From comfort zone to front-line care: perspectives and reflections of community pharmacists entering home-based palliative care.

BACKGROUND: Palliative care requires a multidisciplinary team to assist patients and their families to obtain good quality care at the end of life. Typically, community pharmacists have fewer opportunities to provide services for patients with palliative care needs than hospital pharmacists. Moreover, home-based palliative care (HBPC) by pharmacists remains low and there is a lack of research regarding HBPC provided by pharmacists. Therefore, this study sought to understand the views and reflections of community pharmacists in the clinical frontline providing palliative home services. METHODS: Purposive sampling was used to recruit six community pharmacists for one-on-one, in-depth, semi-structured interviews and the data were analysed using thematic analysis. RESULTS: Five major themes emerged: [1] Engagement, [2] Challenge, [3] Mission, [4] Career metamorphosis, and [5] Outlook. The pharmacists described how they engaged in HBPC and faced the challenges. They regarded opioid management as a burden. Moreover, some mentioned that reimbursement for palliative home care is low or non-profitable. They suggested building a platform to exchange advice and legislation adjustments so that they could pass on their experiences to less experienced pharmacists in HBPC. CONCLUSIONS: The involvement of pharmacists is crucial to provide better palliative care. Although the present study was small and might not fully represent the whole situation, the findings could still inform future education, training, and policy planning to promote pharmacists' participation in palliative care to generalise community palliative care.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h.

BACKGROUND/PURPOSE: In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24 h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24 h. METHODS: This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24 h) and Late groups (>24 h) according to the time of antiplatelet administration after stroke onset. RESULTS: In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p = 0.016) and Late (88.2% versus 76.9%, p = 0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p = 0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p = 0.024) groups. CONCLUSION: In patients with AMIS and an OTDT of more than 24 h, DAPT was associated with a favorable outcome at 90 days.

Heme oxygenase-1 inhibits DENV-induced endothelial hyperpermeability and serves as a potential target against dengue hemorrhagic fever.

Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.

Frailty is Associated With Frontal Cortex-Related Cognitive Function in Patients With Alzheimer Disease.

OBJECTIVE: We compared the cognitive functions of Alzheimer disease (AD) patients who were robust, frail or pre-frail and hypothesized that declines in frontal cortex-related neuropsychological function would be associated with frailty. METHOD: One hundred and sixty outpatients aged 65 years or older with mild AD were enrolled. Cognitive function was assessed using the Cognitive Ability Screening Instrument and further classified into 4 clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Other variables included depressive mood, daily activities, body mass index, handgrip strength (HGS), and normal gait speed (NGS). RESULTS: Performance in daily activities, and slower NGS than robust group. Both the frail and pre-frail groups had lower HGS and more depressive symptoms than robust group. Generalized linear with ordinal logistic analysis showed that increment in age, slowing in NGS, and worse frontal cortex cluster function associated with being in a higher level of frailty. The patients with depression symptoms were the odds of being in a higher level of frailty compared to those without depression symptoms. CONCLUSIONS: In addition to physical and psychological symptoms, frailty is associated with specific cognitive domains in patients with AD. A multidimensional approach should be used to assess the impact of intervention programs focusing on frail patients with AD.

Intracellular Galectin-9 Enhances Proximal TCR Signaling and Potentiates Autoimmune Diseases.

Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9-deficient T cells were less able to induce T cell-mediated colitis. However, several mouse-based studies reported that galectin-9 treatment induces T cell apoptosis and ameliorates autoimmune diseases in an exogenously modulated manner, indicating a complicated regulation of galectin-9 in T cells. We found that galectin-9 is expressed mainly inside T cells, and its secreted form is barely detected under physiological conditions. Endogenous galectin-9 was recruited to immune synapses upon T cell activation. Moreover, proximal TCR signaling was impaired in galectin-9-deficient T cells, and proliferation of these cells was decreased through an intracellularly modulated manner. Th17 cell differentiation was downregulated in galectin-9-deficient T cells, and this impairment can be rescued by strong TCR signaling. Taken together, these findings suggest that intracellular galectin-9 is a positive regulator of T cell activation and modulates the pathogenesis of autoimmune diseases.

MicroRNA-155 inhibits dengue virus replication by inducing heme oxygenase-1-mediated antiviral interferon responses.

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.

Factors associated with do-not-resuscitate document completion among patients hospitalized in geriatric ward.

BACKGROUND: With a rapidly aging population, there is an increasing need for do-not-resuscitate (DNR) and advance care planning (ACP) discussions. This study investigated the factors associated with signing DNR documents of older patients in the geriatric ward. METHODS: We conducted a retrospective cohort study at a geriatric ward in a tertiary hospital in Southern Taiwan. Three hundred and thirty-seven hospitalized older patients aged ≥65 years in the geriatric ward from 2018 to 2019. The Hospital Information System and electronic medical records were accessed to obtain details regarding patients' demographics, daily living activities, serum albumin level, nutrition screening score, intensive care unit transferal, resuscitation procedure, days of hospital stay, and survival status on discharge, and DNR status was recorded retrospectively. Patients were classified into DNR and non-DNR groups, with t-tests and Chi-square tests applied to compare the differences between groups. Logistic regression was performed to predict factors related to the DNR documents. RESULTS: A total of 337 patients were included, 66 of whom had signed a DNR during hospitalization. After multivariate logistic regression, age 85 or more compared to age 65-74 (adjusted odds ratio, aOR 5.94), poor nutrition with screening score two or more (aOR 2.71), albumin level less than 3 (aOR 3.24), Charlson Comorbidity Index higher than 2 (aOR 2.46) and once transferred to ICU (aOR 5.11) were independently associated with DNR documentation during hospitalization. CONCLUSIONS: Several factors related to DNR documents for geriatric patients were identified which could provide clinical information for physicians, patients, and their families to discuss DNR and ACP.

Dynamic Modeling and Experimental Validation of an Impact-Driven Piezoelectric Energy Harvester in Magnetic Field.

In this study, an impact-driven piezoelectric energy harvester (PEH) in magnetic field is presented. The PEH consists of a piezoelectric cantilever beam and plural magnets. At its initial status, the beam tip magnet is attracted by a second magnet. The second magnet is moved away by hand and then the beam tip magnet moves to a third magnet by the guidance of the magnetic fields. The impact occurs when the beam motion is stopped by the third magnet. The impact between magnets produces an impact energy and causes a transient beam vibration. The electric energy is generated by the piezoelectric effect. Based on the energy principle, a multi-DOF (multi-degree of freedom) mathematical model was developed to calculate the displacements, velocities, and voltage outputs of the PEH. A prototype of the PEH was fabricated. The voltages outputs of the beam were monitored by an oscilloscope. The maximum generated energy was about 0.4045 mJ for a single impact. A comparison between numerical and experimental results was presented in detail. It showed that the predictions based on the model agree with the experimental measurements. The PEH was connected to a diode bridge rectifier and a storage capacitor. The charges generated by the piezoelectric beam were stored in the capacitor by ten impacts. The experiments showed that the energy stored in the capacitor can light up the LED.

Sarcopenia in female patients with Alzheimer's disease are more likely to have lower levels of haemoglobin and 25-hydroxyvitamin D.

AIM: Few studies have investigated sarcopenia in patients with cognitive impairment. However, identifying the characteristics and factors associated with sarcopenia in these patients may help to decrease the risk of falls, prevent disabilities, and maintain an independent life, all of which can affect the quality of life of both patient and caregiver. Therefore, the aim of this study was to investigate associated factors of sarcopenia in patients with mild to moderate Alzheimer's disease. METHODS: This cross-sectional study enrolled 125 outpatients aged 65 to 89 years (mean age 79.5 ± 7.9 years) from January 2018 to December 2018. In addition to demographic characteristics, cognitive status, depressive mood, activities of daily living, body mass index (BMI), handgrip strength, gait speed, muscle mass, and serum levels of 25-hydroxyvitamin D (Vit D), haemoglobin (Hb), albumin and creatinine were assessed. Sarcopenia was defined based on the presence of low muscle mass and either low muscle strength or low physical performance. RESULTS: Overall, 29.6% of the patients had sarcopenia. The patients with sarcopenia were mostly male, significantly older, and had a lower BMI and lower levels of Vit D. The female patients with sarcopenia were more likely to have lower levels of Hb. Multiple logistic regression showed that sarcopenia was associated with BMI in both genders. The level of Vit D was associated with sarcopenia in the female patients, whereas age was associated with sarcopenia in the male patients. CONCLUSIONS: A low BMI may be a dementia-related risk factor for sarcopenia. The female patients with sarcopenia were more likely to have lower levels of Hb and Vit D. There may be different risk profiles for sarcopenia in men and women with Alzheimer's disease. Further studies are needed to devise different nutritional support for muscle weakness in patients with cognitive decline by gender.

Prostasin Impairs Epithelial Growth Factor Receptor Activation to Suppress Dengue Virus Propagation.

BACKGROUND: Dengue virus (DENV), a common and widely spread arbovirus, causes life-threatening diseases, such as dengue hemorrhagic fever or dengue shock syndrome. There is currently no effective therapeutic or preventive treatment for DENV infection. METHODS: Next-generation sequencing analysis revealed that prostasin expression was decreased upon DENV infection. Prostasin expression levels were confirmed by real-time quantitative polymerase chain reaction in patients with dengue fever and a DENV-infected mice model. Short hairpin RNA against EGFR and LY294002 were used to investigate the molecular mechanism. RESULTS: Based on clinical studies, we first found relatively low expression of prostasin, a glycosylphosphatidyl inositol-anchored membrane protease, in blood samples from patients with dengue fever compared with healthy individuals and a high correlation of prostasin expression and DENV-2 RNA copy number. DENV infection significantly decreased prostasin RNA levels of in vivo and in vitro models. By contrast, exogenous expression of prostasin could protect ICR suckling mice from life-threatening DENV-2 infection. Mechanistic studies showed that inhibition of DENV propagation by prostasin was due to reducing expression of epithelial growth factor receptor, leading to suppression of the Akt/NF-κB-mediated cyclooxygenase-2 signaling pathway. CONCLUSION: Our results demonstrate that prostasin expression is a noteworthy clinical feature and a potential therapeutic target against DENV infection.

Higher levels of thyroxine may predict a favorable response to donepezil treatment in patients with Alzheimer disease: a prospective, case-control study.

BACKGROUND: Cholinergic hypothesis has been advanced as an etiology of Alzheimer disease (AD) on the basis of the presynaptic deficit found in the diseased brains, and cholinesterase inhibitors (ChEIs) are the treatment of choice for these patients. However, only about half of treatment efficacy was found. Because increasing evidence supports an extensive interrelationship between thyroid hormones (THs), cortisol level and the cholinergic system, the aim of the present study was to evaluate thyroid function and cortisol level in patients with mild to moderate AD before and after ChEIs treatment, and to identify possible variations in response. This was a prospective, case-control, follow-up study. Levels of cortisol and THs were evaluated in 21 outpatients with mild to moderate AD and 20 normal controls. All patients were treated with 5 mg/day of donepezil (DPZ) and were reevaluated after 24-26 weeks of treatment. RESULTS: The patients had worse cognitive function, higher cortisol level, and lower levels of triiodothyronine (T3) and its free fraction than the controls. There were no significant differences in global cognitive function or cortisol level after treatment, however, significant reductions in T3 and thyroxin (T4) levels were observed. Responders had higher levels of T4 than non-responders, followed by a significant reduction after treatment. CONCLUSIONS: These results suggest that relatively higher levels of T4 may predict a favorable response to DPZ treatment. Further studies are warranted to confirm the relationship between THs and ChEIs therapy in AD and to explore new therapeutic strategies. On the other hand, cortisol levels are more likely to respond to interventions for stress-related neuropsychiatric symptoms in patients with AD rather than ChEIs treatment. Further studies are warranted to investigate the association between cortisol level and the severity of stress-related neuropsychiatric symptoms in patients with AD.

Is one day off sufficient for re-adaptation to a daytime routine after two consecutive nights of work?

Fast rotation three-shift working schedules are common in the medical field in Taiwan. This study investigated whether 24 h off is sufficient for re-adaptation to a daytime routine after working two night shifts (NSs) by comparing changes in cognitive function, anxiety state and objectively measured sleep propensity between those working two NSs followed by 24 h off (n = 21, 2NS-off) and an off-duty group (n = 21, OD). The results showed that nurses in the 2NS-off group were less alert and had decreased visual attention performance and executive function ability than the OD group during the daytime. One day off appeared to be insufficient to adapt back to a daytime shift after two NSs. Further studies are warranted to investigate whether a longer sequence of consecutive NSs (e.g. four NSs) followed by two days off is suitable for a fast rotation three-shift work schedule to allow for optimal performance throughout the next daytime shift. Practitioner Summary: The medical field in Taiwan mandates at least 24 h off between night and day shifts, but this appears to be insufficient for re-adapting to a daytime shift after two night shifts. A longer sequence of consecutive night shifts followed by two days off may be more suitable.

[The Influence of Breastfeeding Self-Efficacy and Breastfeeding Intention on Breastfeeding Behavior in Postpartum Women].

BACKGROUND: World Health Organization (WHO) guidelines recommend that infants should be breastfed for six month after childbirth. The average duration of breastfeeding in Taiwan still falls short of this sixth-month timeline. In order to improve the duration of breastfeeding, it is crucial to understand the factors that affect related behavior. PURPOSE: To explore the effects of breastfeeding self-efficacy and breastfeeding intention among exclusive-breastfeeding women during the initial six months after childbirth and to verify the reliability and validity of the infant feeding intentions scale (Chinese version). METHODS: Purposive sampling was used to select and enroll a total of 167 breastfeeding women from a southern metropolitan medical-teaching hospital. Data were collected using a structured questionnaire and phone interviews. Data were analyzed using SPSS 18.0, LISREL8.7, and S-Plus package software to obtain scores for the independent-sample t test, Pearson's product-moment correlation coefficient, one-way analysis of variance, survival analysis, and reliability and validity. RESULTS: Breastfeeding self-efficacy scores ranged from 14 to 70, with a mean score of 44.80 (±11.56). Infant feeding intention scores ranged from 14 to 70, with a mean score of 12.20 (±3.14). Additionally, 29.9% of the participants breastfed exclusively for the entire six months after childbirth. Breastfeeding self-efficacy and breastfeeding intention were positively correlated (r = .45, p < .001). Education level, occupation, and breastfeeding intention were each identified as factors that significantly influenced the success of exclusive breastfeeding during the initial six months after childbirth. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Breastfeeding self-efficacy and breastfeeding intention are correlated with breastfeeding behavior. Based on findings, medical staff should target promotion and education regarding the importance of breastfeeding particularly toward women who have lower levels of education, who are employed, and who express low initial intention to breastfeed.

Nanometer-Scale Permeabilization and Osmotic Swelling Induced by 5-ns Pulsed Electric Fields.

High-intensity nanosecond pulsed electric fields (nsPEFs) permeabilize cell membranes. Although progress has been made toward an understanding of the mechanism of nsPEF-induced membrane poration, the dependence of pore size and distribution on pulse duration, strength, number, and repetition rate remains poorly defined experimentally. In this paper, we characterize the size of nsPEF-induced pores in living cell membranes by isosmotically replacing the solutes in pulsing media with polyethylene glycols and sugars before exposing Jurkat T lymphoblasts to 5 ns, 10 MV/m electric pulses. Pore size was evaluated by analyzing cell volume changes resulting from the permeation of osmolytes through the plasma membrane. We find that pores created by 5 ns pulses have a diameter between 0.7 and 0.9 nm at pulse counts up to 100 with a repetition rate of 1 kHz. For larger number of pulses, either the pore diameter or the number of pores created, or both, increase with increasing pulse counts. But the prevention of cell swelling by PEG 1000 even after 2000 pulses suggests that 5 ns, 10 MV/m pulses cannot produce pores with a diameter larger than 1.9 nm.

Epstein-Barr virus latent membrane protein-1 up-regulates cytokines and correlates with older age and poorer prognosis in Hodgkin lymphoma.

AIMS: Previously, we reported an association between Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL), older age, and poorer prognosis. The aim of this study was to investigate the mechanisms underlying this association. METHODS AND RESULTS: Transfection of HL cell lines with EBV latent membrane protein-1 (LMP1) resulted in up-regulation of many cytokine genes as assessed by the use of oligonucleotide microarrays. The up-regulation of cytokines was validated by using an inflammatory cytokine protein array: macrophage inflammatory protein (MIP)-1α, MIP-1ß, and interleukin (IL)-13. Immunostaining of HL samples (n = 104) showed that expression of MIP-1α, MIP-1ß and IL-13 correlated with EBV infection and LMP1 expression. Combined expression of these cytokines was more common in patients aged >60 years (P < 0.001), and was associated with a poorer prognosis (P = 0.042). In another cohort, serum levels of MIP-1α, MIP-1ß and IL-13 were increased in HL patients (n = 53) and highest in EBV-positive HL patients as compared with healthy controls (n = 40). Xenograft mice injected with EBV-positive HL cells had higher serum levels of MIP-1α, MIP-1ß and IL-13 than mice injected with EBV-negative HL cells, although there was no difference in growth. CONCLUSIONS: EBV infection appears to promote the release of cytokines in HL patients, and negatively impacts on patient survival. Physiological immunosenescence probably explains the association between EBV infection and older age. Cytokine modulation is a potential therapeutic target for EBV-positive HL patients.

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities.

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes - NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases.

Four Night Shifts Have a Degree of Performance Adaptation.

OBJECTIVE: In this case control study, we investigated the process of adaptation to night shift (NS) work and recovery back to a day schedule among nurses working a fast-rotation three-shift schedule. BACKGROUND: There is limited knowledge of how specific patterns of a fast-rotation shift affect nurses' performance. METHOD: The cognitive performance of off-duty nurses (OD; n = 21), those working the first night of an NS (1NS; n = 21) and the last night of two ( n = 21), three ( n = 20), and four (4NS; n = 21) successive NSs were compared. Changes in sleep propensity, cognitive function, and anxiety were compared in the daytime after working four successive NSs followed by 24 hr off (4NS-off; n = 18) and in those off duty. RESULTS: The visual attention task (VAT) of cognitive function was significantly worse in the 1NS group and significantly better on the last night in the 4NS group than in the other NS groups. The nurses in the 4NS-off group were less alert and had poorer VAT performance than the OD group during the daytime. CONCLUSION: The nurses working on NS experienced a decrease in VAT performance due to acute changes in circadian rhythm but also significant performance adaptation after four consecutive NSs. One off-duty day was insufficient to recover back to a daytime shift after four consecutive NSs. APPLICATION: In a fast-rotation three-shift schedule, performance adaptation occurred in the nurses who worked four consecutive NSs, and more than one off-duty day are needed to recover back to daytime shift after those NSs.

Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

Ecdysones from Zoanthus spp. with inhibitory activity against dengue virus 2.

Bioassay-guided fractionation of an ethanolic extract of Zoanthus spp. collected in Taiwan has resulted in the isolation of one new ecdysone, zoanthone A (1), along with thirteen known compounds (2-14). The structures of these compounds were determined by spectroscopic methods, especially 2D NMR analyses. The in vitro antiviral activities of all isolated ecdysones (1-14) against dengue virus type 2 (DENV-2) were evaluated using DENV infectious system. New compound (1) exhibited potent antiviral activity (EC50=19.61 ± 2.46 µM) with a selectivity index (CC50/EC50) value of 36.7. The structure-activity relationships of isolated ecdysones against DENV-2 were concluded. Molecular docking information of 3 and NS5 polymerase was performed either.

Anti-Dengue Virus Constituents from Formosan Zoanthid Palythoa mutuki.

A new marine ecdysteroid with an α-hydroxy group attaching at C-4 instead of attaching at C-2 and C-3, named palythone A (1), together with eight known compounds (2-9) were obtained from the ethanolic extract of the Formosan zoanthid Palythoa mutuki. The structures of those compounds were mainly determined by NMR spectroscopic data analyses. The absolute configuration of 1 was further confirmed by comparing experimental and calculated circular dichroism (CD) spectra. Anti-dengue virus 2 activity and cytotoxicity of five isolated compounds were evaluated using virus infectious system and [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays, respectively. As a result, peridinin (9) exhibited strong antiviral activity (IC50 = 4.50 ± 0.46 µg/mL), which is better than that of the positive control, 2'CMC. It is the first carotene-like substance possessing anti-dengue virus activity. In addition, the structural diversity and bioactivity of the isolates were compared by using a ChemGPS-NP computational analysis. The ChemGPS-NP data suggested natural products with anti-dengue virus activity locate closely in the chemical space.