Soft Corals-derived Dihydrosinularin Attenuates Neuronal Apoptosis in 6-hydroxydopamine-induced Cell Model of Parkinson's Disease by Regulating the PI3K Pathway.

BACKGROUND: Parkinson's disease (PD) is an irreversible, progressive disorder that profoundly impacts both motor and non-motor functions, thereby significantly diminishing the individual's quality of life. Dihydrosinularin (DHS), a natural bioactive molecule derived from soft corals, exhibits low cytotoxicity and anti-inflammatory properties. However, the therapeutic effects of DHS on neurotoxins and PD are currently unknown. OBJECTIVE: This study investigated whether DHS could mitigate 6-hydroxydopamine (6- OHDA)-induced neurotoxicity and explored the role of neuroprotective PI3K downstream signaling pathways, including that of AKT, ERK, JNK, BCL2, and NFκB, in DHS- mediated neuroprotection. METHOD: We treated the human neuroblastoma cell line, SH-SY5Y, with the neurotoxin 6-OHDA to establish a cellular model of PD. Meanwhile, we assessed the anti-apoptotic and neuroprotective properties of DHS through cell viability, apoptosis, and immunostaining assays. Furthermore, we utilized the PI3K inhibitor LY294002 to validate the therapeutic target of DHS. RESULTS: Based on the physicochemical properties of DHS, it can be inferred that it has promising oral bioavailability and permeability across the blood-brain barrier (BBB). It was demonstrated that DHS upregulates phosphorylated AKT and ERK while downregulating phosphorylated JNK. Consequently, this enhances the expression of BCL2, which exerts a protective effect on neuronal cells by inhibiting caspase activity and preventing cell apoptosis. The inhibition of PI3K significantly reduced the relative protective activity of DHS in 6-OHDA-induced neurotoxicity, suggesting that the neuroprotective effects of DHS are mediated through the activation of PI3K signaling. CONCLUSION: By investigating the mechanisms involved in 6-OHDA-induced neurotoxicity, we provided evidence concerning the therapeutic potential of DHS in neuroprotection. Further research into DHS and its mechanisms of action holds promise for developing novel therapeutic strategies for PD.

Water extract of Helminthostachys zeylanica attenuates LPS-induced acute lung injury in mice by modulating NF-κB and MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies showed that Helminthostachys zeylanica (L.) Hook. could reduce inflammatory responses in macrophage and brain astrocytes. AIM OF THE STUDY: In the present study, we evaluated whether an ethyl acetate extract (HZE) or a water extract (HZW) of H. zeylanica could reduce inflammatory responses in lung epithelial cells and ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Human lung epithelial A549 cells were pre-treated with HZE or HZW (1-10µg/mL), then stimulated with LPS. BALB/c mice received oral HZW for 7 consecutive days, then an intratracheal instillation of LPS to induce lung injury. RESULTS: HZW reduced chemokine and proinflammatory cytokine production in LPS-activated A549 cells. HZW also suppressed ICAM-1 expression and reduced the adherence of acute monocytic leukemia cells to inflammatory A549 cells. HZE had less efficacy than HZW in suppressing inflammatory responses in A549 cells. In vivo, HZW significantly suppressed neutrophil infiltration and reduced the TNF-α and IL-6 levels in bronchoalveolar lavage fluid and serum from LPS-treated mice. HZW also modulated superoxide dismutase activity, glutathione, and myeloperoxidase activity in lung tissues from LPS-treated mice. HZW decreased the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B, and promoted heme oxygenase-1 expression in inflamed lung tissue from LPS-treated mice. CONCLUSION: Our findings suggested that HZW reduced lung injury in mice by reducing oxidative stress and inflammatory responses. HZW also reduced inflammatory responses in human lung epithelial cells.

The evaluation of diabetic patients' use of a telehealth program.

Diabetes is a metabolic disorder that, if not treated promptly and appropriately, can cause complex health complications and mortality. Care models that apply technology, such as telehealth, may be useful in working with diabetes patients. The development and application of wireless communication telehealth have significantly affected healthcare in recent years. Thus, the purpose of this study was to evaluate diabetic patients' use of a telehealth program by using questionnaire survey and laboratory data results. A quantitative study, 1-group pretest-posttest design, was conducted. This study recruited 20 diabetic patients who received telehealth service to measure their glucose, heart rate, and blood pressure, with data uploaded back to the hospital daily. A questionnaire survey was conducted in May 2012 and between August and January 2013 with 20 participants. The test values (blood pressure, heart rate, and blood glucose) of subjects were obtained from the hospital telecare platform and the outpatient monthly reporting system. Study findings showed an overall satisfaction rating of 91% by telehealth participants. Nonparametric statistical analysis demonstrated a significant difference (P < .01) in participants' glycosylated hemoglobin and resultant effective control. These findings indicated that participants accepted this care model, and telehealth could improve participants' glucose control.

[Clinical ethic dilemmas and difficulties in reporting child abuse].

The number of reported cases of child abuse has been rising steadily in Taiwan. Although child abuse reporting is mandatory for healthcare professionals, Taiwan-specific social norms and traditional cultural values make the decision to report such abuse more complex and difficult. We used Jonsen's four topics method to examine a suspected case of child abuse and to analyze its associated dilemmas and ethical difficulties. We then discussed the identified conflicts among the three aspects of cultural values, legal obligations, and personal values. Findings indicate that healthcare professionals experience dilemmas among these three aspects. Reporting suspected child abuse appears the best resolution after considering and balancing the principles of non-malfeasance, beneficence, fidelity and follow-up care. Once reported, resources can be provided to the affected child and his ÷ her family. This case analysis provides a reference for healthcare professionals to deal with child abuse cases.

Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson's model: a promising candidate for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and gait impairment. So far, very few pharmacological agents have been isolated or developed that effectively inhibit the progression of PD. However, several studies have demonstrated that inflammatory processes play critical roles in PD. Therefore, anti-inflammatory agents may suppress disease progression in PD. 11-Dehydrosinulariolide was isolated from cultured soft corals. The anti-inflammatory effect of this molecule has been observed through suppression of the expression of two main pro-inflammatory proteins: inducible nitric oxide synthase and cyclooxygenase-2, in lipopolysaccharide-stimulated macrophage cells. We also found that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and apoptosis in a human neuroblastoma cell line (SH-SY5Y). The pharmacological activity of this compound has been studied, and it is associated with the inhibition of 6-OHDA-induced activation of caspase-3 and translocation of nuclear factor kappa B. 11-Dehydrosinulariolide increased the activation of survival-signaling phospho-Akt but not phospho-ERK. The neuroprotective effect of 11-dehydrosinulariolide was assessed here using 6-OHDA-treated SH-SY5Y cells, wherein neuroprotection is mediated through regulation of phosphatidylinositol 3-kinase (PI3K). Furthermore, 11-dehydrosinulariolide caused a significant decrease in caspase-3/7 activity in comparison to the 6-OHDA-treated group, indicating that 11-dehydrosinulariolide has neuroprotective properties. We conclude that 11-dehydrosinulariolide is a promising candidate for the treatment of Parkinson's disease through its anti-apoptotic and anti-inflammatory action via PI3K signaling.

A recombinant lipoprotein containing an unsaturated fatty acid activates NF-kappaB through the TLR2 signaling pathway and induces a differential gene profile from a synthetic lipopeptide.

The lipid moiety of a novel recombinant lipoprotein, which contains a dengue virus envelope protein domain 3, rlipo-D1E3, has been shown to activate antigen-presenting cells (APCs) as an intrinsic adjuvant. Because the lipid moiety of rlipo-D1E3 contains an unsaturated fatty acid, it is unclear if the receptor usage by bacterially derived lipoproteins is the same as that of the synthetic lipopeptide palmitoyl-3-Cys-Ser-(Lys)(4) (Pam3). In the present study, we show that the rlipo-D1E3 lipoprotein can induce the activation of spleen cells and bone marrow-derived dendritic cells (BM-DCs) in wild-type and TLR4-deficient mice, but not in TLR2(-/-) mice. After analyzing the co-receptor usage of TLR2 using TLR1(-/-) or TLR6(-/-) mice, the TLR2 signaling triggered by rlipo-D1E3 and Pam3 could use either TLR1 or TLR6 as a co-receptor. Analysis of the MAPK signaling pathway revealed that rlipo-D1E3 could initiate the phosphorylation of p38, ERK1/2 and JNK1/2 earlier than the synthetic lipopeptide. In addition, the expression levels of IL-23, IL-27 and MIP-1 alpha in BM-DCs stimulated by rlipo-D1E3 were higher than the expression levels in BM-DCs stimulated by Pam3. Taken together, these results demonstrate that different TLR2 ligands can promote various immune responses by inducing different levels of biological cytokines and chemokines.

Kindergarten teachers' experience with reporting child abuse in Taiwan.

OBJECTIVE: The objectives were to examine factors associated with reporting child abuse among kindergarten teachers in Taiwan based on the Theory of Planned Behavior (TPB). METHOD: A stratified quota sampling technique was used to randomly select kindergarten teachers in Taiwan. The Child Abuse Intention Report Scale, which includes demographics, attitudes about child discipline, punishment for perpetrators, and professional responsibility for reporting, subjective norms regarding support for reporting from the general and specific important persons, perceived behavioral control, and vignettes of child abuse, was used to collect data. A total of 598 kindergarten teachers (return rate 47%) provided data. RESULTS: While 97% of teachers reported having no experience with reporting a child abuse case, 11% indicated they had failed to report a suspected case of child abuse. Multiple regression revealed that, except for social norms, attitudes toward child discipline, punishments for perpetrators, and professional responsibility as well as perceived behavioral control explained 22.4% of variance of kindergarten teachers' intention to report child abuse. CONCLUSIONS: With the exception of the subjective norms, the findings of this study supported the TPB that kindergarten teachers' intention to report child abuse is associated with attitudes toward child discipline, punishment for perpetrators, professional responsibility, and perceived behavioral controls over reporting. This study revealed the problem of underreporting child abuse among kindergarten teachers in Taiwan, and highlighted the discrepancy between child abuse training and expected reporting outcomes suggesting an insufficiency in the current training programs on child abuse. PRACTICE IMPLICATIONS: There is a need to scrutinize the current training in child abuse and develop standardized training and clear reporting guidelines that will increase kindergarten teachers' confidence when confronted with suspected victims and perpetrators of child abuse in Taiwan.

Identification of HLA-A11-restricted CTL epitopes derived from HPV type 18 using DNA immunization.

Identification of the cytotoxic T lymphocyte (CTL) epitopes of tumor antigens is important for effective immunotherapy. We report that a combination of epitope prediction, enzyme-linked immunosorbent assay (ELISA)-based epitope-HLA complex formation, and DNA immunization methods can improve the efficiency and accuracy of CTL epitope studies. In this study, two HLA-A11-restricted epitopes derived from human papillomavirus (HPV)18 E6 oncoprotein were identified. HLA-A11-transgenic mice immunized with these epitopes could specifically induce interferon-gamma (IFNgamma) production, cytotoxicity and peptide/HLA-A11 tetramer binding in CD8(+) T-cells. To study intracellular processing of CTL epitopes, we constructed a DNA plasmid containing an endoplasmic reticulum (ER) targeting sequence as well as the HPV18 E6 and E7 genes (pEK/HPV18E6E7). CTL responses against peptide-pulsed T2/A11 cells could be detected after immunizing HLA-A11-transgenic mice with pEK/HPV18E6E7. Furthermore, the identified peptides could stimulate T-cells to secrete IFNgamma from HPV18-infected patients. Our results demonstrate that the antigenic E6 peptides derived from HPV18 are potential candidates for the treatment of HPV 18-associated tumors in HLA-A11(+) populations.