Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii, Engelhardia roxburghiana, Smilax corbularia and Erythroxylum gonocladum, and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i.p) daily for 5 days, to establish a subacute Parkinson's disease model, followed by daily treatment with AST or saline for 7 days. Pole and traction tests showed that AST ameliorated the impaired motor functions in MPTP-induced Parkinson's disease mice. High performance liquid chromatography analysis revealed that AST treatment prevented MPTP-induced decreases in striatal dopamine levels. Immunofluorescence assays showed that AST reduced the loss of dopaminergic neurons and the activation of microglia and astrocytes in the substantia nigra. Western blot analyses revealed that AST suppressed α-synuclein overexpression and activated PI3K/Akt in the striatum following MPTP treatment. AST also prevented the MPTP-induced reduction in total superoxide dismutase and glutathione activity in the striatum. AST exerts neuroprotective effects on MPTP-induced PD mice by suppressing gliosis, α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD.

Sorafenib (Sor) is clinical standard therapy for advanced hepatocellular carcinoma (HCC). However, detailed molecular mechanism behind Sor-exerted pharmacological effect remains unknown. In this study, sera samples, staged hepatic cancer tissues from Sor-treated patients with advanced HCC were harvested for a group of biochemical tests and immunoassays. Compared to non-treated control, blood contents of alanine transaminase (ALT), aspartate transaminase (AST), alphafetoprotein (AFP), fibroblast growth factor 21 (FGF21) were decreased in Sor-treated HCC patients, while the level of interleukin 10 (IL-10) were increased. As well, reduced triglyceride (TG), total cholesterol (T-CHOL), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in sera were checked in Sor-treated HCC patients. In comparison with non-treated cancer sections, Sor-treated HCC cells showed decreased positive cells of proliferative marker for proliferating cell nuclear antigen (PCNA) and metastasized biomarker for cytokeratin 19 (CK19). In addition, elevated immunofluorescence-labeled cells of endoplasmic reticulum (ER)-stress markers of activating transcription factor 6 (ATF6), eukaryotic initiation factor 2α kinase (eIF2α), glucose-regulated protein (GRP-78), X-box binding protein 1 (XBP1) were observed in Sor-treated HCC livers. Further, validated data from Western blot assay exhibited that hepatocellular expressions of ATF6, eIF2α, GRP78, XBP1 in Sor-treated HCC liver cells were up-regulated. Briefly, our present clinicopathologic findings indicate that Sor-induced ER stress may be responsible for therapeutic mechanism against advanced HCC. In addition, induction of intracellular ER stress functions as a promising strategy for treating advanced HCC.

Microcystins produced by some cyanobacteria can cause damages to the liver and kidneys of aquatic animals. In the natural water with cyanobacterial blooms, silver carp may suffer from the most serious affect of the bloom due to their filtering these cyanobacteria and ingesting them as food. In the present study, silver carp was exposed to microcystin-LR by using the method of intraperitoneal injection first to determine the acute toxicity of microcystin-LR on silver carp and then to determine the activity of inflammatory protein and content of inflammatory factors from the serum of silver carp following a subacute exposure of microcystin-LR at doses of 104.9 μg kg-1 (1/5 of LD50) or 262.1 μg kg-1 (1/2 of LD50). The results showed that MC-LR exposure increased fish liver index and promoted the activities of fish serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating the hepatotoxicity of MC-LR on the fish. Moreover, MC-LR exposure also increased the number of leukocytes, complement C3 level, lysozyme activity (at the first 9 h of exposure), and the contents of cytokines TNF-α, IL-1β and IFN-γ in fish serum. In addition, a significant increase in IgM level was observed in the serum and head kidney of silver carp following MC-LR exposure. This result suggests that semi-lethal doses of MC-LR exposure is not only hepatotoxic but also immunotoxic to silver carp.

Antimicrobial-resistant Neisseria gonorrhoeae (NG) infection is a global public health threat, and there is a critical need to monitor patterns of resistance and risk factors. In collaboration with the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the Thailand Department of Disease Control (DDC), Ministry of Public Health (MoPH) implemented the first Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in November 2015. Men presenting with urethritis at two clinical settings in Bangkok, Thailand (Bangrak Hospital [BH] and Silom Community Clinic @TropMed [SCC @TropMed]) provided demographic and behavioral information and had a urethral swab for Gram's stain and NG culture collected. The NG isolates were evaluated for antimicrobial susceptibility by the Epsilometer test (Etest) to determine minimum inhibitory concentrations (MICs) for cefixime (CFM), ceftriaxone (CRO), azithromycin (AZI), gentamicin (GEN), and ciprofloxacin (CIP). From November 2015 -October 2016, 1,102 specimens were collected from 1,026 symptomatic men; 861 (78.1%) specimens were from BH and 241 (21.9%) specimens were from SCC @TropMed. Among the 1,102 specimens, 582 (52.8%) had intracellular Gram-negative diplococci and 591 (53.6%) had NG growth (i.e., NG infection); antimicrobial susceptibility testing (AST) was performed on 590 (99.8%) NG isolates. Among all symptomatic men, 293 (28.6%) had sex with men only, 430 (41.9%) were ages 18-29 years, 349 (34.0%) had antibiotic use in the last 2 weeks, and 564 (55.0%) had NG infection. Among 23 men with repeat NG infection during this first year of surveillance, 20 (87.0%) were infected twice, 2 (8.7%) were infected three times, and 1 (4.3%) was infected more than four times. All NG isolates were susceptible to CFM and CRO, and had MICs below 2 μg/mL for AZI and below 16 μg/mL for GEN. Overall, 545 (92.4%) isolates were resistant to CIP. This surveillance activity assessed individual patients, and included demographic and behavioral data linked to laboratory data. The inclusion of both individual and laboratory information in EGASP could help identify possible persistent infection and NG treatment failures. Expansion of EGASP to additional global settings is critical to assess trends and risk factors for NG, and to monitor for the emergence of resistance.

Freshwater clams (Corbicula fluminea) have long been used as a folk remedy in Chinese tradition. Their hot-water extract has been commercialized as a functional drink for liver protection. The objective of this study was to develop a product of the residual clam meat (FCR) and assess its functional compounds. The ethanol extract of FCR, designated FCRE, was identified to comprise phytosterols, polyunsaturated fatty acids (PUFAs) and carotenoids. FCRE significantly reduced lipid accumulation and cell death in HepG2 cells via decreased fatty acid synthase (FAS) activity and increased activities of carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO), indicative of suppressed lipogenesis and increased β-oxidation of fatty acids. In tilapia fed with high-fat diet (HFD), FCRE mitigated nonalcoholic steatohepatitis (NASH), which was evidenced by decreased levels of plasma aspartate transaminase (AST) and alanine transaminase (ALT), in addition to reduced total cholesterol and accumulation of triacylglycerols, particularly those of saturated and monounsaturated fatty acids. FCRE also suppressed stearoyl-CoA desaturase-1 (SCD-1) index, increased the PUFAs' n3/n6 ratio, and reduced prostaglandin E2 (PGE2) and inflammatory infiltrates in tilapia liver. Tilapia fed with HFD for 2 weeks displayed NASH symptoms, while mice took 10 weeks to display NASH symptoms. No previous study has been reported on the potential use of tilapia as an NASH model for pre-screening hepatoprotective-functional foods.

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.