TMJ-105, an extract of Carpesium cernuum, induced G2/M phase arrest and apoptosis via the JAK2/STAT3 axis and MAPKs signaling pathway in leukemia HEL cells.

Leukemia is a malignant tumor of the hematologic system. Studies have shown that cernuumolide J (TMJ-105), an extract of Carpesium cernuum, has anti-cancer effects, but the underlying mechanism is unclear. In this study, we investigated the effect of TMJ-105 on the proliferation of human leukemia HEL cells and its molecular mechanism. MTT analysis showed TMJ-105 had revealed that it shows significant IC50 in HEL cells at lower doses (1.79 ± 0.29 µmol/L) than in K562 cells (3.89 ± 0.80 µmol/L), and the suppression of HEL cell proliferation was time- and concentration-dependent. Meanwhile, TMJ-105 induced G2/M phase blockage, leading to DNA damage in HEL cells. TMJ-105 promoted HEL cells to release of reactive oxygen species (ROS) and changed mitochondrial membrane potential (MMP). Furthermore, TMJ-105 induced apoptosis by upregulating the cleaved-caspase9 and cleaved-caspase3 protein expression, while caspase pan inhibitor (Z-VAD-FMK) blocked the inhibition effect. Finally, TMJ-105 downregulated the phosphorylation of JAK2, STAT3 and Erk, and activated the phosphorylation of JNK and p38. Collectively, these results demonstrated that TMJ-105 inhibited proliferation of leukemia cells and the underlying mechanism via the JAK2/STAT3 axis and MAPKs signaling pathway. Based on these results, the present study suggested the sesquiterpene lactone TMJ-105 is a new chemotherapeutic agent for the treatment of leukemia.

Lipidomic analyses reveal potential biomarkers for predicting death and heart failure after acute myocardial infarction.

Background Acute myocardial infarction (AMI) and postmyocardial infarction heart failure (pMIHF) have high mortality rates worldwide. This study aimed to explore lipidomic profiles and identify potential biomarkers for the prediction of death and heart failure (HF) after AMI. Methods All serum samples were collected at Xuanwu Hospital, Capital Medical University, and their clinical characteristics and lipidomic profiles were analyzed in different groups. LC-MS/MS was used for lipidomic analyses, and underlying biomarkers were screened by receiver operating characteristic (ROC) curve analysis. Results Lipidomic analyses of the survival and nonsurvival groups revealed that the decrease of the content of SM (d18:1/22:0), PE (P-20:1/18:0), PC (18:2), LPE (18:2), PE (P-20:0/18:0), LPC (18:0) and PC (20:0/20:3) while increase of the content of PG (18:1/18:1) could increase the risk of death after AMI. In parallel, the lipidomic analysis of the HF and non-HF groups revealed that the decrease of the content of PC (20:3/20:4), LPC (20:3), LPC (18:0), LPC (18:2), LPC (20:0), LPC (18:3), LPE (16:1) and PC (18:2/20:3) could increase the risk of HF after AMI. Conclusion Several lipids could be potential biomarkers for the prediction of death and HF after AMI.

Organic Electro-Optic Materials with High Electro-Optic Coefficients and Strong Stability.

The preparation of high-performance electro-optical materials is one of the key factors determining the application of optoelectronic communication technology such as 5G communication, radar detection, terahertz, and electro-optic modulators. Organic electro-optic materials have the advantage of a high electro-optic coefficient (~1000 pm/V) and could allow the utilization of photonic devices for the chip-scale integration of electronics and photonics, as compared to inorganic electro-optic materials. However, the application of organic nonlinear optical materials to commercial electro-optic modulators and other fields is also facing technical bottlenecks. Obtaining an organic electro-optic chromophore with a large electro-optic coefficient (r33 value), thermal stability, and long-term stability is still a difficulty in the industry. This brief review summarizes recent great progress and the strategies to obtain high-performance OEO materials with a high electro-optic coefficient and/or strong long-term stability. The configuration of D-π-A structure, the types of materials, and the effects of molecular engineering on the electro-optical coefficient and glass transition temperature of chromophores were summarized in detail. The difficulties and future development trends in the practical application of organic electro-optic materials was also discussed.

Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

[Three new diterpenoids from whole herb of Carpesium cernuum].

The study investigated the chemical constituents from the whole herb of Carpesium cernuum. Three new diterpenoids were isolated from the whole herb of C. cernuum by column chromatography on silica gel, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified by MS, NMR and other spectral techniques. The isolates were identified as(5Z)-2-oxo-2, 10, 14-trimethylhexadeca-5, 13-diene-11α, 18-diol(1),(2E, 10E)-7-[(acetyloxy)methyl]-3, 11, 15-trimethylhexadeca-2, 10, 14-triene-1, 12α-diol(2),(2E, 6Z)-3, 11, 15-trimethylhexadeca-2, 6, 14-triene-1, 12α, 19-triol(3), respectively. The cytotoxic activity of compounds 1-3 were investigated with DU-145, MCF-7, and A549 cells by MTT. The results showed that compound 1 and 3 had certain inhibitory effects on MCF-7 cells, with the inhibition rates of 45.06% and 29.40%, respectively.

Constituents from Chloranthus multistachys and their cytotoxic activities against various human cancer cell lines.

Two new furanoeremophilane sesquiterpenoids, namely, 6,9-dioxo-1α,4α-dihydroxy-furanoeremophilane (1) and 4α,5α-epoxy-6,9-dioxo-1α-hydroxyl-furanoeremophilane (2), and 10 known compounds were isolated from the whole plant of Chloranthus multistachys, and compound 3 was converted to derivative 3a. Their structures were determined based on extensive spectroscopic analysis. All compounds were evaluated by using five cancer cell lines: PC3, LNcap, A549, K562, and HEL. The derivative 3a exhibited excellent cytotoxic activities, with the IC50 against HEL cells being the lowest at 1.322 ± 0.08 µM, which was comparable to that of the positive control (doxorubicin). Mechanism studies showed that the anticancer activity of 3a may be associated with cell cycle regulation.

Incaspitolide A extracted from Carpesium cernuum induces apoptosis in vitro via the PI3K/AKT pathway in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease that occurs mainly in older men. The pathogenesis of BPH is complex and patients face a prolonged treatment course, and novel drugs with better selectivity and lower toxicity are required. Incaspitolide A (compound TMJ-12) is a germacrane-type sesquiterpenoid compound extracted from the plant Carpesium carnuum. Extracts of C. carnuum are known to exert suppressive effects on BPH-1 cells. In the present study, we investigated the molecular mechanisms underlying the suppressive effect of TMJ-12 specifically on BPH-1 cells. A cytotoxicity assay indicated that TMJ-12 inhibited BPH-1 cell proliferation, while flow cytometry assays showed that TMJ-12 induced G2/M phase cell cycle arrest and the apoptosis of BPH-1 cells. TMJ-12 was also shown to regulate the expression of several apoptosis- and cell cycle-related proteins, namely Bcl-2, Bax, Bad, Caspase-9, Caspase-3, cyclin-dependent kinase 1 (CDK1), Cyclin B1, CDC25C, and c-Myc, among others. Collapse of the mitochondrial membrane potential (ΔΨm) following exposure to TMJ-12 was detected with the JC-1 staining assay. Further investigation revealed that treatment with TMJ-12 inhibited the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway by increasing the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Taken together, the results suggest that TMJ-12 prevents BPH-1 cell proliferation via the PI3K/AKT pathway by inducing apoptosis and cell cycle arrest.

Genotyping and serotyping profiles showed weak Jka presentation for previously typed as Jknull donors.

BACKGROUND AND OBJECTIVES: Kidd blood group system consists of two major antigens: Jka and Jkb . Both the antigens are absent in individuals typed as Jknull and may develop clinically significant anti-Jk3 antibody. Screening donors for provision of Jknull blood is an ongoing task for blood centres with Jknull blood units kept frozen for specific requirements. In 2016, we discovered a previously typed Jknull donor to be Jka weak positive. Therefore, a study was conducted for our donors to verify Jknull status and to reinforce our typing protocol. MATERIALS AND METHODS: In this experiment, donors previously typed and screened as Jknull were tested with four antisera of Jka and Jkb , and each with gel card for serology testing. Sequence analysis was performed for SLC14A1 gene for the detection of JKnull and weak alleles for genetic testing. RESULTS: Among the 30 samples, four were serologically identified as Jk(a+w ) and genotypically identified as heterozygous for the JK*01W.01 allele. The other 26 were confirmed to be Jknull with JK*02N.01 as the most frequent allele. None of JK*B weak alleles were detected, but three were identified as false positives in the tube method. Gel card gave great accuracy for Jkb detection, but failed to give consistent results for weak Jka . CONCLUSION: By combining the tube method and gel card method in serology, along with complementary genetic testing, the possibility of misinterpreting weak Jka expression was eliminated, and we were able to provide Jknull blood for safe clinical transfusion.

[Determination of 23 phthalate esters in scallion and other vegetables by solid-phase extraction coupled with gas chromatography-tandem mass spectrometry].

A method for the simultaneous determination of 23 phthalate esters in vegetables by solid-phase extraction coupled with gas chromatography-triple quadrupole mass spectrometry (SPE-GC-MS/MS) was developed and evaluated. The samples were extracted with acetonitrile, and cleaned-up with glass Florisil SPE columns, and diluted with n-hexane. The separation was performed on a DB-5MS UI capillary column (30 m x 0.25 mm x 0.25 µm) with temperature programming. The identification and quantification were performed by GC-MS/MS in selected reaction monitoring (SRM) mode. The external standard method was used. The processes of extraction and clean-up of scallion and other vegetables were investigated, and the chromatographic and MS parameters were optimized. The matrix effect was compensated by matrix spiked calibration. The extraction processes were investigated. The calibration curves of the phthalate esters showed good linearities in the ranges of 0.02-1 mg/L (0.1-5 mg/L for diisononyl phthalate (DINP) and diisodecyl-o-phthalate (DIDP)) with the correlation coefficients (r) over 0.99 except for bis(2-methoxyethyl) phthalate (DMEP). The limits of detection of phthalate esters in samples ranged from 0.01 to 0.05 mg/kg (S/N = 3) and the limits of quantification ranged from 0.02 to 0.1 mg/kg (S/N = 10). The average recoveries of the 23 analytes spiked in scallions ranged from 81.3% to 104.2% with the relative standard deviations (RSDs, n = 6) of 3.2%-11.2%. The method is suitable for the determination of the 23 phthalate esters simultaneously in vegetables with easy operation, high accuracy and precision.

Vinylbenzyl quaternary ammonium-based polymeric monolith with hydrophilic interaction/strong anion exchange mixed-mode for pressurized capillary electrochromatography.

A novel polymeric monolith with hydrophilic interaction and strong anion-exchange mixed-mode has been fabricated for pressurized capillary electrochromatography by an in situ copolymerization of vinylbenzyl trimethylammonium chloride (VBTA) and bisphenol A glycerolate dimethacrylate (BisGMA). The optimization of the polymerization mixture composition has been investigated, and column characteristics in terms of mechanical stability, permeability and reproducibility have been studied in detail. Linear responses between back pressure and flow rate have been achieved in different solvents. The absolute value of swelling propensity (SP) factor for poly(VBTA-co-BisGMA) monolith is 0.41, and the degree of permeability drop from pure ACN to water is about 45%. An acceptable mechanical stability of the column is obtained. The suitable reproducibility is also measured with the RSD for day-to-day (n=3) of retention time and column efficiency less than 3.3%, and the RSD for batch-to-batch (n=3) less than 5.3%, respectively. Under the optimum conditions, the mixed-mode of hydrophilic interaction and strong anion-exchange has been carried out, and efficient electrochromatography profiling of various polar compounds including neutral phenols, negatively charged benzoic acids and positively charged nucleic acid bases and nucleosides are achieved, respectively.

[HPLC method for determination of tramadol hydrochloride in human plasma].

OBJECTIVE: A reversed-phase high performance liquid chromatography (HPLC) method was established to determine the concentration of tramadol hydrochloride in human plasma. METHODS: HPLC instrument was used with the column: 150 mm x 4.6 mm (Li Chrosorb C18, 5 microns). The mobile phase was composed of phosphate buffer solution (0.02 mol/L, pH = 3.7)-acetamide (83: 17, V/V). Flow rate was 1.0 ml/min. Detection wavelength was 216 nm. RESULTS: The standard curve equation was Y = 0.03244X + 0.6007. The linear range was 25-800 ng/ml. The minimum detection limit was 10.2 ng/ml. CONCLUSION: The reversed-phase HPLC method is simple, rapid and sensitive. It is applicable to the determination of the concentration of tramadol hydrochloride in human plasma.