Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges.

Natural products derived from plants, as well as their bioactive compounds, have been extensively studied in recent years for their therapeutic potential in a variety of neurodegenerative diseases (NDs), including Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease. These diseases are characterized by progressive dysfunction and loss of neuronal structure and function. There has been little progress in designing efficient treatments, despite impressive breakthroughs in our understanding of NDs. In the prevention and therapy of NDs, the use of natural products may provide great potential opportunities; however, many clinical issues have emerged regarding their use, primarily based on the lack of scientific support or proof of their effectiveness and patient safety. Since neurodegeneration is associated with a myriad of pathological processes, targeting multi-mechanisms of action and neuroprotection approaches that include preventing cell death and restoring the function of damaged neurons should be employed. In the treatment of NDs, including AD and PD, natural products have emerged as potential neuroprotective agents. This current review will highlight the therapeutic potential of numerous natural products and their bioactive compounds thatexert neuroprotective effects on the pathologies of NDs.

Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome.

AIMS: In RCT of adults with decompensated cirrhosis, GCSF mobilizes hematopoietic stem cells HSC and improves short-term outcome. An FDA-IND for sequential Kasai-GCSF treatment in biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated. METHODS: GCSF (Neupogen) at 5 or 10 µg/kg (n = 3/group) was given in 3 daily doses starting on day 3 of Kasai surgery (NCT03395028). Serum CD34+ HSC cell counts, and 1-month of GCSF-related adverse events were monitored. The 6-months Phase 1 clinical outcome was compared against 10 subsequent post Phase 1 Kasai patients who did not receive GCSF. RESULTS: With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5-20%) occurred in 5/6 subjects. HSC count increased 12-fold and 17.5-fold for the 5 µg/kg and10 ug/kg dose respectively; with respective median total bilirubin levels for GCSF vs no-GCSF groups of 55 vs 91 µM at 1 month, p = 0.05; 15 vs 37 µM at 3 months, p = 0.24); and the 6-months cholangitis frequency of 40% vs 90%, p = 0.077. CONCLUSIONS: GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct therapy for sequential Kasai and GCSF is pending.

The interactive effect of the season and estuary position on the concentration of persistent organic pollutants in water and sediment from the Cua Dai estuary in Vietnam.

The current study was conducted in the Cua Dai estuary, Vietnam, (1) to assess the status of persistent organic pollutants (POPs) and (2) to examine the interactive effect of season and estuary position on the concentration of the pollutants in surface water and sediment. Fifty-two water and sediment samples were taken in the dry and rainy seasons from inner- and outer-estuary positions to analyze for six POPs, including hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), heptachlor, aldrin, dieldrin, and polychlorinated biphenyl (PCBs). The averaged concentrations of the respective POPs in water samples were 0.07, 0.1, 0.01, 0.03, 0.001, and 0.2 µg L-1 and in sediment samples were 2.6, 3.1, 0.9, 0.2, 0.2, and 121 µg kg-1. Of the six POPs examined, the concentration of DDTs in sediment samples and PCBs in water samples was significantly affected by the interactive effect of the two examined factors. The concentrations of HCHs, DDTs, heptachlor, and aldrin in water samples and of HCHs in sediment samples were significantly higher in the rainy season than in the dry season. Sediment samples collected from the inner position had a significantly higher concentration of HCHs and PCBs than in the outer position. Some mechanisms possibly influenced the varying POP concentration could include (1) greater riverine discharge in the rainy season and (2) the sea dilution effect in the outer position. Therefore, the concentration of the individual examined POPs in water and sediment in the Cua Dai estuary significantly depended on either the season, estuary position, or their combination.