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Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid β-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2018 by the authors.)

Garcinol, which is isolated from fruit rinds of Garcinia indica, is a polyisoprenylated benzophenone. It has been studied for its antitumor activity by inducing apoptosis and inhibiting autophagy in human prostate cancer cells. The Bax/Bcl-2 ratio increased when garcinol was applied to PC-3 cells indicating a presence of apoptosis. Meanwhile, procaspases-9 and -3 were suppressed with attenuating PARP and DFF-45. Autophagy was inhibited through activating p-mTOR and p-PI3 Kinase/AKT by garcinol, which as a result induced the cells to apoptosis directly. In addition, the apoptosis effect of garcinol in a xenograft mouse model was also tested, suggesting a consistent result with PC-3 cell model. The tumor size was reduced more than 80 percent after the mouse accepted the garcinol treatment. Garcinol was demonstrated to have a strong antitumor activity through inhibiting autophagy and inducing apoptosis, which was discovered for the first time. Based on these findings, our data suggests that garcinol deserves further investigation as a potent chemopreventive agent.

Scope: Garcinol is a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica and has exhibited chemopreventive effects on azoxymethane)-induced colonic aberrant crypt foci in mice. In this study, we investigated whether garcinol protects against dextran sulfate sodium (DSS) induced colitis/inflammation and azoxymethane/DSS-induced inflammation-related colon tumorigenesis in male ICR mice. We also aimed to delineate the possible molecular mechanisms responsible for these effects., Methods and Results: Treatment with garcinol prevented shortening of the colon length and the formation of aberrant crypt foci and improved the inflammation score in the mouse colon stimulated by DSS. Moreover, administration of garcinol markedly decreased DSS-induced inducible nitric oxide synthase, cyclooxygenase-2, and proliferating cell nuclear antigen protein expression. The dietary administration of garcinol effectively reduced the tumor size and incidence in the mouse colon. Western blot and immunohistochemical analysis revealed that administration of garcinol significantly downregulated cyclooxygenase-2, cyclin D1, and vascular endothelial growth factor expression via inhibition of the extracellular signal-regulated protein kinase 1/2, phosphatidylinositol 3 kinase/Akt/p70 ribosomal S6 kinase, and Wnt/β-catenin signaling pathways., Conclusion: Our results suggest that garcinol may merit further clinical investigation as a chemoprophylactic food that helps prevent colitis-associated colon cancer., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Supercritical fluid carbon dioxide extraction technology was developed to gain the active components from a Taiwan native plant, Zingiber officinale (ginger). We studied the biological effects of ginger extracts via multiple assays and demonstrated the biofunctions in each platform. Investigations of ginger extracts indicated antioxidative properties in dose-dependant manners on radical scavenging activities, reducing powers and metal chelating powers. We found that ginger extracts processed moderate scavenging values, middle metal chelating levels, and slight ferric reducing powers. The antibacterial susceptibility of ginger extracts on Staphylococcus aureus, Streptococcus sobrinus, S. mutans, and Escherichia coli was determined with the broth microdilution method technique. The ginger extracts had operative antimicroorganism potentials against both Gram-positive and Gram-negative bacteria. We further discovered the strong inhibitions of ginger extracts on lethal carcinogenic melanoma through in vivo xenograft model. To sum up, the data confirmed the possible applications as medical cosmetology agents, pharmaceutical antibiotics, and food supplements.

Mosquitoes known to be involved in the transmission of Japanese encephalitis virus (JE) on Taiwan typically develop in rice fields. However, recent serological evidence indicated that JE virus was being transmitted on Liu-Chiu, a rice-free islet. To identify the mosquito vector in this unusual epidemiological situation, 4 mosquito species commonly found in Liu-Chiu were evaluated for their vector competence for a strain of JE (CH1392) virus isolated from central Taiwan. Armigeres subalbatus (Coquillett) was the most susceptible species, indicating its status as a potential vector. In addition, an isolate of JE (T1P1) virus from Ar. subalbatus collected on Liu-Chiu readily infected the salivary glands of orally infected Ar. subalbatus originating from Liu-Chiu. The infection rate reached 79% (11/14) after a 20-d period of extrinsic incubation at 28 degrees C. We conclude that JE likely was transmitted between vertebrate hosts by Ar. subalbatus in this rice-free islet and that this species should be considered as a potential vector in similar ecological conditions.

Endogenous biochemical regulation of diurnal changes in intraocular pressure was investigated in rabbits. Various biochemical parameters in eye tissues, particularly the iris and ciliary body, were studied at peak (21:00 hr) and trough (09:00 hr) points of IOP. No statistical difference in choline acetyltransferase activity, adrenergic transmitter levels and dopamine concentration could be detected at these points. On the other hand, serotonin N-acetyltransferase activity was significantly higher at 21:00 hr (2.84 +/- 0.14 nmoles/mg protein/hr) than at 09:00 hr (2.18 +/- 0.16 nmoles/mg protein/hr) indicating that melatonin might be involved in the diurnal changes in IOP. Intracameral injections of various agents into rabbit eyes revealed that melatonin but not serotonin nor N-acetylserotonin raised IOP markedly, indicating that melatonin but not its precursors is involved in IOP regulation. Topical application of melatonin did not affect the IOP presumably because it does not cross the cornea effectively.

The proposed role of melatonin as an endogenously synthesized modulator of intraocular pressure in the eye was investigated. Melatonin levels were determined by radioimmunoassay in the iris, ciliary body and retina-choroid of pinealectomized or sham-operated chickens by day and by night. Pinealectomy had no effect on melatonin levels in the ciliary body or retina of chicken eyes; a diurnal rhythm continued to be observed in these tissues, with values higher by night than by day. Chloroform-extracted melatonin levels in the rabbit ciliary body showed a diurnal rhythm but melatonin levels in rabbit retina did not. Intracameral infusion of melatonin into cat eyes caused aqueous humor synthesis to decrease but caused a greater decrease in aqueous humor outflow facility, leading to a significant increase in intraocular pressure. The results suggest that melatonergic mechanisms in the eye could be responsible for the diurnal rhythm in IOP, and the synthesis and diurnal rhythm of this melatonin are independent of the pineal gland.

Among all lipoxygenase inhibitors studied, REV 5901 was found to be the most potent one to reduce lens protein-induced ocular inflammation in rabbits. It reduced ocular inflammation effectively by either injection into the ear vein (10 mg/kg) (65% inhibition) or topical administration (50 microliters of 5% ointment) (40% inhibition). Local administration was less effective than intravenous injection presumably because of slower drug delivery into the eyes.