Chronic Pancreatitis-Associated Metabolic Bone Diseases: Epidemiology, Mechanisms, and Clinical Advances.

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attentions in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs.At molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required for understanding the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.

Based on HPLC and HS-GC-IMS Techniques, the Changes in the Internal Chemical Components of Schisandra chinensis (Turcz.) Baill. Fruit at Different Harvesting Periods Were Analyzed.

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the primary pharmacologically active compound. The volatile chemical components of Schisandra chinensis include a large amount of terpenes, which have been proven to have broad pharmacological activities. However, when to harvest to ensure the highest accumulation of pharmacologically active components in Schisandra chinensis fruits is a critical issue. The Schisandra chinensis fruit trees in the resource nursery were all planted in 2019 and began bearing fruit in 2021. Their nutritional status and tree vigor remain consistently good. The content of lignans and organic acids in the fruits of Schisandra chinensis over seven different harvest periods was tested, and the results of high-performance liquid chromatography (HPLC) indicated that the lignan content was higher, at 35 mg/g, in late July, and the organic acid content was higher, at 72.34 mg/g, in early September. If lignans and organic acids are to be selected as raw materials for pharmacological development, the harvest can be carried out at this stage. Using HS-GC-IMS technology, a total of 67 volatile flavor substances were detected, and the fingerprint of the volatile flavor substances in the different picking periods was established. It was shown by the results that the content of volatile flavor substances was the highest in early August, and 16 flavor substances were selected by odor activity value (OAV). The variable importance in projection (VIP) values of 16 substances were further screened, and terpinolene was identified as the key volatile flavor substance that caused the aroma characteristics of Schisandra chinensis fruit at different harvesting periods. If the aroma component content of Schisandra chinensis fruit is planned to be used as raw material for development and utilization, then early August, when the aroma component content is higher, should be chosen as the time for harvest. This study provides a theoretical basis for the suitable harvesting time of Schisandra chinensis for different uses, and promotes the high-quality development of the Schisandra chinensis industry.

Flavor Quality Analysis of Ten Actinidia arguta Fruits Based on High-Performance Liquid Chromatography and Headspace Gas Chromatography-Ion Mobility Spectrometry.

Actinidia arguta is a fruit crop with high nutritional and economic value. However, its flavor quality depends on various factors, such as variety, environment, and post-harvest handling. We analyzed the composition of total soluble sugars, titratable acids, organic acids, and flavor substances in the fruits of ten A. arguta varieties. The total soluble sugar content ranged from 4.22 g/L to 12.99 g/L, the titratable acid content ranged from 52.55 g/L to 89.9 g/L, and the sugar-acid ratio ranged from 5.39 to 14.17 at the soft ripe stage. High-performance liquid chromatography (HPLC) showed that citric, quinic, and malic acids were the main organic acids in the A. arguta fruits. Headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) detected 81 volatile compounds in 10 A. arguta varieties, including 24 esters, 17 alcohols, 23 aldehydes, 7 ketones, 5 terpenes, 2 acids, 1 Pyrazine, 1 furan, and 1 benzene. Esters and aldehydes had the highest relative content of total volatile compounds. An orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor activity value (OAV) revealed that myrcene, benzaldehyde, methyl isobutyrate, α-phellandrene, 3-methyl butanal, valeraldehyde, ethyl butyrate, acetoin, (E)-2-octenal, hexyl propanoate, terpinolene, 1-penten-3-one, and methyl butyrate were the main contributors to the differences in the aroma profiles of the fruits of different A. arguta varieties. Ten A. arguta varieties have different flavors. This study can clarify the differences between varieties and provide a reference for the evaluation of A. arguta fruit flavor, variety improvement and new variety selection.

Characterization of Key Compounds of Organic Acids and Aroma Volatiles in Fruits of Different Actinidia argute Resources Based on High-Performance Liquid Chromatography (HPLC) and Headspace Gas Chromatography-Ion Mobility Spectrometry (HS-GC-IMS).

Actinidia arguta, known for its distinctive flavor and high nutritional value, has seen an increase in cultivation and variety identification. However, the characterization of its volatile aroma compounds remains limited. This study aimed to understand the flavor quality and key volatile aroma compounds of different A. arguta fruits. We examined 35 A. arguta resource fruits for soluble sugars, titratable acids, and sugar-acid ratios. Their organic acids and volatile aroma compounds were analyzed using high-performance liquid chromatography (HPLC) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). The study found that among the 35 samples tested, S12 had a higher sugar-acid ratio due to its higher sugar content despite having a high titratable acid content, making its fruit flavor superior to other sources. The A. arguta resource fruits can be classified into two types: those dominated by citric acid and those dominated by quinic acid. The analysis identified a total of 76 volatile aroma substances in 35 A. arguta resource fruits. These included 18 esters, 14 alcohols, 16 ketones, 12 aldehydes, seven terpenes, three pyrazines, two furans, two acids, and two other compounds. Aldehydes had the highest relative content of total volatile compounds. Using the orthogonal partial least squares discriminant method (OPLS-DA) analysis, with the 76 volatile aroma substances as dependent variables and different soft date kiwifruit resources as independent variables, 33 volatile aroma substances with variable importance in projection (VIP) greater than 1 were identified as the main aroma substances of A. arguta resource fruits. The volatile aroma compounds with VIP values greater than 1 were analyzed for odor activity value (OAV). The OAV values of isoamyl acetate, 3-methyl-1-butanol, 1-hexanol, and butanal were significantly higher than those of the other compounds. This suggests that these four volatile compounds contribute more to the overall aroma of A. arguta. This study is significant for understanding the differences between the fruit aromas of different A. arguta resources and for scientifically recognizing the characteristic compounds of the fruit aromas of different A. arguta resources.

Comprehensive Evaluation of Ten Actinidia arguta Wines Based on Color, Organic Acids, Volatile Compounds, and Quantitative Descriptive Analysis.

Actinidia arguta wine is a low-alcoholic beverage brewed from A. arguta with a unique flavor and sweet taste. In this study, the basic physicochemical indicators, color, organic acid, and volatile aroma components of wines made from the A. arguta varieties 'Kuilv', 'Fenglv', 'Jialv', 'Wanlv', 'Xinlv', 'Pinglv', 'Lvbao', 'Cuiyu', 'Tianxinbao', and 'Longcheng No.2' were determined, and a sensory evaluation was performed. The findings show that 'Tianxinbao' produced the driest extract (49.59 g/L), 'Kuilv' produced the most Vitamin C (913.46 mg/L) and total phenols (816.10 mg/L), 'Jialv' produced the most total flavonoids (477.12 mg/L), and 'Cuiyu' produced the most tannins (4.63 g/L). We analyzed the color of the A. arguta wines based on CIEL*a*b* parameters and found that the 'Kuilv' and 'Longcheng No.2' wines had the largest L* value (31.65), the 'Pinglv' wines had the greatest a* value (2.88), and the 'Kuilv' wines had the largest b* value (5.08) and C*ab value (5.66) of the ten samples. A total of eight organic acids were tested in ten samples via high-performance liquid chromatography (HPLC), and we found that there were marked differences in the organic acid contents in different samples (p < 0.05). The main organic acids were citric acid, quinic acid, and malic acid. The aroma description of a wine is one of the keys to its quality. A total of 51 volatile compounds were identified and characterized in ten samples with headspace gas chromatography-ion mobility spectrometry, including 24 esters, 12 alcohols, 9 aldehydes, 3 aldehydes, 2 terpenes, and 1 acid, with the highest total volatile compound content in 'Fenglv'. There were no significant differences in the types of volatile compounds, but there were significant differences in the contents (p < 0.05). An orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor activity value (OAV) showed that ethyl butanoate, ethyl pentanoate, ethyl crotonate, ethyl isobutyrate, butyl butanoate, 2-methylbutanal, ethyl isovalerate, and ethyl hexanoate were the main odorant markers responsible for flavor differences between all the A. arguta wines. Sensory evaluation is the most subjective and effective way for consumers to judge A. arguta wine quality. A quantitative descriptive analysis (QDA) of the aroma profiles of ten grapes revealed that the 'fruity' and 'floral' descriptors are the main and most essential parts of the overall flavor of A. arguta wines. 'Tianxinbao' had the highest total aroma score. The flavor and quality of A. arguta wines greatly depend on the type and quality of the A. arguta raw material. Therefore, high-quality raw materials can improve the quality of A. arguta wines. The results of the study provide a theoretical basis for improving the quality of A. arguta wines and demonstrate the application prospects of HS-GC-IMS in detecting A. arguta wine flavors.

Development of o-aminobenzamide salt derivatives for improving water solubility and anti-undifferentiated gastric cancer.

Background: Gastric cancer is one of the cancers with wide incidence, difficult treatment and high mortality in the world, especially in Asia and Africa. In our previous work, a novel o-aminobenzamide analogue F8 was identified as an early preclinical candidate for treatment of undifferentiated gastric cancer (IC50 of 0.26 µM for HGC-27). However, the poor water solubility of compound F8 prevents its further progress in preclinical studies. Aim: To improve the water solubility and drug-likeness of F8 via salt formation. Method: Different acids and F8 were reacted to obtain different salt forms. Physicochemical property screening, pharmacokinetic property research, and antitumor biological activity evaluation in vitro and in vivo were used to obtain the optimal salt form with the best druggability. Results: our continuous efforts have finally confirmed F8·2HCl as the optimal salt form with maintained in vitro antitumor activity, improved water solubility and pharmacokinetic properties. Importantly, the F8·2HCl displayed superior in vivo antitumor efficacy (TGI of 70.1% in 75 mg/kg) in HGC-27 xenograft model. The further immunohistochemical analysis revealed that F8·2HCl exerts an antitumor effect through the regulation of cell cycle-related protein (CDK2 and p21), apoptosis-related protein Cleaved Caspase-3, proliferation marker Ki67, and cell adhesion molecule E-cadherin. In addition, F8·2HCl showed acceptable safety in the in vivo acute toxicity assay. Conclusion: Salting is an effective means to improve the drug-like properties of compound F8, and F8·2HCl can serve as a promising therapeutic agent against undifferentiated gastric cancer.

Effect of powdered vancomycin on stopping surgical site wound infections in neurosurgery: A meta-analysis.

We performed a meta-analysis to evaluate the effect of powdered vancomycin on stopping surgical site wound infections in neurosurgery. A systematic literature search up to July 2022 was performed and 24 137 subjects with neurosurgery at the baseline of the studies; 10 496 of them were using the powdered vancomycin, and 13 641 were not using the powdered vancomycin as a control. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of powdered vancomycin on stopping surgical site wound infections in neurosurgery using dichotomous methods with a random or fixed-effect model. The powdered vancomycin had significantly lower surgical site wound infections after spinal surgery (OR, 0.53; 95% CI, 0.41-0.70, P < .001), deep surgical site wound infections after spinal surgery (OR, 0.45; 95% CI, 0.35-0.57, P < .001), superficial surgical site wound infections after spinal surgery (OR, 0.60; 95% CI, 0.43-0.83, P = .002), and surgical site wound infections after cranial surgery (OR, 0.37; 95% CI, 0.22-0.61, P < .001) compared to control in subjects with neurosurgery. The powdered vancomycin had significantly lower surgical site wound infections after spinal surgery, deep surgical site wound infections after spinal surgery, superficial surgical site wound infections after spinal surgery, and surgical site wound infections after cranial surgery compared to control in subjects with neurosurgery. The analysis of outcomes should be done with caution even though the low number of studies with low sample size, 3 out of the 42 studies, in the meta-analysis, and a low number of studies in certain comparisons.

Circulating Glycan Monosaccharide Composite-Based Biomarker Diagnoses Colorectal Cancer at Early Stages and Predicts Prognosis.

Introduction: Early diagnosis could lead to a cure of colorectal cancer (CRC). Since CRC is related to aging and lifestyles, we tested if the environmental information-enriched monosaccharide composite (MC) of circulating glycans could serve as an early diagnostic biomarker for CRC. Meanwhile, we evaluated its role in predicting prognosis. Methods: HPAEC-PAD was used to quantify glycan monosaccharide compositions from a total of 467 serum samples including CRC patients, colorectal adenoma (CRA) patients and healthy individuals. Two diagnostic model was constructed by logistic regression analysis. The diagnostic performance of the two models was verified in the retrospective validation group and the prospective validation group. The prognostic performance of the model was assessed by survival analysis. Results: The concentrations of monosaccharides in serum were significantly higher in CRA and CRC patients than in healthy individuals. Two diagnostic models were constructed: MC1 was used to distinguish between healthy individuals and CRC; MC2 was used to distinguish between healthy individuals and CRA. Area under receptor operating characteristic curve (AUC) of MC2 and MC1 was 0.8025 and 0.9403 respectively. However, the AUC of CEA between healthy individuals and CRC was 0.7384. Moreover, in early stage of CRC (without lymph node metastasis), the positive rates of CEA and MC1 were 28% and 80%, respectively. The follow-up data showed that the increased MC1 value was associated with poor survival in patients with CRC (p=0.0010, HR=5.30). Discussion: The MC1 model is superior to CEA in the diagnosis of CRC, especially in the early diagnosis. MC1 can be used for predicting prognosis of CRC patients, and elevated MC1 values indicate poor survival.

Study on the mechanism of Cortex Lycii on lung cancer based on network pharmacology combined with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Xie Bai San is a Chinese medicine prescription that has been used to treat lung cancer in China for a long time. It has been proven to alleviate the symptoms and extend the survival time of lung cancer patients. Xie Bai San comprises Cortex Lycii, Cortex Mori, and Radix Glycyrrhizae Preparata. The effects and mechanisms of Cortex Mori and Glycyrrhizae on lung cancer have been reported, whereas the underlying mechanism of Cortex Lycii remains unknown. MATERIAL AND METHODS: Network pharmacology was used to explore the unknown mechanisms underlying the effect of Cortex Lycii on lung cancer. Molecular docking was used to predict the binding of a compound to the protein. The fingerprint of Cortex Lycii was obtained by HPLC. Cell counting Kit-8 assay was used to determine the appropriate concentration of Cortex Lycii extract for human lung adenocarcinoma cells, A549 and H1299. Wound healing assay and Matrigel invasion assay were used to detect the influence of Cortex Lycii extract on the migration and invasion ability of A549 and H1299. The protein expression level was detected by western blot and immunohistochemical staining. RESULTS: Using network pharmacology, 38 components of Cortex Lycii and 79 possible lung cancer-related target genes of Cortex Lycii were obtained. The targets were assigned to 35 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and the PI3K-AKT signaling pathway contained the most targets and had the second-lowest P-value. The molecular docking showed the components of Cortex Lycii bound to HSP90AB1. Among them, 6 components bound to HSP90AB1 in which HSP90AB1 binds to and phosphorylates AKT. The functional experiments showed that Cortex Lycii suppressed the migration and invasion of human lung cancer cells in a dose-dependent manner. Cortex Lycii up-regulated E-Cadherin and down-regulated N-Cadherin, Vimentin, and MMP2. Furthermore, Cortex Lycii made no change in the total AKT and mTOR protein levels, but caused the down-regulation of p-AKT and p-mTOR in human lung cancer cells, which was reversed by Terazosin, an agonist of HSP90. Moreover, acacetin and apigenin, two components of Cortex Lycii, reduced the protein level of p-AKT and p-mTOR, and the reduction was also inhibited by Terazosin. CONCLUSION: Cortex Lycii suppressed epithelial-mesenchymal transition (EMT) in lung cancer cells through the PI3K-AKT-mTOR signaling pathway, possibly by targeting HSP90AB1 and inhibiting HSP90AB1-AKT binding.

CSE1L silencing impairs tumor progression via MET/STAT3/PD-L1 signaling in lung cancer.

CSE1L is involved in the cancer progression of several types of cancer. Its expression status, potential oncogenic role and underlying mechanism in lung cancer, however, are unclear. Here, we investigated CSE1L expression in primary lung adenocarcinoma based on multiple datasets and then investigated its oncologic role in lung cancer. We also examined the potential molecular mechanisms of CSE1L in cancer progression. CSE1L levels were increased in cancer as compared to normal lung tissues. CSE1L expression was higher in poorly-differentiated late stage and lymph node positive metastatic tumors. Higher CSE1L level was correlated with worse patient outcome. Knockdown of CSE1L using siRNAs impaired cell proliferation, invasion, migration and induced cell apoptosis. Mechanistically, MET, STAT3 and PD-L1 proteins were decreased upon CSE1L silencing. These results suggest that CSE1L may affect tumor progression through MET/STAT3/PD-L1 signaling. CSE1L may have potential as a biomarker and therapeutic target for lung cancer.

Long non-coding RNA MIR22HG inhibits glioma progression by downregulating microRNA-9/CPEB3.

Glioma is one of the most common and aggressive malignant intracranial tumors worldwide. Recently, non-coding RNAs have been found to play critical roles in the development of glioma. However, the exact mechanisms have not been fully elucidated. In the present study, reverse transcription-quantitative PCR was used to determine the expression level of the long non-coding RNA MIR22HG and microRNA (miR)-9, while western blot analysis was used to detect the protein expression level of CPEB3. The potential binding sites were predicted using the StarBase v2.0 online tool and the hypothesis was verified using a luciferase reporter assay. A Cell Counting Kit-8 assay was used to assess cell viability, while wound healing and Matrigel assays were used to determine the migration and invasion ability of glioma cancer cells. The results showed that MIR22HG expression level was decreased but miR-9 expression level was elevated in glioma tissues and cell lines. Furthermore, MIR22HG was found to sponge miR-9, while CPEB3 was the direct target of miR-9 in the glioma cell line. Functionally, MIR22HG regulated the proliferation, invasion and migration of the glioma cell line by targeting miR-9. CPEB3 may be involved in the progression of the glioma cell line. Taken together, these findings confirmed that MIR22HG suppressed glioma development by inhibiting the miR-9/CPEB3 axis and provides a novel therapeutic strategy for glioma treatment.

Effect of an outpatient copayment scheme on health outcomes of hypertensive adults in a community-managed population in Xinjiang, China.

Hypertension remains the leading risk factor for death and disability in China, and the ability of hypertensive patients to pay for outpatient care and medication has become a critical issue. To report the effect of an outpatient copayment scheme on health outcomes of hypertensive adults in a community-managed population in Xinjiang, we compared changes in outcomes between insured and uninsured groups from baseline to the first follow-up appointment in a community-managed hypertensive population and evaluated these changes based on propensity score matching and the difference-in-difference method. A total of 1,095 individuals in a community-managed hypertension population were selected for investigation at baseline, among which 805 (73.5%) had follow-up data and 749 (68.4%) were included in our analysis. After accounting for the self-reported severity of hypertension and individual characteristics, there were statistically significant improvements in drug treatment of hypertension and self-reported health. We also found increases in drug treatment for hypertension between groups, after correcting for confounding variables (Odds Ratio, OR 8.05, 95% Confidence interval, CI, 1.31-49.35), and in self-reported health between groups after correcting confounders (OR 1.96, 95% CI, 1.12 to 3.42). Adjusted estimates (confounding variables) were corrected for age, sex, income, marital status, education level, employment, family size, self-reported severity of hypertension, course of hypertension, and number of medications. As a result, decreased outpatient copayment was associated with an increase in antihypertensive treatment coverage, and an improvement in self-reported health among community-managed hypertensive populations in Xinjiang, China.

Network Pharmacology and Experimental Evidence Reveal Dioscin Suppresses Proliferation, Invasion, and EMT via AKT/GSK3b/mTOR Signaling in Lung Adenocarcinoma.

PURPOSE: Dioscin, a natural glycoside derived from many plants, has been proved to exert anti-cancer activity. Several studies have found that it reverses TGF-ß1-induced epithelial-mesenchymal transition (EMT). Whether dioscin can reverse EMT by pathways other than TGF-ß is still unknown. METHODS: We used network-based pharmacological methods to systematically explore the potential mechanisms by which dioscin acts on lung cancer. Cell Counting Kit-8 assay, scratch healing, Transwell assay, Matrigel invasion assay, immunofluorescence assay, and Western blotting were employed to confirm the prediction of key targets and the effects of dioscin on EMT. RESULTS: Here, using network-based pharmacological methods, we found 42 possible lung cancer-related targets of dioscin, which were assigned to 98 KEGG pathways. Among the 20 with the lowest p-values, the PI3K-AKT signaling pathway is involved and significantly related to EMT. AKT1 and mTOR, with high degrees (reflecting higher connectivity) in the compound-target analysis, participate in the PI3K-AKT signaling pathway. Molecular docking indicated the occurrence of dioscin-AKT1 and dioscin-mTOR binding. Functional experiments demonstrated that dioscin suppressed the proliferation, migration, invasion, and EMT of human lung adenocarcinoma cells in a dose-dependent manner, without TGF-ß stimulation. Furthermore, we determined that dioscin downregulated p-AKT, p-mTOR and p-GSK3ß in human lung adenocarcinoma cells without affecting their total protein levels. The PI3K inhibitor LY294002 augmented these changes. CONCLUSION: Dioscin suppressed proliferation, invasion and EMT of lung adenocarcinoma cells via the inactivation of AKT/mTOR/GSK3ß signaling, probably by binding to AKT and mTOR, and inhibiting their phosphorylation.

A single injection of bleomycin reduces glycosaminoglycan sulfation up to 30 days in the C57BL/6 mouse model of lung fibrosis.

Bleomycin is a clinically used anticancer drug, but it induces lung fibrosis in certain cancer patients with unknown mechanism. Glycosaminoglycans (GAGs) are required for lung morphogenesis during animal development. In current study, GAG disaccharides including heparan sulfate (HS) and chondroitin sulfate (CS) from bleomycin-induced and control lung tissues in lung fibrosis mouse model were tagged with 1-phenyl-3-methyl-5-pyrazolone (PMP) and deuterated PMP, respectively. The differentially isotope-tagged disaccharides were quantitatively compared by LC-MS. At day 10, the amount of CS disaccharides (U0a0, U0a6, and U0a4) and non-sulfated HS disaccharide (U0A0) were increased by 1.3-, 1.6-, 11.7-, and 2.2-fold, respectively, whereas the amount of CS disaccharide (U0a2), hyaluranan disaccharide (UßA0), and six HS disaccharides (U0A6, U2A0, U0H6, U0S0, U2S0, and U2S6) were decreased from1.1- to 14.3-fold compared to that of the controls. At day 15, under-sulfation of both HS and CS disaccharides was persisted. At day 30, the CS disaccharide compositions were recovered to that of the control levels whereas the HS were still remarkably under-sulfated. In conclusion, GAGs, especially HS, from fibrotic lungs induced by a single injection of bleomycin were significantly under-sulfated up to 30 days, suggesting GAGs might be another class of defective signaling molecules involved in bleomycin-induced lung fibrosis.

Pingyangmycin inhibits glycosaminoglycan sulphation in both cancer cells and tumour tissues.

Pingyangmycin is a clinically used anticancer drug and induces lung fibrosis in certain cancer patients. We previously reported that the negatively charged cell surface glycosaminoglycans are involved in the cellular uptake of the positively charged pingyangmycin. However, it is unknown if pingyangmycin affects glycosaminoglycan structures. Seven cell lines and a Lewis lung carcinoma-injected C57BL/6 mouse model were used to understand the cytotoxicity of pingyangmycin and its effect on glycosaminoglycan biosynthesis. Stable isotope labelling coupled with LC/MS method was used to quantify glycosaminoglycan disaccharide compositions from pingyangmycin-treated and untreated cell and tumour samples. Pingyangmycin reduced both chondroitin sulphate and heparan sulphate sulphation in cancer cells and in tumours. The effect was persistent at different pingyangmycin concentrations and at different exposure times. Moreover, the cytotoxicity of pingyangmycin was decreased in the presence of soluble glycosaminoglycans, in the glycosaminoglycan-deficient cell line CHO745, and in the presence of chlorate. A flow cytometry-based cell surface FGF/FGFR/glycosaminoglycan binding assay also showed that pingyangmycin changed cell surface glycosaminoglycan structures. Changes in the structures of glycosaminoglycans may be related to fibrosis induced by pingyangmycin in certain cancer patients.

Molecular elucidating of an unusual growth mechanism for polycyclic aromatic hydrocarbons in confined space.

Extension and clustering of polycyclic aromatic hydrocarbons (PAHs) are key mechanistic steps for coking and deactivation in catalysis reactions. However, no unambiguous mechanistic picture exists on molecule-resolved PAHs speciation and evolution, due to the immense experimental challenges in deciphering the complex PAHs structures. Herein, we report an effective strategy through integrating a high resolution MALDI FT-ICR mass spectrometry with isotope labeling technique. With this strategy, a complete route for aromatic hydrocarbon evolution is unveiled for SAPO-34-catalyzed, industrially relevant methanol-to-olefins (MTO) as a model reaction. Notable is the elucidation of an unusual, previously unrecognized mechanistic step: cage-passing growth forming cross-linked multi-core PAHs with graphene-like structure. This mechanistic concept proves general on other cage-based molecule sieves. This preliminary work would provide a versatile means to decipher the key mechanistic step of molecular mass growth for PAHs involved in catalysis and combustion chemistry.

Prognostic significance of CXCR4 expression in acute myeloid leukemia.

BACKGROUND: CXCR4 chemokine receptors play an important role in leukemia proliferation, extramedullary migration, infiltration, adhesion, and resistance to chemotherapy drugs. METHODS: The CXCR4 expression by flow cytometry in 122 acute myeloid leukemia (AML) patients between 2010 and 2014 was analyzed. RESULTS: The expression of CXCR4 in AML-M4/M5 was found to be significantly higher than that of other subtypes according to both FAB subtype and WHO classification. The FLT3-ITD mutant was significantly higher in high CXCR4 expression group (P = .0086). Our data also showed that CXCR4 expression was correlated with CD64 expression. Low CXCR4 expression on AML cells was associated with better prognosis, and the median overall survival (OS) for low CXCR4 expression patients was 318 days, compared with 206 days for patients with high CXCR4 expression (P = .045). Multivariate analysis revealed that CXCR4 expression, age, and extramedullary infiltration were independent prognostic factors. CONCLUSIONS: Our study demonstrated that CXCR4 expression in AML was an independent prognostic predictor for disease survival that could be rapidly and easily determined by flow cytometry at disease presentation.

Myricetin Inhibits Breast Tumor Growth and Angiogenesis by Regulating VEGF/VEGFR2 and p38MAPK Signaling Pathways.

Tumor angiogenesis is an important cause of tumor growth and metastasis. Myricetin is a flavonoid component used in traditional Chinese medicine that has been demonstrated to have anticancer activity. However, to the best of our knowledge, the effect of myricetin on tumor angiogenesis remains unknown. The present study reports the identification of myricetin as a potential chemopreventive agent by reason of its inhibition of tumor angiogenesis and demonstrates the anticancer effects of myricetin in vivo. Cell Counting Kit-8 assays revealed that myricetin inhibits the proliferation of tumor cells but not that of human umbilical vein endothelial cells (HUVECs), and a transwell assay demonstrated that myricetin could inhibit the migration of HUVECs. A rat aortic ring assay revealed that myricetin could also affect the development of microvessels and the formation of vascular networks. Further, an ELISA showed that myricetin reduced the levels of vascular endothelial growth factor (VEGF) in vivo and in vitro. Western blot analysis indicated that myricetin could downregulate VEGFR2 and p38MAPK. Therefore, myricetin could significantly inhibit tumor angiogenesis and has potential as a chemopreventive agent because of its inhibition to angiogenesis. Anat Rec, 302:2186-2192, 2019. © 2019 American Association for Anatomy.

High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia.

BACKGROUND: Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. METHODS: In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann-Whitney U test, Fisher exact test, logistic regression, Kaplan-Meier and Cox regression analyses were used. RESULTS: In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). CONCLUSIONS: High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML.

Dynamic metabolic profiles of the marine macroalga Ulva prolifera during fragmentation-induced proliferation.

Ulva prolifera, a type of marine macroalgae, is the causative species behind green tides mainly in the Yellow Sea and adjacent regions. Nevertheless, it can be used as food or animal feed in South China. The vegetative fragments of U. prolifera are an important seed source for successive green tide blooms. Fragmentation shortens the transition time from the vegetative state to the reproductive state. However, the translation of the algal metabolites during gametogenesis is far from well understood. In this study, the dynamic metabolic profiles of U. prolifera thallus during fragmentation-induced proliferation were investigated using non-targeted metabolomics approach via a series of time course experiments in June 2017. After a 30 min low temperature shock, fragmentation induced a reproductive response of 91.57% of U. prolifera in 48 h, whereas the value was only 21.43% in the control group. A total of 156 chromatographic peaks were detected, and 63 metabolites were significantly changed in U. prolifera during reproduction. Aanlysis of the kinetic metabolic pattern showed that the fragments not only induced the formation of sporangia, but also led to complex metabolite accumulation. During fragmentation-induced proliferation, U. prolifera consumed different sugars at different time points. γ-Aminobutyric acid (GABA), glutamic acid, gallic acid, and malic acid may play important roles in germ cell formation and in the release of U. prolifera, whereas n-hexanol, 2-methyl-3-phenylindole, and 3-indoleacetonitrile may be beneficial for biotic stress resistance. Compared with the control group, in the treatment group, metabolites such as alcohols and organic acids also showed significant difference with the photoperiod at the initial stage of proliferation (before 60 h). In conclusion, changes in the levels of metabolites, including sugars, organic acids, and alcohol with photoperiod may be the strategy adopted by U. prolifera to cope with fragmentation in nature.