The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

Photochromism and photoswitchable luminescence in a Zn7 cluster-based metal-organic framework with an organic guest.

Photochromic materials coupled with photoswitchable luminescence functionalities are of particular interest due to their potential applications in switches and optical memory devices. However, the construction of such materials, especially those with two-color emission states, is still challenging. In this context, a rare Zn7 cluster-based host-guest MOF material, (bbmp)[Zn7(IPA)6(OH)4(H2O)2] (1) (H2IPA = isophthalic acid, bbmp·2I = 4,4'-([1,1'-biphenyl]-4,4'-diyl)bis(1-methylpyridin-1-ium) diiodide), was prepared by encapsulating an organic cation into an anionic MOF produced from zinc cations and isophthalic acid ligands, which exhibits reversible naked detectable photochromic properties varying from yellow to green upon UV-Vis light irradiation. The photoactive guest bbmp2+ and the short O⋯N+ distances between the oxygen atoms of the carboxylate groups and the pyridine ring play a crucial role in the photochromism of this compound. More interestingly, the luminescence color of this cluster-based host-guest material can be reversibly switched from green to blue upon irradiation, exhibiting photoswitchable luminescence properties.

EPO promotes axonal sprouting via upregulating GDF10.

Erythropoietin (EPO) has an exact neuroprotective effect on stroke. However, it remains unknown whether it participates in axonal sprouting after neuron damage. Growth and differentiation factor 10 (GDF10) has been shown to be a trigger of axonal sprouting after stroke. Hence, it was hypothesized that EPO promotes axonal sprouting mainly through GDF10. In the present in vitro experiment, it was found that EPO could promote axonal sprouting and GDF10 expression in a dose-dependent manner. The knockdown of GDF10 using siRNA abolished the effect of EPO-mediated axonal sprouting, indicating that GDF10 is the executor of EPO-mediated axonal sprouting. The treatment of neurons with nuclear factor-kappaB (NF-κB) inhibitor JSH-23 could inhibit the accumulation of NF-κB phospho-p65 (p-p65) in the nucleus, the upregualtion of GDF10 and extending of axonal length. Furthermore, the addition of Janus kinase 2 (JAK2) inhibitor CEP-33779 or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 to the culture medium also blocked the nuclear translocation of p-p65, the expression of GDF10, and axonal sprouting, suggesting that EPO induces axonal sprouting via activating cellular JAK2 and PI3K signaling. Impeding JAK2 signaling with CEP-33779 can suppress the phosphorylation of PI3K, and this confirms that the upstream of PI3K signaling is JAK2. These present results provide a novel insight into the role of EPO and the molecular mechanism of axonal sprouting, which is beneficial for the development of novel approaches for neurological recovery after brain injury, including stroke.

Physiological response of Cu and Cu mine tailing remediation of Paulownia fortunei (Seem) Hemsl.

The physiological responses and Cu accumulation of Paulownia fortunei (Seem) Hemsl. were studied under 15.7-157 µmol L(-1) Cu treatments in liquid culture for 14 days; the impacts of Cu concentration in the seedlings were evaluated under Cu mine tailing culture with acetic acid and EDTA treatment for 60 days. Results showed that the concentrations of Chl-a, Chl-b and Carotenoids significantly increased (p < 0.05) at 15.7-78.7 µmol L(-1)Cu treatment and significantly decreased at 157 µmol L(-1) treatment after 14 days of Cu exposure. The activities of superoxide dismutase (SOD) and catalase (CAT) significantly increased as Cu levels were enhanced and the activities of both SOD and CAT under 157 µmol L(-1) Cu stress were 2.9 and 1.9 times higher than that of control, respectively. The concentrations of proline and soluble sugars in the leaves of P. fortunei significantly increased as the Cu concentrations were elevated. Cu concentrations in roots, stems and leaves of P. fortunei increased significantly as Cu levels increased and reached 1911, 101 and 93 µg g(-1) dry weights (DW) at 157 µmol L(-1) Cu treatment, respectively. The seedlings of P. fortunei cultivated in Cu tailing experienced unsuccessful growth and loss of leaves in all treatments due to poor nutrition of the Cu tailing. The dry weight of P. fortunei increased under all the treatments of acetic acid after 60 days exposure. However, dry weight significantly decreased under both levels of EDTA. The Cu concentrations increased significantly in roots and decreased in leaves when each was treated with both concentrations of acetic acid. The Cu concentrations in the roots, stems and leaves increased significantly, and the concentrations of Cu in the stems and leaves under the treatment of 2 µmol L(-1) EDTA reached 189.5 and 763.1 µg g(-1) DW, respectively. The result indicated that SOD, CAT, proline and soluble sugars played an important role in coping with the oxidative stress of copper. Acetic acid could promote growth and EDTA at the experimental levels, which could also enhance Cu absorption and translocation into the stems and leaves of P. fortune. Furthermore, acetic acid and EDTA could be rationally utilized in Cu-contaminated soil.

The physiological response and sub-cellular localization of lead and cadmium in Iris pseudacorus L.

The seedling development and physiological responses of Iris pseudacorus L. to Pb and Cd and their combination were studied for 28 days liquid culture and sub-cellular localization of Pb and Cd in the root tip cells treated with 2,070 mg L(-1) Pb and 1,000 mg L(-1)Cd for 16 days sand culture was evaluated. Results showed that the dry weights (DWs) of shoots and roots of I. pseudacorus were significantly decreased at 500 mg L(-1)Pb and 25 mg L(-1)Cd + 500 mg L(-1)Pb treatments and the root DWs under all treatments were significantly decreased in comparison with that of control. The concentrations of Chla in the leaves were decreased at all treatments, while, the concentrations of Chlb and total carotenoids were not significantly decreased under 25 mg L(-1)Cd and 25 mg L(-1)Cd + 500 mg L(-1)Pb treatments. The MDA and proline concentrations and POD activities in the shoots and roots were increased under treatments of 500 mg L(-1)Pb and 25 mg L(-1)Cd + 500 mg L(-1)Pb, but POD activities in the shoots and roots and MDA concentrations in the shoots were significantly decreased at 25 mg L(-1) Cd treatment. The results of sub-cellular localization of Pb and Cd showed that numerous Pb deposits were found on the inner surface of died cell walls in the cortex treated with 2,070 mg L(-1) Pb and Cd deposits were found in the cell wall treated with 1,000 mg L(-1) Cd. Pb and Cd deposits were not found in the cytoplasm. The results indicated that POD and proline showed strong beneficial properties against Pb and Cd stress and there were some mechanisms keeping most cells with normal activities in the plant from Pb toxicity by sacrificing a few cells that accumulated a large amount Pb. Sub-cellular localizations of Pb and Cd in the root tip cells of I. pseudacorus were little difference with the localizations in other species of Iris in the previous studies.

Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat.

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats. In parallel, Western blotting and RT-PCR showed a similar reduction of GSTM2 in left ventricles and aortas of 4-, 8-, and 16-week-old SHR, which is before the onset of hypertension. This suggests that differential expression is not attributable to long-term changes in blood pressure. Meanwhile, the activities of GSTM2 were significantly decreased in different ages old SHR. Conversely, there was an enhanced generation of superoxide anion and activation of NADPH oxidase in SHR, which was accompanied by an increase in the protein expression of p47phox, a subunit of NADPH oxidase. These data suggest that it maybe a reduction in antioxidant defenses, evident by a reduced expression and activity of GSTM2, in the left ventricles and aortas of SHR that leads to increased levels of superoxide anion and activation of NADPH oxidase.