Honokiol, a Polyphenol Natural Compound, Attenuates Cisplatin-Induced Acute Cytotoxicity in Renal Epithelial Cells Through Cellular Oxidative Stress and Cytoskeleton Modulations.

Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalis exhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro. The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells. By promoting the polymerization of actin (1.6-fold increase) and tubulin (1.8-fold increase) cytoskeleton, honokiol not only maintained epithelial cell morphology, but also stabilized cellular localizations of tight junction protein Occludin and adhesion junction protein E-Cadherin. With stabilized junction protein complexes and structural polymerized cytoskeleton network, honokiol preserved epithelial cell polarity and morphology and thus reduced cisplatin-induced cell disruption and damages. Our data demonstrated for the first time that honokiol could counteract with cisplatin-induced damages in renal epithelial cells in vitro, future in vivo studies would further validate the potential clinical application of honokiol in cisplatin-based cancer treatments with reduced nephrotoxicity.

Roles of the reproductive tract in modifications of the sperm membrane surface.

Successful fertilization requires viable and functional spermatozoa to recognize and fuse with the oocyte. In most mammalian species, mature spermatozoa are not capable of fertilizing the oocytes immediately after ejaculation. However, unlike somatic cells, spermatozoa, after leaving the testis, are transcriptionally and translationally silent; therefore, upon completion of spermiogenesis, spermatozoa carry only a minimal amount of essential proteins on their membranes as well as within their restricted volume of cytoplasm. To develop into a fully functional and competent sperm that is capable of successful fertilization, modifications of the sperm membrane surface during its transit in the reproductive tracts is critical. These post-spermatogenesis modifications advance the maturation of epididymal spermatozoa. In addition, components secreted into the lumen of the reproductive tracts that are later added onto the sperm membrane surface also regulate (inhibit or activate) the functions of the spermatozoa. This acquisition of additional proteins from the reproductive tracts may compensate for the inactivity of morphologically mature spermatozoa. In this review, we discuss the contributions of the male and female genital tracts to modifications of the sperm membrane surface at different stages of fertilization.

Involvement of complexin 2 in docking, locking and unlocking of different SNARE complexes during sperm capacitation and induced acrosomal exocytosis.

Acrosomal exocytosis (AE) is an intracellular multipoint fusion reaction of the sperm plasma membrane (PM) with the outer acrosomal membrane (OAM). This unique exocytotic event enables the penetration of the sperm through the zona pellucida of the oocyte. We previously observed a stable docking of OAM to the PM brought about by the formation of the trans-SNARE complex (syntaxin 1B, SNAP 23 and VAMP 3). By using electron microscopy, immunochemistry and immunofluorescence techniques in combination with functional studies and proteomic approaches, we here demonstrate that calcium ionophore-induced AE results in the formation of unilamellar hybrid membrane vesicles containing a mixture of components originating from the two fused membranes. These mixed vesicles (MV) do not contain the earlier reported trimeric SNARE complex but instead possess a novel trimeric SNARE complex that contained syntaxin 3, SNAP 23 and VAMP 2, with an additional SNARE interacting protein, complexin 2. Our data indicate that the earlier reported raft and capacitation-dependent docking phenomenon between the PM and OAM allows a specific rearrangement of molecules between the two docked membranes and is involved in (1) recruiting SNAREs and complexin 2 in the newly formed lipid-ordered microdomains, (2) the assembly of a fusion-driving SNARE complex which executes Ca(2+)-dependent AE, (3) the disassembly of the earlier reported docking SNARE complex, (4) the recruitment of secondary zona binding proteins at the zona interacting sperm surface. The possibility to study separate and dynamic interactions between SNARE proteins, complexin and Ca(2+) which are all involved in AE make sperm an ideal model for studying exocytosis.

Fabrication of high-aspect-ratio Fresnel zone plates by e-beam lithography and electroplating.

The fabrication of gold Fresnel zone plates, by a combination of e-beam lithography and electrodeposition, with a 30 nm outermost zone width and a 450 nm-thick structure is described. The e-beam lithography process was implemented with a careful evaluation of applied dosage, tests of different bake-out temperatures and durations for the photoresist, and the use of a developer without methylisobutylketone. Electrodeposition with a pulsed current mode and with a specially designed apparatus produced the desired high-aspect-ratio nanostructures. The fabricated zone plates were examined by electron microscopy and their performances were assessed using a transmission X-ray microscope. The results specifically demonstrated an image resolution of 40 nm.

The clinical significance of a new monoclonal antibody defined antigen CA195 as a tumor marker in colorectal cancer.

We evaluated a new monoclonal antibody defined antigen CA195 as a tumor marker in patients with colorectal adenocarcinoma and compared the results with CA19-9 and carcinoembryonic antigen (CEA). This study included 37 patients with colorectal adenocarcinoma, 118 healthy subjects, 20 hepatitis with or without jaundice, and 20 duodenal ulcer with or without smoking habits. The average concentration of CA195 in serum from 118 healthy subjects is 5.80 +/- 6.83 U/ml. In the 37 patients with colorectal adenocarcinoma, 13 had elevated levels (greater than 30 U/ml) of CA195 (35%), 10 had elevated levels (greater than 37 U/ml) of CA19-9 (27%), and 18 and elevated levels (greater than 5 ng/ml) of CEA (48%). The sensitivity of CA195 is correlated well with the extent of the malignancy, 9% in Duke's stage A and B, and 79% in advanced stage C and D. Although the sensitivity of CA195 is less than CEA (35% vs. 48%), this difference is not statistically significant scaled (P greater than 0.05). Combined use CA195 with CEA can increase detecting rate from 48% (CEA alone) to 59%. CA-195 level may be elevated in some patients with hepatocellular disease, but its level is not affected by smoking. Therefore CA-195 can be applied as complementary tumor marker in colorectal cancer.

Abnormal thyroid function and hypercholesterolemia in a case of acute intermittent porphyria.

Acute intermittent porphyria is a genetic hepatic porphyria characterized by acute gastrointestinal and neurological symptoms, and accompanied by excess excretion of delta-aminolevulinic acid and porphobilinogen. Here, we report a case of acute intermittent porphyria with attacks of abdominal pain, an elevated serum thyroxine level, and hypercholesterolemia with an increased level of high-density lipoprotein-cholesterol concentration. The diagnosis of acute intermittent porphyria was confirmed by a high urinary excretion of porphobilinogen and a low level of erythrocyte hydroxymethylbilane synthase activity. After being treated with a high carbohydrate intake and propranolol, the patient improved gradually during the following 3 weeks. The patient remained asymptomatic during the 6-month follow-up period. The serum thyroxin and cholesterol levels returned to normal 6 months later. In conclusion, we suggest that for any patient who presents with unexplained abdominal pain, abnormal thyroid function and hypercholesterolemia, a simple Watson-Schwartz urine test should be performed for the screening of acute intermittent porphyria. If the Watson-Schwartz test is positive, the erythrocyte hydroxymethylbilane synthase activity should be determined to confirm the diagnosis of acute intermittent porphyria.