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Chronic hyperglycemia causes a progressive decrease of β-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect β cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate chronic high glucose (HG)-induced β-cell injury through modulation of autophagy. Prolonged exposure to HG decreased cell viability, increased cell apoptosis and impaired basal insulin secretion and glucose-stimulated insulin secretion of INS-1 cells, but BM-MSC treatment significantly alleviated these glucotoxic alternations. In addition, western blotting displayed upregulated expression of Beclin1 and LC3-II in INS-1 cells co-cultured with BM-MSCs. Results from immunofluorescence staining and transmission electronic microscope analysis also revealed that BM-MSCs promoted autophagosomes and autolysosomes formation in HG-treated INS-1 cells. However, it should be noted that inhibition of autophagy significantly diminished the protective effects of BM-MSCs on HG-treated INS-1 cells, suggesting that the improvement of β-cell function and survival induced by BM-MSCs was mediated through autophagy. Furthermore, our results showed that BM-MSCs improved mitochondrial function and reduced reactive oxygen species production in HG-treated INS-1 cells, largely owing to autophagic clearance of impaired mitochondria. In vivo study was performed in rats with type 2 diabetes (T2D). BM-MSC infusion not only ameliorated hyperglycemia, but also promoted restoration of pancreatic β cells in T2D rats. Meanwhile, BM-MSC infusion upregulated LAMP2 expression and enhanced formation of autophagosomes and autolysosomes, combined with reduced β-cell apoptosis and increased number of insulin granules. These findings together indicated that BM-MSCs could protect β cells against chronic HG-induced injury through modulation of autophagy in vitro and in vivo. This study unveiled novel evidence of BM-MSCs as an ideal strategy to enhance autophagy for treatment of T2D mellitus.

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In order to investigate the mechanisms and therapeutic effects of valproate combined with lithium carbonate on mouse model of Parkinson's disease (PD), male C57BL/6 mice were injected into intraperitoneal with valproate (20 μg/ml) combined with lithium carbonate (10 μg/ml) for 7 days following 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) (30 mg/kg) administration, and the effects on motor function were analyzed. Immunohistochemistry and Western blotting were used to detect alterations in the expression of PD biomarkers, including tyrosine hydroxylase (TH), and the level of autophagy was evaluated by the detection of microtubule-associated protein light chain 3 (LC3). In addition, the levels of monoamine neurotransmitters were measured in the striatum using high performance liquid chromatography (HPLC). After MPTP exposure, all groups manifested decreased rolling bar latency and spontaneous activity, in addition to increased pole-climbing time. The combined treatment group exhibited a recovery of rolling bar latency and pole-climbing time. The number of dopaminergic neurons in the substantia nigra following MPTP treatment was higher in the combined treatment group compared with the positive control group (p = .003). Immunoreactivity for LC3 was higher in the combined treatment group than in the controls (p = .003). The concentrations of both striatal dopamine and the dopamine metabolite dihydroxyphenyl acetic acid (DOPAC) were decreased in both MPTP-treated groups compared with the controls. The loss of DOPAC was less severe in the combined treatment group relative to the positive control group (p = .001). Therefore, we infer that valproate combined with lithium carbonate can rescue dopaminergic neurons and ameliorate the loss of DOPAC following MPTP treatment, likely via activation of autophagic/lysosomal pathways.

In order to find multifunction anticancer complexes, three Mn(II) complexes of N-substituted di(2-pyridylmethyl)amine were characterized and used as agents to interfere with the functions of mitochondria and the metabolite of O(2) in cancer cells. It was found that carboxylate-bridged dimanganese(II) systems are good models of catalase and exhibit good inhibition of the proliferation of U251 and HeLa cells. The inhibiting activity of these manganese(II) complexes on the tumor cells in vitro was related to their disproportionating H(2)O(2) activity. The reaction of carboxylate-bridged dimanganese Mn(II) complex with H(2)O(2) forms a stable Mn(III)-(μ-O)(2)-Mn(IV) complex. Extensive experimental results show that chloride-bridged dimanganese(II) complexes could inhibit the swelling of calcium(II) overloaded mitochondria, and carboxylate-bridged manganese(II) complexes enhance the swelling of calcium(II) overloaded mitochondria. These results indicate that the interactions between Mn(II) complexes of N-substituted di(picolyl)amine and mitochondria are influenced by the structure and conformation of the complexes. Mn(II) complexes of N-substituted di(picolyl)amine could be developed as multifunctional anticancer complexes to interfere with the absorption of calcium(II) in mitochondria and the metabolite of O(2) through the H(2)O(2) or ROS involved signaling induced apoptosis of cancer cells.

The impact of sandwich foehn on air pollution in Urumqi, a gap town located on the northern lee side of the Tianshan Mountains of China, is analyzed. The results show that during days with high pollution, the boundary layer over the city and the down-valley area can be divided into a three-layer structure, with the southeasterly foehn sandwiched between the northwesterly winds on top and the cold air surface pool beneath. The southeasterly foehn at heights between 480 and 2100 m results in a very stable boundary layer structure. In combination with the decoupling between the foehn flow and cold air pool, such boundary layer structure prevents vertical mixing of atmospheric pollutants. In the up-valley area from the northern lee side flank to the southern urban area, the ground-based foehn confronts the thermally driven valley breeze and forms a "minifront," which moves northward in the morning and retreats southward in the afternoon. Although the minifront disappears in the early evening, the wind shear of the mountain breeze between the southern suburb and downtown areas is still remarkable, which is favorable for a convergence line to persist around the city all day long. In this case, air pollutants emitted from the up-valley and down-valley areas are transported toward the urban area. Therefore, the air pollutants accumulate daily, leading to the frequent occurrence of heavy pollution events in Urumqi. This indicates that the sandwich foehn plays a critical role in the formation of heavy air pollution events in Urumqi.