Dopamine-Modified Zero-Valent Iron Nanoparticles for Dual-Modality Photothermal and Photodynamic Breast Cancer Therapy.

Phototherapy has the advantages of minimal invasion, few side effects, and improved accuracy for cancer therapy. The application of a polydopamine (PDA)-modified nano zero-valent iron (nZVI@PDA) as a new synergistic agent in combination with photodynamic/photothermal (PD/PT) therapy to kill cancer cells is discussed here. The nZVI@PDA offered high light-to-heat conversion and ROS generation efficiency under near-infrared (NIR) irradiation (808 nm), thus leading to irreversible damage to nZVI@PDA-treated MCF-7 cells at low concentration, without inducing apoptosis in normal cells. Irradiation of nZVI@PDA using an NIR laser converted the energy of the photons to heat and ROS. Our results showed that modification of the PDA on the surface of nZVI can improve the biocompatibility of the nZVI@PDA. This work integrated the PD and PT effects into a single nanodevice to afford a highly efficient cancer treatment. Meanwhile, nZVI@PDA, which combines the advantages of PDA and nZVI, displayed excellent biocompatibility and tumoricidal ability, thus suggesting its huge potential for future clinical research in cancer therapy.

Butylidenephthalide antagonizes cromakalim-induced systolic pressure reduction in conscious normotensive rats.

BACKGROUND: Butylidenephthalide (Bdph), a main constituent of Ligusticum chuanxiong Hort., was reported to have selective antianginal effect without changing blood pressure in conscious rat. Recently, we have observed that Bdph antagonized cromakalim, an ATP-dependent K(+) channel opener, in guinea-pig trachea. Thus, we were interested in investigating whether Bdph at the dose without changing blood pressure antagonized cromakalim-induced systolic pressure reduction in conscious rats. METHODS: Systolic arterial pressures of conscious rats were determined by using the indirect tail-cuff method. RESULTS: Bdph (30 mg/kg, i.p.) did not affect baseline systolic pressure in conscious normotensive and spontaneous hypertensive rats. Bdph (30 mg/kg, i.p.) also did not affect log dose-response curves of prazosin, clonidine and Bay K 8644, a Ca(2+) channel activator, in normotensive rats. However, Bdph (30 mg/kg, i.p.) similar to 4-aminopyridine (4-AP, 0.4 mg/kg, i.p.), a K(+) channel blocker, non-parallelly but surmountably, and partially similar to glibenclamide (GBC, 10 mg/kg, i.v.), an ATP-sensitive K(+) channel blocker, surmountably but not parallelly rightward shifted the log dose-systolic pressure reduction curve of cromakalim, an ATP-sensitive K(+) channel opener, in normotensive rats, respectively. DISCUSSION: The antagonistic effect of Bdph against cromakalim was similar to that of 4-AP, a K+ channel blocker of Kv1 family, and partially similar to that of GBC, an ATP-sensitive K+ channel blocker. Thus, Bdph may be a kind of K+ channel blockers, which have been reviewed to have a potential clinical use for Alzheimer disease. Indeed, Bdph has also been reported to reverse the deficits of inhibitory avoidance performance and improve memory in rats. Recently, 4-AP was reported to treat Episodic ataxia type 2 (EA2) which is a form of hereditary neurological disorder. Consistently, Bdph was recently reported to have antihyperglycemic activity in mice, since GBC is a powerful oral hypoglycemic drug. CONCLUSIONS: Bdph similar to 4-AP and partially similar to GBC may block Kv1 family and ATP-sensitive K(+) channels in conscious normotensive rats.

Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes.

AIM: To investigate the acute and chronic effects of nateglinide versus acarbose on plasma asymmetric dimethylarginine (ADMA) levels and lipid profiles in patients with newly-diagnosed type 2 diabetes. METHODS: A crossover trial of nateglinide and acarbose was conducted on 16 drug-naïve patients with newly-diagnosed type 2 diabetes during a total period of 9 weeks. Plasma glucose, serum insulin, free fatty acids (FFA), lipids and lipoproteins, and plasma ADMA were measured. RESULTS: The efficiencies of a single dose of nateglinide (120 mg) and acarbose (50 mg) for lowering postprandial hyperglycemia were similar. Compared to acarbose, nateglinide significantly increased postprandial insulin release after a standard meal test in patients with type 2 diabetes. Nateglinide acutely decreased postprandial 120 min FFA concentrations and 240 min ADMA levels more significantly than acarbose. The fasting high-density lipoprotein cholesterol level increased and the low-density lipoprotein cholesterol level decreased significantly, but the fasting levels of triglycerides, total cholesterol, and ADMA were unchanged after 4 weeks of treatment with nateglinide. Acarbose did not affect fasting lipid profiles or the ADMA levels after 4 weeks of treatment. CONCLUSION: These results suggest that the reduction of postprandial FFA and ADMA concentrations induced by nateglinide may be associated with the partial restoration of early-phase insulin secretion and may impart a cardiovascular advantage in comparison with acarbose.