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Melanoma is one of the most aggressive and metastatic skin cancers, of these metastatic melanoma is a lethal disease with invasive behavior. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, hepatocellular carcinoma, and breast cancer, the expression and functions of them in melanoma remain unknown. Therefore, the purpose of this study is to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma. Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma and normal skin. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells treated with siRNA was performed in Cell viability assay, Phase contrast images, DAPI staining, Cell cycle analysis, Apoptosis assay, Wound healing assay, Colony formation assay, and Western blotting. We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo. Inhibition of Dock180 or Elmo1 following siRNA treatment in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE(+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulaton of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib treatment decreased cell viability in a concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability compared to non-transfected cells. Collectively, these findings suggest that both Dock180 and Elmo1 may be associated with cancer progression such as cell survival and migration in melanoma, and can be potential targets for treatment of melanoma.

Nymphaea rubra flowers (NRF) are widely used as a food and in folk medicine throughout the subtropical regions due to their health-promoting characteristics. This study characterized the phytochemical composition of various extracts/fractions of NRF by establishing a quadrupole-cyclic ion mobility-time-of-flight (Q-cIM-TOF) mass spectrometry method in both positive and negative electrospray ionization modes. Over 100 phytoconstituents were tentatively identified, among which 53 phytochemicals belonging to phenolic acids, tannins, flavonoids, terpenoids, alkaloids, xanthones, and naphthopyrones have never been documented in NRF before. Moreover, the ethyl acetate fraction of NRF demonstrated strong antioxidant potential (IC

Very few studies have assessed infant capacity for bidirectional, contingent communication at birth, and to our knowledge there are none with preterm infants in the neonatal period. Presence versus absence of such interactive contingency makes a difference for our theories of development. We examined whether preterm infants can contingently coordinate behaviors with mothers and fathers in spontaneous communication in the Neonatal Intensive Care Unit (NICU), and whether mother-infant versus father-infant engagement and contingency differ. Twenty Italian preterm infants (60% girls, born 27-33 weeks, largely middle-class families) lying in a heated cot in the NICU were videotaped at 35 weeks with mothers, and fathers (counterbalanced), in face-to-face communication. Videotapes were coded on a 1-s time-base with parent and infant engagement scales. Multilevel time-series models evaluated self-contingency (auto-correlation) and interactive contingency (lagged cross-correlation). Mothers (vs. fathers) showed higher levels of engagement, interpreted as more arousing. Fathers (vs. mothers) showed more midrange engagement, interpreted as less "demanding" of infant engagement. Infants were more gaze-on-parent's-face and gaze-on-environment with mothers than fathers. Fathers interacted contingently with infants, whereas mothers did not. However, infants interacted contingently with mothers, but not fathers. When infants were in lower engagement levels 1 s prior, fathers stayed in lower engagement levels in the current second, closer to infants than mothers. We suggest that fathers were more coordinated because fathers were more able to join the infant's dampened state. We suggest that infants were more coordinated with mothers because mothers were more socially stimulating, and more familiar. We conclude that preterm infants, shortly after birth, are capable of contingent communication. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Ajwa date (Phoenix dactylifera L., Arecaceae family) is a popular edible fruit consumed all over the world. The profiling of the polyphenolic compounds of optimized unripe Ajwa date pulp (URADP) extracts is scarce. The aim of this study was to extract polyphenols from URADP as effectively as possible by using response surface methodology (RSM). A central composite design (CCD) was used to optimize the extraction conditions with respect to ethanol concentration, extraction time, and temperature and to achieve the maximum amount of polyphenolic compounds. High-resolution mass spectrometry was used to identify the URADP’s polyphenolic compounds. The DPPH-, ABTS-radical scavenging, α-glucosidase, elastase and tyrosinase enzyme inhibition of optimized extracts of URADP was also evaluated. According to RSM, the highest amounts of TPC (24.25 ± 1.02 mgGAE/g) and TFC (23.98 ± 0.65 mgCAE/g) were obtained at 52% ethanol, 81 min time, and 63 °C. Seventy (70) secondary metabolites, including phenolic, flavonoids, fatty acids, and sugar, were discovered using high-resolution mass spectrometry. In addition, twelve (12) new phytoconstituents were identified for the first time in this plant. Optimized URADP extract showed inhibition of DPPH-radical (IC50 = 87.56 mg/mL), ABTS-radical (IC50 = 172.36 mg/mL), α-glucosidase (IC50 = 221.59 mg/mL), elastase (IC50 = 372.25 mg/mL) and tyrosinase (IC50 = 59.53 mg/mL) enzymes. The results revealed a significant amount of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.

Mothers who were pregnant and widowed on September 11, 2001, and their 4-6-month infants (in utero on 9/11) were filmed during face-to-face interaction and their vocal dialogues were examined via microanalysis. Mothers were White, well-educated, mean age 34.3 years, and far from the World Trade Center site on 9/11; infants were 4-6 months, half female. We examined the bi-directional, moment-by-moment co-regulation of the timing of vocal dialogue, and particularly turn taking, in mother-infant and stranger-infant interactions, with time-series models. We analyzed the contingent coordination of durations of (1) vocalizations of the turn-holder, and (2) switching-pauses at the moment of the turn exchange. The switching pause is an aspect of the rhythm of the turn-holder who, after taking a turn, yields the floor to the partner through the switching pause. Turn taking is the lynchpin of dialogue, and the bi-directional contingent coordination of the switching-pause regulates the turn exchange. Both partners showed signs of risk and resilience. The 9/11 mothers did not coordinate the timing of turn taking with their infants, a highly unusual finding. In contrast, the 9/11 infants did coordinate the timing of turn taking with their mothers, and with the "stranger," forms of resilience. We propose that the 9/11 mother's difficulty coordinating with the infant's turn taking rhythm is a mode of transmission of her trauma to the infant. This work expands our knowledge of the specificities of co-regulation in the context of the 9/11 trauma.

Object. Extracellular acidosis of the tumor microenvironment plays an important role in cancer progression. In the 2D monolayer and 3D spheroid cultures of prostate cancer cells, we investigated the efficacy of curcumin in targeting glycolysis and the role of ERK1/2 as an upstream signaling molecule in this process. Methods. Cell viability, glycolytic activity, Annexin V-PE binding activity, reactive oxygen species levels, mitochondrial membrane potential, ATP content, Western blot analysis, and spheroid viability were measured for this study. Results. Acidic pH-tolerant prostate cancer cells, PC-3AcT and DU145AcT, increased cytotoxicity with ERK1/2 inhibition in a curcumin concentration-dependent manner at concentrations that resulted in >90% cell viability in normal prostate epithelial HPrEC cells. ERK1/2 inhibition by curcumin and/or PD98059 suppressed cell growth, reduced glucose consumption, and downregulated the expression of key regulatory enzymes in glucose metabolism including hexokinases, phosphofructokinase, and pyruvate dehydrogenase. In addition, these compounds caused loss of mitochondrial membrane potential with increased intracellular ROS levels, decreased levels of complexes I, III, and IV in the mitochondrial electron transport chain, and cellular ATP depletion, leading to upregulation of marker proteins in apoptosis (cleaved caspase-3 and cleaved PARP) and necroptosis (p-MLKL and p-RIP3). The results of curcumin and/or PD98059 treatment in 3D cultures showed similar trends to those in 2D cultures. Conclusion. Taken together, the results provide mechanistic evidence for the antiglycolytic and cytotoxic roles of curcumin through inhibition of the MEK/ERK signaling pathway in prostate carcinoma cells preadapted to acidic conditions.

Arctigenin derived from the seeds of Arctium lappa Linnaeus is known as an anticancer drug candidate by targeting various pathways involved in anticancer therapy. Using 2D monolayer and 3D spheroid culture systems in nasal septum carcinoma RPMI-2650 cells, the effects of arctigenin and dexamethasone on cell viability, ROS levels, ATP level, mitochondrial function, apoptosis and necroptosis were examined. The combination treatment of both compounds induced strong cytotoxicity, accompanied by increases of sub-G0/G1 peak, annexin V-PE-positive cells, and ROS levels, loss of mitochondrial membrane potential, and decrease of cellular ATP content. These changes were observed as simultaneous induction of DNA damage, apoptosis, and necroptosis. A series of changes by arctigenin and dexamethasone were efficiently restored by decreasing ROS levels or supplementing ATP. Treatment of 3D spheroids with arctigenin and dexamethasone decreased cell viability in the spheroids, but it was slightly resistant than cells under 2D conditions. In addition, this phenomenon was accompanied by an increase in mediators for both apoptosis and necroptosis. Results of this study suggest that the apoptosis and necroptosis-inducing effects of arctigenin are associated with ATP depletion due to oxidative mitochondrial dysfunction.

To reduce microbial loads in medicinal herbs, Cnidii Rhizoma and Alismatis Rhizoma were subjected to electron-beam (e-beam) irradiation at doses (≤10 kGy) as permitted by the Korean Food Code. The effects of e-beam irradiation on the microbial load, stability of the active components, and anti-inflammatory activity of medicinal herbs were determined. We observed that the total aerobic bacteria (TAB; 4.0-7.0 log CFU/g), yeasts and molds (YM; 3.3-6.8 log CFU/g), and coliform counts (CC; 3.2-3.8 log CFU/g) in both herb samples were effectively reduced in a dose-dependent manner, resulting in acceptable levels of3.0 log CFU/g in TAB and YM and negative in CC at 10 kGy irradiation. The concentration of the active components (0.87-4.22 mg/g) of Cnidii Rhizoma, including z-ligustilide, chlorogenic acid, senkyunolide A, and ferulic acid, in order of prevalence and those (0.86-2.76 mg/g) of Alismatis Rhizoma, including Alisol B acetate and Alisol B, were not changed at irradiation doses of ≤10 kGy. The extracts of e-beam irradiated Cnidii Rhizoma and Alismatis Rhizoma showed a reduced production of inflammation-related factors, such as nitric oxide, prostaglandin E

We investigated the distributions of the artificial radionuclides 137Cs, 239+240Pu, and 90Sr in the various marine products around Korean Peninsula collected in 2015–2017. The activities of 137Cs, 239+240Pu, and 90Sr were in the ranges of 12.2–258.4 mBq kg−1, 0.014–1.879 mBq kg−1, and 11.3–18.3 mBq kg−1, respectively. The higher 239+240Pu (a factor of 10–50) relative to fishes were observed in mollusks. 137Cs in fishes were significantly enriched with growths. The calculated concentration factors (CFs) of 137Cs, 239+240Pu, and 90Sr in marine products were 7–143, 3–407, and 15–25, respectively. Overall, no noticeable artificial radioactivity was detected in marine organisms when comparing these results with previous data reported before the Fukushima nuclear accident and recommended CF values. The annual effective doses of 137Cs, 239+240Pu, and 90Sr by seafood consumption in South Korea were estimated to be 1.1 × 10−4, 1.6 × 10−5 and, 2.9 × 10−5 mSv yr−1, respectively, which is insignificant relative to that of natural radionuclides.

교정시설의 규모에 비해 수용인원의 증가폭이 훨씬 크게 나타나면서 과밀수용이 더 심각하게 되어 수형자의 인권문제가 대두되고 있다. 그런데 교정시설 과밀화현상의 원인은 법률의 중형화 경향과 양형기준제 시행에 따른 형의 중형선고, 그리고 교정시설 부족 등에 있을 것이다. 과밀화수용을 해소하는 가장 쉬운 방법은 교정시설을 확충일 수 있지만, 형사사법체계를 유지할 수 있는 자원은 한계가 있을 수밖에 없으며, 특히 국민의 수형자에 대한 인식과 사법체계 전체에서 행형이 차지하는 현실적인 위치를 고려할 때 현재로서는 이러한 대대적인 물적·인적 확충을 기대하기 어려운 실정이다. 이러한 과밀수용 해소방안으로는 예방과 응보로서의 형집행을 통한 국민적 법감정에 부합하면서도 교화와 사회복귀라는 교정목적 달성에도 부합하는 올바른 가석방제도의 활용을 논의할 수 있다. 첫째, 가석방 신청단계에서 가석방의 현실적 요건완화가 필요할 것이고, 석방 심사를 받기 위한 신청권을 교도소장에게만 줄 것이 아니라 수형자 본인에게도 부여할 필요가 있을 것이다. 둘째, 가석방 심사단계에서 가석방심사의 공정성과 실질적인 평가를 위하여 수형생활과 관련된 자들의 참여를 통한 다양한 심사가 필요하다. 끝으로 가석방 허가단계에서 가석방제도의 취지와 과밀수용 해결 및 범죄예방측면 등을 고려하면 좀 더 다양한 조건을 세분화하여 가석방 조건의 척도로 삼을 필요가 있다. 그리고 가석방을 활성화시키기 위한 보완하는 방법으로 재택구금을 통한 전자감독이 좋은 방안이라 생각된다. 재택구금이라는 방법은 시설내처우로서 형벌을 사회내처우로서 형벌로 변형된 것이므로 그에 따라 사법 판단이 필요할 것이고 법률에 따른 적법절차를 따라야 할 것이다. 이러한 내용은 법률에 구체적으로 명시할 필요가 있다. 이와 같은 가석방 제도는 국가 형사사법의 이념과 목적의 실현이라는 전제 하에서 통일된 정책으로 지속적으로 이루어져야 할 것이다.

In the process of screening the extracts of various medicinal herbs exhibiting with potent anti-atopic activity, we first confirmed the effect of the anti-atopic activity of the aqueous fraction of Lonicera japonica stem extract (afLj) ontained by the solid fermentation process by Phellinus baumii was identified to show anti-atopic activity for the first time. Further animal experiments revealed that the antioxidative activity of afLj had decreased, while the anti-atopic activity was increased compared to control. Moreover, treatment with afLj significantly decreased the infiltration of immune cells into inflammatory sites to 32% level observed with the control treatment in a DNFB-induced mouse model (NT). In particular, afLj dramatically decreased the number of eosinophils by afLj than those compared to Lj. The overall decrease in antioxidant activity and lack of significant differences in the β-hexosaminidase activity of afLj imply that the activity possessed by Lj itself was converted into an anti-atopic active substance through biotransformation during solid fermentation. Overall, these results suggest that the potential of afLj will be possible to use as a new functional biomaterial or functional food ingredient related with anti-atopic benefits.

In order to assess whether the fine powder of Jeju citrus can be used for better quality characteristics in food processing, we first prepared ultra-fine powder C20 (20 mesh of citrus), C40 (40 mesh of citrus), and C100 (100 mesh of citrus). The mean particle size of C20, C40, and C100 were 662.6±176.9, 344.6±126.8, and 91.7±54.9 μm, respectively. The antioxidant activity measured by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay and ferric Reducing Antioxidant Power (FRAP) assay was the highest in C100. Moreover, increasing mesh of citrus increased the L* and b* values of citrus, but not the a* value of citrus. Using a prototype developed from the powder, we performed sensory tests for taste, color, texture, flavor and overall preference. C100 showed the highest score compared to C20 and C40 in the sensory evaluation. Particularly, C100 had excellent flavor among all the powders. Our results collectively indicate that the Jeju citrus supplementation has better quality characteristics during food processing; this may aid in the development of food ingredients for functional food materials. Furthermore, a high mesh of citrus provides better quality in citrus-based food processing.

We assessed the applicability of the nutrient diol index (NDI) as a proxy for sea surface nutrients by analyzing sediments from a box core (ES14-BC03) collected in the southwestern continental slope of the East Sea, or the Japan Sea (hereafter the East Sea). The estimated sedimentation rate based on the 210Pb chronology was 0.15 cm yr−1 over the last 240 yrs. The NDI-derived phosphate (0.69 μmol L−1) and nitrate (8.63 μmol L−1) concentrations for the core-top sediment were within the average phosphate (0.26 ± 0.08 μmol L−1) and nitrate (3.38 ± 2.32 μmol L−1) concentration ranges for the last ∼20 years, accounting for both estimation error and variation in observational data. The distributions of the NDI-diols varied slightly through time, grouping into two distinct clusters (Cluster 1 and Cluster 2) in both principle component analysis (PCA) and hierarchical clustering of principal components (HCPC). Cluster 2 represented a time period with higher relative abundances of the C28 and C30 1,14-diols, resulting in higher NDI-derived nutrient concentrations than those of other periods. Interestingly, during this period, the U 37 K ' -derived sea surface temperatures (SSTs) also decreased. These results indicate that higher surface nutrient conditions and colder SSTs occurred between 1884 CE and 1911 CE, which might be associated with stronger upwelling intensity at the study site. This study is the first application of the NDI to a down-core, demonstrating that the NDI can be a useful proxy that provides helpful information about past sea surface nutrient conditions.

Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathologies in individuals with DS, including progressive cognitive dysfunction and learning and memory deficits which worsen with age. Further exacerbating neurological dysfunction associated with DS is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer’s disease (AD) pathology in early mid-life. Recent single population RNA sequencing (RNA-seq) analysis in the Ts65Dn mouse model of DS, specifically the medial septal cholinergic neurons of the basal forebrain (BF), revealed the mitochondrial oxidative phosphorylation pathway was significantly impacted, with a large subset of genes within this pathway being downregulated. We further queried oxidative phosphorylation pathway dysregulation in Ts65Dn mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration (6 months of age). In select Ts65Dn mice we demonstrate significant deficits in gene and/or encoded protein levels of Complex I-V of the mitochondrial oxidative phosphorylation pathway in the BF. In the frontal cortex (Fr Ctx) these complexes had concomitant alterations in select gene expression but not of the proteins queried from Complex I-V, suggesting that defects at this time point in the BF are more severe and occur prior to cortical dysfunction within the basocortical circuit. We propose dysregulation within mitochondrial oxidative phosphorylation complexes is an early marker of cognitive decline onset and specifically linked to BFCN degeneration that may propagate pathology throughout cortical memory and executive function circuits in DS and AD.

The cold-tolerant yeast Saccharomyces cerevisiae is industrially useful for lager fermentation, high-quality wine, and frozen dough production. S. cerevisiae Cheongdo is a recent isolate from frozen peach samples which has a good fermentation performance at low temperatures and desirable flavor profiles. Here, phenotype microarray was used to investigate industrial potentials of S. cerevisiae Cheongdo using 192 carbon sources. Compared to commercial wine yeast S. cerevisiae EC1118, Cheongdo showed significantly different growth rates on 34 substrates. The principal component analysis of the results highlighted that the better growth of Cheongdo on galactose than on EC1118 was the most significant difference between the two strains. The intact GAL4 gene and the galactose fermentation performance at a low temperatures suggested that S. cerevisiae Cheongdo is a promising host for industrial fermentation rich in galactose, such as lactose and agarose.

In this study, we conducted response surface methodology (RSM) and artificial neural network (ANN) to predict and estimate the optimized extraction condition of Nypa fruticans Wurmb. (NF). The effect of ethanol concentration (X

The aim of this study is to investigate the antidiabetic effect of lariciresinol (LSR) in C2C12 myotubes and streptozotocin (STZ)-induced diabetic mice.To investigate antidiabetic potential of LSR, α-glucosidase inhibitory assay, molecular docking, glucose uptake assay, western blot assay on antidiabetic biomarkers are performed. STZ-induced diabetic model is used for in vivo study by calculating oral glucose tolerance test, histochemical examination, and glycogen assay. LSR inhibits α-glucosidase activity with an ICThe findings indicate a potential usefulness for oral LSR in the management and prevention of diabetes by enhancing glucose homeostasis.

The Prunus mume seed is a by-product of the food industry, and we studied its potential as a food biomaterial, particularly for nutraceutical and inner beauty products. Alternative animal tests showed that an extract of P. mume ripened seed (PmRS) was not toxic on the skin. PmRS exhibited protective effects against ultraviolet- (UV-) induced skin aging in mice, confirmed by phenotypic indications, including increased collagen levels and decreased skin thickness. Compared with the UV-saline group, the UV-PmRS group showed increased levels of silent mating type information regulation 2 homolog 1 (SIRT1) and collagen and decreased matrix metalloproteinase- (MMP-) 1 expression. The protective effect of PmRS treatment against UVB-mediated cell viability was observed in vitro without any cytotoxicity, and PmRS prevented UVB-induced reactive oxygen species generation in HaCaT cells. PmRS downregulated MMP-1 and MMP-13 compared with the UVB-irradiated group. However, mRNA expressions of tissue inhibitor of metalloproteinase-1 and SIRT1 were upregulated by PmRS treatment. MMP-1 and SIRT1 treated with PmRS were decreased and increased, respectively, at the protein level. Moreover, PmRS treatment reduced c-Jun N-terminal kinase and p38 phosphorylation compared with the UVB-treated group. We postulate that P. mume seed could be a useful ingredient in nutraceuticals and inner beauty-purpose foods.

BACKGROUND: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. METHODS: We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). RESULTS: Ts65Dn mice had unique MSN BFCN transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. CONCLUSIONS: We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamatergic, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate an interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.

High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of Manilkara zapota L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against &alpha, glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of &alpha, glucosidase enzyme at a lower concentration (IC50 2.51 &plusmn, 0.15 &micro, g/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 &plusmn, 0.15% following the treatment with ZLE at 30 &micro, g/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC50 27.51 &plusmn, 1.70 &micro, g/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI&ndash, MS) detected more m/z peaks than electrospray ionization mass spectrometry (ESI&ndash, MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting &alpha, glucosidase activity and enhancing glucose uptake.

Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo−/− mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.

Ultraviolet B (UV-B) radiation induces the extreme production of either reactive oxygen species (ROS) or inflammatory mediators. The aim of this study was to evaluate the antioxidant activities of 70% ethanolic extract of Lablab purpureus (LPE) and the underlying mechanisms using HaCaT cells exposed to UV-B. High-performance liquid chromatography (HPLC) confirmed the presence of gallic acid, catechin, and epicatechin in LPE. LPE was shown to have a very potent capacity to scavenge free radicals. The results showed that LPE prevented DNA damage and inhibited the generation of ROS in HaCaT cells without causing any toxicity. LPE increased the expression of endogenous antioxidant enzymes such as superoxide dismutase-1 and catalase. Furthermore, LPE treatment facilitates the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), boosting the phase II detoxifying enzyme heme oxygenase-1 (HO-1) leading to the combatting of oxidative stress. However, pretreatment of LPE also caused the phosphorylation of mitogen-activated protein kinases (MAPK kinase) (p38 kinase) and extracellular signal-regulated kinase (ERK), whereas treatment with p38 and ERK inhibitors substantially suppressed LPE-induced Nrf2 and heme oxygenase (HO)-1 expression. These findings suggest that LPE exhibits antioxidant activity via Nrf-2-mediated HO-1 signaling through the activation of p38 and ERK, indicating that LPE can potentially be used as a remedy to combat oxidative stress-induced disorder.

Prolonged inflammatory responses can lead to the development of several chronic diseases, such as autoimmune disorders and the development of natural therapeutic agents is required. A murine model was used to assess the anti-inflammatory effects of the megastigmane glucoside, icariside B2 (ICSB), and the assessment was carried out in vitro, and in vivo. The in vitro anti-inflammatory effects of ICSB were tested using LPS-stimulated BV2 cells, and the protein expression levels of inflammatory genes and cytokines were assessed. Mice were subcutaneously injected with 1% carrageenan (CA) to induce acute phase inflammation in the paw. Inflammation was assessed by measuring paw volumes hourly, subsequently, the mice were euthanized and the right hind paw skin was expunged and processed for reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. ICSB inhibits LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) generation by reducing the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). ICSB also inhibits the COX-2 enzyme with an IC50 value of 7.80&plusmn, 0.26 &micro, M. Molecular docking analysis revealed that ICSB had a strong binding affinity with both murine and human COX-2 proteins with binding energies of &minus, 8 kcal/mol and &minus, 7.4 kcal/mol, respectively. ICSB also reduces the manifestation of pro-inflammatory cytokines, such as TNF-&alpha, IL-6, and IL-1&beta, at their transcriptional and translational level. ICSB hinders inhibitory protein &kappa, B&alpha, (I&kappa, ) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-&kappa, B) nuclear translocation. ICSB also represses the mitogen-activated protein kinases (MAPKs) signaling pathways. ICSB (50 mg/kg) showed an anti-edema effect in CA-induced mice and suppressed the CA-induced increases in iNOS and COX-2 protein levels. ICSB attenuated inflammatory responses by downregulating NF-&kappa, B expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-&alpha, IL-1&beta, and IL-6.

Ultraviolet B (UVB) irradiation is major causative factor in skin aging. The aim of the present study was to investigate the protective effect of a 50% ethanol extract from Nypa fruticans (NF50E) against UVB-induced skin aging. The results indicated that NF50E exerted potent antioxidant activity (IC50 = 17.55 ± 1.63 and 10.78 ± 0.63 μg/mL for DPPH and ABTS-radical scavenging activity, respectively) in a dose-dependent manner. High-performance liquid chromatography revealed that pengxianencin A, protocatechuic acid, catechin, chlorogenic acid, epicatechin, and kaempferol were components of the extract. In addition, the extract exhibited elastase inhibitory activity (IC50 = 17.96 ± 0.39 μg/mL). NF50E protected against UVB-induced HaCaT cell death and strongly suppressed UVB-stimulated cellular reactive oxygen species generation without cellular toxicity. Moreover, topical application of NF50E mitigated UVB-induced photoaging lesions including skin erythema and skin thickness in BALB/C mice. NF50E treatment inhibited UVB-induced collagen degradation as well as MMP-1 and IL-1β expressions and significantly stimulated SIRT1 expression. Furthermore, the extract treatment markedly suppressed the activation of NF-κB and AP-1 (p-c-Jun) by deactivating the p38 and JNK proteins. Taken together, current data suggest that NF50E exhibits potent antioxidant potential and protection against photoaging by attenuating MMP-1 activity and collagen degradation possibly through the downregulation of MAPK/NF-κB/AP-1 signaling and SIRT1 activation.

Background/objectives The study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms. Materials/methods Using 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting. Results At concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G0/G1 peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine. Conclusions We report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.

In this study, paper spray ionization (PSI) coupled to high-resolution mass spectrometry has been used to identify secondary metabolites from ethanol extracts of Averrhoa carambola L. bark (ABE). Various phytoconstituents including phenolic acids, flavonoids, xanthones and terpenoids were identified from the bark. ABE shows potential antioxidant activity as well as markedly inhibited α-glucosidase, elastase, and tyrosinase enzyme activities in a concentration-dependent fashion, respectively. ABE significantly inhibited α-glucosidase at lower concentration (IC50: 7.15 ± 0.06 μg/mL). Identified compounds were tested to understand the biological activity of ABE. Experimental results suggest that norathyriol, one of the identified compounds, has significant α-glucosidase (IC50: 0.81 ± 0.01 μg/mL) inhibition and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities (IC50: 4.90 ± 0.09 μg/mL). At a dose of 100 mg/kg, ABE significantly decreased the postprandial blood glucose level in oral glucose tolerance test (OGTT). This study shows that carambola bark can be a potential source of bioactive compounds.

We report on the ongoing R21 project “Social Reward Learning in Schizophrenia”. Impairments in social cognition are a hallmark of schizophrenia. However, little work has been done on social reward learning deficits in schizophrenia. The overall goal of the project is to assess social reward learning in schizophrenia. A probabilistic reward learning (PRL) task is being used in the MRI scanner to evaluate reward learning to negative and positive social feedback. Monetary reward learning is used as a comparison to assess specificity. Behavioral outcomes and brain areas, included those involved in reward, are assessed in patients with schizophrenia or schizoaffective disorder and controls. It is also critical to determine whether decreased expected value (EV) of social stimuli and/or reward prediction error (RPE) learning underlie social reward learning deficits to inform potential treatment pathways. Our central hypothesis is that the pattern of social learning deficits is an extension of a more general reward learning impairment in schizophrenia and that social reward learning deficits critically contribute to deficits in social motivation and pleasure. We hypothesize that people with schizophrenia will show impaired behavioral social reward learning compared to controls, as well as decreased ventromedial prefrontal cortex (vmPFC) EV signaling at time of choice and decreased striatal RPE signaling at time of outcome, with potentially greater impairment to positive than negative feedback. The grant is in its second year. It is hoped that this innovative approach may lead to novel and more targeted treatment approaches for social cognitive impairments, using cognitive remediation and/or brain stimulation.

This letter presents a wireless power transfer (WPT) system for wristband device charging. By using dual receiver coils with power switches in an interleaved manner, the proposed WPT system can simultaneously operate to accumulate energy from the primary coil and transfer the previously accumulated energy to the battery in each coil. As a result, the WPT efficiency can be increased with the small coils, even at high load resistance. The proposed WPT system is theoretically analyzed by a lumped circuit model and verified by measurement using prototype boards. Compared with the conventional WPT structure that uses one receiver coil ( $\text{2}\,{\text{cm}}\,\times \,\text{5}\,{\text{cm}}$ ), the proposed WPT system with two receiver coils (each $\text{2}\,{\text{cm}}\,\times \,{\text{2.5}}\,{\text{cm}}$ ) achieved a 6.67% end-to-end power efficiency improvement at the output resistance of 100 Ω under the same condition of the coil dimension and the resonant frequency of 140 kHz.

Although preterm infants are at risk for social deficits, interventions to improve mother-infant interaction in the neonatal intensive care unit (NICU) are not part of standard care (SC). Study participants were a subset from a randomized controlled trial of a new intervention for premature infants, the Family Nurture Intervention (FNI), designed to help mothers and infants establish an emotional connection. At infants' 4 months corrected age, mother-infant face-to-face interaction was filmed and coded on a 1-s time base for mother touch, infant vocal affect, mother gaze, and infant gaze. Time-series models assessed self- and interactive contingency. Comparing FNI to SC dyads, FNI mothers showed more touch and calmer touch patterns, and FNI infants showed more angry-protest but less cry. In maternal touch self-contingency, FNI mothers were more likely to sustain positive touch and to repair moments of negative touch by transitioning to positive touch. In maternal touch interactive contingency, when infants looked at mothers, FNI mothers were likely to respond with more positive touch. In infant vocal affect self-contingency, FNI infants were more likely to sustain positive vocal affect and to transition from negative to positive vocal affect. In maternal gaze interactive contingency, following infants' looking at mother, FNI mothers of male infants were more likely to look at their sons. In maternal gaze self-contingency, following mothers' looking away, FNI mothers of male infants were more likely to look at their sons. Documentation of positive effects of the FNI for 4-month mother-infant face-to-face communication is useful clinically and has important implications for an improved developmental trajectory of these infants. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

β-Escin, a natural triterpene saponin was extracted from Aesculus hippocastanum seeds, which have been widely used to treat inflammation in traditional medicine. In an effort to study the possible anti-tumor effects of β-escin, we performed wound healing, invasion, and adhesion assays to examine the effects of β-escin on cell migration, invasion, and angiogenesis. Our results revealed that β-escin inhibits cell migration as well as motility in B16F10 and SK-MEL5 cells in a dose-dependent manner. RT-PCR and Western blot analysis showed that β-escin increased TIMP-1, -2 while significantly downregulated phosphorylated extracellular signal-regulated kinase (p-ERK) expression, and suppressing nuclear factor-kappa B (NF-κB) and inhibitor of nuclear factor-kappa B (IκB) expression. Overall, the data from the current study suggest that β-escin has the potential for inhibiting both metastatic and angiogenic activities, and are the earliest evidence for the involvement of the NF-κB/IκB signaling in β-escin-induced anti-tumor effects.

Separability is an attractive feature of covariance matrices or matrix variate data, which can improve and simplify many multivariate procedures. Due to its importance, testing separability has attracted much attention in the past. The procedures in the literature are of two types, likelihood ratio test (LRT) and Rao’s score test (RST). Both are based on the normality assumption or the large-sample asymptotic properties of the test statistics. In this paper, we develop a new approach that is very different from existing ones. We propose to reformulate the null hypothesis (the separability of a covariance matrix of interest) into many sub-hypotheses (the separability of the sub-matrices of the covariance matrix), which are testable using a permutation based procedure. We then combine the testing results of sub-hypotheses using the Bonferroni and two-stage additive procedures. Our permutation based procedures are inherently distribution free; thus it is robust to non-normality of the data. In addition, unlike the LRT, they are applicable to situations when the sample size is smaller than the number of unknown parameters in the covariance matrix. Our numerical study and data examples show the advantages of our procedures over the existing LRT and RST.

This paper presents a phase-cut dimmable ac–dc buck LED driver for electrolytic capacitor-less LED lighting applications. In the driver, the sine-reference band (SRB)-controlled average current technique is proposed to perform rectified sine-average current control and phase-cut dimming control. The rectified sine-average current control can regulate the average value of sine-wave LED current, maintaining a high power factor (PF) over a wide range of ac input voltage and output LED load. The phase-cut dimming control not only makes the LED driver compatible with two types of phase-cut dimmers, namely, leading-edge and trailing-edge dimming types, but also eliminates visible dimming flicker at the ac line frequency. Fabricated in a 0.35 μ m CMOS process, experimental results show the line regulation of ±2.36% over 90 to 260 VAC and the load regulation of ±0.65% within the load range of 10 to 36 LEDs. The PF exceeds 0.95 under all conditions, and the peak efficiency of 90.7% is achieved. The analysis of the flicker frequency verifies that the proposed dimmable LED driver completely eliminates visible flicker owing to the phase dimming variations without an output electrolytic capacitor.

We examined the anti-inflammatory effects of (+)-syringaresinol (SGRS), a lignan isolated from Rubia philippinensis, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells using enzyme-based immuno assay, Western blotting, and RT-PCR analyses. Additionally, in vivo effects of SGRS in the acute inflammatory state were examined by using the carrageenan-induced hind paw edema assay in experimental mice. As a result, treatment with SGRS (25, 50, and 100 μM) inhibited protein expression of lipopolysaccharide-stimulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) as well as production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) induced by LPS. Moreover, SGRS also reduced LPS-induced mRNA expression levels of iNOS and COX-2, including NO, PGE2, TNF-α, IL-1β, and IL-6 cytokines in a dose-dependent fashion. Furthermore, carrageenan-induced paw edema assay validated the in vivo anti-edema effect of SGRS. Interestingly, SGRS (30 mg/kg) suppressed carrageenan-induced elevation of iNOS, COX-2, TNF-α, IL-1β, and IL-6 mRNA levels as well as COX-2 and NF-κB protein levels, suggesting SGRS may possess anti-inflammatory activities.

The Korea Research Institute of Standards and Science (KRISS) participated in the BIPM.RI(II)-K4.Tc-99 m comparison of activity measurements of 99mTc. We develop the national primary standard for 99mTc solution used during the comparison. We use two primary liquid scintillation counting techniques for the standardization: digital coincidence counting with the 4πβ(LS)-γ(NaI(T1))system and triple-to-double coincidence ratio counting. Both methods give consistent results for the specific activity of a 99mTc solution. Adopting the result from the DCC method as the reference value of the 99mTc measurement, we evaluate the standard uncertainty of 0.856% for the KRISS primary standard of the 99mTc activity. The K4 comparison result shows that the newly-established KRISS primary standard lies within the standard uncertainty with the key comparison reference value defined from other 99mTc measurements.

This letter presents a 2-phase 3-level (2P3L) envelope tracking supply modulator (ETSM) for a long-term evolution 20 MHz (LTE20) radio frequency power amplifier as a solution for the ET system. This 2P3L ETSM that is composed of only switching converters achieves high efficiency, fast transient response, and a small output current ripple. To properly operate the proposed 2P3L ETSM, 4 pulse width modulatiop (PWM) signals with a 90° phase shift from each PWM signal are required without any mismatch between duty cycles. To remove the mismatch, a time-division multiplexing comparator and a duty-cycle calibrator are proposed. Thanks to the proposed techniques, the proposed ETSM fabricated in 0.18-μm CMOS achieved the highest peak dynamic efficiency of 88.6% with an LTE20 signal, which is superior to the state-of-the-art systems.

본 연구에서는 국내산 상황버섯의 효소 가수분해 전처리를 통한 β-glucan의 최적 추출조건을 확립하고 그에 따른 활성을 알아보고자 추출 조건에 따른 생이화학적활성을 측정하였다. 효소 가수분해 조건을 최적화하기 위해 실시한 반응표면분석법의 결과 0.66%(v/v)의 viscozyme 농도에서 6.08시간 반응하는 것이 최적이라 예측되었으며(R2=0.9245), 이에 따라 최적 추출 조건에서 추출한 시료의 β-glucan 함량은 1.9594 g/100 g으로 측정되었다. 추출 수율(0.76-16.40%)은 EBE가 NEBE에 비해 약 3배 높았다. β-glucan 순도(11.15-59.05%)로 가장 높았으며, β-glucan 함량 또한 0.26-3.38 g/100 g으로 EB (3.38 g/100 g)가 가장 높았다. 총당 함량(0.61-1.17 mg/mL)은 NEB, EB가 NEBE, EBE보다 높았으며, EB가 가장 높았다. 구성당 분석 결과, 모든 추출물에서 glucose의 함량이 가장 높았으며, 대조구와 효소 전처리구 모두 정제하면서 그 비율이 증가하였다. 단백질 함량(0.44-11.73 mg/mL)은 NEBE, EBE가 NEB, EB보다 높았으며, EBE가 가장 높았다. FT-IR 분석 결과 890 cm-1 부근에서 peak가 확인되었기에 β-glycosidic linkage를 가지고 있는 것으로 판단하였다. MTT assay를 통해 B6F10과 SK-MEL-5 세포 독성을 측정한 결과 B6F10의 경우 대조구의 세포 생존율을 100%로 하였을 때 세포 생존율이 80% 이상으로 나타나 세포독성을 보이지 않았으나, SK-MEL-5에서는 EBE를 100 μg/mL의 농도로 처리하였을 때 세포 생존율이 75%로 나타나 약간의 세포독성을 보였다. Wound healing assay를 통해 암세포 증식 억제 활성 측정 결과, 정제한 NEB, EB가 NEBE, EBE보다 활성이 높았으며, 특히 12시간일 때 EB 30 μg/mL를 처리한 경우 B6F10과 SK-MEL-5 모두에서 가장 높은 활성을 나타내었다.

In this study, the high-pressure steaming and enzymatic pre-treatment (SET) was used to improve β-glucan extraction from Ganoderma lucidum (G. lucidum), an oriental medicinal mushroom. Response surface methodology and central composite design were used to determine the optimum pre-treatment conditions: high-pressure steaming, enzymatic hydrolysis, and Viscozyme L concentrations. The optimal conditions were 15.51 min for high-pressure steaming, 0.84 g/100 mL of Viscozyme L, and 4.16 h for hydrolysis. The predicted β-glucan content in G. lucidum extract at optimal conditions, approximately twofold (8.05 g/100 g) of the control treatment value, was consistent with the empirical value. The total sugar and protein contents through SET were higher than those values of the control treatment. The cell migration assay showed that SET-processed G. lucidum extracts significantly suppressed B16F10 murine melanoma cell growth. SET process using Viscozyme L could be utilized for β-glucan extraction from G. lucidum to develop the functional food.

Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer’s disease (AD), there is a lack of systematic assessments of gene expression and encoded proteins within individual vulnerable cell populations, precluding translational investigations at the molecular and cellular level. Further, no effective treatment exists to combat intellectual disability and basal forebrain cholinergic neurodegeneration seen in DS. To further our understanding of gene expression changes before and following cholinergic degeneration in a well-established mouse model of DS/AD, the Ts65Dn mouse, we assessed RNA expression levels from CA1 pyramidal neurons at two adult ages (~6 months of age and ~11 months of age) in both Ts65Dn and their normal disomic (2N) littermates. We further examined a therapeutic intervention, maternal choline supplementation (MCS), which has been previously shown to lessen dysfunction in spatial cognition and attention, and have protective effects on the survival of basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model. Results indicate that MCS normalized expression of several genes in key gene ontology categories, including synaptic plasticity, calcium signaling, and AD-associated neurodegeneration related to amyloid-beta peptide (Aβ) clearance. Specifically, normalized expression levels were found for endothelin converting enzyme-2 (Ece2), insulin degrading enzyme (Ide), Dyrk1a, and calcium/calmodulin-dependent protein kinase II (Camk2a), among other relevant genes. Single population expression profiling of vulnerable CA1 pyramidal neurons indicates that MCS is a viable therapeutic for long-term reprogramming of key transcripts involved in neuronal signaling that are dysregulated in the trisomic mouse brain which have translational potential for DS and AD.

Objective CD16+ /CD163+ macrophages (MΦs) and microglia accumulate in the brains of patients with human immunodeficiency virus (HIV) encephalitis (HIVE), a neuropathological correlate of the most severe form of HIV-associated neurocognitive disorders, HIV-associated dementia. Recently, we found that some parenchymal microglia in brain of HIV+ subjects without encephalitis (HIV/noE) but with varying degrees of neurocognitive impairment express CD16 and CD163, even in the absence of detectable virus production. To further our understanding of microglial activation in HIV, we investigated expression of specific genes by profiling parenchymal microglia from archival brain tissue of patients with HIVE and HIV/noE, and HIV- controls. Methods Single-population microarray analyses were performed on ∼2,500 laser capture microdissected CD163+ , CD16+ , or CD68+ MΦs/microglia per case, using terminal continuation RNA amplification and a custom-designed array platform. Results Several classes of microglial transcripts in HIVE and HIV/noE were altered, relative to HIV- subjects, including factors related to cell stress, immune activation, and apoptosis. Additionally, several neurotrophic factors were reduced in HIV infection, suggesting an additional mechanism of neuropathogenesis. The majority of transcripts altered in HIVE displayed intermediate changes in HIV/noE. Interpretation Our results support the notion that microglia contribute to the maintenance of brain homeostasis and their potential loss of function in the context of chronic inflammation contributes to neuropathogenesis. Furthermore, they indicate the utility of profiling MΦs/microglia to increase our understanding of microglia function, as well as to ascertain alterations in specific pathways, genes, and potentially, encoded proteins that may be amenable to targeted treatment modalities in diseases affecting the brain. Ann Neurol 2018;83:406-417.

Aim Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase involved in various biological functions via deacetylation of proteins, including histone protein. Hepatic fat accumulation from aging and excess caloric intake contribute to development of non-alcoholic fatty liver disease. The study aim was to elucidate the role of SIRT2 in lipid metabolism homeostasis. Materials and methods SIRT2+/+ (C57BL/6) and SIRT2−/− were randomly assigned to normal diet or high-fat diet (HFD) groups and fed for 6 weeks. Histological features of the livers were evaluated by hematoxylin and eosin and Masson's trichrome staining, and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction and western blot analysis. Key findings Although the SIRT2−/− mice were viable, their livers exhibited higher glycogen accumulation, and skeletal muscle showed features of increased metabolic demand. The SIRT2−/− mice attenuated HFD-induced weight gain, visceral adipose tissue formation, and fat accumulation in the liver in which the expressions of genes involved in metabolic substrate transport were modified. Additionally, the hepatocellular senescence and upregulated cell-cycle factors upon HFD intake in SIRT2−/− livers suggested a role of SIRT2 in gene expression during abnormal metabolism. Moreover, the fibrotic phenotype of liver tissue without fat accumulation and the increased expression of genes involved in liver fibrosis in the HFD-fed SIRT2−/− mice indicated that SIRT2 had a role in hepatocyte and hepatic stellate cell activation. Significance Our results indicated that SIRT2 has a critical role in regulating lipid metabolic homeostasis and in sustaining liver integrity by modulating related gene expression.

A novel antioxidant peptide YD1 (∼1.0kDa), purified from the strain Bacillus amyloliquefaciens CBSYD1, displayed activity in several in vitro assays and was also efficient against Gram-positive, Gram-negative as well as multidrug-resistant (MDR) bacteria. Strain growth was adapted to bile-salt conditions where a clear halos-zone was observed in a bile-salt plate assay and was viable in different digestive track conditions. YD1 treatment on RAW 264.7 cells increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) through the enhanced levels of heme oxygenase-1 (HO-1). Furthermore, the YD1-treated group showed higher levels of antioxidant enzymes compared to the oxidative stress group. YD1 demonstrated a strong antioxidant activity by decreasing nitric oxide (NO) and reactive oxygen species (ROS) in RAW 264.7 cells. This study suggests that YD1 and the strain could be a natural antioxidant and a probiotic candidate respectively.