Metasequoia glyptostroboides potentiates anticancer effect against cervical cancer via intrinsic apoptosis pathway.

This study was undertaken to investigate the anticancer effects of organic extracts derived from the floral cones of Metasequoia glyptostroboides. Dried powder of M. glyptostroboides floral cones was subjected to methanol extraction, and the resulting extract was further partitioned by liquid-liquid extraction using the organic solvents n-hexane, dichloromethane (DME), chloroform, and ethyl acetate in addition to deionized water. HeLa cervical and COS-7 cells were used as a cancer cell model and normal cell control, respectively. The anticancer effect was evaluated by using the Cell Counting Kit-8 assay. The viability of COS-7 cells was found to be 12-fold higher than that of the HeLa cells under the administration of 50 µg/ml of the DME extract. Further, the sub-G1 population was determined by FACS analysis. The number of cells at the sub-G1 phase, which indicates apoptotic cells, was increased approximately fourfold upon treatment with the DME and CE extracts compared with that in the negative control. Furthermore, RT-qPCR and western blotting were used to quantitate the relative RNA and protein levels of the cell death pathway components, respectively. Our results suggest that the extracts of M. glyptostroboides floral cones, especially the DME extract, which possesses several anticancer components, as determined by GC-MS analysis, could a potential natural anticancer agent.

Clinical Impact of Dysglycemia in Patients with an Acute Myocardial Infarction.

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial infarctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak troponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E' ratio was U-shaped based on euglycemia. The 30-day mortality also increased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, especially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.

Antioxidant and anti-aging potential of a peptide formulation (Gal2-Pep) conjugated with gallic acid.

Skin is highly vulnerable to premature aging due to external stress, therefore, in this study, a peptide formulation, (galloyl)2-KTPPTTP (Gal2-Pep) was synthesized by combining TPPTTP peptide, and gallic acid (GA). All peptides were synthesized on 2-chlorotrityl chloride resin using solid-phase peptide synthesis (SPPS), and analyzed on an electrospray ionization (ESI)/quadrupole-time-of-flight (Q-TOF) tandem mass spectroscopy (MS) system. Initially, Gal2-Pep showed no toxicity below the concentration 100 µM with cell survival rate of 88% for keratinocytes and fibroblasts. The reactive oxygen species (ROS) scavenging activity of Gal2-Pep was more stable compared to GA alone; and after four weeks at room temperature, its ROS scavenging activity remained higher than 50%. Moreover, the peptide formulation, Gal2-Pep also exhibited elastase inhibitory effect in CCD-1064Sk fibroblast cells. Based on the results of RT-qPCR, it was proved in this study that Gal2-Pep increased the expression of PGC-1α to prevent oxidative stress, and validated its potential as an anti-aging agent through increasing the expression of type I collagen and by decreasing the expression of matrix metalloproteinase-1 (MMP1). The findings obtained reinforce the suggestion that the peptide formulation synthesized in this study could be used as a natural antioxidant and anti-aging agent for its cosmetic applications.

Folic acid-modified bovine serum albumin nanoparticles with doxorubicin and chlorin e6 for effective combinational chemo-photodynamic therapy.

We herein describe a facile method to synthesize stable bovine serum albumin-based nanoparticles (BNPs) loaded with two anticancer therapeutics, doxorubicin (DOX) and a photosensitizer, chlorin e6 (Ce6), in combination with folic acid (FA) as a target cancer cell receptor for the development of an effective combined chemo and photodynamic (FA-Ce6/DOX/BNPs) therapy against cervical cancer. FA-Ce6/DOX/BNPs exhibited excellent monodispersity with an average diameter of 103.5 ± 3.8 nm, a negative zeta potential of approximately -30.44 ± 0.35 mV, and long-term stability. As a result, FA-Ce6/DOX/BNPs exhibited severe toxicity to cervical HeLa cancer cells. Also, a higher drug release rate was observed under acidic pH conditions (pH 5.0). Moreover, FA-Ce6/DOX/BNPs potentiated mitochondrial reactive oxygen species (ROS) production in HeLa cells under 671-nm laser exposure, leading to activation of key regulator proteins of apoptosis such as BH3 interacting-domain death agonist (BID), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (BAX), as well as induction of the caspase cascade and mitochondrial ROS-mediated cell death. Confocal microscopy analysis further validated cellular uptake of FA-Ce6/DOX/BNPs by HeLa cells. Furthermore, results of real-time quantitative PCR (RT-qPCR) and western blot analysis further validated the anticancer effect of FA-Ce6/DOX/BNPs, as evidenced by elevated gene/protein expression levels of apoptotic biomarkers p53, BID, caspase-3, cleaved poly(ADP-ribose) polymerase 1 (PARP-1), and BAX, contrary to levels of the anti-apoptotic marker Bcl-2. Moreover, in vivo toxicity results of FA-Ce6/DOX/BNPs using laser irradiation in zebrafish larvae, as a chemo-photodynamic therapy confirmed that it does not affect the larval development without causing any adverse toxic effect in zebrafish larvae. Altogether these findings strongly support the anticancer effect of FA-Ce6/DOX/BNPs combinational chemo-photodynamic therapy, which could be a promising candidate for cervical cancer therapy.

Fluorescent immunoliposomal nanovesicles for rapid multi-well immuno-biosensing of histamine in fish samples.

Scombroid poisoning in fish-based and other food products has raised concerns due to toxicity outbreaks and incidences associated with histamine, thus measuring the amount of histamine toxic molecule is considered crucial quality indicator of food safety and human health. In this study, liposome-based measurement of histamine was performed via rupturing mechanism of sulforhodamine B dye encapsulated anti-histamine antibody conjugated liposomal nanovesicles. The immunosensing ability of immuno-liposomal format was assessed by monitoring the fluorescence at excitation/emission wavelength of 550/585 nm. Immuno-liposomal format assays were considered, one based on single wash procedure (Method 1), which had a detection limit of 10 ppb and quantification limit 15-80 ppb. While Method 2 based on one-by-one wash procedure had a detection limit of 2-3 ppb and quantification limit 8.5 ppb-200 ppm that required 2 h 30 min to perform. In view of better quantification limit, Method 2 was chosen for further tests required to validate its applicability in real samples. The feasibility of Method 2 was reconfirmed in fresh mackerel fish, and canned fish (tuna and salmon) with a similar detection limits but with low amplified fluorescence signals and sufficient levels of histamine recovery from fresh mackerel (73.50-99.98%), canned tuna (79.08-103.74%) and salmon (74.56-99.02%). The specificity and method accuracy were expressed as % CV in the range 5.34%-8.48%. Overall, the developed multi-well sensing system (Method 2) showed satisfactory specificity, cost effectiveness, rapidity, and stability for monitoring histamine toxicity as a practical food diagnostic device.