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Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

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Abstract:Changes in the water level of Qinghai Lake, the largest inland lake in China, directly affect the ecological security of Qinghai province and even the northwest of China. This study aimed to investigate the lake level and identify causes of changes in the lake level of Qinghai Lake. The results showed that the lake level was 3196.55 m in 1959 and gradually declined to 3192.86 m in 2004, with an average decreasing rate of 8.2 cm·year −1 over 45 years. However, the lake level increased continuously by 1.04 m from 2005 to 2010. During the period 1961-2010, the annual average temperature showed an increasing trend in the Qinghai Lake basin, at a rate of 0.32 • C/decade, and the annual precipitation showed obvious fluctuations with an average precipitation of 381.70 mm/year. Annual evaporation showed a decreasing trend (−30.80 mm/decade). The change in lake level was positively correlated to precipitation, surface runoff water and groundwater inflow into the lake and negatively correlated to evaporation from the lake surface. The total water consumption by human activities merely accounted for a very small part of precipitation, surface runoff inflow and groundwater inflow (1.97%) and of lake evaporation (1.87%) in Qinghai Lake basin. The annual water consumption of artificial afforestation and grass plantation accounting for 5.07% of total precipitation, surface runoff inflow and groundwater inflow and 5.43% of the lake evaporation. Therefore, the water level depended more on climatic factors than on anthropogenic factors.

Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated Z. latifolia extract (ETZL) was studied as a potential agent for treating alcohol-induced liver disease. In addition, its underlying mechanisms were elucidated. In the binge model, ETZL was pretreated with alcohol (5 g/kg) three times at 12-h intervals. Our results showed that ETZL pretreatment decreased the serum levels of ALT, AST, ALP, and TG. ETZL treatment appeared to prevent an increase in hepatic TG and MDA levels, and there was a decrease in total GSH following alcohol treatment. Histopathological examination showed that lipid droplets were significantly reduced in the ETZL group compared to the control group. ETZL also exhibited radical scavenging activity. It significantly reduced t-BHP-induced cytotoxicity and the production of reactive oxygen species (ROS) in HepG2 cells. ETZL also enhanced NRF2 nuclear translocation and increased expression of the downstream target genes HO-1, NQO1, and GCLC as an antioxidant defense. Finally, ETZL treatment significantly reduced cell death. Our study suggests that ETZL ameliorates binge ethanol-induced liver injury by upregulating the antioxidant defense mechanism.