Inhibitory Effect of Depolymerized Sulfated Galactans from Marine Red Algae on the Growth and Adhesion of Diarrheagenic Escherichia coli.

Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia coli (ETEC) K88. Results showed that the sulfated polysaccharides with molecular weight distribution ≤20.0 kDa exhibited antibacterial activity against ETEC K88. A structure-activity study revealed that the anti-ETEC K88 activity of sulfated polysaccharides is strictly determined by their molecular weight distribution, sulfate group content, and monosaccharide composition. In addition, the promoted nucleic acid release and the fluorescence quenching of membrane proteins were observed after the treatment with selected polysaccharides. Scanning electron microscopy further confirmed that the depolymerized sulfated galactans can effectively inhibit ETEC K88 adhesion. In conclusion, depolymerized sulfated galactans exhibited an inhibitory effect on the growth and adhesion of ETEC K88.

Design, Synthesis, and Cytotoxic Activity of 3-Aryl-N-hydroxy-2-(sulfonamido)propanamides in HepG2, HT-1080, KB, and MCF-7 Cells.

A new series of (sulfonamido)propanamides (6a1-6a13, 6b1-6b15, 7c1-7c5, 6d1-6d5, 6e1-6e6) was designed and synthesized. All the synthesized compounds were characterized by NMR and mass spectrometry. The target compounds were evaluated for their in vitro cytotoxic activity against hepatocellular carcinoma (HepG2), fibrosarcoma (HT-1080), mouth epidermal carcinoma (KB), and breast adenocarcinoma (MCF-7) cell lines with the sulforhodamine B (SRB) assay, with gemcitabine and mitomycin C as positive controls. Most of these compounds exhibit a more potent cytotoxic effect than the positive control group on various cancer cell lines and the most potent compound, 6a7, shows the IC50 values of 29.78±0.516 µm, 30.70±0.61 µm, and 64.89±3.09 µm in HepG2, HT-1080, KB, and MCF-7 cell lines, respectively. Thus, these compounds with potent cytotoxic activity have potential for development as new chemotherapy agents.

Tat/HA2 Peptides Conjugated AuNR@pNIPAAm as a Photosensitizer Carrier for Near Infrared Triggered Photodynamic Therapy.

To achieve an efficiency of intracellular photosensitizers (PSs) delivery and efficacy of photodynamic therapy, we have developed a novel class of PS formulation for encapsulating sulfonated aluminum phthalocyanine (AlPcS4) by taking advantage of the membrane-disruptive peptides Tat/HA2 and the photothermally triggered delivery system using AuNR@pNIPAAm. The coordinated effects of cell penetrating peptide Tat and fusogenic peptide HA2 could enhance the efficient cellular internalization and endo/lysosome escape of PSs delivery systems. Singlet oxygen generation was inhibited due to the reaction between loaded AlPcS4 and Au nanorods, which indicated that the AlPcS4-loaded, AuNR@pNIPAAm delivery system might be nonphototoxic in the circulatory system. However, this PSs-loaded nanosystem became highly phototoxic as it underwent the near-infrared irradiation by using the combined lights of 808 and 680 nm. Upon irradiation, the Tat/HA2 conjugated AuNR@pNIPAAm-Pc elicited an active photodynamic response against the cancer cells, leading to effective cells killing via mitochondria-associated apoptotic pathway. This study also demonstrated improved PDT therapeutic efficacy after intravenous administration of Tat/HA2-AuNR@pNIPAAm-Pc and the subsequent lights irradiations in tumor-bearing mice. We describe here a strategy for enhanced photodynamic eradication of solid tumors by endo/lysosomal escape and highlight the great promise of peptide-based nanocarriers used for cancer therapy.

Description of a new toad of Megophrys Kuhl amp; Van Hasselt, 1822 (Amphibia: Anura: Megophryidae) from western Yunnan Province, China.

A new species of genus Megophrys from Gaoligong Mountains, Yunnan Province, China is described. Phylogenetic analyses based on mitochondrial DNA and nuclear DNA all clustered the new species as an independent clade nested into the subgenus Panophrys. The smallest genetic distance based on 16S rRNA gene between the new species and its congeners was 3.0%. The new species could be identified from its congeners by a combination of following characters: moderate body size (SVL 31.0-34.8 mm in males); vomerine ridge weak, vomerine teeth absent; dorsal skin relatively smooth; tongue slightly notched behind; tympanum rounded and relatively large, 0.54 times of eye length; a horn-like tubercle on edge of each upper eyelid small; tibio-tarsal articulation reaches middle eye when leg stretched forward; finger tips rounded, not expanded to small pad; toes with narrow fringes and rudimentary webbing; ventral hindlimbs semitransparent purplish with greyish white pigments; ventral body scattered with distinct dark patches in the middle.

PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

Determination of nucleic acids by near-infrared fluorescence quenching of hydrophobic thiacyanine dye in the presence of Triton X-100.

A near-infrared (near-IR) fluorescence quenching method was developed for the determination of nucleic acids in aqueous solution by using a cationic heptamethylene thiacyanine as a probe. The near-IR cationic cyanine showed maximum excitation and emission wavelengths at 800 and 825 nm, respectively, in the presence of Triton X-100; the fluorescence of the cyanine could be greatly quenched by DNA. The calibration graphs were linear over the range of 10-400 ng/mL for CT (calf thymus) DNA and over the range 5-400 ng/mL for FS (fish sperm) DNA under optimal conditions. The corresponding detection limits were 5.2 ng/mL for CT DNA and 2.5 ng/mL for FS DNA. The relative standard deviation (n = 8) was 3.1% for 75 ng/mL CT DNA and 2.2% for 75 ng/mL FS DNA, respectively. Preliminary research showed that the fluorescence quenching might be ascribed to the formation of dye aggregate facilitated by DNA.

Fluorescence quenching method for the determination of sodium dodecyl sulphate with near-infrared hydrophobic dye in the presence of Triton X-100.

A fluorophotometric method for the determination of anionic surfactant sodium dodecyl sulphate (SDS) was proposed. The method is based on the quenching effect of SDS on the fluorescence of near-infrared (NIR) hydrophobic dye, 2-[4'chloro-7'(3''hexadecyl-2''benzothiazolinylidene)-3',5'-(1''',3'''-propanediyl)-1',3',5'-heptatriene-1'-yl]-3-ethylbenzothiazolium iodide (dye I) in the presence of Triton X-100. The calibration graph is linear in the concentration range from 0 to 2 x 10(-6) mol L(-1) of SDS with a detection limit (LOD) of 8.3 x 10(-8) mol L(-1). The relative standard deviation for the determination of 7 x 10(-7) mol L(-1) SDS was 4.1%. Recoveries of 95.3-110.3% were found for the addition to 1.0 x 10(-6) mol L(-1) SDS in the analysis of environmental water samples. Preliminary research shows that the fluorescence quenching is due to the formation of dye aggregate facilitated by SDS.