpful to seek high-powered perovskite solar cells by optimizing the perovskite synthetic process.