Species selection as a key factor in the afforestation of coastal salt-affected lands: Insights from pot and field experiments.

Soil salinization is a significant global issue that leads to land degradation and loss of ecological function. In coastal areas, salinization hampers vegetation growth, and forestation efforts can accelerate the recovery of ecological functions and enhance resilience to extreme climates. However, the salinity tolerance of tree species varies due to complex biological factors, and results between lab/greenhouse and field studies are often inconsistent. Moreover, in salinized areas affected by extreme climatic and human impacts, afforestation with indigenous species may face adaptability challenges. Therefore, it is crucial to select appropriate cross-species salinity tolerance indicators that have been validated in the field to enhance the success of afforestation and reforestation efforts. This study focuses on five native coastal tree species in Taiwan, conducting afforestation experiments on salt-affected soils mixed with construction and demolition waste. It integrates short-term controlled experiments with potted seedlings and long-term field observations to establish growth performance and physiological and biochemical parameters indicative of salinity tolerance. Results showed that Heritiera littoralis Dryand. exhibited the highest salinity tolerance, accumulating significant leaf proline under increased salinity. Conversely, Melia azedarach Linn. had the lowest tolerance, evidenced by complete defoliation and reduced biomass under salt stress. Generally, the field growth performance of these species aligns with the results of short-term pot experiments. Leaf malondialdehyde content from pot experiments proved to be a reliable cross-species salinity tolerance indicator, correlating negatively with field relative height growth and survival rates. Additionally, parameters related to the photosynthetic system or water status, measured using portable devices, also moderately indicated field survival, aiding in identifying potential salt-tolerant tree species. This study underscores the pivotal role of species selection in afforestation success, demonstrating that small-scale, short-term salinity control experiments coupled with appropriate assessment tools can effectively identify species suitable for highly saline and degraded environments. This approach not only increases the success of afforestation but also conserves resources needed for field replanting and maintenance, supporting sustainable development goals.

A Potent Recombinant Polyclonal Antibody Therapeutic for Protection Against New Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) possess mutations that prevent antibody therapeutics from maintaining antiviral binding and neutralizing efficacy. Monoclonal antibodies (mAbs) shown to neutralize Wuhan-Hu-1 SARS-CoV-2 (ancestral) strain have reduced potency against newer variants. Plasma-derived polyclonal hyperimmune drugs have improved neutralization breadth compared with mAbs, but lower titers against SARS-CoV-2 require higher dosages for treatment. We previously developed a highly diverse, recombinant polyclonal antibody therapeutic anti-SARS-CoV-2 immunoglobulin hyperimmune (rCIG). rCIG was compared with plasma-derived or mAb standards and showed improved neutralization of SARS-CoV-2 across World Health Organization variants; however, its potency was reduced against some variants relative to ancestral, particularly omicron. Omicron-specific antibody sequences were enriched from yeast expressing rCIG-scFv and exhibited increased binding and neutralization to omicron BA.2 while maintaining ancestral strain binding and neutralization. Polyclonal antibody libraries such as rCIG can be utilized to develop antibody therapeutics against present and future SARS-CoV-2 threats.

Sequencing the B Cell Receptor Repertoires of Antibody-Deficient Individuals With and Without Infection Susceptibility.

PURPOSE: Most individuals with antibody deficiency (hypogammaglobulinemia) need immunoglobulin replacement therapy (IgG-RT) from healthy plasma donors to stay clear of infections. However, a small subset of hypogammaglobulinemic patients do not require this substitution therapy. We set out to investigate this clinical conundrum by asking whether the peripheral B cell receptor repertoires differ between antibody-deficient patients who do and do not need IgG-RT. METHODS: We sequenced and analyzed IgG and IgM heavy chain B cell receptor repertoires from peripheral blood mononuclear cells (PBMCs) isolated from patients with low serum IgG concentrations who did or did not require IgG-RT. RESULTS: Compared to the patients who did not need IgG-RT, those who needed IgG-RT had higher numbers of IgG antibody clones, higher IgM diversity, and less oligoclonal IgG and IgM repertoires. The patient cohorts had different heavy chain variable gene usage, and the patients who needed IgG-RT had elevated frequencies of IgG clones with higher germline identity (i.e., fewer somatic hypermutations). CONCLUSION: Antibody-deficient patients with infection susceptibility who needed IgG-RT had more diverse peripheral antibody repertoires that were less diverged from germline and thus may not be as optimal for targeting pathogens, possibly contributing to infection susceptibility.

AuAg nanocomposites suppress biofilm-induced inflammation in human osteoblasts.

Staphylococcus aureus (S. aureus)forms biofilm that causes periprosthetic joint infections and osteomyelitis (OM) which are the intractable health problems in clinics. The silver-containing nanoparticles (AgNPs) are antibacterial nanomaterials with less cytotoxicity than the classic Ag compounds. Likewise, gold nanoparticles (AuNPs) have also been demonstrated as excellent nanomaterials for medical applications. Previous studies have showed that both AgNPs and AuNPs have anti-microbial or anti-inflammatory properties. We have developed a novel green chemistry that could generate the AuAg nanocomposites, through the reduction of tannic acid (TNA). The bioactivity of the nanocomposites was investigated inS. aureusbiofilm-exposed human osteoblast cells (hFOB1.19). The current synthesis method is a simple, low-cost, eco-friendly, and green chemistry approach. Our results showed that the AuAg nanocomposites were biocompatible with low cell toxicity, and did not induce cell apoptosis nor necrosis in hFOB1.19 cells. Moreover, AuAg nanocomposites could effectively inhibited the accumulation of reactive oxygen species (ROS) in mitochondria and in rest of cellular compartments after exposing to bacterial biofilm (by reducing 0.78, 0.77-fold in the cell and mitochondria, respectively). AuAg nanocomposites also suppressed ROS-triggered inflammatory protein expression via MAPKs and Akt pathways. The current data suggest that AuAg nanocomposites have the potential to be a good therapeutic agent in treating inflammation in bacteria-infected bone diseases.

Water, Sanitation, and Hygiene (WaSH) insecurity in unhoused communities of Los Angeles, California.

BACKGROUND: Access to water and sanitation is a basic human right; however, in many parts of the world, communities experience water, sanitation, and hygiene (WaSH) insecurity. While WaSH insecurity is prevalent in many low and middle-income countries, it is also a problem in high-income countries, like the United States, as is evident in vulnerable populations, including people experiencing homelessness. Limited knowledge exists about the coping strategies unhoused people use to access WaSH services. This study, therefore, examines WaSH access among unhoused communities in Los Angeles, California, a city with the second-highest count of unhoused people across the nation. METHODS: We conducted a cross-sectional study using a snowball sampling technique with 263 unhoused people living in Skid Row, Los Angeles. We calculated frequencies and used multivariable models to describe (1) how unhoused communities cope and gain access to WaSH services in different places, and (2) what individual-level factors contribute to unhoused people's ability to access WaSH services. RESULTS: Our findings reveal that access to WaSH services for unhoused communities in Los Angeles is most difficult at night. Reduced access to overnight sanitation resulted in 19% of the sample population using buckets inside their tents and 28% openly defecating in public spaces. Bottled water and public taps are the primary drinking water source, but 6% of the sample reported obtaining water from fire hydrants, and 50% of the population stores water for night use. Unhoused people also had limited access to water and soap for hand hygiene throughout the day, with 17% of the sample relying on hand sanitizer to clean their hands. Shower and laundry access were among the most limited services available, and reduced people's ability to maintain body hygiene practices and limited employment opportunities. Our regression models suggest that WaSH access is not homogenous among the unhoused. Community differences exist; the odds of having difficulty accessing sanitation services is two times greater for those living outside of Skid Row (Adj OR: 2.52; 95% CI: 1.08-6.37) and three times greater for people who have been unhoused for more than six years compared to people who have been unhoused for less than a year (Adj OR: 3.26; 95% CI: 1.36-8.07). CONCLUSION: Overall, this study suggests a need for more permanent, 24-h access to WaSH services for unhoused communities living in Skid Row, including toilets, drinking water, water and soap for hand hygiene, showers, and laundry services.

Tanshinone IIA suppresses burning incense-induced oxidative stress and inflammatory pathways in astrocytes.

The burning incense (BI) behavior could be widely observed in Asia families. Incense sticks are often believed to be made from natural herbs and powders, and to have minimal impact on human health; however, there is limited research to support this claim. The current study aimed to identify the components of BI within the particulate matter 2.5 µm (PM2.5) range and explore if BI has bio-toxicity effects on rat astrocytes (CTX-TNA2). The study also examined the protective effects and underlying molecular mechanisms of tanshinone IIA, a primary lipid-soluble compound found in the herb danshen (Salvia miltiorrhiza Bunge), which has been shown to benefit the central nervous system. Results showed that despite the differences in BI components compared to the atmospheric particulate matter (PM) standards, BI still had a bio-toxicity on astrocytes. BI exposure caused early and late apoptosis, reactive oxygen species (ROS) production, MAPKs (JNK, p38, and ERK), and Akt signaling activation, and inflammation-related proteins (cPLA2, COX-2, HO-1, and MMP-9) increases. Our results further exhibit that the tanshinone IIA pre-treatment could significantly avoid the BI-induced apoptosis and inflammatory signals on rat astrocytes. These findings suggest that BI exposure may cause oxidative stress in rat astrocytes and increase inflammation-related proteins and support the potential of tanshinone IIA as a candidate for preventing BI-related adverse health effects.

Highly efficient magnetic ablation and the contrast of various imaging using biocompatible liquid-metal gallium.

BACKGROUND: Although the powerful clinical effects of radiofrequency and microwave ablation have been established, such ablation is associated with several limitations, including a small ablation size, a long ablation time, the few treatment positioning, and biosafety risks. To overcome these limitations, biosafe and efficient magnetic ablation was achieved in this study by using biocompatible liquid gallium as an ablation medium and a contrast medium for imaging. RESULTS: Magnetic fields with a frequency (f) lower than 200 kHz and an amplitude (H) × f value lower than 5.0 × 109 Am-1 s-1 were generated using the proposed method. These fields could generate an ablation size of 3 cm in rat liver lobes under a temperature of approximately 300 °C and a time of 20 s. The results of this study indicate that biomedical gallium can be used as a contrast medium for the positioning of gallium injections and the evaluation of ablated tissue around a target site. Liquid gallium can be used as an ablation medium and imaging contrast medium because of its stable retention in normal tissue for at least 3 days. Besides, the high anticancer potential of gallium ions was inferred from the self-degradation of 100 µL of liquid gallium after around 21 days of immersion in acidic solutions. CONCLUSIONS: The rapid wireless ablation of large or multiple lesions was achieved through the simple multi-injection of liquid gallium. This approach can replace the currently favoured procedure involving the use of multiple ablation probes, which is associated with limited benefits and several side effects. METHODS: Magnetic ablation was confirmed to be highly efficient by the consistent results obtained in the simulation and in vitro tests of gallium and iron oxide as well as the electromagnetic specifics and thermotherapy performance comparison detailed in this study Ultrasound imaging, X-ray imaging, and magnetic resonance imaging were found to be compatible with the proposed magnetic ablation method. Self-degradation analysis was conducted by mixing liquid gallium in acidic solutions with a pH of approximately 5-7 (to imitate a tumour-containing microenvironment). X-ray diffraction was used to identify the gallium oxides produced by degraded gallium ions.

Naringenin Induces ROS-Mediated ER Stress, Autophagy, and Apoptosis in Human Osteosarcoma Cell Lines.

Osteosarcoma, a primary bone tumor, responds poorly to chemotherapy and radiation therapy in children and young adults; hence, as the basis for an alternative treatment, this study investigated the cytotoxic and antiproliferative effects of naringenin on osteosarcoma cell lines, HOS and U2OS, by using cell counting kit-8 and colony formation assays. DNA fragmentation and the increase in the G2/M phase in HOS and U2OS cells upon treatment with various naringenin concentrations were determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Annexin V/propidium iodide double staining, respectively. Flow cytometry was performed, and 2',7'-dichlorodihydrofluorescein diacetate, JC-1, and Fluo-4 AM ester probes were examined for reactive oxygen species (ROS) generation, mitochondrial membrane potential, and intracellular calcium levels, respectively. Caspase activation, cell cycle, cytosolic and mitochondrial, and autophagy-related proteins were determined using western blotting. The results indicated that naringenin significantly inhibited viability and proliferation of osteosarcoma cells in a dose-dependent manner. In addition, naringenin induced cell cycle arrest in osteosarcoma cells by inhibiting cyclin B1 and cyclin-dependent kinase 1 expression and upregulating p21 expression. Furthermore, naringenin significantly inhibited the growth of osteosarcoma cells by increasing the intracellular ROS level. Naringenin induced endoplasmic reticulum (ER) stress-mediated apoptosis through the upregulation of ER stress markers, GRP78 and GRP94. Naringenin caused acidic vesicular organelle formation and increased autophagolysosomes, microtubule-associated protein-light chain 3-II protein levels, and autophagy. The findings suggest that the induction of cell apoptosis, cell cycle arrest, and autophagy by naringenin through mitochondrial dysfunction, ROS production, and ER stress signaling pathways contribute to the antiproliferative effect of naringenin on osteosarcoma cells.

Protective mechanisms of Taiwanese green propolis toward high glucose-induced inflammation via NLRP3 inflammasome signaling pathway in human gingival fibroblasts.

OBJECTIVE: To investigate protective effects of Taiwanese green propolis (TGP) against high glucose-induced inflammatory responses in human gingival fibroblasts (HGFs) through NLRP3 inflammasome signaling pathway. BACKGROUND: NLRP3 inflammasome has been implicated in the progression of both diabetes mellitus and periodontitis, suggesting a common potential therapeutic target for these diseases. Propolis is renowned for various biological activities, particularly anti-inflammation and antioxidant, representing a promising therapy for many conditions. However, underlying mechanisms remain unclear. METHODS: The cytotoxicity of TGP was evaluated by cell viability assay. The mRNA levels and protein expression or secretion of various inflammatory molecules and NLRP3 inflammasome-related molecules in high glucose-exposed HGFs with or without pretreatment of TGP (5 µg/ml) were determined by real-time PCR and western blot or specific kits, respectively. Intracellular and mitochondrial ROS measurements, NADPH oxidase activity determination, and subcellular fractions were performed to assess ROS generation. The transcriptional activity of NF-κB was measured by luciferase reporter kit. The signaling components were further differentiated using pharmacological inhibitors of ROS and small interfering RNAs of TLR2, TLR4, or NF-κB. RESULTS: High glucose could induce IL-1ß-driven inflammatory responses in HGFs via the activation of NLRP3 inflammasome regulated by TLR2/TLR4 coupled ROS in NF-κB-dependent manner. TGP had no adverse impact on the cell viability of HGFs at concentrations no greater than 10 µg/ml, and could exert inhibitory effects on high glucose-induced inflammatory responses via the interruption of NLRP3 inflammasome signaling pathway. CONCLUSION: Taiwanese green propolis could elicit protective effects against IL-1ß-driven inflammation in high glucose-exposed HGFs through TLR2/TLR4 combined ROS/NF-κB/NLRP3 inflammasome pathway.

RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells.

Human ADAR3 is a catalytically inactive member of the Adenosine Deaminase Acting on RNA (ADAR) protein family, whose active members catalyze A-to-I RNA editing in metazoans. Until now, the reasons for the catalytic incapability of ADAR3 has not been defined and its biological function rarely explored. Yet, its exclusive expression in the brain and involvement in learning and memory suggest a central role in the nervous system. Here we describe the engineering of a catalytically active ADAR3 enzyme using a combination of computational design and functional screening. Five mutations (A389V, V485I, E527Q, Q549R and Q733D) engender RNA deaminase in human ADAR3. By way of its catalytic activity, the ADAR3 pentamutant was used to identify potential binding targets for wild type ADAR3 in a human glioblastoma cell line. Novel ADAR3 binding sites discovered in this manner include the 3'-UTRs of the mRNAs encoding early growth response 1 (EGR1) and dual specificity phosphatase 1 (DUSP1); both known to be activity-dependent immediate early genes that respond to stimuli in the brain. Further studies reveal that the wild type ADAR3 protein can regulate transcript levels for DUSP1 and EGR1, suggesting a novel role ADAR3 may play in brain function.

W-TSS: A Wavelet-Based Algorithm for Discovering Time Series Shapelets.

Many approaches to time series classification rely on machine learning methods. However, there is growing interest in going beyond black box prediction models to understand discriminatory features of the time series and their associations with outcomes. One promising method is time-series shapelets (TSS), which identifies maximally discriminative subsequences of time series. For example, in environmental health applications TSS could be used to identify short-term patterns in exposure time series (shapelets) associated with adverse health outcomes. Identification of candidate shapelets in TSS is computationally intensive. The original TSS algorithm used exhaustive search. Subsequent algorithms introduced efficiencies by trimming/aggregating the set of candidates or training candidates from initialized values, but these approaches have limitations. In this paper, we introduce Wavelet-TSS (W-TSS) a novel intelligent method for identifying candidate shapelets in TSS using wavelet transformation discovery. We tested W-TSS on two datasets: (1) a synthetic example used in previous TSS studies and (2) a panel study relating exposures from residential air pollution sensors to symptoms in participants with asthma. Compared to previous TSS algorithms, W-TSS was more computationally efficient, more accurate, and was able to discover more discriminative shapelets. W-TSS does not require pre-specification of shapelet length.

Effects of Visfatin on Intracellular Mechanics and Catabolism in Human Primary Chondrocytes through Glycogen Synthase Kinase 3ß Inactivation.

Osteoarthritis (OA) is still a recalcitrant musculoskeletal disease on account of its complex biochemistry and mechanical stimulations. Apart from stimulation by external mechanical forces, the regulation of intracellular mechanics in chondrocytes has also been linked to OA development. Recently, visfatin has received significant attention because of the clinical finding of the positive correlation between its serum/synovial level and OA progression. However, the precise mechanism involved is still unclear. This study determined the effect of visfatin on intracellular mechanics and catabolism in human primary chondrocytes isolated from patients. The intracellular stiffness of chondrocytes was analyzed by the particle-tracking microrheology method. It was shown that visfatin damages the microtubule and microfilament networks to influence intracellular mechanics to decrease the intracellular elasticity and viscosity via glycogen synthase kinase 3ß (GSK3ß) inactivation induced by p38 signaling. Further, microtubule network destruction in human primary chondrocytes is predominantly responsible for the catabolic effect of visfatin on the cyclooxygenase 2 upregulation. The present study shows a more comprehensive interpretation of OA development induced by visfatin through biochemical and biophysical perspectives. Finally, the role of GSK3ß inactivation, and subsequent regulation of intracellular mechanics, might be considered as theranostic targets for future drug development for OA.

Particulate matter exposure aggravates osteoarthritis severity.

Several diseases have been linked to particulate matter (PM) exposure. Outdoor activities, such as road running or jogging, are popular aerobic exercises due to few participatory limitations. Osteoarthritis (OA) is a progressive degenerative joint disease, usually observed at age 40, and not noticed before pain or diagnosis. Although exercise has health benefits, it is unclear whether outdoor jogging in higher PM (standard reference material 1649b, SRM 1649b) concentration environments could affect OA development or severity. Hence, a PM exposure monosodium iodoacetate (MIA)-induced OA animal jogged model was established for investigation. Results showed that high doses of PM (5 mg) significantly increased pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and IL-6, and M1 macrophages in the lung region, also obtained in systemic IL-6 and TNF-α expressions in this MIA-OA rat model. Moreover, levels of osteocalcin, cartilage oligomeric matrix protein (COMP), and N-telopeptides of type I collagen were especially influenced in MIA+PM groups. Morphological and structural changes of the knee joint were detected by micro-computed tomography images (micro-CT) and immunohistochemistry. MIA + PM rats exhibited severe bone density decrease, cartilage wear, and structure damages, accompanied by lower levels of physical activity, than the sham group and groups receiving MIA or PM alone. The findings suggest that the severity of OA could be promoted by PM exposure with a PM concentration effect via systemic inflammatory mechanisms. To the best of our knowledge, this is the first study to provide direct effects of PM exposure on OA severity.

Spreading Depression Promotes Astrocytic Calcium Oscillations and Enhances Gliotransmission to Hippocampal Neurons.

Spreading depression (SD) is a pathophysiological phenomenon characterized by propagating waves of profound neuronal and glial depolarization in central nervous system gray matter. Although SD is primarily mediated by neurons with a subsequent astrocytic response, it remains unclear how astrocytic activity is modulated after SD and how altered astrocyte signaling contribute to neuronal excitability. Here, we report that after the concurrent Ca2+ wave, SD enhanced astrocytic activity by promoting a secondary period of Ca2+ oscillations. SD-induced Ca2+ oscillations did not require the activation of metabotropic glutamate receptors or purinergic receptors; instead, they were mediated by the activation of GABAB receptors and 1,4,5-trisphosphate (IP3) receptors. Furthermore, SD increased the number of NMDA receptor-mediated slow inward currents (SICs) in CA1 pyramidal neurons. The frequency of SD-induced SICs was reduced by blockade of GABAB receptors or by limiting Ca2+ efflux from the ER. Selective inhibition of astrocytic Ca2+ signals by dialysis of BAPTA into astrocytes or by knocking out the astrocytic type of IP3 receptors suppressed SICs after SD. These results demonstrated a causative link between the SD-induced Ca2+ oscillations and the enhanced glutamatergic astrocyte-neuron signaling. Therefore, we conclude that SD enhances the astrocyte Ca2+ signals and further promotes gliotransmission and neuronal excitability.

Water-Soluble Fullerenol C60(OH)36 toward Effective Anti-Air Pollution Induced by Urban Particulate Matter in HaCaT Cell.

Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.

Emerging trends in geospatial artificial intelligence (geoAI): potential applications for environmental epidemiology.

Geospatial artificial intelligence (geoAI) is an emerging scientific discipline that combines innovations in spatial science, artificial intelligence methods in machine learning (e.g., deep learning), data mining, and high-performance computing to extract knowledge from spatial big data. In environmental epidemiology, exposure modeling is a commonly used approach to conduct exposure assessment to determine the distribution of exposures in study populations. geoAI technologies provide important advantages for exposure modeling in environmental epidemiology, including the ability to incorporate large amounts of big spatial and temporal data in a variety of formats; computational efficiency; flexibility in algorithms and workflows to accommodate relevant characteristics of spatial (environmental) processes including spatial nonstationarity; and scalability to model other environmental exposures across different geographic areas. The objectives of this commentary are to provide an overview of key concepts surrounding the evolving and interdisciplinary field of geoAI including spatial data science, machine learning, deep learning, and data mining; recent geoAI applications in research; and potential future directions for geoAI in environmental epidemiology.

Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway.

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.

[The Effectiveness of the Use by Nurses of the Interdisciplinary Care Information System].

BACKGROUND: Using patient records and information systems not only improves collaboration among healthcare professionals but also enhances patient-care outcomes. Based on this, inter-professional collaboration has been increasingly applied in patient care in recent years. PURPOSE: To explore the acceptance of nurses of the inter-disciplinary care system, the patient-record completion rate, and the consultation response rate. METHODS: A questionnaire was developed based on Davis Technology Acceptance Model and DeLone & McLean Information Systems Success Model that included the key elements of system success (system quality and information quality) and attitudes toward use (perceived usefulness and perceived ease of use). A patient record checklist and the number of consultation responses were collected as well. RESULTS: This study collected 185 completed questionnaires and 817 copies of patient records as well as the associated consultation response rates. The results revealed that nurses held positive attitudes and that questionnaire variables were positively correlated. Additionally, perceived usefulness explained 60% of the variation in attitude toward use. In addition, the rate of completion for patient records in subcategories increased from 41% to 62%. Finally, while the overall team response rate of the social-worker and respiratory groups increased, that of the rehabilitation group decreased. CONCLUSIONS: Nurses accept the need to use inter-disciplinary care systems to enhance the completeness of patient records. However, the decreased consultation response rate may relate to the inability to update system functions. It is suggested that an auto-consultation response function be designed to provide reminders in order to improve the consultation response rate.

Reduced dosing and liability in methadone maintenance treatment by targeting oestrogen signal for morphine addiction.

Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. There have gender differences reported in response to MMT. This study discovered that the estrogen-response element single nucleotide polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone catabolic enzyme) responded differently to MMT dosing. Oestradiol was associated with high MMT dosing, high enantiomer (R- or S-) of 2-ethylidene-1,5-dimethyl-3,3-dipheny-pyrrolidine (EDDP; methadone metabolite) to methadone ratio and increased drug-seeking behaviour, implicating oestradiol-CYP-EDDP/methadone axis decreasing MMT efficacy. In mouse model, oestrogen mitigates methadone antinociceptive response, facilitates methadone catabolism and up-regulates methadone-associated metabolizing enzymes. Oestrogen also ablates chronic methadone administration-induced rewarding response. Mechanism dissection revealed the CC genotype of CYP2B6-ERE-SNP exerts higher ERE sequence alignment score, higher estrogenic response as compared to TT genotype. At last, preclinical study via targeting estrogen signal that tamoxifen (TMX; selective estrogen receptor modulator, SERM) could facilitate the tolerance phase rewarding response of methadone. Strikingly, TMX also reduces tapering/abstinence phases methadone liability in mice. In conclusion, this study demonstrates altering methadone metabolism through targeting estrogen signals might be able to free morphine addictive patients from the addiction of opioid replacement therapy. Therefore, the add-on therapy clinical trial introducing SERM in MMT regimen is suggested.